An inter-laboratory comparison of urinary 3-hydroxypropylmercapturic acid measurement demonstrates good reproducibility between laboratories

Directory of Open Access Journals (Sweden)

Bailey Brian

2011-10-01

Full Text Available Abstract Background Biomarkers have been used extensively in clinical studies to assess toxicant exposure in smokers and non-smokers and have recently been used in the evaluation of novel tobacco products. The urinary metabolite 3-HPMA, a metabolite of the major tobacco smoke toxicity contributor acrolein, is one example of a biomarker used to measure exposure to tobacco smoke. A number of laboratories have developed liquid chromatography with tandem mass spectrometry (LC-MS/MS based methods to measure urinary 3-HPMA; however, it is unclear to what extent the data obtained by these different laboratories are comparable. Findings This report describes an inter-laboratory comparison carried out to evaluate the comparability of 3-HPMA measurement between four laboratories. A common set of spiked and authentic smoker and non-smoker urine samples were used. Each laboratory used their in-house LC-MS/MS method and a common internal standard. A comparison of the repeatability ('r', reproducibility ('R', and coefficient of variation for 3-HPMA demonstrated that within-laboratory variation was consistently lower than between-laboratory variation. The average inter-laboratory coefficient of variation was 7% for fortified urine samples and 16.2% for authentic urine samples. Together, this represents an inter-laboratory variation of 12.2%. Conclusion The results from this first inter-laboratory comparison for the measurement of 3-HPMA in urine demonstrate a reasonably good consensus between laboratories. However, some consistent measurement biases were still observed between laboratories, suggesting that additional work may be required to further reduce the inter-laboratory coefficient of variation.

N-nitrosodimethylamine in effluents and groundwater. Interlaboratory study No. 91-2

Energy Technology Data Exchange (ETDEWEB)

Cussion, S

1992-01-01

Interlaboratory study 91-2 was initiated as part of an on-going program of laboratory performance management studies to assess the performance of participating laboratories for the analysis of N-nitrosodimethylamine (NDMA) in spiked effluents and in groundwater. Thirteen government, industry and commercial laboratories agreed to participate in the study and results were received from 11 participants.

Centrally Determined Standardization of Flow Cytometry Methods Reduces Interlaboratory Variation in a Prospective Multicenter Study.

Science.gov (United States)

Westera, Liset; van Viegen, Tanja; Jeyarajah, Jenny; Azad, Azar; Bilsborough, Janine; van den Brink, Gijs R; Cremer, Jonathan; Danese, Silvio; D'Haens, Geert; Eckmann, Lars; Faubion, William; Filice, Melissa; Korf, Hannelie; McGovern, Dermot; Panes, Julian; Salas, Azucena; Sandborn, William J; Silverberg, Mark S; Smith, Michelle I; Vermeire, Severine; Vetrano, Stefania; Shackelton, Lisa M; Stitt, Larry; Jairath, Vipul; Levesque, Barrett G; Spencer, David M; Feagan, Brian G; Vande Casteele, Niels

2017-11-02

Flow cytometry (FC) aids in characterization of cellular and molecular factors involved in pathologic immune responses. Although FC has potential to facilitate early drug development in inflammatory bowel disease, interlaboratory variability limits its use in multicenter trials. Standardization of methods may address this limitation. We compared variability in FC-aided quantitation of T-cell responses across international laboratories using three analytical strategies. Peripheral blood mononuclear cells (PBMCs) were isolated from three healthy donors, stimulated with phorbol 12-myristate 13-acetate and ionomycin at a central laboratory, fixed, frozen, and shipped to seven international laboratories. Permeabilization and staining was performed in triplicate at each laboratory using a common protocol and centrally provided reagents. Gating was performed using local gating with a local strategy (LGLS), local gating with a central strategy (LGCS), and central gating (CG). Median cell percentages were calculated across triplicates and donors, and reported for each condition and strategy. The coefficient of variation (CV) was calculated across laboratories. Between-strategy comparisons were made using a two-way analysis of variance adjusting for donor. Mean interlaboratory CV ranged from 1.8 to 102.1% depending on cell population and gating strategy (LGLS, 4.4-102.1%; LGCS, 10.9-65.6%; CG, 1.8-20.9%). Mean interlaboratory CV differed significantly across strategies and was consistently lower with CG. Central gating was the only strategy with mean CVs consistently lower than 25%, which is a proposed standard for pharmacodynamic and exploratory biomarker assays.

Interlaboratory Collaborations in the Undergraduate Setting

Science.gov (United States)

Megehee, Elise G.; Hyslop, Alison G.; Rosso, Richard J.

2005-01-01

A novel approach to cross-disciplinary and group learning, known as interlaboratory collaborations, was developed. The method mimics an industrial or research setting, fosters teamwork, and emphasizes the importance of good communication skills in the sciences.

Inter-laboratory assessment of a prototype multiplex kit for determination of recent HIV-1 infection.

Directory of Open Access Journals (Sweden)

Kelly A Curtis

Full Text Available BACKGROUND: Accurate and reliable laboratory-based assays are needed for estimating HIV-1 incidence from cross-sectional samples. We recently described the development of a customized, HIV-1-specific Bio-Plex assay that allows for the measurement of HIV-specific antibody levels and avidity to multiple analytes for improved HIV-1 incidence estimates. METHODS: To assess intra- and inter-laboratory assay performance, prototype multiplex kits were developed and evaluated by three distinct laboratories. Longitudinal seroconversion specimens were tested in parallel by each laboratory and kit performance was compared to that of an in-house assay. Additionally, the ability of the kit to distinguish recent from long-term HIV-1 infection, as compared to the in-house assay, was determined by comparing the reactivity of known recent (infected 12 months drug naïve specimens. RESULTS: Although the range of reactivity for each analyte varied between the prototype kit and in-house assay, a measurable distinction in reactivity between recent and long-term specimens was observed with both assays in all three laboratories. Additionally, kit performance was consistent between all three laboratories. The intra-assay coefficient of variation (CV, between sample replicates for all laboratories, ranged from 0.5% to 6.1%. The inter-laboratory CVs ranged from 8.5% to 21.3% for gp160-avidity index (a and gp120-normalized mean fluorescent intensity (MFI value (n, respectively. CONCLUSION: We demonstrate the feasibility of producing a multiplex kit for measuring HIV antibody levels and avidity, with the potential for improved incidence estimates based on multi-analyte algorithms. The availability of a commercial kit will facilitate the transfer of technology among diverse laboratories for widespread assay use.

First international 26Al interlaboratory comparison - Part II

International Nuclear Information System (INIS)

Merchel, Silke; Bremser, Wolfram

2005-01-01

After finishing Part I of the first international 26 Al interlaboratory comparison with accelerator mass spectrometry (AMS) laboratories [S. Merchel, W. Bremser, Nucl. Instr. and Meth. B 223-224 (2004) 393], the evaluation of Part II with radionuclide counting laboratories took place. The evaluation of the results of the seven participating laboratories on four meteorite samples shows a good overall agreement between laboratories, i.e. it does not reveal any statistically significant differences if results are compared sample-by-sample. However, certain interlaboratory bias is observed with a more detailed statistical analysis including some multivariate approaches

Inter-laboratory exercise on steroid estrogens in aqueous samples

DEFF Research Database (Denmark)

Heath, E.; Kosjek, T.; Andersen, Henrik Rasmus

2010-01-01

to the analytical techniques applied, the accuracy and reproducibility of the analytical methods and the nature of the sample matrices. Overall, the results obtained in this inter-laboratory exercise reveal a high level of competence among the participating laboratories for the detection of steroid estrogens......An inter-laboratory comparison exercise was organized among European laboratories, under the aegis of EU COST Action 636: "Xenobiotics in Urban Water Cycle" The objective was to evaluate the performance of testing laboratories determining "Endocrine Disrupting Compounds" (EDC) in various aqueous...

Centrally Determined Standardization of Flow Cytometry Methods Reduces Interlaboratory Variation in a Prospective Multicenter Study

Science.gov (United States)

Westera, Liset; van Viegen, Tanja; Jeyarajah, Jenny; Azad, Azar; Bilsborough, Janine; van den Brink, Gijs R; Cremer, Jonathan; Danese, Silvio; D'Haens, Geert; Eckmann, Lars; Faubion, William; Filice, Melissa; Korf, Hannelie; McGovern, Dermot; Panes, Julian; Salas, Azucena; Sandborn, William J; Silverberg, Mark S; Smith, Michelle I; Vermeire, Severine; Vetrano, Stefania; Shackelton, Lisa M; Stitt, Larry; Jairath, Vipul; Levesque, Barrett G; Spencer, David M; Feagan, Brian G; Vande Casteele, Niels

2017-01-01

Objectives: Flow cytometry (FC) aids in characterization of cellular and molecular factors involved in pathologic immune responses. Although FC has potential to facilitate early drug development in inflammatory bowel disease, interlaboratory variability limits its use in multicenter trials. Standardization of methods may address this limitation. We compared variability in FC-aided quantitation of T-cell responses across international laboratories using three analytical strategies. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from three healthy donors, stimulated with phorbol 12-myristate 13-acetate and ionomycin at a central laboratory, fixed, frozen, and shipped to seven international laboratories. Permeabilization and staining was performed in triplicate at each laboratory using a common protocol and centrally provided reagents. Gating was performed using local gating with a local strategy (LGLS), local gating with a central strategy (LGCS), and central gating (CG). Median cell percentages were calculated across triplicates and donors, and reported for each condition and strategy. The coefficient of variation (CV) was calculated across laboratories. Between-strategy comparisons were made using a two-way analysis of variance adjusting for donor. Results: Mean interlaboratory CV ranged from 1.8 to 102.1% depending on cell population and gating strategy (LGLS, 4.4–102.1% LGCS, 10.9–65.6% CG, 1.8–20.9%). Mean interlaboratory CV differed significantly across strategies and was consistently lower with CG. Conclusions: Central gating was the only strategy with mean CVs consistently lower than 25%, which is a proposed standard for pharmacodynamic and exploratory biomarker assays. PMID:29095427

Inter-laboratory proficiency tests to detect viral fish diseases

DEFF Research Database (Denmark)

Kahns, Søren; Nicolajsen, Nicole; Skall, Helle Frank

An inter-laboratory proficiency test has ben provided by the European Community Laboratory (CRL) for Fish Diseases every year since 1996. The test is provided to all European National Reference Laboratories (NRLs) that are obliged to participate and to a limited number of non-European NRLs, making......) but also to assess their ability to differentiate other fish viruses as spring viraemia of carp virus, infectious pancreatic necrosis virus, perch rhabdovirus etc. Five coded ampoules are provided to participants containing lyophilised supernatant from infected cell cultures. The CRL collect the data...

Radiocarbon dating of interlaboratory check samples

International Nuclear Information System (INIS)

Blake, W.

1983-01-01

This note presents the results of a series of interlaboratory age determinations in which the Geological Survey of Canada's Radiocarbon Dating Laboratory has been involved. There is good agreement between laboratories, although there may be other problems related to the interpretation of individual samples

Interlaboratory quality assurance studies: Their use in certifying natural waters for major constituents and trace elements

International Nuclear Information System (INIS)

Alkema, H.; Simser, J.; Hjelm, L.

1998-01-01

Environmental programs throughout North America have demonstrated a strong awareness of the usefulness of interlaboratory studies for disclosing the quality of analytical results. The Ecosystem Interlaboratory Quality Assurance Program offered by the National Water Research Institute has a wide participation base of laboratories. Many of these laboratories are accredited and employ a number of recognized analytical methods. The interlaboratory study data archives contain a wealth of data for natural surface and rain waters from across the continent. These archives have proven to be a reliable means of characterizing a variety of constituents. Data assessments from these studies accurately identify the variability of data and the presence of any outliers. Repeated use of selected samples in a regular QA program confirms their stability. Time charts and statistical techniques are used to illustrate this stability and yield the precision of pooled analyses. The availability of archived data from interlaboratory studies has enabled the Institute to develop and certify natural water and trace element standards. The natural water CRM, ION-911, has been available for several years. Its historical aspects are discussed as well as the processes leading to the certification of TMRain-95, a soft water standard certifying 22 trace elements. This paper focuses on the use of select laboratories in round-robin evaluations to provide accurate values for constituent concentrations. Natural water and fortified trace element CRMs meet a recognized need in the generation of accurate data for environmental programs. (orig.)

Inter-laboratory exercise on steroid estrogens in aqueous samples

International Nuclear Information System (INIS)

Heath, E.; Kosjek, T.; Andersen, H.R.; Holten Luetzhoft, H.-C.; Adolfson Erici, M.; Coquery, M.; Duering, R.-A.; Gans, O.; Guignard, C.; Karlsson, P.; Manciot, F.; Moldovan, Z.; Patureau, D.; Cruceru, L.; Sacher, F.; Ledin, A.

2010-01-01

An inter-laboratory comparison exercise was organized among European laboratories, under the aegis of EU COST Action 636: 'Xenobiotics in Urban Water Cycle'. The objective was to evaluate the performance of testing laboratories determining 'Endocrine Disrupting Compounds' (EDC) in various aqueous matrices. As the main task three steroid estrogens: 17α-ethinylestradiol, 17β-estradiol and estrone were determined in four spiked aqueous matrices: tap water, river water and wastewater treatment plant influent and effluent using GC-MS and LC-MS/MS. Results were compared and discussed according to the analytical techniques applied, the accuracy and reproducibility of the analytical methods and the nature of the sample matrices. Overall, the results obtained in this inter-laboratory exercise reveal a high level of competence among the participating laboratories for the detection of steroid estrogens in water samples indicating that GC-MS as well as LC-MS/MS can equally be employed for the analysis of natural and synthetic hormones. - Herein are presented the results of the first international inter-laboratory study on determination of selected steroid hormones in environmental aqueous samples.

Practical methodological guide for hydrometric inter-laboratory organisation

Science.gov (United States)

Besson, David; Bertrand, Xavier

2015-04-01

Discharge measurements performed by the French governmental hydrometer team feed a national database. This data is available for general river flows knowkedge, flood forecasting, low water survey, statistical calculations flow, control flow regulatory and many other uses. Regularly checking the measurements quality and better quantifying its accuracy is therefore an absolute need. The practice of inter-laboratory comparison in hydrometry particularly developed during the last decade. Indeed, discharge measurement can not easily be linked to a standard. Therefore, on-site measurement accuracy control is very difficult. Inter-laboratory comparison is thus a practical solution to this issue. However, it needs some regulations in order to ease its practice and legitimize its results. To do so, the French government hydrometrics teams produced a practical methodological guide for hydrometric inter-laboratory organisation in destination of hydrometers community in view of ensure the harmonization of inter-laboratory comparison practices for different materials (ADCP, current meter on wadind rod or gauging van, tracer dilution, surface speed) and flow range (flood, low water). Ensure the results formalization and banking. The realisation of this practice guide is grounded on the experience of the governmental teams & their partners (or fellows), following existing approaches (Doppler group especially). The guide is designated to validate compliance measures and identify outliers : Hardware, methodological, environmental, or human. Inter-laboratory comparison provides the means to verify the compliance of the instruments (devices + methods + operators) and provides methods to determine an experimental uncertainty of the tested measurement method which is valid only for the site and the measurement conditions but does not address the calibration or periodic monitoring of the few materials. After some conceptual definitions, the guide describes the different stages of an

Inter-laboratory study to characterize the detection of serum antibodies against porcine epidemic diarrhoea virus.

Science.gov (United States)

Strandbygaard, Bertel; Lavazza, Antonio; Lelli, Davide; Blanchard, Yannick; Grasland, Béatrice; Poder, Sophie Le; Rose, Nicolas; Steinbach, Falko; van der Poel, Wim H M; Widén, Frederik; Belsham, Graham J; Bøtner, Anette

2016-12-25

Porcine epidemic diarrhea virus (PEDV) has caused extensive economic losses to pig producers in many countries. It was recently introduced, for the first time, into North America and outbreaks have occurred again in multiple countries within Europe as well. To assess the properties of various diagnostic assays for the detection of PEDV infection, multiple panels of porcine sera have been shared and tested for the presence of antibodies against PEDV in an inter-laboratory ring trial. Different laboratories have used a variety of "in house" ELISAs and also one commercial assay. The sensitivity and specificity of each assay has been estimated using a Bayesian analysis applied to the ring trial results obtained with the different assays in the absence of a gold standard. Although different characteristics were found, it can be concluded that each of the assays used can detect infection of pigs at a herd level by either the early European strains of PEDV or the recently circulating strains (INDEL and non-INDEL). However, not all the assays seem suitable for demonstrating freedom from disease in a country. The results from individual animals, especially when the infection has occurred within an experimental situation, show more variation. Copyright © 2016. Published by Elsevier B.V.

Results of a European interlaboratory comparison on CO2 sorption on activated carbon and coals

Science.gov (United States)

Gensterblum, Yves; Busch, Andreas; Krooss, Bernhard; de Weireld, Guy; Billemont, Pierre; van Hemert, Patrick; Wolf, Karl-Heinz

2013-04-01

For the assessment of CO2 storage in coal seams or enhanced coalbed methane production (ECBM), the sorption properties of natural coals are important parameters. Since more and more laboratories worldwide are concerned with measurements of gas sorption on coal it is indispensable to establish quality standards for such experiments. The first two interlaboratory studies on CO2 sorption on coal (Goodman et al. 2004, 2007) revealed a poor agreement of sorption isotherms among the participating laboratories, particularly in the high-pressure range. During the MOVECBM (http://www.movecbm.eu/) project funded by the European Commission (6th framework), an interlaboratory comparison of CO2 sorption on selected coals and activated carbon was initiated. Measurements were performed on dry samples at 45° C using the manometric and the gravimetric method. up to a final pressure of 15 MPa. The first set of high-pressure sorption measurements was performed on a Filtrasorb 400 activated carbon sample in order to minimise heterogeneity effects and to optimize the experimental procedures for the individual (manometric or gravimetric) methods (Gensterblum et al. 2009). Since comparability for the activated carbon was excellent, the measurements were continued using natural coals of various rank (anthracite, bituminous coal and lignite) to study the influence of heterogeneities and varying starting conditions on the CO2 sorption properties (Gensterblum et al. 2010). Compared to the poor reproducibility observed in previous interlaboratory studies (Goodman et al., 2004, 2007) this European study showed excellent agreement (van Hemert, P. Billemont, A. Busch, B.M. Krooss, G. de Weireld, D. Prinz , K.-H.A.A. Wolf, "European inter-laboratory comparison of high pressure CO2 sorption isotherms. II: natural coals" IJCG, 2010, 84, 115-124 Gensterblum Y., P. van Hemert, P. Billemont, A. Busch, D. Charriére, D. Li, B.M. Krooss, G. de Weireld, D. Prinz , K.-H.A.A. Wolf, "European inter-laboratory

Inter-laboratory exercise on steroid estrogens in aqueous samples

Energy Technology Data Exchange (ETDEWEB)

Heath, E., E-mail: ester.heath@ijs.s [Department of Environmental Sciences, Jozef Stefan Institute, Jamova 39, 1000 Ljubljana (Slovenia); Kosjek, T. [Department of Environmental Sciences, Jozef Stefan Institute, Jamova 39, 1000 Ljubljana (Slovenia); Andersen, H.R.; Holten Luetzhoft, H.-C. [Department of Environmental Engineering, Technical University of Denmark, Miljoevej 113, DK-2800 Kgs. Lyngby (Denmark); Adolfson Erici, M. [Stockholm University, ITM SE-106 91 Stockholm (Sweden); Coquery, M. [Cemagref, U.R. QELY, F-69336 Lyon (France); Duering, R.-A. [Giessen University, Institute of Soil Science and Soil Conservation, Giessen (Germany); Gans, O. [Umweltbundesamt GmbH, Unit Organic Analysis, Spittelauer Laende 5, 1090 Vienna (Austria); Guignard, C. [CRP Gabriel Lippmann, EVA, 41 rue du Brill, L-4422 Belvaux (Luxembourg); Karlsson, P. [Lantmannen Analycen AB, Research and Development, Sjoehagsgatan 3 Box 905, 5319, Lidkoeping (Sweden); Manciot, F. [CAE VEOLIA ENVIRONMENT, 1 Place de Turenne, 94417 Saint Maurice Cedex (France); Moldovan, Z. [National Institute of Research and Development for Isotopic and Molecular Technology, Mass Spectrometry Department, Str. Donath 65-103, 400293 Cluj-Napoca (Romania); Patureau, D. [INRA, UR50, Laboratoire de Biotechnologie de l' Environnemet (LBE), Avenue des etangs, F-11100 Narbonne (France); Cruceru, L. [Pollution Control Department, National Research Institute for Industrial Ecology (ECOIND), Sos.Panduri 90-92, sector 5, Bucharest (Romania); Sacher, F. [DVGW-Technologiezentrum Wasser, Karlsruher Strasse 84, 76139 Karlsruhe (Germany); Ledin, A. [Department of Environmental Engineering, Technical University of Denmark, Miljoevej 113, DK-2800 Kgs. Lyngby (Denmark)

2010-03-15

An inter-laboratory comparison exercise was organized among European laboratories, under the aegis of EU COST Action 636: 'Xenobiotics in Urban Water Cycle'. The objective was to evaluate the performance of testing laboratories determining 'Endocrine Disrupting Compounds' (EDC) in various aqueous matrices. As the main task three steroid estrogens: 17alpha-ethinylestradiol, 17beta-estradiol and estrone were determined in four spiked aqueous matrices: tap water, river water and wastewater treatment plant influent and effluent using GC-MS and LC-MS/MS. Results were compared and discussed according to the analytical techniques applied, the accuracy and reproducibility of the analytical methods and the nature of the sample matrices. Overall, the results obtained in this inter-laboratory exercise reveal a high level of competence among the participating laboratories for the detection of steroid estrogens in water samples indicating that GC-MS as well as LC-MS/MS can equally be employed for the analysis of natural and synthetic hormones. - Herein are presented the results of the first international inter-laboratory study on determination of selected steroid hormones in environmental aqueous samples.

Interlaboratory comparisons in kerma in the air measures and absorbed dose in water using 60Co beams in radiotherapy

International Nuclear Information System (INIS)

Rosado, Paulo Henrique Goncalves; Silva, Cosme Norival Mello da

2013-01-01

In order to ensure that the measures of a quantity have high reliability and traceability interlaboratory comparisons are performed. The LNMRI has participated in several these interlaboratory comparisons. In the period 2000-2013 the LNMRI participated in 5 interlaboratory comparisons for measurement of kerma coefficients in the air and absorbed dose coefficients in the water. The results of interlaboratory comparisons indicate that the measures taken are appropriate to the LNMRI regarding the accuracy and precision measuring of these quantities

Interlaboratory comparison: Radionuclides in Irish sea water. IAEA-443

International Nuclear Information System (INIS)

2009-01-01

Our society is giving increasing importance to the study and assessment of the state and health of the environment. Organizations involved in such activities rely on the quality of the information provided and, ultimately, on the precision and accuracy of the data on which the information is based. Many laboratories are involved in the production of environmental data, in many cases leading to wider assessments. These laboratories may develop and validate new analytical methods, study the environmental impact of human activities, provide services to other organizations, etc. In particular, laboratories are providing data on levels of radioactivity in a variety of marine matrixes such as water, suspended matter, sediments and biota. Because of the need to base scientific conclusions on valid and internationally comparable data, the need to provide policy makers with correct information and the need for society to be informed of the state of the environment, it is indispensable to ensure the quality of the data produced by each laboratory. Principles of good laboratory practice require both internal and external procedures to verify the quality of the data produced. Internal quality is verified in a number of ways, such as the use of laboratory information systems, keeping full records of equipment performance and standardization of analytical procedures. External quality can also be ascertained in a number of ways, notably accreditation by an external body under a defined quality scheme but also, amongst others, the use of internationally accepted calibration standards that are traceable to the SI international system of units, the participation in interlaboratory comparisons or the regular use of Reference Materials to test laboratory performance. The Radiometrics Laboratory of the International Atomic Energy Agency's Marine Environment Laboratories has been providing quality products for the last 40 years, which include the organization of interlaboratory

Statistical evaluation of an interlaboratory comparison for the determination of uranium by potentiometric titration

International Nuclear Information System (INIS)

Ketema, D.J.; Harry, R.J.S.; Zijp, W.L.

1990-09-01

Upon request of the ESARDA working group 'Low enriched uranium conversion - and fuel fabrication plants' an interlaboratory comparison was organized, to assess the precision and accuracy concerning the determination of uranium by the potentiometric titration method. This report presents the results of a statistical evaluation on the data of the first phase of this exercise. (author). 9 refs.; 5 figs.; 24 tabs

Lupus anticoagulants: first French interlaboratory Etalonorme survey.

Science.gov (United States)

Roussi, J; Roisin, J P; Goguel, A

1996-06-01

In 1994, the, French National Quality Control Group for Hematology, Etalonorme, conducted a large-scale interlaboratory survey concerning the detection of lupus anticoagulants (LA) involving all the 4,500 French laboratories. Each laboratory received the same batch of a lyophilized citrated plasma (94B3) prepared from a patient with LA that had been confirmed by all the techniques used in the intralaboratory study. In the interlaboratory survey, the screening test was activated partial thromboplastin time (APTT); mean APTT calculated from the results reported by 4,029 labs was prolonged (clotting ratio = 1.44) with a large dispersion (coefficients of variation = 18.8%). APTT of the mixture 94B3 + normal plasma were performed by 2,698 laboratories. No correction of APTT was obtained (R = 1.36, Rosner index = 24) with a wide variation between reagents (17 kaolin. This survey allowed Etalonorme to inform French biologists and draft an educational program for the biologic detection of LA and the identification of its mechanism of action.

Interlaboratory comparison of the measurement of retention curves

DEFF Research Database (Denmark)

Hansen, M. H.; Houvenaghel, G.; Janz, M.

1999-01-01

The results of an interlaboratory comparison of the measurement of apparent density, solid density, open porosity and retention curves are presented. Baumberger sandstone and Sander sandstone were used as test materials.Repeatability standard deviation and reproducibility standard deviation...

First Interlaboratory Comparison on Calibration of Temperature-Controlled Enclosures in Turkey

Science.gov (United States)

Uytun, A.; Kalemci, M.

2017-11-01

The number of accredited laboratories in the field of calibration of temperature-controlled enclosures has been increasing in Turkey. One of the main criteria demonstrating the competence of a calibration laboratory is successful participation in interlaboratory comparisons. Therefore, TUBITAK UME Temperature Laboratory organized the first interlaboratory comparison on "Calibration of Temperature-Controlled Enclosures" in Turkey as a pilot laboratory between January and November, 2013. Forty accredited laboratories which provide routine calibration services to the industry in this field participated in the comparison. The standards used during the comparison was a climatic chamber for the measurements at -40 {°}C, -20 {°}C, 40 {°}C and 100 {°}C and an oven for the measurements at 200 {°}C. The protocol of the comparison was prepared considering guide EURAMET cg-20 and BS EN/IEC standards 600068-3-5 and 600068-3-11. During the comparison measurements, each participant had the liberty to choose the most convenient calibration points in terms of their accreditation scope among the values mentioned above and carried out on-site measurements at UME. The details and the results of this comparison are given in the paper. Determination of the statistical consistency of the results with the uncertainties given by the participants can be assessed by the method of En value assessment for each laboratory. En values for all measurement results based on the results of pilot and participating laboratories were calculated.

Inter-laboratory project q calibration of SANS instruments using silver behenate

International Nuclear Information System (INIS)

Ikram, Abarrul; Gunawan; Edy Giri, Putra; Suzuki, Jun-ichi; Knott, Robert

2000-01-01

The inter-laboratory project for q-calibration of SANS (small angle neutron scattering) using silver behenate was carried out among Indonesia National Nuclear Energy Agency (BATAN), Japan Atomic Energy Research Institute (JAERI) and Australian Nuclear Science and Technology Organization (ANSTO). The standard sample of silver behenate, [CH 3 (CH 2 ) 20 COOAg](AgBE), has been assessed as an international standard for the calibration of both x-ray and neutron scattering instruments. The results indicate excellent agreement for q calibration obtained among the three laboratories, BATAN, JAERI and ANSTO. (Y. Kazumata)

Results of the Interlaboratory Exercise CSN/CIEMAT-100 Among Environmental Radioactivity Laboratories (Soil)

International Nuclear Information System (INIS)

Romero Gonzalez, M. L.

2002-01-01

The document describes the outcome of the CSN/CIEMAT-00 interlaboratory test comparison among environmental radioactivity laboratories. the exercise was organised according to the ISO-43 and the ISO/IUPAC/AOAC Harmonized Protocol for the proficiency testing of analytical laboratories. the test sample was a soil containing environmental levels of K-40, Ra-226, Ac-228, Sr-90, Cs-137, Cs-134, Pu (239-240) y Am-241. the Universidad Autonoma de Barcelona prepared the material and reported adequate statistical studies of homogeneity. The results of the exercise were computed for 30 participating laboratories, and their analytical performance was assessed using the u-score approach. A raised percentage of satisfactory laboratory performance has been obtained for all the analysis, being the best performance in gamma measurements. The exercise has drawn that several laboratories have difficulties in the evaluation of combined uncertainty, mainly in analysis involving radiochemical steps. The study has shown an homogeneous inter-laboratory behaviour, and the improvement achieved through subsequent exercises in the quality of the data they are producing. (Author) 10 refs

Toward the Standardization of Biochar Analysis: The COST Action TD1107 Interlaboratory Comparison.

Science.gov (United States)

Bachmann, Hans Jörg; Bucheli, Thomas D; Dieguez-Alonso, Alba; Fabbri, Daniele; Knicker, Heike; Schmidt, Hans-Peter; Ulbricht, Axel; Becker, Roland; Buscaroli, Alessandro; Buerge, Diane; Cross, Andrew; Dickinson, Dane; Enders, Akio; Esteves, Valdemar I; Evangelou, Michael W H; Fellet, Guido; Friedrich, Kevin; Gasco Guerrero, Gabriel; Glaser, Bruno; Hanke, Ulrich M; Hanley, Kelly; Hilber, Isabel; Kalderis, Dimitrios; Leifeld, Jens; Masek, Ondrej; Mumme, Jan; Carmona, Marina Paneque; Calvelo Pereira, Roberto; Rees, Frederic; Rombolà, Alessandro G; de la Rosa, José Maria; Sakrabani, Ruben; Sohi, Saran; Soja, Gerhard; Valagussa, Massimo; Verheijen, Frank; Zehetner, Franz

2016-01-20

Biochar produced by pyrolysis of organic residues is increasingly used for soil amendment and many other applications. However, analytical methods for its physical and chemical characterization are yet far from being specifically adapted, optimized, and standardized. Therefore, COST Action TD1107 conducted an interlaboratory comparison in which 22 laboratories from 12 countries analyzed three different types of biochar for 38 physical-chemical parameters (macro- and microelements, heavy metals, polycyclic aromatic hydrocarbons, pH, electrical conductivity, and specific surface area) with their preferential methods. The data were evaluated in detail using professional interlaboratory testing software. Whereas intralaboratory repeatability was generally good or at least acceptable, interlaboratory reproducibility was mostly not (20% < mean reproducibility standard deviation < 460%). This paper contributes to better comparability of biochar data published already and provides recommendations to improve and harmonize specific methods for biochar analysis in the future.

Assessing variability in chemical acute toxicity of unionid mussels: Influence of intra- and inter-laboratory testing, life stage, and species

Science.gov (United States)

The authors developed a toxicity database for unionid mussels to examine the extent of intra- and interlaboratory variability in acute toxicity tests with mussel larvae (glochidia) and juveniles; the extent of differential sensitivity of the 2 life stages; and the variation in se...

High Interlaboratory Reprocucibility of DNA Sequence-based Typing of Bacteria in a Multicenter Study

DEFF Research Database (Denmark)

Sousa, MA de; Boye, Kit; Lencastre, H de

2006-01-01

Current DNA amplification-based typing methods for bacterial pathogens often lack interlaboratory reproducibility. In this international study, DNA sequence-based typing of the Staphylococcus aureus protein A gene (spa, 110 to 422 bp) showed 100% intra- and interlaboratory reproducibility without...... extensive harmonization of protocols for 30 blind-coded S. aureus DNA samples sent to 10 laboratories. Specialized software for automated sequence analysis ensured a common typing nomenclature....

Empirical insights and considerations for the OBT inter-laboratory comparison of environmental samples

International Nuclear Information System (INIS)

Kim, Sang-Bog; Roche, Jennifer

2013-01-01

Organically bound tritium (OBT) is an important tritium species that can be measured in most environmental samples, but has only recently been recognized as a species of tritium in these samples. Currently, OBT is not routinely measured by environmental monitoring laboratories around the world. There are no certified reference materials (CRMs) for environmental samples. Thus, quality assurance (QA), or verification of the accuracy of the OBT measurement, is not possible. Alternatively, quality control (QC), or verification of the precision of the OBT measurement, can be achieved. In the past, there have been differences in OBT analysis results between environmental laboratories. A possible reason for the discrepancies may be differences in analytical methods. Therefore, inter-laboratory OBT comparisons among the environmental laboratories are important and would provide a good opportunity for adopting a reference OBT analytical procedure. Due to the analytical issues, only limited information is available on OBT measurement. Previously conducted OBT inter-laboratory practices are reviewed and the findings are described. Based on our experiences, a few considerations were suggested for the international OBT inter-laboratory comparison exercise to be completed in the near future. -- Highlights: ► Inter-laboratory OBT comparisons would provide a good opportunity for developing reference OBT analytical procedures. ► The measurement of environmental OBT concentrations has a higher associated uncertainty. ► Certified reference materials for OBT in environmental samples are required

An inter-laboratory comparison of Si isotope reference materials

NARCIS (Netherlands)

Reynolds, B.C.; Aggarwal, J.; André, L.; Baxter, B.; Beucher, C.; Brzezinski, M.A.; Engström, E.; Georg, R.B.; Land, M.; Leng, M.J.; Opfergelt, S.; Rodushkin, I.; Sloane, H.J.; Van den Boorn, S.H.J.M.; Vroon, P.Z.; Cardinal, D.

2007-01-01

Three Si isotope materials have been used for an inter-laboratory comparison exercise to ensure reproducibility between international laboratories investigating natural Si isotope variations using a variety of chemical preparation methods and mass spectrometric techniques. These proposed standard

ASSESSMENT OF INTERLABORATORY PRETREATMENT PROTOCOLS BY RADIOCARBON DATING AN ELK BONE FOUND BELOW LAACHER SEE TEPHRA AT MIESENHEIM IV (RHINELAND, GERMANY)

NARCIS (Netherlands)

Fiedel, Stuart J.; Southon, John R.; Taylor, R. E.; Kuzmin, Yaroslav V.; Street, Martin; Higham, Thomas F. G.; van der Plicht, Johannes; Nadeau, Marie-Josee; Nalawade-Chavan, Shweta; Hatté, C.; Jull, A.J.T.

2013-01-01

Four accelerator mass spectrometry (AMS) facilities undertook an interlaboratory exercise designed to examine the reliability and reproducibility of radiocarbon determinations on bone by dating a sample of elk (Alces alces) from Miesenheim IV. This specimen is derived from a secure geological

PSF interlaboratory comparison

International Nuclear Information System (INIS)

Kellogg, L.S.; Lippincott, E.P.

1982-01-01

Two experiments for interlaboratory verification of radiometric analysis methods have been conducted with dosimeters irradiated in the Oak Ridge Research Reactor (ORR) Poolside Facility (PSF) Surveillance Dosimeter Measurement Facility (SDMF). In a preliminary analysis of data supplied by the six participants, biases as large as 60% were observed which could lead to errors of this general magnitude in reported surveillance capsule fluence values. As a result of these comparisons, problems were identified and the spread in final values was greatly reduced. Relative agreement among the final results reported by four of the laboratories now appears to be satisfactory (the non-fission dosimeter results generally falling within +-5% and the fission dosimeter results within +-10%), but improvement is required in order to routinely meet Reactor Vessel Material Surveillance Program goals

Worldwide Interlaboratory Comparison on the Determination of Trace Elements in the IAEA-457 Marine Sediment Sample

International Nuclear Information System (INIS)

2016-01-01

The primary goal of the IAEA Environment Laboratories is to assist Member States in the use of both stable and radioisotope analytical techniques to understand, monitor and protect the environment. In this context, the major impact of large coastal cities on marine ecosystems is an issue of primary concern for the IAEA and the IAEA Environment Laboratories. The marine pollution assessments required to understand such impacts depend on accurate knowledge of contaminant concentrations in various environmental compartments. Through the IAEA Environment Laboratories, the IAEA has been assisting national laboratories and regional laboratory networks since the early 1970s through the provision of a reference material programme for the analysis of radionuclides, trace elements and organic compounds in marine samples. Quality assurance and quality control are two fundamental requirements to ensure the reliability of analytical results. Data that are not based on adequate quality assurance and quality control can be erroneous, and their misuse can lead to poor environmental management decisions. In this regard, the IAEA has a long history of organizing interlaboratory studies, which have evolved to include an increasing array of potential contaminants in the marine environment. Relevant activities comprise global interlaboratory comparison, regional proficiency tests, the production of marine reference materials and the development of reference methods for trace elements and organic pollutants analysis in marine samples. This publication summarizes the results of the IAEA-457 interlaboratory comparison on the determination of trace elements in a marine sediment sample

Consensus building for interlaboratory studies, key comparisons, and meta-analysis

Science.gov (United States)

Koepke, Amanda; Lafarge, Thomas; Possolo, Antonio; Toman, Blaza

2017-06-01

Interlaboratory studies in measurement science, including key comparisons, and meta-analyses in several fields, including medicine, serve to intercompare measurement results obtained independently, and typically produce a consensus value for the common measurand that blends the values measured by the participants. Since interlaboratory studies and meta-analyses reveal and quantify differences between measured values, regardless of the underlying causes for such differences, they also provide so-called ‘top-down’ evaluations of measurement uncertainty. Measured values are often substantially over-dispersed by comparison with their individual, stated uncertainties, thus suggesting the existence of yet unrecognized sources of uncertainty (dark uncertainty). We contrast two different approaches to take dark uncertainty into account both in the computation of consensus values and in the evaluation of the associated uncertainty, which have traditionally been preferred by different scientific communities. One inflates the stated uncertainties by a multiplicative factor. The other adds laboratory-specific ‘effects’ to the value of the measurand. After distinguishing what we call recipe-based and model-based approaches to data reductions in interlaboratory studies, we state six guiding principles that should inform such reductions. These principles favor model-based approaches that expose and facilitate the critical assessment of validating assumptions, and give preeminence to substantive criteria to determine which measurement results to include, and which to exclude, as opposed to purely statistical considerations, and also how to weigh them. Following an overview of maximum likelihood methods, three general purpose procedures for data reduction are described in detail, including explanations of how the consensus value and degrees of equivalence are computed, and the associated uncertainty evaluated: the DerSimonian-Laird procedure; a hierarchical Bayesian

Results for PCDD/PCDF and dl-PCBs in the first Round of UNEPs Biennial Global Interlaboratory Assessment on Persistent Organic Pollutants

NARCIS (Netherlands)

Abalos, M.; Abad, E.; Leeuwen, van S.P.J.; Lindström, G.; Fiedler, H.; Boer, de J.; Bavel, van B.

2013-01-01

The first worldwide interlaboratory assesment on persistent organic pollutants (POPs) under the Stockholm Convention was organized in the Asian/Pacific, Latin American and African regions during 2009–11. A relatively large number of laboratories reported data for the PCDDs/PCDFs and dioxin-like

Interlaboratory comparison on high-temperature superconductor critical-current measurements

International Nuclear Information System (INIS)

Wiejaczka, J.A.; Goodrich, L.F.

1997-01-01

An extensive interlaboratory comparison was conducted on high temperature superconductor (HTS) critical-current measurements. This study was part of an international cooperative effort through the Versailles Project on Advanced Materials and Standards (VAMAS). The study involved six US laboratories that are recognized leaders in the field of HTS. This paper includes the complete results from this comparison of critical-current measurements on Ag-sheathed Bi 2 Sr 2 Ca 2 Cu 3 O 10-x (2223) tapes. The effects of sample characteristics, specimen mounting, measurement technique, and specimen damage were studied. The future development of a standard HTS measurement method is also discussed. Most of the evolution of this emerging technology has occurred in improvement of the performance of the conductors. The successful completion of this interlaboratory comparison is an important milestone in the evolution of HTS technology and marks a level of maturity that the technology has reached

Advancing the Use of Passive Sampling in Risk Assessment and Management of Sediments Contaminated with Hydrophobic Organic Chemicals: Results of an International Ex Situ Passive Sampling Interlaboratory Comparison.

Science.gov (United States)

Jonker, Michiel T O; van der Heijden, Stephan A; Adelman, Dave; Apell, Jennifer N; Burgess, Robert M; Choi, Yongju; Fernandez, Loretta A; Flavetta, Geanna M; Ghosh, Upal; Gschwend, Philip M; Hale, Sarah E; Jalalizadeh, Mehregan; Khairy, Mohammed; Lampi, Mark A; Lao, Wenjian; Lohmann, Rainer; Lydy, Michael J; Maruya, Keith A; Nutile, Samuel A; Oen, Amy M P; Rakowska, Magdalena I; Reible, Danny; Rusina, Tatsiana P; Smedes, Foppe; Wu, Yanwen

2018-03-20

This work presents the results of an international interlaboratory comparison on ex situ passive sampling in sediments. The main objectives were to map the state of the science in passively sampling sediments, identify sources of variability, provide recommendations and practical guidance for standardized passive sampling, and advance the use of passive sampling in regulatory decision making by increasing confidence in the use of the technique. The study was performed by a consortium of 11 laboratories and included experiments with 14 passive sampling formats on 3 sediments for 25 target chemicals (PAHs and PCBs). The resulting overall interlaboratory variability was large (a factor of ∼10), but standardization of methods halved this variability. The remaining variability was primarily due to factors not related to passive sampling itself, i.e., sediment heterogeneity and analytical chemistry. Excluding the latter source of variability, by performing all analyses in one laboratory, showed that passive sampling results can have a high precision and a very low intermethod variability (sampling, irrespective of the specific method used, is fit for implementation in risk assessment and management of contaminated sediments, provided that method setup and performance, as well as chemical analyses are quality-controlled.

Variation in the measurement of DNA damage by comet assay measured by the ECVAG dagger inter-laboratory validation trial

DEFF Research Database (Denmark)

Forchhammer, Lykke; Johansson, Clara; Loft, Steffen

2010-01-01

the level of DNA damage in monocyte-derived THP-1 cells by either visual classification or computer-aided image analysis of pre-made slides, coded cryopreserved samples of cells and reference standard cells (calibration curve samples). The reference standard samples were irradiated with ionizing radiation...... by the different laboratories as evidenced by an inter-laboratory coefficient of variation (CV) of 47%. Adjustment of the primary comet assay end points by a calibration curve prepared in each laboratory reduced the CV to 28%, a statistically significant reduction (P test). A large fraction...

IAEA interlaboratory exercise for water chemistry

International Nuclear Information System (INIS)

Joe, Kih Soo; Choi, Kwang Soon; Han, Sun Ho; Suh, Moo Yul; Jeon, Young Shin; Choi, Ke Chun; Kim, Yong Bok; Kim, Jong Gu; Kim, Won Ho

2003-09-01

KAERI Analytical laboratory participated in the IAEA Interlaboratory exercise for water chemistry of groundwater(RAS/8/084). 13 items such as pH, electroconductivity, HCO 3 , Cl, SO 4 , SiO 2 , B, Li, Na, K, Ca, Mg and NH 3 were analyzed. The result of this exercise showed that KAERI laboratory was ranked on the top level of the participants. Major analytical methods applied for this activity were ICP-AES, AAS, IC, pH meter, conductometer and acid titration

Interlaboratory study of a liquid chromatography method for erythromycin: determination of uncertainty.

Science.gov (United States)

Dehouck, P; Vander Heyden, Y; Smeyers-Verbeke, J; Massart, D L; Marini, R D; Chiap, P; Hubert, Ph; Crommen, J; Van de Wauw, W; De Beer, J; Cox, R; Mathieu, G; Reepmeyer, J C; Voigt, B; Estevenon, O; Nicolas, A; Van Schepdael, A; Adams, E; Hoogmartens, J

2003-08-22

Erythromycin is a mixture of macrolide antibiotics produced by Saccharopolyspora erythreas during fermentation. A new method for the analysis of erythromycin by liquid chromatography has previously been developed. It makes use of an Astec C18 polymeric column. After validation in one laboratory, the method was now validated in an interlaboratory study. Validation studies are commonly used to test the fitness of the analytical method prior to its use for routine quality testing. The data derived in the interlaboratory study can be used to make an uncertainty statement as well. The relationship between validation and uncertainty statement is not clear for many analysts and there is a need to show how the existing data, derived during validation, can be used in practice. Eight laboratories participated in this interlaboratory study. The set-up allowed the determination of the repeatability variance, s(2)r and the between-laboratory variance, s(2)L. Combination of s(2)r and s(2)L results in the reproducibility variance s(2)R. It has been shown how these data can be used in future by a single laboratory that wants to make an uncertainty statement concerning the same analysis.

Multielement trace determination in SiC powders: assessment of interlaboratory comparisons aimed at the validation and standardization of analytical procedures with direct solid sampling based on ETV ICP OES and DC arc OES.

Science.gov (United States)

Matschat, Ralf; Hassler, Jürgen; Traub, Heike; Dette, Angelika

2005-12-01

The members of the committee NMP 264 "Chemical analysis of non-oxidic raw and basic materials" of the German Standards Institute (DIN) have organized two interlaboratory comparisons for multielement determination of trace elements in silicon carbide (SiC) powders via direct solid sampling methods. One of the interlaboratory comparisons was based on the application of inductively coupled plasma optical emission spectrometry with electrothermal vaporization (ETV ICP OES), and the other on the application of optical emission spectrometry with direct current arc (DC arc OES). The interlaboratory comparisons were organized and performed in the framework of the development of two standards related to "the determination of mass fractions of metallic impurities in powders and grain sizes of ceramic raw and basic materials" by both methods. SiC powders were used as typical examples of this category of material. The aim of the interlaboratory comparisons was to determine the repeatability and reproducibility of both analytical methods to be standardized. This was an important contribution to the practical applicability of both draft standards. Eight laboratories participated in the interlaboratory comparison with ETV ICP OES and nine in the interlaboratory comparison with DC arc OES. Ten analytes were investigated by ETV ICP OES and eleven by DC arc OES. Six different SiC powders were used for the calibration. The mass fractions of their relevant trace elements were determined after wet chemical digestion. All participants followed the analytical requirements described in the draft standards. In the calculation process, three of the calibration materials were used successively as analytical samples. This was managed in the following manner: the material that had just been used as the analytical sample was excluded from the calibration, so the five other materials were used to establish the calibration plot. The results from the interlaboratory comparisons were summarized and

Quantifying inter-laboratory variability in stable isotope analysis of ancient skeletal remains.

Directory of Open Access Journals (Sweden)

William J Pestle

Full Text Available Over the past forty years, stable isotope analysis of bone (and tooth collagen and hydroxyapatite has become a mainstay of archaeological and paleoanthropological reconstructions of paleodiet and paleoenvironment. Despite this method's frequent use across anthropological subdisciplines (and beyond, the present work represents the first attempt at gauging the effects of inter-laboratory variability engendered by differences in a sample preparation, and b analysis (instrumentation, working standards, and data calibration. Replicate analyses of a 14C-dated ancient human bone by twenty-one archaeological and paleoecological stable isotope laboratories revealed significant inter-laboratory isotopic variation for both collagen and carbonate. For bone collagen, we found a sizeable range of 1.8‰ for δ13Ccol and 1.9‰ for δ15Ncol among laboratories, but an interpretatively insignificant average pairwise difference of 0.2‰ and 0.4‰ for δ13Ccol and δ15Ncol respectively. For bone hydroxyapatite the observed range increased to a troublingly large 3.5‰ for δ13Cap and 6.7‰ for δ18Oap, with average pairwise differences of 0.6‰ for δ13Cap and a disquieting 2.0‰ for δ18Oap. In order to assess the effects of preparation versus analysis on isotopic variability among laboratories, a subset of the samples prepared by the participating laboratories were analyzed a second time on the same instrument. Based on this duplicate analysis, it was determined that roughly half of the isotopic variability among laboratories could be attributed to differences in sample preparation, with the other half resulting from differences in analysis (instrumentation, working standards, and data calibration. These findings have serious implications for choices made in the preparation and extraction of target biomolecules, the comparison of results obtained from different laboratories, and the interpretation of small differences in bone collagen and hydroxyapatite

Quantifying inter-laboratory variability in stable isotope analysis of ancient skeletal remains.

Science.gov (United States)

Pestle, William J; Crowley, Brooke E; Weirauch, Matthew T

2014-01-01

Over the past forty years, stable isotope analysis of bone (and tooth) collagen and hydroxyapatite has become a mainstay of archaeological and paleoanthropological reconstructions of paleodiet and paleoenvironment. Despite this method's frequent use across anthropological subdisciplines (and beyond), the present work represents the first attempt at gauging the effects of inter-laboratory variability engendered by differences in a) sample preparation, and b) analysis (instrumentation, working standards, and data calibration). Replicate analyses of a 14C-dated ancient human bone by twenty-one archaeological and paleoecological stable isotope laboratories revealed significant inter-laboratory isotopic variation for both collagen and carbonate. For bone collagen, we found a sizeable range of 1.8‰ for δ13Ccol and 1.9‰ for δ15Ncol among laboratories, but an interpretatively insignificant average pairwise difference of 0.2‰ and 0.4‰ for δ13Ccol and δ15Ncol respectively. For bone hydroxyapatite the observed range increased to a troublingly large 3.5‰ for δ13Cap and 6.7‰ for δ18Oap, with average pairwise differences of 0.6‰ for δ13Cap and a disquieting 2.0‰ for δ18Oap. In order to assess the effects of preparation versus analysis on isotopic variability among laboratories, a subset of the samples prepared by the participating laboratories were analyzed a second time on the same instrument. Based on this duplicate analysis, it was determined that roughly half of the isotopic variability among laboratories could be attributed to differences in sample preparation, with the other half resulting from differences in analysis (instrumentation, working standards, and data calibration). These findings have serious implications for choices made in the preparation and extraction of target biomolecules, the comparison of results obtained from different laboratories, and the interpretation of small differences in bone collagen and hydroxyapatite isotope values

Assessing variability in chemical acute toxicity of unionid mussels: Influence of intra- and inter-laboratory testing, life stage, and species - SETAC Abstract

Science.gov (United States)

We developed a toxicity database for unionid mussels to examine the extent of intra- and inter-laboratory variability in acute toxicity tests with mussel larvae (glochidia) and juveniles; the extent of differential sensitivity of the two life stages; and the variation in sensitiv...

Inter-laboratory analysis of selected genetically modified plant reference materials with digital PCR.

Science.gov (United States)

Dobnik, David; Demšar, Tina; Huber, Ingrid; Gerdes, Lars; Broeders, Sylvia; Roosens, Nancy; Debode, Frederic; Berben, Gilbert; Žel, Jana

2018-01-01

Digital PCR (dPCR), as a new technology in the field of genetically modified (GM) organism (GMO) testing, enables determination of absolute target copy numbers. The purpose of our study was to test the transferability of methods designed for quantitative PCR (qPCR) to dPCR and to carry out an inter-laboratory comparison of the performance of two different dPCR platforms when determining the absolute GM copy numbers and GM copy number ratio in reference materials certified for GM content in mass fraction. Overall results in terms of measured GM% were within acceptable variation limits for both tested dPCR systems. However, the determined absolute copy numbers for individual genes or events showed higher variability between laboratories in one third of the cases, most possibly due to variability in the technical work, droplet size variability, and analysis of the raw data. GMO quantification with dPCR and qPCR was comparable. As methods originally designed for qPCR performed well in dPCR systems, already validated qPCR assays can most generally be used for dPCR technology with the purpose of GMO detection. Graphical abstract The output of three different PCR-based platforms was assessed in an inter-laboratory comparison.

Standardization and interlaboratory reproducibility assessment of pulsed-field gel electrophoresis-generated fingerprints of Acinetobacter baumannii.

Science.gov (United States)

Seifert, Harald; Dolzani, Lucilla; Bressan, Raffaela; van der Reijden, Tanny; van Strijen, Beppie; Stefanik, Danuta; Heersma, Herre; Dijkshoorn, Lenie

2005-09-01

A standard procedure for pulsed-field gel electrophoresis (PFGE) of macrorestriction fragments of Acinetobacter baumannii was set up and validated for its interlaboratory reproducibility and its potential for use in the construction of an Internet-based database for international monitoring of epidemic strains. The PFGE fingerprints of strains were generated at three different laboratories with ApaI as the restriction enzyme and by a rigorously standardized procedure. The results were analyzed at the respective laboratories and also centrally at a national reference institute. In the first phase of the study, 20 A. baumannii strains, including 3 isolates each from three well-characterized hospital outbreaks and 11 sporadic strains, were distributed blindly to the participating laboratories. The local groupings of the isolates in each participating laboratory were identical and allowed the identification of the epidemiologically related isolates as belonging to three clusters and identified all unrelated strains as distinct. Central pattern analysis by using the band-based Dice coefficient and the unweighted pair group method with mathematical averaging as the clustering algorithm showed 95% matching of the outbreak strains processed at each local laboratory and 87% matching of the corresponding strains if they were processed at different laboratories. In the second phase of the study, 30 A. baumannii isolates representing 10 hospital outbreaks from different parts of Europe (3 isolates per outbreak) were blindly distributed to the three laboratories, so that each laboratory investigated 10 epidemiologically independent outbreak isolates. Central computer-assisted cluster analysis correctly identified the isolates according to their corresponding outbreak at an 87% clustering threshold. In conclusion, the standard procedure enabled us to generate PFGE fingerprints of epidemiologically related A. baumannii strains at different locations with sufficient

NVN 5694 intra laboratory validation. Feasibility study for interlaboratory- validation

International Nuclear Information System (INIS)

Voors, P.I.; Baard, J.H.

1998-11-01

Within the project NORMSTAR 2 a number of Dutch prenormative protocols have been defined for radioactivity measurements. Some of these protocols, e.g. the Dutch prenormative protocol NVN 5694, titled Methods for radiochemical determination of polonium-210 and lead-210, have not been validated, neither by intralaboratory nor interlaboratory studies. Validation studies are conducted within the framework of the programme 'Normalisatie and Validatie van Milieumethoden 1993-1997' (Standardization and Validation of test methods for environmental parameters) of the Dutch Ministry of Housing, Physical Planning and the Environment (VROM). The aims of this study were (a) a critical evaluation of the protocol, (b) investigation on the feasibility of an interlaboratory study, and (c) the interlaboratory validation of NVN 5694. The evaluation of the protocol resulted in a list of deficiencies varying from missing references to incorrect formulae. From the survey by interview it appeared that for each type of material, there are 4 to 7 laboratories willing to participate in a interlaboratory validation study. This reflects the situation in 1997. Consequently, if 4 or 6 (the minimal number) laboratories are participating and each laboratory analyses 3 subsamples, the uncertainty in the repeatability standard deviation is 49 or 40 %, respectively. If the ratio of reproducibility standard deviation to the repeatability standard deviation is equal to 1 or 2, then the uncertainty in the reproducibility standard deviation increases from 42 to 67 % and from 34 to 52 % for 4 or 6 laboratories, respectively. The intralaboratory validation was established on four different types of materials. Three types of materials (milkpowder condensate and filter) were prepared in the laboratory using the raw material and certified Pb-210 solutions, and one (sediment) was obtained from the IAEA. The ECN-prepared reference materials were used after testing on homogeneity. The pre-normative protocol can

New preparation of fish material for interlaboratory study on PFCs

NARCIS (Netherlands)

Korytar, P.; Lohman, M.; Kwadijk, C.J.A.F.; Barneveld, van E.

2007-01-01

The Institute for Environmental Studies, Vrije Universiteit (IVM) has requested Wageningen IMARES to prepare a new fish material for use in the interlaboratory performance study on analysis of perfluorinated compounds (PFCs) due to the low amount of contaminants in the previously prepared material.

Use of an excess variance approach for the certification of reference materials by interlaboratory comparison

International Nuclear Information System (INIS)

Crozet, M.; Rigaux, C.; Roudil, D.; Tuffery, B.; Ruas, A.; Desenfant, M.

2014-01-01

In the nuclear field, the accuracy and comparability of analytical results are crucial to insure correct accountancy, good process control and safe operational conditions. All of these require reliable measurements based on reference materials whose certified values must be obtained by robust metrological approaches according to the requirements of ISO guides 34 and 35. The data processing of the characterization step is one of the key steps of a reference material production process. Among several methods, the use of interlaboratory comparison results for reference material certification is very common. The DerSimonian and Laird excess variance approach, described and implemented in this paper, is a simple and efficient method for the data processing of interlaboratory comparison results for reference material certification. By taking into account not only the laboratory uncertainties but also the spread of the individual results into the calculation of the weighted mean, this approach minimizes the risk to get biased certified values in the case where one or several laboratories either underestimate their measurement uncertainties or do not identify all measurement biases. This statistical method has been applied to a new CETAMA plutonium reference material certified by interlaboratory comparison and has been compared to the classical weighted mean approach described in ISO Guide 35. This paper shows the benefits of using an 'excess variance' approach for the certification of reference material by interlaboratory comparison. (authors)

Empirical insights and considerations for the OBT inter-laboratory comparison of environmental samples.

Science.gov (United States)

Kim, Sang-Bog; Roche, Jennifer

2013-08-01

Organically bound tritium (OBT) is an important tritium species that can be measured in most environmental samples, but has only recently been recognized as a species of tritium in these samples. Currently, OBT is not routinely measured by environmental monitoring laboratories around the world. There are no certified reference materials (CRMs) for environmental samples. Thus, quality assurance (QA), or verification of the accuracy of the OBT measurement, is not possible. Alternatively, quality control (QC), or verification of the precision of the OBT measurement, can be achieved. In the past, there have been differences in OBT analysis results between environmental laboratories. A possible reason for the discrepancies may be differences in analytical methods. Therefore, inter-laboratory OBT comparisons among the environmental laboratories are important and would provide a good opportunity for adopting a reference OBT analytical procedure. Due to the analytical issues, only limited information is available on OBT measurement. Previously conducted OBT inter-laboratory practices are reviewed and the findings are described. Based on our experiences, a few considerations were suggested for the international OBT inter-laboratory comparison exercise to be completed in the near future. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Interlaboratory comparison exercise for the determination of uranium by potentiometric titration (first phase)

International Nuclear Information System (INIS)

Verdingh, V.; Le Duigou, Y.

1991-01-01

Upon request of the Esarda working group on low-enriched uranium conversion and fuel fabrication plants an interlaboratory comparison was organized, to assess the precision and accuracy concerning the determination of uranium by the potentiometric titration method. This report presents the results of the first phase of this exercise (pure uranyl-nitrate solutions). The solutions used in this intercomparison have been certified for their uranium content by the CBNM, Geel. Comparison of the laboratory results with the certified values shows excellent, good and fairly good agreement for many of the participating laboratories. 10 tabs., 5 figs., 10 refs

Interlaboratory comparison of real-time pcr protocols for quantification of general fecal indicator bacteria

Science.gov (United States)

Shanks, O.C.; Sivaganesan, M.; Peed, L.; Kelty, C.A.; Blackwood, A.D.; Greene, M.R.; Noble, R.T.; Bushon, R.N.; Stelzer, E.A.; Kinzelman, J.; Anan'Eva, T.; Sinigalliano, C.; Wanless, D.; Griffith, J.; Cao, Y.; Weisberg, S.; Harwood, V.J.; Staley, C.; Oshima, K.H.; Varma, M.; Haugland, R.A.

2012-01-01

The application of quantitative real-time PCR (qPCR) technologies for the rapid identification of fecal bacteria in environmental waters is being considered for use as a national water quality metric in the United States. The transition from research tool to a standardized protocol requires information on the reproducibility and sources of variation associated with qPCR methodology across laboratories. This study examines interlaboratory variability in the measurement of enterococci and Bacteroidales concentrations from standardized, spiked, and environmental sources of DNA using the Entero1a and GenBac3 qPCR methods, respectively. Comparisons are based on data generated from eight different research facilities. Special attention was placed on the influence of the DNA isolation step and effect of simplex and multiplex amplification approaches on interlaboratory variability. Results suggest that a crude lysate is sufficient for DNA isolation unless environmental samples contain substances that can inhibit qPCR amplification. No appreciable difference was observed between simplex and multiplex amplification approaches. Overall, interlaboratory variability levels remained low (<10% coefficient of variation) regardless of qPCR protocol. ?? 2011 American Chemical Society.

Determination of the moisture content of instant noodles: interlaboratory study.

Science.gov (United States)

Hakoda, Akiko; Kasama, Hirotaka; Sakaida, Kenichi; Suzuki, Tadanao; Yasui, Akemi

2006-01-01

Determination of the moisture content of instant noodles, currently under discussion by the Codex Alimentarius Commission (CAC) requires 2 methods: one for fried noodles and the other for nonfried noodles. The method to determine the moisture content of fried noodles by drying at 105 degrees C for 2 h used in the Japanese Agricultural Standard (JAS) system of Japan can be applied to this purpose. In the present study, the JAS method for fried noodles was modified to be suitable for nonfried noodles by extending the drying time to 4 h. An interlaboratory study was conducted to evaluate interlaboratory performance statistics for these 2 methods. Ten participating laboratories each analyzed 5 test materials of fried and nonfried noodles as blind duplicates. After removal of outliers statistically, the repeatability (RSDr) and the reproducibility (RSD(R)) of these methods were 1.6-2.6 and 3.9-4.8% for fried noodles, and 0.3-1.5 and 1.3-2.9% for nonfried noodles, respectively.

An interlaboratory trial on the identification of irradiated spices, herbs, and spice-herb mixtures by thermoluminescence analysis

International Nuclear Information System (INIS)

Schreiber, G.A.; Helle, N.; Bögl, K.W.

1995-01-01

Thermoluminescence analysis was used in an interlaboratory study to detect irradiation treatment of spices, herbs, and spice-herb mixtures in the dose range used for the reduction of microbial counts. About 3 and 9 months after irradiation, 14 participating laboratories determined the thermoluminescence of mineral contaminants that had been isolated from coded samples. A total of 18 different products (6 spices, 6 herbs, and 6 spice-herb mixtures) were examined. The method gave correct identifications as irradiated or nonirradiated in 99.1% of 317 samples. Only 3 irradiated samples were not correctly identified. This result was achieved by integration of whole glow curves. By glow curve analysis, a temperature range could be determined in which differentiation between irradiated and nonirradiated samples was even better than on the basis of the total integral values

An interlaboratory comparison between similar methods for determination of melatonin, cortisol and testosterone in saliva

DEFF Research Database (Denmark)

Jensen, Marie Aarrebo; Mortier, Leen; Koh, Eitetsu

2014-01-01

/L for melatonin, 0.56 and 6.72 nmol/L for cortisol and 11.9 and 73.8 pmol/L for testosterone. This indicates a large interlaboratory variation. The present study emphasizes the importance of external quality control for the analysis of melatonin, cortisol and testosterone in saliva.......An interlaboratory comparison study for melatonin, cortisol and testosterone in saliva in which five laboratories participated is reported in this study. Each laboratory blindly measured eight samples prepared from natural saliva spiked with melatonin, cortisol and testosterone in the range 0...

Interlaboratory niobium dosimetry comparison

International Nuclear Information System (INIS)

Wille, P.

1980-01-01

For an interlaboratory comparison of neutron dosimetry using niobium the 93 sup(m)Nb activities of irradiated niobium monitors were measured. This work was performed to compare the applied techniques of dosimetry with Nb in different laboratories. The niobium monitors were irradiated in the fast breeder EBRII, USA and the BR2, Belgium. The monitors were dissolved and several samples were prepared. Their niobium contents were determined by the 94 Nb-count rates. since the original specific count rate was known. The KX radiations of the 93 sup(m)Nb of the samples and of a calibrated Nb-foil were compared. This foil was measured by PTB, Braunschweig and CBNM, Geel, which we additionally compared with the KX radiation of 88 Sr produced by a thin 88 Y source from a 88 Y-standard solution (PTB). (orig.) [de

International and interlaboratory collaboration on Neutron Science Project

Energy Technology Data Exchange (ETDEWEB)

Oyama, Yukio [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

1997-11-01

For effectiveness of facility development for Neutron Science Projects at JAERI, international and interlaboratory collaborations have been extensively planned and promoted, especially in the areas of accelerator and target technology. Here status of two collaborations relevant to a spallation neutron target development is highlighted from those collaborations. The two collaborations are experiments on BNL-AGS spallation target simulation and PSI materials irradiation. Both are planned to start in spring of 1997. (author)

An Interlaboratory study of lipid effects on steroid radioimmunoassay

International Nuclear Information System (INIS)

Bolelli, G.F.; Franceschetti, F.; Mimmi, P.; Malvano, R.; Pilo, A.; Zucchelli; Rota, G.

1986-01-01

The lipid effects on the performances of routine steroid radioimmunoassay (RIA) have been assessed using the scheme of the CNR interlaboratory quality control program. Cortisol, estradiol, progesterone and testosterone assays have been considered. In the study, ca 80 laboratories were supplied with two sets of control plasma samples with different triglyceride contents (pool N, ca 120 mg/dl; pool L, ca 310 mg/dl), each corresponding to three steroid levels (level 0: charcoaldeprived samples; levels 1 and 2: the same added with increasing steroid amounts). A comparison of the neat results obtained by partecipants for both levels 1 and 2 of N and P panels - after subtraction of the concentrations estimated for level 0 - gave a direct information on lipid effects (triglycerides being assumed as an index of lipemia). In no case the abnormality high triglyceride content proved effective in practical terms, though significant differences were observed for testosterone and progesterone (ca 10% underestimation in pool L) and for estradiol (ca 10% overestimation in pool L)

Interlaboratory validation data on real-time polymerase chain reaction detection for unauthorized genetically modified papaya line PRSV-YK

Directory of Open Access Journals (Sweden)

Kosuke Nakamura

2016-06-01

Real-time polymerase chain reaction (PCR detection method for unauthorized genetically modified (GM papaya (Carica papaya L. line PRSV-YK (PRSV-YK detection method was developed using whole genome sequence data (DDBJ Sequenced Read Archive under accession No. PRJDB3976. Interlaboratory validation datasets for PRSV-YK detection method were provided. Data indicating homogeneity of samples prepared for interlaboratory validation were included. Specificity and sensitivity test data for PRSV-YK detection method were also provided.

Inter-Laboratory Comparison for Calibration of Relative Humidity Devices Among Accredited Laboratories in Malaysia

Science.gov (United States)

Hussain, F.; Khairuddin, S.; Othman, H.

2017-01-01

An inter-laboratory comparison in relative humidity measurements among accredited laboratories has been coordinated by the National Metrology Institute of Malaysia. It was carried out to determine the performance of the participating laboratories. The objective of the comparison was to acknowledge the participating laboratories competencies and to verify the level of accuracies declared in their scope of accreditation, in accordance with the MS ISO/IEC 17025 accreditation. The measurement parameter involved was relative humidity for the range of 30-90 %rh at a nominal temperature of 50°C. Eight accredited laboratories participated in the inter-laboratory comparison. Two units of artifacts have been circulated among the participants as the transfer standards.

Reference materials and interlaboratory comparison for actinide analysis

International Nuclear Information System (INIS)

Hanssens, Alain; Viallesoubranne, Carole; Roche, Claude; Liozon, Gerard

2008-01-01

Measurement quality is crucial for the safety of nuclear facilities and is a primary requirement for fissile material monitoring and accountancy. CETAMA (Cea Committee for the establishment of analysis methods), in collaboration with Cea and AREVA laboratories, fabricates certified reference materials and organizes interlaboratory comparison programs for plutonium and uranium assay in solution. A new plutonium metal measurement standard (MP3) is currently being prepared by Cea and is a subject of cooperative work in view of its certification and use by analysis laboratories. U and Pu interlaboratory comparisons are carried out at regular intervals on benchmark samples in coordination with working groups from French nuclear laboratories. These programs are supported by international cooperation. 'Chemical' methods (potentiometry, gravimetric analysis, etc.) generally provide the best accuracy. Coulometry is the benchmark technique for plutonium assay: its metrological qualities should be an incentive for wider use by laboratories performing precise control assays of plutonium as well as uranium. Gravimetric analysis provides excellent results for analysis of pure uranyl nitrate solutions. In view of its many advantages we encourage laboratories to employ this technique to assay pure U or Pu solutions. 'Physical' or 'physicochemical' methods are increasingly used, and their performance has improved. K-edge absorption spectrometry and isotope dilution mass spectrometry are capable of reaching measurement quality levels comparable to those of the best 'chemical' methods. (authors)

Retrospective radiation dosimetry using OSL of electronic components: Results of an inter-laboratory comparison

International Nuclear Information System (INIS)

Bassinet, C.; Woda, C.; Bortolin, E.; Della Monaca, S.; Fattibene, P.; Quattrini, M.C.; Bulanek, B.; Ekendahl, D.; Burbidge, C.I.; Cauwels, V.; Kouroukla, E.; Geber-Bergstrand, T.; Mrozik, A.; Marczewska, B.; Bilski, P.; Sholom, S.; McKeever, S.W.S.; Smith, R.W.; Veronese, I.

2014-01-01

In the framework of the EU-FP7 MULTIBIODOSE project, two protocols using OSL of resistors removed from the circuit board of mobile phones were developed with the aim to use the resistors as fortuitous dosimeters in the event of a large scale radiological accident. This paper presents the results of an inter-laboratory comparison carried out under the umbrella of EURADOS. The two aims of this exercise were the validation of the MULTIBIODOSE protocols by a large number of laboratories and the dissemination of the method with the objective of preparing the basis for a network that could increase Europe's response capacity in the case of a mass casualty radiological emergency. Twelve institutes from eleven European countries and one institute from the USA, with various degrees of expertise in OSL dosimetry, took part in the OSL inter-laboratory comparison. Generally, a good agreement within uncertainties was observed between estimated and nominal doses. - Highlights: • Resistors in mobile phones could function as reliable fortuitous dosimeters in case of a large scale radiological accident. • Two OSL protocols were validated by an inter-laboratory comparison. • It is feasible to set up a network of laboratories so as to increase the measurement capacity

129I Interlaboratory comparison: phase I and phase II

International Nuclear Information System (INIS)

Caffee, M. W.; Roberts, M. L.

1999-01-01

An interlaboratory comparison exercise for 129 I was organized and conducted. Nine laboratories participated in the exercise to either a full or limited extent. In Phase I of the comparison, 11 samples were measured. The suite of samples contained both synthetic ''standard type'' materials (i.e., AgI) and environmental materials. The isotopic 129 I/ 127 I ratios of the samples varied from 10 -8 to 10 -14 . In this phase, each laboratory was responsible for its own chemical preparation of the samples. In Phase I, the 129 I AMS measurements for prepared AgI were in good agreement. However, large discrepancies were seen in 129 I AMS measurements of environmental samples. Because of the large discrepancies seen in the Phase I 129 I intercomparison, a subsequent study was conducted. In Phase II of the 129 I intercomparison, three separate laboratories prepared AgI from two environmental samples (IAEA 375 soil and maples leaves). Each laboratory used its own chemical preparation method with each of the methods being distinctly different. The resulting six samples (two sets of three) were then re-distributed to the participating 129 I AMS facilities and 129 I/ 127 I ratios measured. Results and discussion of both the Phase I and Phase II interlaboratory comparison are presented

Interlaboratory control among INCO-DEV MYCOTOX PROJECT LABORATORIES

Directory of Open Access Journals (Sweden)

E.A Vargas

2011-04-01

Full Text Available The Work Package 1 “ Development and standardization of effective analytical tools for mycotoxin (aflatoxins B1, B2  G1, G2  ochratoxin A, zearalenone, fumonisin B1, B2  and tricothecenes determination in wheat and maize”  aim to implement the interlaboratory control between the partners laboratories from Brazil, Uruguay, Chile and Argentina as part of the objectives of INCO-DEV MYCOTOX PROJECT 2003-2005  “The Development of a Food Quality Management System for the Control of Mycotoxins in cereal Production and Processing Chains in Latin America South Cone Countries”.  The ojectives of the interlaboratory control were: evaluate the performance of the laboratories and the main difficulties encountered in performing the analytical procedure for mycotoxins  determination in maize and wheat; contribute to the harmonization of analytical procedures of the partners laboratories and contribute to the laboratory’s proficiency in mycotoxin analysis.  Maize reference materials for aflatoxins and zearealenone were prepared and used to the implementation of the interlaboratory control.  In summary, the preparation of these samples involved: milling (<20 mesh, homogeneization, analysis to verify the homogeneity of the bulk material and packing (labelled vacuum “sachets” or plastic bottles and mycotoxin analysis.  The homogeneity of the material was investigated by the analysis of variance – ANOVA- according to International Harmonized Protocol for the Proficiency testing of (ChemicalAnalytical Laboratories as established by ISO 43-1 – Annex at 95% of confidence level by calculating an F-statistic ans Ss/ÿ (ÿ =15%. All batches of test material were stored under – 18ºC and protected from light prior to and after packaging.  Aflatoxins in the test materials were determinated by immunoaffinity with liquid chromatography (LC with pos-column derivatization and thin layer chromatography (TLC.  Zearalenone in the test materials

Comet assay in reconstructed 3D human epidermal skin models—investigation of intra- and inter-laboratory reproducibility with coded chemicals

Science.gov (United States)

Pfuhler, Stefan

2013-01-01

Reconstructed 3D human epidermal skin models are being used increasingly for safety testing of chemicals. Based on EpiDerm™ tissues, an assay was developed in which the tissues were topically exposed to test chemicals for 3h followed by cell isolation and assessment of DNA damage using the comet assay. Inter-laboratory reproducibility of the 3D skin comet assay was initially demonstrated using two model genotoxic carcinogens, methyl methane sulfonate (MMS) and 4-nitroquinoline-n-oxide, and the results showed good concordance among three different laboratories and with in vivo data. In Phase 2 of the project, intra- and inter-laboratory reproducibility was investigated with five coded compounds with different genotoxicity liability tested at three different laboratories. For the genotoxic carcinogens MMS and N-ethyl-N-nitrosourea, all laboratories reported a dose-related and statistically significant increase (P 30% cell loss), and the overall response was comparable in all laboratories despite some differences in doses tested. The results of the collaborative study for the coded compounds were generally reproducible among the laboratories involved and intra-laboratory reproducibility was also good. These data indicate that the comet assay in EpiDerm™ skin models is a promising model for the safety assessment of compounds with a dermal route of exposure. PMID:24150594

Reference materials and interlaboratory comparison for actinide analysis

Energy Technology Data Exchange (ETDEWEB)

Hanssens, Alain; Viallesoubranne, Carole; Roche, Claude; Liozon, Gerard [Commissariat a l' Energie Atomique, Marcoule: BP 17171, 30207 Bagnols sur Ceze (France)

2008-07-01

Measurement quality is crucial for the safety of nuclear facilities and is a primary requirement for fissile material monitoring and accountancy. CETAMA (Cea Committee for the establishment of analysis methods), in collaboration with Cea and AREVA laboratories, fabricates certified reference materials and organizes interlaboratory comparison programs for plutonium and uranium assay in solution. A new plutonium metal measurement standard (MP3) is currently being prepared by Cea and is a subject of cooperative work in view of its certification and use by analysis laboratories. U and Pu interlaboratory comparisons are carried out at regular intervals on benchmark samples in coordination with working groups from French nuclear laboratories. These programs are supported by international cooperation. 'Chemical' methods (potentiometry, gravimetric analysis, etc.) generally provide the best accuracy. Coulometry is the benchmark technique for plutonium assay: its metrological qualities should be an incentive for wider use by laboratories performing precise control assays of plutonium as well as uranium. Gravimetric analysis provides excellent results for analysis of pure uranyl nitrate solutions. In view of its many advantages we encourage laboratories to employ this technique to assay pure U or Pu solutions. 'Physical' or 'physicochemical' methods are increasingly used, and their performance has improved. K-edge absorption spectrometry and isotope dilution mass spectrometry are capable of reaching measurement quality levels comparable to those of the best 'chemical' methods. (authors)

Final report on fourth interlaboratory comparison exercise for δ2H and δ18O analysis of water samples (WICO2011)

International Nuclear Information System (INIS)

Ahmad, M.; Aggarwal, P.; Duren, M. van; Poltenstein, L.; Araguas, L.; Kurttas, T.; Wassenaar, L.I.

2012-01-01

The IAEA Isotope Hydrology Laboratory organized the fourth interlaboratory comparison exercise for laboratories engaged in routine analysis of hydrogen and oxygen stable isotope composition of water samples in 2011. Three similar exercises were carried out in 1995, in 1999 and in 2002. However, the tradition of IAEA water stable isotope inter-laboratory comparison is much older. Two interlaboratory comparison trials for isotope hydrology laboratories were carried out in the sixties and seventies, which revealed problems with use of the NBS-1 international standard; these data were used to calibrate the newly produced primary reference materials VSMOW and SLAP. The WICO2011 exercise was announced in February 2011 on the internet, via the ISOGEOCHEM news group of Isogeochemistry and by email to all participants of the former intercomparisons. Altogether 174 laboratories expressed interest to participate in the exercise. Four water samples prepared and calibrated at the IAEA Isotope Hydrology Laboratory were labelled IAEA-OH-13 to IAEA-OH-16, which are referred to in this report as OH-13 to OH-16. By the end of the reporting deadline (the end of August 2011) altogether 137 laboratories from 53 countries had submitted 172 datasets back to the IAEA on the oxygen and hydrogen isotopic composition of these water samples. The four water samples cover the range of δ18O and δ2H values typical for the majority of natural waters. The samples were bottled from 30 L stainless steel storage barrels into 30 mL securely-capped brown glass bottles, serially numbered at the time of filling. Each laboratory received a set of four samples with a corresponding code. This code (assigned randomly) forms the Identification (ID) code used throughout the exercise and in the tables and graphs of this report for each laboratory. The ID code is not related to the order of the list of participating laboratories. The identity of participating laboratories will not be revealed unless each

How well can we measure U and Pu on an interlaboratory basis?

International Nuclear Information System (INIS)

De Bievre, P.; Mayer, K.

1991-01-01

In measurements in general, and nuclear measurements in particular, it is no more a secret that the real state-of-the-practice (SOP) is frequently different from what is said at Conferences, written in books or claimed in meetings. Frequently the latter refer to the state-of-the-art (SOA) in research laboratories or to the ultimate possible only achievable in a few highly specialized institutes. Since it is important to have an objective basis to determine where the authors stand in SOP, CBNM is running a program to regularly determine the SOP on an interlaboratory basis for U and Pu element and isotope assay: REIMEP (Regular European Interlaboratory Measurement Evaluation Program). Participation is open to non-European countries. Well characterized samples are distributed to participants with characteristics undisclosed until participants' measurements have been received. Subsequently pictures are provided displaying (a) the interlaboratory spread, (b) the deviation of each participant to the carefully characterized reference value, (c) the participant's own estimate of his uncertainty allowing comparison with other participant's uncertainties and the uncertainty of the reference value. Thus the pictures act as instant photographs (snapshots) of the real SOP. The choice of the analytical method is up to the participant (titrimetry, coulometry, α-spectrometry, gas mass spectrometry, γ-spectrometry, thermionic mass spectrometry,...). The quoted uncertainty is also the participant's choice, but should be an accuracy defined as an uncertainty range claiming, for all practical purposes, to contain the true value. Up to now a number of rounds have been performed on various U and/or Pu containing materials such as pellets, powders, solutions, UF 6 . A number of graphs displaying the SOP will be shown

Interlaboratory tests to identify irradiation treatment of various foods via gas chromatographic detection of hydrocarbons, ESR spectroscopy and TL analysis

Energy Technology Data Exchange (ETDEWEB)

Schreiber, G.A.; Helle, N.; Schulzki, G.; Linke, B.; Spiegelberg, A.; Mager, M.; Boegl, K.W. [BgVV - Federal Inst. for Health Protection of Consumers and Veterinary Medicine, Berlin (Germany)

1996-12-31

The gas chromatographic (GC) analysis of radiation-induced volatile hydrocarbons (HC) and 2-alkylcyclobutanones, the ESR spectroscopic detection of radiation-specific radicals and the thermoluminescence (TL) analysis of silicate mineral are the most important methods for identification of irradiated foods. After successful performance in interlaboratory studies on meat products, fish, spices, herbs and shells of nuts, all or some of these methods have been approved by national authorities in Germany and the United Kingdom. Recently, draft European Standards have been elaborated for approval by member states of the European Committee for Standardization (CEN). Several research laboratories have shown that these methods can be applied to various foods not yet tested in collaborative studies. However, for an effective application in food control it is necessary to prove their suitability in interlaboratory studies. Therefore, in 1993/94, various interlaboratory tests were organised by the BgVV. In an ESR spectroscopic test, shrimps and paprika powder were examined. Shrimps were also the subject of examination in a TL test. Finally, GC detection of radiation-induced hydrocarbons in the fat fraction of foods was used in another test to identify irradiated Camembert, avocado, papaya and mango. In the following paper, results of the interlaboratory tests are summarised. Detailed reports are published by this institute. (author).

Interlaboratory tests to identify irradiation treatment of various foods via gas chromatographic detection of hydrocarbons, ESR spectroscopy and TL analysis

International Nuclear Information System (INIS)

Schreiber, G.A.; Helle, N.; Schulzki, G.; Linke, B.; Spiegelberg, A.; Mager, M.; Boegl, K.W.

1996-01-01

The gas chromatographic (GC) analysis of radiation-induced volatile hydrocarbons (HC) and 2-alkylcyclobutanones, the ESR spectroscopic detection of radiation-specific radicals and the thermoluminescence (TL) analysis of silicate mineral are the most important methods for identification of irradiated foods. After successful performance in interlaboratory studies on meat products, fish, spices, herbs and shells of nuts, all or some of these methods have been approved by national authorities in Germany and the United Kingdom. Recently, draft European Standards have been elaborated for approval by member states of the European Committee for Standardization (CEN). Several research laboratories have shown that these methods can be applied to various foods not yet tested in collaborative studies. However, for an effective application in food control it is necessary to prove their suitability in interlaboratory studies. Therefore, in 1993/94, various interlaboratory tests were organised by the BgVV. In an ESR spectroscopic test, shrimps and paprika powder were examined. Shrimps were also the subject of examination in a TL test. Finally, GC detection of radiation-induced hydrocarbons in the fat fraction of foods was used in another test to identify irradiated Camembert, avocado, papaya and mango. In the following paper, results of the interlaboratory tests are summarised. Detailed reports are published by this institute. (author)

Interlaboratory comparison of three microbial source tracking quantitative polymerase chain reaction (qPCR) assays from fecal-source and environmental samples

Science.gov (United States)

Stelzer, Erin A.; Strickler, Kriston M.; Schill, William B.

2012-01-01

During summer and early fall 2010, 15 river samples and 6 fecal-source samples were collected in West Virginia. These samples were analyzed by three laboratories for three microbial source tracking (MST) markers: AllBac, a general fecal indicator; BacHum, a human-associated fecal indicator; and BoBac, a ruminant-associated fecal indicator. MST markers were analyzed by means of the quantitative polymerase chain reaction (qPCR) method. The aim was to assess interlaboratory precision when the three laboratories used the same MST marker and shared deoxyribonucleic acid (DNA) extracts of the samples, but different equipment, reagents, and analyst experience levels. The term assay refers to both the markers and the procedure differences listed above. Interlaboratory precision was best for all three MST assays when using the geometric mean absolute relative percent difference (ARPD) and Friedman's statistical test as a measure of interlaboratory precision. Adjustment factors (one for each MST assay) were calculated using results from fecal-source samples analyzed by all three laboratories and applied retrospectively to sample concentrations to account for differences in qPCR results among labs using different standards and procedures. Following the application of adjustment factors to qPCR results, ARPDs were lower; however, statistically significant differences between labs were still observed for the BacHum and BoBac assays. This was a small study and two of the MST assays had 52 percent of samples with concentrations at or below the limit of accurate quantification; hence, more testing could be done to determine if the adjustment factors would work better if the majority of sample concentrations were above the quantification limit.

Evaluation of interlaboratory round robin study (2000-2003) in Japan

Energy Technology Data Exchange (ETDEWEB)

Shiozaki, T. [Japan Environmental Sanitation Center, Kawasaki, Kanagawa (Japan); Takasuga, T. [Shimadzu Techno Research (Japan); Iwaki, K. [Ebara Research (Japan); Mochizuki, T. [Kokan Keisoku (Japan); Miyazaki, T. [Nittech Research (Japan); Tanaka, K. [Toray Research Center (Japan)

2004-09-15

Inter-laboratory round robin is available for maintaining dioxin analytical quality/skills by testing or certified laboratories. There are over 150 dioxin testing laboratories available in Japan consequently, Ministry of Environment (MOE) and Ministry of Economy Trade and Industry (METI) have began to investigate quality of dioxin testing laboratory and to upgrade their skills with in 4 years. On the other hands, Research Group for Dioxin Analysis which have technical experts from 33 private dioxin testing laboratories had carried out inter-laboratory round robin 4 times since 1998. These studies has been transferred to new research group namely, Research Group on Ultra trace Analyses (UTA) which is accompanied organization of Japan Environmental Measurement and Chemical Analysis Association (JEMCA) in 2003. The UTA consists 83 private dioxin testing laboratories and has been subjected to grow up the technical potential for not only dioxins but other trace level analysis of well known persistent organic pollutants (POPs), endocrine disrupting chemicals (EDCs) and ubiquitous contaminants in the environment. Former research group had run final round (4{sup th}) and new UTA carried out first round studies in 2001 And 2003, respectively. Percentage relative standard deviations (RSD) for each polychlorinated dibenzo-pdioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (DL-PCBs) have become smaller than past studies.

Inter-laboratory optimization of protein extraction, separation, and fluorescent detection of endogenous rice allergens.

Science.gov (United States)

Satoh, Rie; Teshima, Reiko; Kitta, Kazumi; Lang, Gang-Hua; Schegg, Kathleen; Blumenthal, Kenneth; Hicks, Leslie; Labory-Carcenac, Bénédicte; Rouquié, David; Herman, Rod A; Herouet-Guicheney, Corinne; Ladics, Gregory S; McClain, Scott; Poulsen, Lars K; Privalle, Laura; Ward, Jason M; Doerrer, Nancy; Rascle, Jean-Baptiste

2016-07-11

In rice, several allergens have been identified such as the non-specific lipid transfer protein-1, the α-amylase/trypsin-inhibitors, the α-globulin, the 33 kDa glyoxalase I (Gly I), the 52-63 kDa globulin, and the granule-bound starch synthetase. The goal of the present study was to define optimal rice extraction and detection methods that would allow a sensitive and reproducible measure of several classes of known rice allergens. In a three-laboratory ring-trial experiment, several protein extraction methods were first compared and analyzed by 1D multiplexed SDS-PAGE. In a second phase, an inter-laboratory validation of 2D-DIGE analysis was conducted in five independent laboratories, focusing on three rice allergens (52 kDa globulin, 33 kDa glyoxalase I, and 14-16 kDa α-amylase/trypsin inhibitor family members). The results of the present study indicate that a combination of 1D multiplexed SDS-PAGE and 2D-DIGE methods would be recommended to quantify the various rice allergens.

Detection of antigen in sera of patients with invasive aspergillosis : Intra- and interlaboratory reproducibility

NARCIS (Netherlands)

Verweij, PE; Erjavec, Z; Sluiters, W; Goessens, W; Rozenberg-Arska, M; Debets-Ossenkopp, YJ; Guiot, HFL; Meis, JFGM

The intra-and interlaboratory reproducibilities of a commercial sandwich enzyme-linked immunosorbent assay (ELISA) for the detection of Aspergillus galactomannan in serum (Platelia Aspergillus; Sanofi Diagnostics Pasteur, Marnes-La-Coquette, France) were evaluated in six laboratories of university

Advancing the Use of Passive Sampling in Risk Assessment and Management of Sediments Contaminated with Hydrophobic Organic Chemicals: Results of an International Ex Situ Passive Sampling Interlaboratory Comparison

Science.gov (United States)

This work presents the results of an international interlaboratory comparison on ex situ passive sampling in sediments. The main objectives were to map the state of the science in passively sampling sediments, identify sources of variability, provide recommendations and practica...

Interlaboratory validation of small-scale solubility and dissolution measurements of poorly water-soluble drugs

DEFF Research Database (Denmark)

Andersson, Sara B. E.; Alvebratt, Caroline; Bevernage, Jan

2016-01-01

The purpose of this study was to investigate the interlaboratory variability in determination of apparent solubility (Sapp) and intrinsic dissolution rate (IDR) using a miniaturized dissolution instrument. Three poorly water-soluble compounds were selected as reference compounds and measured at m...

Determination of maduramicin in feedingstuffs and premixtures by liquid chromatography : development, validation and interlaboratory study

NARCIS (Netherlands)

Jong, de J.; Stoisser, B.; Wagner, K.; Tomassen, M.J.H.; Driessen, J.J.M.; Hofman, P.; Putzka, H.A.

2004-01-01

A reversed-phase liquid chromatography method for determination of maduramicin in feedingstuffs and premixtures was developed, validated, and interlaboratory studied. The extraction solvent was methanol. Maduramicin was detected at 520 nm after postcolumn derivatization with vanillin. Recovery was

Characterisation of humic material for inter-laboratory comparison

International Nuclear Information System (INIS)

Peachy, D.; Bradley, A.D.; Davis, A.E.; Stuart, M.E.; Tait, B.A.R.; Vickers, B.P.; Williams, G.M.

1988-01-01

The characterisation and interlaboratory comparison of common humic materials by members of the European Commission's COCO group (set up to study complexes and colloids), forms part of a study of the effects of natural organic compounds in groundwater on the complexation and mobility of radionuclides. Three samples have been characterised: a sodium salt and a protonated form of the commercially available humic acid from Aldrich Chemicals; and a protonated humic acid from the Gorleben research site in Germany. Characterisation undertaken by BGS includes moisture content, elemental analysis, metal content, functional group analysis, infra-red spectroscopy, ultra-violet absorbance (E 4 /E 6 ratios), and ultra-filtration. (author)

Assessing the readability of ClinicalTrials.gov.

Science.gov (United States)

Wu, Danny T Y; Hanauer, David A; Mei, Qiaozhu; Clark, Patricia M; An, Lawrence C; Proulx, Joshua; Zeng, Qing T; Vydiswaran, V G Vinod; Collins-Thompson, Kevyn; Zheng, Kai

2016-03-01

ClinicalTrials.gov serves critical functions of disseminating trial information to the public and helping the trials recruit participants. This study assessed the readability of trial descriptions at ClinicalTrials.gov using multiple quantitative measures. The analysis included all 165,988 trials registered at ClinicalTrials.gov as of April 30, 2014. To obtain benchmarks, the authors also analyzed 2 other medical corpora: (1) all 955 Health Topics articles from MedlinePlus and (2) a random sample of 100,000 clinician notes retrieved from an electronic health records system intended for conveying internal communication among medical professionals. The authors characterized each of the corpora using 4 surface metrics, and then applied 5 different scoring algorithms to assess their readability. The authors hypothesized that clinician notes would be most difficult to read, followed by trial descriptions and MedlinePlus Health Topics articles. Trial descriptions have the longest average sentence length (26.1 words) across all corpora; 65% of their words used are not covered by a basic medical English dictionary. In comparison, average sentence length of MedlinePlus Health Topics articles is 61% shorter, vocabulary size is 95% smaller, and dictionary coverage is 46% higher. All 5 scoring algorithms consistently rated CliniclTrials.gov trial descriptions the most difficult corpus to read, even harder than clinician notes. On average, it requires 18 years of education to properly understand these trial descriptions according to the results generated by the readability assessment algorithms. Trial descriptions at CliniclTrials.gov are extremely difficult to read. Significant work is warranted to improve their readability in order to achieve CliniclTrials.gov's goal of facilitating information dissemination and subject recruitment. Published by Oxford University Press on behalf of the American Medical Informatics Association 2015. This work is written by US Government

[Interlaboratory Study on Evaporation Residue Test for Food Contact Products (Report 2)].

Science.gov (United States)

Ohno, Hiroyuki; Mutsuga, Motoh; Abe, Tomoyuki; Abe, Yutaka; Amano, Homare; Ishihara, Kinuyo; Ohsaka, Ikue; Ohno, Haruka; Ohno, Yuichiro; Ozaki, Asako; Kakihara, Yoshiteru; Kobayashi, Hisashi; Sakuragi, Hiroshi; Shibata, Hiroshi; Shirono, Katsuhiro; Sekido, Haruko; Takasaka, Noriko; Takenaka, Yu; Tajima, Yoshiyasu; Tanaka, Aoi; Tanaka, Hideyuki; Nakanishi, Toru; Nomura, Chie; Haneishi, Nahoko; Hayakawa, Masato; Miura, Toshihiko; Yamaguchi, Miku; Yamada, Kyohei; Watanabe, Kazunari; Sato, Kyoko

2018-01-01

An interlaboratory study was performed to evaluate the equivalence between an official method and a modified method of evaporation residue test using heptane as a food-simulating solvent for oily or fatty foods, based on the Japanese Food Sanitation Law for food contact products. Twenty-three laboratories participated, and tested the evaporation residues of nine test solutions as blind duplicates. In the official method, heating for evaporation was done with a water bath. In the modified method, a hot plate was used for evaporation, and/or a vacuum concentration procedure was skipped. In most laboratories, the test solutions were heated until just prior to dryness, and then allowed to dry under residual heat. Statistical analysis revealed that there was no significant difference between the two methods. Accordingly, the modified method provides performance equal to the official method, and is available as an alternative method. Furthermore, an interlaboratory study was performed to evaluate and compare two leaching solutions (95% ethanol and isooctane) used as food-simulating solvents for oily or fatty foods in the EU. The results demonstrated that there was no significant difference between heptane and these two leaching solutions.

First European interlaboratory comparison of tetracycline and age determination with red fox teeth following oral rabies vaccination programs.

Science.gov (United States)

Robardet, Emmanuelle; Demerson, Jean-Michel; Andrieu, Sabrina; Cliquet, Florence

2012-10-01

The first European interlaboratory comparison of tetracycline and age determination with red fox (Vulpes vulpes) tooth samples was organized by the European Union Reference Laboratory for rabies. Performance and procedures implemented by member states were compared. These techniques are widely used to monitor bait uptake in European oral rabies vaccination campaigns. A panel of five red fox half-mandibles comprising one weak positive juvenile sample, two positive adult samples, one negative juvenile sample, and one negative adult sample were sent, along with a technical questionnaire, to 12 laboratories participating on a voluntary basis. The results of only three laboratories (25%) were 100% correct. False-negative results were more frequently seen in weak positive juvenile samples (58%) but were infrequent in positive adult samples (4%), probably due to differences in the ease of reading the two groups of teeth. Four laboratories (44%) had correct results for age determination on all samples. Ages were incorrectly identified in both adult and juvenile samples, with 11 and 17% of discordant results, respectively. Analysis of the technical questionnaires in parallel with test results suggested that all laboratories cutting mandible sections between the canine and first premolar obtained false results. All the laboratories using longitudinal rather than transverse sections and those not using a mounting medium also produced false results. Section thickness appeared to affect the results; no mistakes were found in laboratories using sections <150 μm thick. Factors having a potential impact on the success of laboratories were discussed, and recommendations proposed. Such interlaboratory trials underline the importance of using standardized procedures for biomarker detection in oral rabies vaccination campaigns. Several changes can be made to improve analysis quality and increase the comparability of bait uptake frequencies among member states.

The As-76 interlaboratory experiment on the alpha spectrometric determination of Pu-238. Pt. 2

International Nuclear Information System (INIS)

Bortels, G.; Spannagel, G.; Beyrich, W.

1979-12-01

The AS-76 interlaboratory program furnished 828 alpha spectra. A selection of these spectra was evaluated in more detail by use of information supplied by the laboratories and by application of a common procedure of evaluation. (orig.) 891 HP/orig. 892 MKO [de

Results of the Interlaboratory Exercise CSN/CIEMAT-100 Among Environmental Radioactivity Laboratories (Soil); Resultados del Ejercicio Interlaboratorios de Radiactividad Ambiental CSN/CIEMAT-00 (Suelo)

Energy Technology Data Exchange (ETDEWEB)

Romero Gonzalez, M. L.

2002-07-01

The document describes the outcome of the CSN/CIEMAT-00 interlaboratory test comparison among environmental radioactivity laboratories. the exercise was organised according to the ISO-43 and the ISO/IUPAC/AOAC Harmonized Protocol for the proficiency testing of analytical laboratories. the test sample was a soil containing environmental levels of K-40, Ra-226, Ac-228, Sr-90, Cs-137, Cs-134, Pu (239-240) y Am-241. the Universidad Autonoma de Barcelona prepared the material and reported adequate statistical studies of homogeneity. The results of the exercise were computed for 30 participating laboratories, and their analytical performance was assessed using the u-score approach. A raised percentage of satisfactory laboratory performance has been obtained for all the analysis, being the best performance in gamma measurements. The exercise has drawn that several laboratories have difficulties in the evaluation of combined uncertainty, mainly in analysis involving radiochemical steps. The study has shown an homogeneous inter-laboratory behaviour, and the improvement achieved through subsequent exercises in the quality of the data they are producing. (Author) 10 refs.

Preliminary report on SG126 Task 3: 129I interlaboratory comparison

International Nuclear Information System (INIS)

Roberts, M.L.; Caffee, M.W.; Proctor, I.D.

1996-01-01

An interlaboratory comparison exercise for 129 I has been organized and conducted. A total of seven laboratories participated in the exercise to either a full or limited extent. In the comparison, a suite of 11 samples was used. This suite of standards contained both synthetic 'standard type' materials (i.e., AgI) and environmental materials. The isotopic 129 I/ 127 I ratio of the samples varied from 10 -8 to 10 -14 . Results of the comparison are presented

Reliability on intra-laboratory and inter-laboratory data of hair mineral analysis comparing with blood analysis.

Science.gov (United States)

Namkoong, Sun; Hong, Seung Phil; Kim, Myung Hwa; Park, Byung Cheol

2013-02-01

Nowadays, although its clinical value remains controversial institutions utilize hair mineral analysis. Arguments about the reliability of hair mineral analysis persist, and there have been evaluations of commercial laboratories performing hair mineral analysis. The objective of this study was to assess the reliability of intra-laboratory and inter-laboratory data at three commercial laboratories conducting hair mineral analysis, compared to serum mineral analysis. Two divided hair samples taken from near the scalp were submitted for analysis at the same time, to all laboratories, from one healthy volunteer. Each laboratory sent a report consisting of quantitative results and their interpretation of health implications. Differences among intra-laboratory and interlaboratory data were analyzed using SPSS version 12.0 (SPSS Inc., USA). All the laboratories used identical methods for quantitative analysis, and they generated consistent numerical results according to Friedman analysis of variance. However, the normal reference ranges of each laboratory varied. As such, each laboratory interpreted the patient's health differently. On intra-laboratory data, Wilcoxon analysis suggested they generated relatively coherent data, but laboratory B could not in one element, so its reliability was doubtful. In comparison with the blood test, laboratory C generated identical results, but not laboratory A and B. Hair mineral analysis has its limitations, considering the reliability of inter and intra laboratory analysis comparing with blood analysis. As such, clinicians should be cautious when applying hair mineral analysis as an ancillary tool. Each laboratory included in this study requires continuous refinement from now on for inducing standardized normal reference levels.

Performance evaluation of nitrogen isotope ratio determination in marine and lacustrine sediments: An inter-laboratory comparison

NARCIS (Netherlands)

Bahlmann, E.; Bernasconi, S.M.; Bouillon, S.; Houtekamer, M.J.; Korntheuer, M.; Langenberg, F.; Mayr, C.; Metzke, M.; Middelburg, J.J.; Nagel, B.; Struck, U.; Voß, M.; Emeis, K.C.

2010-01-01

Nitrogen isotopes of organic matter are increasingly studied in marine biogeochemistry and geology, plant and animal ecology, and paleoceanography. Here, we present results of an inter-laboratory test on determination of nitrogen isotope ratios in marine and lacustrine sediments. Six different

Inter-laboratory comparisons. Determination of actinides in excreta

International Nuclear Information System (INIS)

Berard, P.; Cavadore, D.; Harduin, J.C.

1995-01-01

Inter-laboratory tests are a means of assessing the analytical coherence of medical laboratories. In radio toxicology, this kind of exercise makes it possible to keep up with laboratory know-how and with the evolution and relative performances of analytical techniques (precision and reproducibility). However, the goal of the laboratories taking part in these annual exercises is not only to check the accuracy of their results. The analytical discussions and the chance to compare experience enrich the groups general competence. French biologists have been organizing annual radio toxicology intercomparison exercises since 1978. The exercises are carried out within the framework of a working group (GT1) operating under the aegis of the French Atomic Energy Commission's (CEA) Medical Coordinator. Using reports and diagrams which present the results obtained by the participants in the form of syntheses, the authors describe how the exercises for determining actinides in excreta (urine and faeces) are organized, how the results are evaluated in terms of the analytical methods used, and the improvements made in analytical and metrological performance. Up until 1985, these exercises were limited to French laboratories. Since then, the exercises have acquired an international dimension, opening up to include interested foreign radio chemists, initially from European laboratories, and now from laboratories worldwide. At the present time, 35 laboratories representing 9 countries take part regularly in these intercomparison exercises. (author). 6 refs., 9 figs

Impact of Uniform Methods on Interlaboratory Antibody Titration Variability: Antibody Titration and Uniform Methods.

Science.gov (United States)

Bachegowda, Lohith S; Cheng, Yan H; Long, Thomas; Shaz, Beth H

2017-01-01

-Substantial variability between different antibody titration methods prompted development and introduction of uniform methods in 2008. -To determine whether uniform methods consistently decrease interlaboratory variation in proficiency testing. -Proficiency testing data for antibody titration between 2009 and 2013 were obtained from the College of American Pathologists. Each laboratory was supplied plasma and red cells to determine anti-A and anti-D antibody titers by their standard method: gel or tube by uniform or other methods at different testing phases (immediate spin and/or room temperature [anti-A], and/or anti-human globulin [AHG: anti-A and anti-D]) with different additives. Interlaboratory variations were compared by analyzing the distribution of titer results by method and phase. -A median of 574 and 1100 responses were reported for anti-A and anti-D antibody titers, respectively, during a 5-year period. The 3 most frequent (median) methods performed for anti-A antibody were uniform tube room temperature (147.5; range, 119-159), uniform tube AHG (143.5; range, 134-150), and other tube AHG (97; range, 82-116); for anti-D antibody, the methods were other tube (451; range, 431-465), uniform tube (404; range, 382-462), and uniform gel (137; range, 121-153). Of the larger reported methods, uniform gel AHG phase for anti-A and anti-D antibodies had the most participants with the same result (mode). For anti-A antibody, 0 of 8 (uniform versus other tube room temperature) and 1 of 8 (uniform versus other tube AHG), and for anti-D antibody, 0 of 8 (uniform versus other tube) and 0 of 8 (uniform versus other gel) proficiency tests showed significant titer variability reduction. -Uniform methods harmonize laboratory techniques but rarely reduce interlaboratory titer variance in comparison with other methods.

An ECVAG trial on assessment of oxidative damage to DNA measured by the comet assay

DEFF Research Database (Denmark)

Johansson, Clara; Møller, Peter; Forchhammer, Lykke

2010-01-01

The increasing use of single cell gel electrophoresis (the comet assay) highlights its popularity as a method for detecting DNA damage, including the use of enzymes for assessment of oxidatively damaged DNA. However, comparison of DNA damage levels between laboratories can be difficult due...... to differences in assay protocols (e.g. lysis conditions, enzyme treatment, the duration of the alkaline treatment and electrophoresis) and in the end points used for reporting results (e.g. %DNA in tail, arbitrary units, tail moment and tail length). One way to facilitate comparisons is to convert primary comet...... assay end points to number of lesions/10(6) bp by calibration with ionizing radiation. The aim of this study was to investigate the inter-laboratory variation in assessment of oxidatively damaged DNA by the comet assay in terms of oxidized purines converted to strand breaks with formamidopyrimidine DNA...

Inter-laboratory validation of the measurement of follicle stimulating hormone (FSH after various lengths of frozen storage

Directory of Open Access Journals (Sweden)

Behr Barry

2010-11-01

Full Text Available Abstract Background Serum follicle stimulating hormone (FSH levels are used clinically to evaluate infertility, pituitary and gonadal disorders. With increased frequency of research collaborations across institutions, it is essential that inter-laboratory validation is addressed. Methods An inter-laboratory validation of three commercial FSH immunoassays was performed with human serum samples of varying frozen storage length (2 batches of 15 samples each at -25 degree C. Percentage differences and Bland-Altman limits of agreement were calculated. Results The inter- and intra-laboratory consistency of FSH values with the same assay manufacturer was much higher after shorter-term storage (frozen for less than 11 months, mean percentage degradation less than 4% than after long-term storage (2-3 years, mean percentage degradation = 23%. Comparing assay results from different manufacturers, there was similar overall long term degradation as seen with the same manufacturer (-25%, however the degradation was greater when the original FSH was greater than 20 mIU/mL relative to less than 10 mIU/mL (p Conclusion The findings suggest that degradation of serum samples stored between 11 months and 2-3 years at -25 degrees C can lead to unstable FSH measurements. Inter-laboratory variability due to frozen storage time and manufacturer differences in assay results should be accounted for when designing and implementing research or clinical quality control activities involving serum FSH at multiple study sites.

Determination of the acid value of instant noodles: interlaboratory study.

Science.gov (United States)

Hakoda, Akiko; Sakaida, Kenichi; Suzuki, Tadanao; Yasui, Akemi

2006-01-01

An interlaboratory study was performed to evaluate the method for determining the acid value of instant noodles, based on the Japanese Agricultural Standard (JAS), with extraction of lipid using petroleum ether at a volume of 100 mL to the test portion of 25 g. Thirteen laboratories participated and analyzed 5 test samples as blind duplicates. Statistical treatment revealed that the repeatability (RSDr) of acid value was noodles per unit weight, using the equation [acid value = percent free fatty acids (as oleic) x 1.99] and the extracted lipid contents. This method was shown to have acceptable precision by the present study.

Validation of a PCR-based method for detection of food-borne thermotolerant Campylobacters in a multicenter collaborative trial

DEFF Research Database (Denmark)

Josefsen, Mathilde Hartmann; Cook, N.; D'Agostino, M.

2004-01-01

A PCR-based method for rapid detection of food-borne thermotolerant campylobacters was evaluated through a collaborative trial with 12 laboratories testing spiked carcass rinse samples. The method showed an interlaboratory diagnostic sensitivity of 96.7% and a diagnostic specificity of 100% for c......% for chicken samples, while these values were 94.2 and 83.3%, respectively, for pig samples....

Determination of total dietary fiber in selected foods containing resistant maltodextrin by a simplified enzymatic-gravimetric method and liquid chromatography: interlaboratory study in China.

Science.gov (United States)

Fu, Boqiang; Wang, Jing; Roturier, Jean Michel; Tang, Zhiyu; Li, Huan; Wei, Guangyan

2008-01-01

An interlaboratory study was conducted in China to validate the modified AOAC Official Method 2001.03 for the determination of total dietary fiber (TDF) in foods containing resistant maltodextrin (RMD), which will be adopted as the National Standard Method of China. The kind of buffer solution, the volume of filtrate evaporation, the volume of eluent for desalting and residual solution after evaporation, etc. were modified, which had been proved to have acceptable accuracy and precision in the routine assay. TDF contents in 3 representative foods and 2 kinds of RMD ingredient (i.e., NUTRIOSE 06 and NUTRIOSE 10) were measured using the modified method in 6 eligible laboratories representing commercial, industrial, and governmental laboratories in China. The results of the interlaboratory study indicated that the intralaboratory repeatability, interlaboratory reproducibility, and precision of the modified method are adequate for reliable analysis of TDF in food containing RMD, as well as resistant dextrin. Compared to AOAC Official Method 2001.03, the modified method is time- and cost-saving.

76 FR 48119 - Oral Rabies Vaccine Trial; Availability of a Risk Assessment and an Environmental Assessment

Science.gov (United States)

2011-08-08

...] Oral Rabies Vaccine Trial; Availability of a Risk Assessment and an Environmental Assessment AGENCY... environmental assessment relative to an oral rabies vaccination field trial in West Virginia. The environmental... rabies vaccine, analyzes the use of that vaccine in field safety and efficacy trials in West Virginia...

Interlaboratory validation of the modified murine local lymph node assay based on adenosine triphosphate measurement.

Science.gov (United States)

Omori, Takashi; Idehara, Kenji; Kojima, Hajime; Sozu, Takashi; Arima, Kazunori; Goto, Hirohiko; Hanada, Tomohiko; Ikarashi, Yoshiaki; Inoda, Taketo; Kanazawa, Yukiko; Kosaka, Tadashi; Maki, Eiji; Morimoto, Takashi; Shinoda, Shinsuke; Shinoda, Naoki; Takeyoshi, Masahiro; Tanaka, Masashi; Uratani, Mamoru; Usami, Masahito; Yamanaka, Atsushi; Yoneda, Tomofumi; Yoshimura, Isao; Yuasa, Atsuko

2008-01-01

The murine local lymph node assay (LLNA) is a well-established alternative to the guinea pig maximization test (GPMT) or Buehler test (BT) for the assessment of the skin sensitizing ability of drugs and chemicals. Daicel Chemical Industries Ltd. has developed a modified LLNA based on the adenosine triphosphate (ATP) content (LLNA-DA). We conducted 2 interlaboratory validation studies to evaluate the reliability and relevance of LLNA-DA. The experiment involved 17 laboratories, wherein 14 chemicals were examined under blinded conditions. In the first study, 3 chemicals were examined in 10 laboratories and the remaining 9 were examined in 3 laboratories. In the second study, 1 chemical was examined in 7 laboratories and the remaining 4 chemicals were examined in 4 laboratories. The data were expressed as the ATP content for each chemical-treated group, and the stimulation index (SI) for each chemical-treated group was determined as the increase in the ATP content relative to the concurrent vehicle control group. An SI of 3 was set as the cut-off value for exhibiting skin sensitization activity. The results of the first study obtained in the experiments conducted for the 3 chemicals that were examined in all the 10 laboratories and for 5 of the remaining 9 chemicals were sufficiently consistent with small variations in their SI values. The sensitivity, specificity, and accuracy of LLNA-DA against those of GPMT/BT were 7/8 (87.5%), 3/3 (100%), and 10/11 (90.9%), respectively. In the second study, all the 5 chemicals studied demonstrated acceptably small interlaboratory variations. In the first study, a large variation was observed for 2 chemicals; in the second study, this variation was small. It was attributed to the application of dimethylsulfoxide as the solvent for the metallic salts. In conclusion, these 2 studies provide good evidence for the reliability of the LLNA-DA.

The AS-76 interlaboratory experiment on the alpha spectrometric determination of Pu-238. Pt. 1

International Nuclear Information System (INIS)

Beyrich, W.; Spannagel, G.

1979-12-01

In cooperation with 26 laboratories of 11 countries or international organizations, the Safeguards Project of the Karlsruhe Nuclear Research Center carried out the interlaboratory program AS-76. It focused on the alpha-spectrometric determination of the Pu-238 isotope. The performance of the program as well as the results obtained are described. (orig.) 891 HP/orig. 892 MKO [de

Canadian inter-laboratory organically bound tritium (OBT) analysis exercise.

Science.gov (United States)

Kim, S B; Olfert, J; Baglan, N; St-Amant, N; Carter, B; Clark, I; Bucur, C

2015-12-01

Tritium emissions are one of the main concerns with regard to CANDU reactors and Canadian nuclear facilities. After the Fukushima accident, the Canadian Nuclear Regulatory Commission suggested that models used in risk assessment of Canadian nuclear facilities be firmly based on measured data. Procedures for measurement of tritium as HTO (tritiated water) are well established, but there are no standard methods and certified reference materials for measurement of organically bound tritium (OBT) in environmental samples. This paper describes and discusses an inter-laboratory comparison study in which OBT in three different dried environmental samples (fish, Swiss chard and potato) was measured to evaluate OBT analysis methods currently used by CANDU Owners Group (COG) members. The variations in the measured OBT activity concentrations between all laboratories were less than approximately 20%, with a total uncertainty between 11 and 17%. Based on the results using the dried samples, the current OBT analysis methods for combustion, distillation and counting are generally acceptable. However, a complete consensus OBT analysis methodology with respect to freeze-drying, rinsing, combustion, distillation and counting is required. Also, an exercise using low-level tritium samples (less than 100 Bq/L or 20 Bq/kg-fresh) would be useful in the near future to more fully evaluate the current OBT analysis methods. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Confirmation of synthetic glucocorticoids with liquid chromatography/mass spectrometry: Organization and results of an international interlaboratory comparison test

NARCIS (Netherlands)

Hauwe, O. van den; Campbell, K.; Crooks, S.R.H.; Schilt, R.; Peteghem, C.H. van

2005-01-01

Within the framework of a European Union (EU) research project entitled "Food Safety Screening: Synthetic Glucocorticoids (QLK1-1999-00122)," an international interlaboratory ring test was organized to compare and evaluate different liquid chromatography/mass spectrometry (LC/MS) confirmatory

Be-10 and Cl-36 interlaboratory comparisons

Energy Technology Data Exchange (ETDEWEB)

Merchel, Silke [CEREGE, Aix-en-Provence (France); FZD, Dresden (Germany); Bremser, Wolfram [BAM, Berlin (Germany); Alfimov, Vasily; Christl, Marcus; Kubik, Peter W. [PSI/ETH Zurich (Switzerland); Arnold, Maurice; Aumaitre, Georges; Benedetti, Lucilla; Bourles, Didier L.; Braucher, Regis [CEREGE, Aix-en-Provence (France); Caffee, Marc [PRIME Lab, Purdue, IN (United States); Fifield, L. Keith; Tims, Stephen G. [ANU, Canberra (Australia); Finkel, Robert C. [CEREGE, Aix-en-Provence (France); LLNL, Livermore, CA (United States); Freeman, Stewart P.H.T.; Wilcken, Klaus M.; Xu, Sheng [SUERC, East Kilbride (United Kingdom); Ruiz-Gomez, Aaron [CNA, Sevilla (Spain); Rood, Dylan H. [LLNL, Livermore, CA (United States); Sasa, Kimikazu [University of Tsukuba (Japan); Steier, Peter; Wallner, Anton [VERA, Wien (Austria)

2009-07-01

Driven by the progress in AMS and its spreading application within geosciences, measurements of increasing numbers of samples with low isotopic ratios will be required in the future. Therefore, we have examined the linearity of {sup 10}Be/{sup 9}Be as a function of isotope ratio by distributing 3 secondary standards (dilutions of NIST4325: 10{sup -12}-10{sup -14}) to 9 AMS labs. The problem of low ratio samples is even more crucial for {sup 36}Cl mainly due to the high volatility of chlorine. Thus, we have prepared large quantities of 3 {sup 36}Cl/Cl solutions from a certified {sup 36}Cl activity (NIST4943) by dilution with NaCl. AgCl precipitated from these solutions (10{sup -11}-10{sup -13}) has been distributed to 9 AMS labs. Some measurements are still ongoing. First results from 6 labs for each nuclide show that these interlaboratory exercises are very valuable.

First worldwide UNEP interlaboratory study on persistent organic pollutants (POPs) with data on polychlorinated biphenyls and organochlorine pesticides

NARCIS (Netherlands)

Leeuwen, van S.P.J.; Bavel, van B.; Boer, de J.

2013-01-01

The first worldwide interlaboratory study on persistent organic pollutants (POPs) under the Stockholm Convention was organized, with a participation of 103 laboratories from Asia, Europe, the Americas, Africa and Australia, of which the majority submitted data on polychlorinated biphenyls (PCBs) and

Participation in the 1999 IAEA interlaboratory comparison on chemical analysis of groundwater

International Nuclear Information System (INIS)

Joe, Kih Soo; Choi, Kwang Soon; Han, Sun Ho; Suh, Moo Yul; Park, Kyung Kyun; Choi, Ke Chun; Kim, Won Ho

2000-08-01

KAERI analytical laboratory participated in the 1999 IAEA interlaboratory comparison on chemical analysis of groundwater organized by IAEA Hydrology Laboratory(RAS/8/084). 13 items such as pH, electroconductivity, HCO 3 , Cl, SO 4 , NO 3 , SiO 2 , B, Li, Na, K, Ca, Mg were analyzed. The result of this program showed that KAERI laboratory was ranked within 10% range from top level. An analytical expert in KAERI attended the 'Consultants' Meeting' at IAEA headquater and prepared the guideline for chemical analysis of groundwater

Interlaboratory comparison of measuring results of magnetic field near 400 kV overhead power line

Directory of Open Access Journals (Sweden)

Grbić Maja

2012-01-01

Full Text Available The paper presents a comparison of measured results of magnetic field near 400 kV overhead power lines obtained by three laboratories. This interlaboratory comparison was performed to ensure confidence in the quality of the test results. The measured results were analyzed with standard methods, using En number, based on which the evaluation of the laboratories was performed.

Inter-laboratory variation in DNA damage using a standard comet assay protocol

DEFF Research Database (Denmark)

Forchhammer, Lykke; Ersson, Clara; Loft, Steffen

2012-01-01

determined the baseline level of DNA strand breaks (SBs)/alkaline labile sites and formamidopyrimidine DNA glycosylase (FPG)-sensitive sites in coded samples of mononuclear blood cells (MNBCs) from healthy volunteers. There were technical problems in seven laboratories in adopting the standard protocol...... analysed by the standard protocol. The SBs and FPG-sensitive sites were measured in the same experiment, indicating that the large spread in the latter lesions was the main reason for the reduced inter-laboratory variation. However, it remains worrying that half of the participating laboratories obtained...

Participation in the 1999 IAEA interlaboratory comparison on chemical analysis of groundwater

Energy Technology Data Exchange (ETDEWEB)

Joe, Kih Soo; Choi, Kwang Soon; Han, Sun Ho; Suh, Moo Yul; Park, Kyung Kyun; Choi, Ke Chun; Kim, Won Ho

2000-08-01

KAERI analytical laboratory participated in the 1999 IAEA interlaboratory comparison on chemical analysis of groundwater organized by IAEA Hydrology Laboratory(RAS/8/084). 13 items such as pH, electroconductivity, HCO{sub 3}, Cl, SO{sub 4}, NO{sub 3}, SiO{sub 2}, B, Li, Na, K, Ca, Mg were analyzed. The result of this program showed that KAERI laboratory was ranked within 10% range from top level. An analytical expert in KAERI attended the 'Consultants' Meeting' at IAEA headquater and prepared the guideline for chemical analysis of groundwater.

Round-Robin Studies on Roll-Processed ITO-free Organic Tandem Solar Cells Combined with Inter-Laboratory Stability Studies

DEFF Research Database (Denmark)

Livi, Francesco; Søndergaard, Roar R.; Andersen, Thomas Rieks

2015-01-01

Roll-processed, indium tin oxide (ITO)-free, flexible, organic tandem solar cells and modules have been realized and used in round-robin studies as well as in parallel inter-laboratory stability studies. The tandem cells/modules show no significant difference in comparison to their single...

An Interlaboratory Evaluation of Drift Tube Ion Mobility–Mass Spectrometry Collision Cross Section Measurements

Energy Technology Data Exchange (ETDEWEB)

Stow, Sarah M. [Department; Causon, Tim J. [Division; Zheng, Xueyun [Biological; Kurulugama, Ruwan T. [Agilent Technologies, Santa Clara, California 95051, United States; Mairinger, Teresa [Division; May, Jody C. [Department; Rennie, Emma E. [Agilent Technologies, Santa Clara, California 95051, United States; Baker, Erin S. [Biological; Smith, Richard D. [Biological; McLean, John A. [Department; Hann, Stephan [Division; Fjeldsted, John C. [Agilent Technologies, Santa Clara, California 95051, United States

2017-08-14

Collision cross section (CCS) measurements resulting from ion mobility-mass spectrometry (IM-MS) experiments provide a promising orthogonal dimension of structural information in MS-based analytical separations. As with any molecular identifier, interlaboratory standardization must precede broad range integration into analytical workflows. In this study, we present a reference drift tube ion mobility mass spectrometer (DTIM-MS) where improvements on the measurement accuracy of experimental parameters influencing IM separations provide standardized drift tube, nitrogen CCS values (DTCCSN2) for over 120 unique ion species with the lowest measurement uncertainty to date. The reproducibility of these DTCCSN2 values are evaluated across three additional laboratories on a commercially available DTIM-MS instrument. The traditional stepped field CCS method performs with a relative standard deviation (RSD) of 0.29% for all ion species across the three additional laboratories. The calibrated single field CCS method, which is compatible with a wide range of chromatographic inlet systems, performs with an average, absolute bias of 0.54% to the standardized stepped field DTCCSN2 values on the reference system. The low RSD and biases observed in this interlaboratory study illustrate the potential of DTIM-MS for providing a molecular identifier for a broad range of discovery based analyses.

Interlaboratory Comparison Test as an Evaluation of Applicability of an Alternative Edible Oil Analysis by 1H NMR Spectroscopy.

Science.gov (United States)

Zailer, Elina; Holzgrabe, Ulrike; Diehl, Bernd W K

2017-11-01

A proton (1H) NMR spectroscopic method was established for the quality assessment of vegetable oils. To date, several research studies have been published demonstrating the high potential of the NMR technique in lipid analysis. An interlaboratory comparison was organized with the following main objectives: (1) to evaluate an alternative analysis of edible oils by using 1H NMR spectroscopy; and (2) to determine the robustness and reproducibility of the method. Five different edible oil samples were analyzed by evaluating 15 signals (free fatty acids, peroxides, aldehydes, double bonds, and linoleic and linolenic acids) in each spectrum. A total of 21 NMR data sets were obtained from 17 international participant laboratories. The performance of each laboratory was assessed by their z-scores. The test was successfully passed by 90.5% of the participants. Results showed that NMR spectroscopy is a robust alternative method for edible oil analysis.

Participation in the 2001 IAEA interlaboratory comparison on geothermal water chemistry

Energy Technology Data Exchange (ETDEWEB)

Joe, Kih Soo; Choi, Kwang Soon; Han, Sun Ho; Suh, Moo Yul; Jeon, Young Shin; Choi, Ke Chun; Pyo, Hyung Yul; Kim, Yong Bok; Kim, Jong Gu; Kim, Won Ho [Korea Atomic Energy Research Institute, Taejeon (Korea)

2002-04-01

Korea Atomic Energy Research Institute Analytical laboratory participated in the 2001 IAEA Interlaboratory Comparison on chemical analysis of Geothermal Water containing high salinity organized by IAEA Hydrology Laboratory(INT/0/060). 14 items such as pH, electroconductivity, HCO{sub 3}, Cl, F, SO{sub 4}, SiO{sub 2}, B, Li, Na, K, Ca, Mg were analyzed. The result of this program showed that Korea Atomic Energy Research Institute laboratory was ranked within 15% range from top level. Major analytical methods were applied for this activity such as ICP-AES, AAS, IC, pH meter, conductometer and acid titration. 8 refs., 48 figs., 9 tabs. (Author)

Inter-laboratory evaluation of three flagellin PCR/RFLP methods for typing Campylobacter jejuni and C-coli: the CAMPYNET experience

DEFF Research Database (Denmark)

Harrington, Clare S.; Moran, L.; Ridley, A.M.

2003-01-01

Aims: To compare typeability, discriminatory ability, and inter-laboratory reproducibility of three flagellin PCR/RFLP(fla typing) methods previously described for Campylobacter. Methods and Results: The sample set(n = 100) was diverse, including both C. jejuni (n = 85) and C. coli (n = 15). Two ...

An inter-laboratory comparison of arsenic analysis in Bangladesh. Draft report

International Nuclear Information System (INIS)

Aggarwal, P.K.; Dargie, M.; Groening, M.; Kulkarni, K.M.; Gibson, J.J.

2001-03-01

The International Atomic Energy Agency (IAEA) conducted an evaluation of the quality of arsenic analysis in Bangladesh through an inter-laboratory comparison of the analysis of synthetic standards and field samples. A set of 8 synthetic standards with arsenic concentrations ranging from 0 to about 500 μg/kg, traceable to an internationally recognized standard solution of arsenic, were prepared by the IAEA and provided to the participating laboratories. In addition, two samples of drinking water were collected from near Dhaka by the local office of the World Health Organization (WHO) and provided to all participating laboratories and the IAEA for analysis. Out of the 25 laboratories who received the synthetic standards and field samples, 17 laboratories submitted results to the IAEA for comparison. The reported arsenic concentrations have a wide range with values much higher or much lower than the expected value. Analysis of field samples shows a range of values from 0 to 396 μg/kg. Less than one third of the participating laboratories obtained results that were within about 20% of the expected values (about 60 μg/kg) obtained by a laboratory cooperating with the IAEA (University of Rochester). Results of this inter-laboratory comparison point to a lack of consistency in the analytical results that have been and are being obtained in Bangladesh. More importantly, drinking water wells where elevated arsenic concentrations have been found may in fact have low concentrations. Similarly, wells that have been found to be free of arsenic may in fact have substantially higher arsenic concentrations. The quality and reliability of arsenic analysis needs to be established and continually evaluated in order to identify all affected areas and to provide appropriate mitigation

Reporting methods of blinding in randomized trials assessing nonpharmacological treatments.

Directory of Open Access Journals (Sweden)

Isabelle Boutron

2007-02-01

Full Text Available BACKGROUND: Blinding is a cornerstone of treatment evaluation. Blinding is more difficult to obtain in trials assessing nonpharmacological treatment and frequently relies on "creative" (nonstandard methods. The purpose of this study was to systematically describe the strategies used to obtain blinding in a sample of randomized controlled trials of nonpharmacological treatment. METHODS AND FINDINGS: We systematically searched in Medline and the Cochrane Methodology Register for randomized controlled trials (RCTs assessing nonpharmacological treatment with blinding, published during 2004 in high-impact-factor journals. Data were extracted using a standardized extraction form. We identified 145 articles, with the method of blinding described in 123 of the reports. Methods of blinding of participants and/or health care providers and/or other caregivers concerned mainly use of sham procedures such as simulation of surgical procedures, similar attention-control interventions, or a placebo with a different mode of administration for rehabilitation or psychotherapy. Trials assessing devices reported various placebo interventions such as use of sham prosthesis, identical apparatus (e.g., identical but inactivated machine or use of activated machine with a barrier to block the treatment, or simulation of using a device. Blinding participants to the study hypothesis was also an important method of blinding. The methods reported for blinding outcome assessors relied mainly on centralized assessment of paraclinical examinations, clinical examinations (i.e., use of video, audiotape, photography, or adjudications of clinical events. CONCLUSIONS: This study classifies blinding methods and provides a detailed description of methods that could overcome some barriers of blinding in clinical trials assessing nonpharmacological treatment, and provides information for readers assessing the quality of results of such trials.

O papel dos programas interlaboratoriais para a qualidade dos resultados analíticos Interlaboratorial programs for improving the quality of analytical results

Directory of Open Access Journals (Sweden)

Queenie Siu Hang Chui

2004-12-01

Full Text Available Interlaboratorial programs are conducted for a number of purposes: to identify problems related to the calibration of instruments, to assess the degree of equivalence of analytical results among several laboratories, to attribute quantity values and its uncertainties in the development of a certified reference material and to verify the performance of laboratories as in proficiency testing, a key quality assurance technique, which is sometimes used in conjunction with accreditation. Several statistics tools are employed to assess the analytical results of laboratories participating in an intercomparison program. Among them are the z-score technique, the elypse of confidence and the Grubbs and Cochran test. This work presents the experience in coordinating an intercomparison exercise in order to determine Ca, Al, Fe, Ti and Mn, as impurities in samples of silicon metal of chemical grade prepared as a candidate for reference material.

Interlaboratory determinations of isotopically enriched metals by field desorption mass spectroscopy

International Nuclear Information System (INIS)

Bahr, U.; Schulten, H.R.; Achenbach, C.; Ziskoven, R.

1982-01-01

The isotopic distribution of stable isotopes in six enriched metals (calcium, copper, barium, rubidium, strontium and thallium) has been determined by field desorption mass spectrometry. A first evaluation of the interlaboratory reproducibility of the application of this method for trace determination of metals was made using three different types of mass spectrometers in three different laboratories. The standard deviations for the most abundant isotopes of the metals investigated are between +-0.1 and +-0.5%. Within these standard deviations, the values obtained by the three mass spectrometry groups are the same. To support the accuracy of our quantification, thermal ionization mass spectrometry has been employed and confirms the results of the field desorption method. (orig.) [de

Rethinking risk assessment for emerging technology first-in-human trials.

Science.gov (United States)

Genske, Anna; Engel-Glatter, Sabrina

2016-03-01

Recent progress in synthetic biology (SynBio) has enabled the development of novel therapeutic opportunities for the treatment of human disease. In the near future, first-in-human trials (FIH) will be indicated. FIH trials mark a key milestone in the translation of medical SynBio applications into clinical practice. Fostered by uncertainty of possible adverse events for trial participants, a variety of ethical concerns emerge with regards to SynBio FIH trials, including 'risk' minimization. These concerns are associated with any FIH trial, however, due to the novelty of the approach, they become more pronounced for medical applications of emerging technologies (emTech) like SynBio. To minimize potential harm for trial participants, scholars, guidelines, regulations and policy makers alike suggest using 'risk assessment' as evaluation tool for such trials. Conversely, in the context of emTech FIH trials, we believe it to be at least questionable to contextualize uncertainty of potential adverse events as 'risk' and apply traditional risk assessment methods. Hence, this issue needs to be discussed to enable alterations of the evaluation process before the translational phase of SynBio applications begins. In this paper, we will take the opportunity to start the debate and highlight how a misunderstanding of the concept of risk, and the possibilities and limitations of risk assessment, respectively, might impair decision-making by the relevant regulatory authorities and research ethics committees, and discuss possible solutions to tackle the issue.

Interlaboratory reaction rate program. 12th progress report, November 1976-October 1979

International Nuclear Information System (INIS)

Lippincott, E.P.; McElroy, W.N.; Preston, C.C.

1980-09-01

The Interlaboratory Reaction Rate UILRR) program is establishing the capability to accurately measure neutron-induced reactions and reaction rates for reactor fuels and materials development programs. The goal for the principal fission reactions, 235 U, 238 U and 239 Pu, is an accuracy to within +- 5% at the 95% confidence level. Accurate measurement of other fission and nonfission reactions is also required, but to a lesser accuracy, between +- 5% and 10% at the 95% confidence level. A secondary program objective is improvement in knowledge of the nuclear parameters involved in the standarization of fuels and materials dosimetry measurements of neutron flux, spectra, fluence and burnup

An examination of the hexokinase method for serum glucose assay using external quality assessment data.

Science.gov (United States)

Westwood, A; Bullock, D G; Whitehead, T P

1986-01-01

Hexokinase methods for serum glucose assay appeared to give slightly but consistently higher inter-laboratory coefficients of variation than all methods combined in the UK External Quality Assessment Scheme; their performance over a two-year period was therefore compared with that for three groups of glucose oxidase methods. This assessment showed no intrinsic inferiority in the hexokinase method. The greater variation may be due to the more heterogeneous group of instruments, particularly discrete analysers, on which the method is used. The Beckman Glucose Analyzer and Astra group (using a glucose oxidase method) showed the least inter-laboratory variability but also the lowest mean value. No comment is offered on the absolute accuracy of any of the methods.

Assessment of blinding success among dental implant clinical trials: A systematic review

Directory of Open Access Journals (Sweden)

Jafar Kolahi

2015-01-01

Full Text Available Introduction: It is widely believed that blinding is a cornerstone of randomized clinical trials and that significant bias may result from unsuccessful blinding. However, it is not enough to claim that a clinical trial is single- or double-blinded and that assessment of the success of blinding is ideal. The aim of this study was to evaluate the prevalence of assessment of blinding success among dental implant clinical trials and to introduce methods of blinding assessment to the implant research community. Methods: In November 2014, PubMed was searched by blinded and experienced researchers with the query "implant AND (blindFNx01 OR maskFNx01" using the following filters: (1 Article type: clinical trial; (2 Journal categories: dental journals; (3 Field: title/abstract. Consequently, title/abstract was reviewed in all relevant articles to find any attempt to assess the success of blinding in dental implant clinical trials. Results: The PubMed search results yielded 86 clinical trials. The point of interest is that when "blindFNx01 OR maskFNx01" was deleted from the query, the number of results increased to 1688 clinical trials. This shows that only 5% of dental implant clinical trials tried to use blinding. Disappointingly, we could not find any dental implant clinical trial reporting any attempt to assess the success of blinding. Conclusion: The current status of turning a blind eye to unblinding in dental implant clinical trials is not tolerable and needs to be improved. Researchers, protocol reviewers, local ethical committees, journal reviewers, and editors should make a concerted effort to incorporate, report, and publish such information to understand its potential impact on study results.

No short-cut in assessing trial quality: a case study

Directory of Open Access Journals (Sweden)

Hirji Karim F

2009-01-01

Full Text Available Abstract Background Assessing the quality of included trials is a central part of a systematic review. Many check-list type of instruments for doing this exist. Using a trial of antibiotic treatment for acute otitis media, Burke et al., BMJ, 1991, as the case study, this paper illustrates some limitations of the check-list approach to trial quality assessment. Results The general verdict from the check list type evaluations in nine relevant systematic reviews was that Burke et al. (1991 is a good quality trial. All relevant meta-analyses extensively used its data to formulate therapeutic evidence. My comprehensive evaluation, on the other hand, brought to the surface a series of serious problems in the design, conduct, analysis and report of this trial that were missed by the earlier evaluations. Conclusion A check-list or instrument based approach, if used as a short-cut, may at times rate deeply flawed trials as good quality trials. Check lists are crucial but they need to be augmented with an in-depth review, and where possible, a scrutiny of the protocol, trial records, and original data. The extent and severity of the problems I uncovered for this particular trial warrant an independent audit before it is included in a systematic review.

Inter-laboratory comparisons of hexenuronic acid measurements in kraft eucalyptus pulps using a UV-Vis spectroscopic method

Science.gov (United States)

J.Y. Zhu; H.F Zhou; Chai X.S.; Donna Johannes; Richard Pope; Cristina Valls; M. Blanca Roncero

2014-01-01

An inter-laboratory comparison of a UV-Vis spectroscopic method (TAPPI T 282 om-13 “Hexeneuronic acid content of chemical pulp”) for hexeneuronic acid measurements was conducted using three eucalyptus kraft pulps. The pulp samples were produced in a laboratory at kappa numbers of approximately 14, 20, and 35. The hexeneuronic acid contents of the three pulps were...

INTERLABORATORY STUDY OF A THERMOSPRAY-LIQUID CHROMATOGRAPHIC/MASS SPECTROMETRIC METHOD FOR SELECTED N-METHYL CARBAMATES, N-METHYL CARBAMOYLOXIMES, AND SUBSTITUTED UREA PESTICIDES

Science.gov (United States)

A thermospray-liquid chromatographic/mass spectrometric (TS-LC/MS) method was evaluated in an interlaboratory study for determining 3 N-methyl carbamates (bendiocarb, carbaryl, and carbofuran), 3-N-methyl carbamoyloximes (aldicarb, methomyl, and oxamyl), 2 substituted urea pestic...

Evaluating the reliability of uranium concentration and isotope ratio measurements via an interlaboratory comparison program

International Nuclear Information System (INIS)

Oliveira Junior, Olivio Pereira de; Oliveira, Inez Cristina de; Pereira, Marcia Regina; Tanabe, Eduardo

2009-01-01

The nuclear fuel cycle is a strategic area for the Brazilian development because it is associated with the generation of electricity needed to boost the country economy. Uranium is one the chemical elements in this cycle and its concentration and isotope composition must be accurately known. In this present work, the reliability of the uranium concentration and isotope ratio measurements carried out at the CTMSP analytical laboratories is evaluated by the results obtained in an international interlaboratory comparison program. (author)

77 FR 40322 - Oral Rabies Vaccine Trial; Availability of an Environmental Assessment

Science.gov (United States)

2012-07-09

...] Oral Rabies Vaccine Trial; Availability of an Environmental Assessment AGENCY: Animal and Plant Health... assessment relative to an oral rabies vaccination field trial in New Hampshire, New York, Ohio, Vermont, and West Virginia. The environmental assessment analyzes the use of an experimental rabies vaccine in field...

Traditional and new composite endpoints in heart failure clinical trials : facilitating comprehensive efficacy assessments and improving trial efficiency

NARCIS (Netherlands)

Anker, Stefan D. t; Schroeder, Stefan; Atar, Dan; Bax, Jeroen J.; Ceconi, Claudio; Cowie, Martin R.; AdamCrisp,; Dominjon, Fabienne; Ford, Ian; Ghofrani, Hossein-Ardeschir; Gropper, Savion; Hindricks, Gerhard; Hlatky, Mark A.; Holcomb, Richard; Honarpour, Narimon; Jukema, J. Wouter; Kim, Albert M.; Kunz, Michael; Lefkowitz, Martin; Le Floch, Chantal; Landmesser, Ulf; McDonagh, Theresa A.; McMurray, John J.; Merkely, Bela; Packer, Milton; Prasad, Krishna; Revkin, James; Rosano, Giuseppe M. C.; Somaratne, Ransi; Stough, Wendy Gattis; Voors, Adriaan A.; Ruschitzka, Frank

Composite endpoints are commonly used as the primary measure of efficacy in heart failure clinical trials to assess the overall treatment effect and to increase the efficiency of trials. Clinical trials still must enrol large numbers of patients to accrue a sufficient number of outcome events and

20 years of interlaboratory tests in the service of radioactivity measurement quality. 20 ans de tests interlaboratoires au service de la qualite des mesures de radioactivite

Energy Technology Data Exchange (ETDEWEB)

Cance, M. (CEA Centre d' Etudes de Saclay, 91 - Gif-sur-Yvette (France). Dept. des Applications et de la Metrologie des Rayonnements Ionisants)

1992-01-01

In the framework of French national metrological coordination, the Laboratoire de Metrologie des Rayonnements Ionisants (LMRI) organizes since 20 years, each year an interlaboratory test program. The tests concern radioactivity, radio analysis and neutron and gamma dosimetry. In this paper, a review of interlaboratory tests proposed by LMRI is proposed from 1971 to 1991. For the last twenty years, 97 tests have been realized, half in activity measurement, third in radio analysis and 20% in dosimetry. About forty radionuclides (from Tritium to Americium 241) are concerned by these tests with an activity range from 1 Becquerel to 100 megabecquerels. The 120 laboratories having participated at these tests belong essentially to CEA group, EDF or medical sector.

Quality assessment of reports on clinical trials in the Journal of Hepatology

DEFF Research Database (Denmark)

Gluud, C; Nikolova, D

1998-01-01

Electronic searches on databases for randomised clinical trials and controlled clinical trials do not identify as many trials as handsearches, and trial reporting may be flawed. The aims were to identify all fully reported randomised clinical trials in the Journal of Hepatology and to make...... a qualitative assessment of the reporting....

An European inter-laboratory validation of alternative endpoints of the murine local lymph node assay

International Nuclear Information System (INIS)

Ehling, G.; Hecht, M.; Heusener, A.; Huesler, J.; Gamer, A.O.; Loveren, H. van; Maurer, Th.; Riecke, K.; Ullmann, L.; Ulrich, P.; Vandebriel, R.; Vohr, H.-W.

2005-01-01

The original local lymph node assay (LLNA) is based on the use of radioactive labelling to measure cell proliferation. Other endpoints for the assessment of proliferation are also authorized by the OECD Guideline 429 provided there is appropriate scientific support, including full citations and description of the methodology (OECD, 2002. OECD Guideline for the Testing of Chemicals; Skin Sensitization: Local Lymph Node Assay, Guideline 429. Paris, adopted 24th April 2002.). Here, we describe the outcome of the second round of an inter-laboratory validation of alternative endpoints in the LLNA conducted in nine laboratories in Europe. The validation study was managed and supervised by the Swiss Agency for Therapeutic Products (Swissmedic) in Bern. Ear-draining lymph node (LN) weight and cell counts were used to assess LN cell proliferation instead of [3H]TdR incorporation. In addition, the acute inflammatory skin reaction was measured by ear weight determination of circular biopsies of the ears to identify skin irritation properties of the test items. The statistical analysis was performed in the department of statistics at the university of Bern. Similar to the EC 3 values defined for the radioactive method, threshold values were calculated for the endpoints measured in this modification of the LLNA. It was concluded that all parameters measured have to be taken into consideration for the categorisation of compounds due to their sensitising potencies. Therefore, an assessment scheme has been developed which turned out to be of great importance to consistently assess sensitisation versus irritancy based on the data of the different parameters. In contrast to the radioactive method, irritants have been picked up by all the laboratories applying this assessment scheme

Assessing Clinical Trial-Associated Workload in Community-Based Research Programs Using the ASCO Clinical Trial Workload Assessment Tool.

Science.gov (United States)

Good, Marjorie J; Hurley, Patricia; Woo, Kaitlin M; Szczepanek, Connie; Stewart, Teresa; Robert, Nicholas; Lyss, Alan; Gönen, Mithat; Lilenbaum, Rogerio

2016-05-01

Clinical research program managers are regularly faced with the quandary of determining how much of a workload research staff members can manage while they balance clinical practice and still achieve clinical trial accrual goals, maintain data quality and protocol compliance, and stay within budget. A tool was developed to measure clinical trial-associated workload, to apply objective metrics toward documentation of work, and to provide clearer insight to better meet clinical research program challenges and aid in balancing staff workloads. A project was conducted to assess the feasibility and utility of using this tool in diverse research settings. Community-based research programs were recruited to collect and enter clinical trial-associated monthly workload data into a web-based tool for 6 consecutive months. Descriptive statistics were computed for self-reported program characteristics and workload data, including staff acuity scores and number of patient encounters. Fifty-one research programs that represented 30 states participated. Median staff acuity scores were highest for staff with patients enrolled in studies and receiving treatment, relative to staff with patients in follow-up status. Treatment trials typically resulted in higher median staff acuity, relative to cancer control, observational/registry, and prevention trials. Industry trials exhibited higher median staff acuity scores than trials sponsored by the National Institutes of Health/National Cancer Institute, academic institutions, or others. The results from this project demonstrate that trial-specific acuity measurement is a better measure of workload than simply counting the number of patients. The tool was shown to be feasible and useable in diverse community-based research settings. Copyright © 2016 by American Society of Clinical Oncology.

Results of the 1988 interlaboratory comparison on the gamma spectrometry of dried whey

International Nuclear Information System (INIS)

Wiechen, A.; Tait, D.; Bundesanstalt fuer Milchforschung, Kiel

1988-01-01

Following the accident in Chernobyl in 1986 the number of units available for monitoring radioactivity, mainly gamma spectrometers, has been increased considerably in the Federal Republic of Germany. Furthermore, new legislation requires that all official monitoring laboratories verify the quality of their analytical technique by participating in interlaboratory comparison studies organized by Federal institutions. Such a study was therefore organized in March 1988. 86 laboratories collaborated on the gamma-spectrometry analysis of the radionuclides Cs-137, Cs-134 and K-40 in dried whey. This paper describes the statistical evaluation of the 144 sets of data received. The results of the study were surprisingly good. (orig./DG) [de

Using an interlaboratory study to revise methods for conducting 10-d to 42-d water or sediment toxicity tests with Hyalella azteca

Science.gov (United States)

Ivey, Chris D.; Ingersoll, Christopher G.; Brumbaugh, William G.; Hammer, Edward J.; Mount, David R.; Hockett, J. Russell; Norberg-King, Teresa J.; Soucek, Dave; Taylor, Lisa

2016-01-01

Studies have been conducted to refine US Environmental Protection Agency, ASTM International, and Environment Canada standard methods for conducting 42-d reproduction tests with Hyalella azteca in water or in sediment. Modifications to the H. azteca method include better-defined ionic composition requirements for exposure water (i.e., >15 mg/L of chloride and >0.02 mg/L of bromide) and improved survival, growth, and reproduction with alternate diets provided as increased rations over time in water-only or whole-sediment toxicity tests. A total of 24 laboratories volunteered to participate in the present interlaboratory study evaluating the performance of H. azteca in 42-d studies in control sand or control sediment using the refined methods. Improved growth and reproduction of H. azteca was observed with 2 alternate diets of 1) ramped diatoms (Thalassiosira weissflogii) + ramped Tetramin or 2) yeast–cerophyll–trout chow (YCT) + ramped Tetramin, especially when compared with results from the traditional diet of 1.8 mg YCT/d. Laboratories were able to meet proposed test acceptability criteria and in most cases had lower variation in growth or reproduction compared with previous interlaboratory studies using the traditional YCT diet. Laboratory success in conducting 42-d H. azteca exposures benefited from adherence to several key requirements of the detailed testing, culturing, and handling methods. Results from the present interlaboratory study are being used to help revise standard methods for conducting 10-d to 42-d water or sediment toxicity exposures with H. azteca.

Investigating the effect of independent, blinded digital image assessment on the STOP GAP trial.

Science.gov (United States)

Patsko, Emily; Godolphin, Peter J; Thomas, Kim S; Hepburn, Trish; Mitchell, Eleanor J; Craig, Fiona E; Bath, Philip M; Montgomery, Alan A

2017-02-02

Blinding is the process of keeping treatment assignment hidden and is used to minimise the possibility of bias. Trials at high risk of bias have been shown to report larger treatment effects than low-risk studies. In dermatology, one popular method of blinding is to have independent outcome assessors who are unaware of treatment allocation assessing the endpoint using digital photographs. However, this can be complex, expensive and time-consuming. The objective of this study was to compare the effect of blinded and unblinded outcome assessment on the results of the STOP GAP trial. The STOP GAP trial compared prednisolone to ciclosporin in treating pyoderma gangrenosum. Participants' lesions were measured at baseline and at 6 weeks to calculate the primary outcome, speed of healing. Independent blinded assessors obtained measurements from digital photographs using specialist software. In addition, unblinded treating clinicians estimated lesion area by measuring length and width. The primary outcome was determined using blinded measurements where available, otherwise unblinded measurements were used (method referred to as trial measurements). In this study, agreement between the trial and unblinded measurements was determined using the intraclass correlation coefficient (ICC). The STOP GAP trial's primary analysis was repeated using unblinded measurements only. We introduced differential and nondifferential error in unblinded measurements and investigated the effect on the STOP GAP trial's primary analysis. Eighty-six (80%) of the 108 patients were assessed using digital images. Agreement between trial and unblinded measurements was excellent (ICC = 0.92 at baseline; 0.83 at 6 weeks). There was no evidence that the results of the trial primary analysis differed according to how the primary outcome was assessed (p value for homogeneity = 1.00). Blinded digital image assessment in the STOP GAP trial did not meaningfully alter trial conclusions compared with

A randomized trial assessing the impact of written information on outpatients' knowledge about and attitude toward randomized clinical trials. The Info Trial Group

DEFF Research Database (Denmark)

Kruse, A Y; Kjaergard, L L; Krogsgaard, K

2000-01-01

To improve the patient education process in clinical research, three information materials describing general aspects of design and conduct of randomized clinical trials were developed. The materials varied in length, reading ability level, and reader appeal. Their influence on knowledge about...... and attitude toward randomized clinical trials was assessed in a randomized, parallel group, evaluator-blinded trial among 415 outpatients. The patients were randomized to the following groups: control (no intervention), leaflet, brochure, or booklet. Knowledge was assessed by a 17-item multiple......-choice questionnaire and attitude was assessed by a 32-item Likert questionnaire at entry and 2 weeks after the intervention. The interventions and the questionnaires were pilot tested and power calculations were performed. At entry, the mean knowledge score was 7.9 points. At follow-up, the knowledge scores increased...

Versailles Project on Advanced Materials and Standards Interlaboratory Study on Measuring the Thickness and Chemistry of Nanoparticle Coatings Using XPS and LEIS

NARCIS (Netherlands)

Belsey, N.A.; Cant, D.J.H.; Minelli, C.; Araujo, J.R.; Bock, B.; Brüner, P.; Castner, D.G.; Ceccone, C.; Counsell, J.D.P.; Dietrich, P.M.; Engelhard, M.H.; Fearn, S.; Galhardo, C.E.; Kalbe, H.; Kim, J.W.; Lartundo-Rojas, L.; Luftman, H.S.; Nunney, T.S.; Pseiner, J.; Smith, E.F.; Spampinato, V.; Sturm, Jacobus Marinus; Thomas, A.G.; Treacy, J.P.W.; Veith, L.; Wagstaffe, M.; Wang, H.; Wang, M..; Wang, Y.C.; Werner, W.; Yang, L.; Shard, A.G.

2016-01-01

We report the results of a Versailles Project on Advanced Materials and Standards (VAMAS) interlaboratory study on the measurement of the shell thickness and chemistry of nanoparticle coatings. Peptide-coated gold particles were supplied to laboratories in two forms: a colloidal suspension in pure

Pasteurization: A reliable method for preservation of nutrient in seawater samples for inter-laboratory and field applications

OpenAIRE

Daniel, Anne; Kerouel, Roger; Aminot, Alain

2012-01-01

Following previous work, the production of reference material for nutrients in seawater, using pasteurization as a preservation method, was carried out seven times between 2006 and 2010 in the framework of inter-laboratory exercises. The preparation of samples from natural seawater allowed to become depleted in nutrients then spiked, bottled and pasteurized, is described. Five main nutrients are involved in this study: ammonium, nitrite, nitrate, phosphate and silicate. Bottles are in glass f...

Inter-laboratory comparison of cell lines for susceptibility to three viruses: VHSV, IHNV and IPNV

DEFF Research Database (Denmark)

Lorenzen, Ellen; Carstensen, Bendix; Olesen, Niels Jørgen

1999-01-01

Eleven European National Reference Laboratories participated in an inter-laboratory comparison of the susceptibility of 5 selected cell lines to 3 fish pathogenic viruses. The test included viral hemorrhagic septicaemia virus (VHSV), infectious hematopoietic necrosis virus (IHNV) and infectious...... pancreatic necrosis Virus (IPNV), and the cell lines derived from bluegill fry (BF-2), chinook salmon embryo (CHSE-214), epithelioma papulosum cyprini (EPC), fathead minnow (FHM) and rainbow trout gonad (RTG-2). The results showed that for isolation of VHSV, BF-2 and RTG-2 cells performed equally well...

Modifying the Clinical Research Infrastructure at a Dedicated Clinical Trials Unit: Assessment of Trial Development, Activation, and Participant Accrual.

Science.gov (United States)

Tang, Chad; Hess, Kenneth R; Sanders, Dwana; Davis, Suzanne E; Buzdar, Aman U; Kurzrock, Razelle; Lee, J Jack; Meric-Bernstam, Funda; Hong, David S

2017-03-15

Purpose: Information on processes for trials assessing investigational therapeutics is sparse. We assessed the trial development processes within the Department of Investigational Cancer Therapeutics (ICT) at MD Anderson Cancer Center (Houston, TX) and analyzed their effects on the trial activation timeline and enrolment. Experimental Design: Data were from a prospectively maintained registry that tracks all clinical studies at MD Anderson. From this database, we identified 2,261 activated phase I-III trials; 221 were done at the ICT. ICT trials were matched to trials from other MD Anderson departments by phase, sponsorship, and submission year. Trial performance metrics were compared with paired Wilcoxon signed rank tests. Results: We identified three facets of the ICT research infrastructure: parallel processing of trial approval steps; a physician-led research team; and regular weekly meetings to foster research accountability. Separate analyses were conducted stratified by sponsorship [industry (133 ICT and 133 non-ICT trials) or institutional (68 ICT and 68 non-ICT trials)]. ICT trial development was faster from IRB approval to activation (median difference of 1.1 months for industry-sponsored trials vs. 2.3 months for institutional) and from activation to first enrolment (median difference of 0.3 months for industry vs. 1.2 months for institutional; all matched P infrastructure within a large academic cancer center was associated with efficient trial development and participant accrual. Clin Cancer Res; 23(6); 1407-13. ©2016 AACR . ©2016 American Association for Cancer Research.

Performance of mycological media in enumerating desiccated food spoilage yeasts: an interlaboratory study.

Science.gov (United States)

Beuchat, L R; Frandberg, E; Deak, T; Alzamora, S M; Chen, J; Guerrero, A S; López-Malo, A; Ohlsson, I; Olsen, M; Peinado, J M; Schnurer, J; de Siloniz, M I; Tornai-Lehoczki, J

2001-10-22

Dichloran 18% glycerol agar (DG18) was originally formulated to enumerate nonfastidious xerophilic moulds in foods containing rapidly growing Eurotium species. Some laboratories are now using DG18 as a general purpose medium for enumerating yeasts and moulds, although its performance in recovering yeasts from dry foods has not been evaluated. An interlaboratory study compared DG18 with dichloran rose bengal chloramphenicol agar (DRBC), plate count agar supplemented with chloramphenicol (PCAC), tryptone glucose yeast extract chloramphenicol agar (TGYC), acidified potato dextrose agar (APDA), and orange serum agar (OSA) for their suitability to enumerate 14 species of lyophilized yeasts. The coefficient of variation for among-laboratories repeatability within yeast was 1.39% and reproducibility of counts among laboratories was 7.1%. The order of performance of media for recovering yeasts was TGYC > PCAC = OSA > APDA > DRBC > DG 18. A second study was done to determine the combined effects of storage time and temperature on viability of yeasts and suitability of media for recovery. Higher viability was retained at -18 degrees C than at 5 degrees C or 25 degrees C for up to 42 weeks, although the difference in mean counts of yeasts stored at -18 degrees C and 25 degrees C was only 0.78 log10 cfu/ml of rehydrated suspension. TGYC was equal to PCAC and superior to the other four media in recovering yeasts stored at -18 degrees C, 5 degrees C, or 25 degrees C for up to 42 weeks. Results from both the interlaboratory study and the storage study support the use of TGYC for enumerating desiccated yeasts. DG18 is not recommended as a general purpose medium for recovering yeasts from a desiccated condition.

Clinical outcomes assessment in clinical trials to assess treatment of femoroacetabular impingement

DEFF Research Database (Denmark)

Harris-Hayes, Marcie; McDonough, Christine M; Leunig, Michael

2013-01-01

Patient-reported outcome measures are an important component of outcomes assessment in clinical trials to assess the treatment of femoroacetabular impingement (FAI). This review of disease-specific measures and instruments used to assess the generic quality of life and physical activity levels...... developed recently and have not been established in the literature. Although currently used generic and activity-level measures have limitations, as well, they should be considered, depending on the specific goals of the study. Additional research is needed to assess the properties of these measures fully...

Standardization of reflectance measurements in dispersed organic matter: results of an exercise to improve interlaboratory agreement

Science.gov (United States)

Hackley, Paul C.; Araujo, Carla Viviane; Borrego, Angeles G.; Bouzinos, Antonis; Cardott, Brian; Cook, Alan C.; Eble, Cortland; Flores, Deolinda; Gentzis, Thomas; Gonçalves, Paula Alexandra; Filho, João Graciano Mendonça; Hámor-Vidó, Mária; Jelonek, Iwona; Kommeren, Kees; Knowles, Wayne; Kus, Jolanta; Mastalerz, Maria; Menezes, Taíssa Rêgo; Newman, Jane; Pawlewicz, Mark; Pickel, Walter; Potter, Judith; Ranasinghe, Paddy; Read, Harold; Reyes, Julito; Rodriguez, Genaro De La Rosa; de Souza, Igor Viegas Alves Fernandes; Suarez-Ruiz, Isabel; Sýkorová, Ivana; Valentine, Brett J.

2015-01-01

Vitrinite reflectance generally is considered the most robust thermal maturity parameter available for application to hydrocarbon exploration and petroleum system evaluation. However, until 2011 there was no standardized methodology available to provide guidelines for vitrinite reflectance measurements in shale. Efforts to correct this deficiency resulted in publication of ASTM D7708: Standard test method for microscopical determination of the reflectance of vitrinite dispersed in sedimentary rocks. In 2012-2013, an interlaboratory exercise was conducted to establish precision limits for the D7708 measurement technique. Six samples, representing a wide variety of shale, were tested in duplicate by 28 analysts in 22 laboratories from 14 countries. Samples ranged from immature to overmature (0.31-1.53% Ro), from organic-lean to organic-rich (1-22 wt.% total organic carbon), and contained Type I (lacustrine), Type II (marine), and Type III (terrestrial) kerogens. Repeatability limits (maximum difference between valid repetitive results from same operator, same conditions) ranged from 0.03-0.11% absolute reflectance, whereas reproducibility limits (maximum difference between valid results obtained on same test material by different operators, different laboratories) ranged from 0.12-0.54% absolute reflectance. Repeatability and reproducibility limits degraded consistently with increasing maturity and decreasing organic content. However, samples with terrestrial kerogens (Type III) fell off this trend, showing improved levels of reproducibility due to higher vitrinite content and improved ease of identification. Operators did not consistently meet the reporting requirements of the test method, indicating that a common reporting template is required to improve data quality. The most difficult problem encountered was the petrographic distinction of solid bitumens and low-reflecting inert macerals from vitrinite when vitrinite occurred with reflectance ranges overlapping

Proficiency Testing by Interlaboratory Comparison Performed in 2010-2015 for Neutron Activation Analysis and Other Analytical Techniques

International Nuclear Information System (INIS)

2017-12-01

The IAEA supports its Member States to increase the utilization of their research reactors. Small and medium sized reactors are mostly used for neutron activation analysis (NAA). Although the markets for NAA laboratories have been identified, demonstration of valid analytical results and organizational quality of the work process are preconditions for expanding the stakeholder community, particularly in commercial routine application of this powerful technique. The IAEA has implemented a new mechanism for supporting NAA laboratories in demonstrating their analytical performance by participation in proficiency testing schemes by interlaboratory comparison. This activity makes possible the identification of deviations and non-conformities, their causes and the process to implement effective approaches to eliminate them. Over 30 laboratories participated between 2010 and 2015 in consecutive proficiency tests organized by the IAEA in conjunction with the Wageningen Evaluating Programmes for Analytical Laboratories (WEPAL) to assess their analytical performances. This publication reports the findings and includes lessons learned of this activity. An attached CD-ROM contains many individual participating laboratory papers sharing their individual results and experience gained through this participation.

Interlaboratory comparability of serum cotinine measurements at smoker and nonsmoker concentration levels: A round-robin study

Science.gov (United States)

Jacob, Peyton; Holiday, David B.; Benowitz, Neal L.; Sosnoff, Connie S.; Doig, Mira V.; Feyerabend, Colin; Aldous, Kenneth M.; Sharifi, Mehran; Kellogg, Mark D.; Langman, Loralie J.

2009-01-01

Introduction: Cotinine, the primary proximate metabolite of nicotine, is commonly measured as an index of exposure to tobacco in both active users of tobacco and nonsmokers with possible exposure to secondhand smoke (SHS). A number of laboratories have implemented analyses for measuring serum cotinine in recent years, but there have been few interlaboratory comparisons of the results. Among nonsmokers exposed to SHS, the concentration of cotinine in blood can be quite low, and extensive variability in these measurements has been reported in the past. Methods: In this study, a group of seven laboratories, all experienced in serum cotinine analysis, measured eight coded serum pools with concentrations ranging from background levels of about 0.05 ng/ml to relatively high concentrations in the active smokers range. All laboratories used either gas–liquid chromatography with nitrogen–phosphorus detection or liquid chromatography with mass spectrometric detection. Results: All seven laboratories reliably measured the cotinine concentrations in samples that were within the range of their methods. In each case, the results for the pools were correctly ranked in order, and no significant interlaboratory bias was observed at the 5% level of significance for results from any of the pools. Discussion: We conclude that present methods of chromatographic analysis of serum cotinine, as used by these experienced laboratories, are capable of providing accurate and precise results in both the smoker and the nonsmoker concentration range. PMID:19933777

Results of the Interlaboratory Exercise CSN/CIEMAT-02 Among Environmental Radioactivity Laboratories (Sea Fish)

International Nuclear Information System (INIS)

Romero Gonzalez, M.L.

2003-01-01

The document describes the outcome of the CSN/CIEMAT-02 interlaboratory test comparison among environmental radioactivity laboratories. The exercise was organised according to the ISO-43 and the ISO/IUPAC/AOAC Harmonized Protocol for the proficiency testing of analytical laboratories. The test sample was a reference materials provided by the IAEA-MEL (IAE Marine Environmental Laboratory, Monaco), a sea fish containing environmental levels of U-238, U-234, K-40, Pb-210, Ra-226, Sr-90, Cs-137, Co-60, Pu-(239+240), Am-241 and Tc-99. The results of the exercise were computed for 32 participating laboratories, and their analytical performance was assessed using the z-score approach. A raised percentage of satisfactory laboratory performance has been obtained for all the analysis, being the best performance in gamma measurements. The laboratories have made an effort to calculate the combined uncertainty of the radiochemical determinations. Most of the laboratories have demonstrated its competence in performing the study analysis and also the adequate measuring capability of their detection equipment even in conditions close to detection limits. The study has shown the capacity of participant laboratories to perform radioactive determinations in environmental sea fish samples with satisfactory quality levels. (Author) 6 refs

Results from an interlaboratory exercise on the determination of plutonium isotopic ratios by gamma spectrometry

International Nuclear Information System (INIS)

Ottmar, H.

1981-07-01

Results form interlaboratory comparison measurements on the determination of plutonium isotopic ratios by gamma spectrometry, organized by the ESARDA Working Group on Techniques and Standards for Nondestructive Analysis, are presented and discussed. Nine laboratories from nine countries or international organizations participated in the intercomparison exercise, which included both laboratories' own measurements on the plutonium isotopic reference materials NBS-SRM 946, 947, 948 and comparison analyses of gamma spectra from these materials distributed to the participating laboratories. Results from the intercomparison analyses have been used to reevaluate some gamma branching intensity ratios required for plutonium isotopic ratio measurements. (orig.) [de

CIRP Interlaboratory Comparison of Coordinate Measuring Machines using an Optomechanical Hole Plate

DEFF Research Database (Denmark)

De Chiffre, Leonardo; Hansen, Hans Nørgaard; Morace, Renata Erica

An interlaboratory comparison on mechanical and optical coordinate measuring machines (CMMs) has been organized by the Centre for Geometrical Metrology (CGM), Department of Manufacturing Engineering and Management (IPL), Technical University of Denmark (DTU) and carried out within Collège...... plate [1], designed and manufactured by DTU. A measurement procedure was sent to each participant together with the hole plate to be measured. The procedure consists mainly of two parts [2]: 1) four reversal measurements, by which the systematic errors in the measuring plane (X,Y) on the CMM...... are eliminated, except the positioning errors; 2) transfer of traceability by comparator measurement using a length reference chosen by the participant, by which the positioning errors are eliminated. Furthermore, a third optional part could be carried out by the participant, using a different measurement...

Chelation therapy after the Trial to Assess Chelation Therapy: results of a unique trial

Science.gov (United States)

Avila, Maria D.; Escolar, Esteban; Lamas, Gervasio A.

2014-01-01

Purpose of review EDTA chelation therapy has been in off-label use for the treatment of atherosclerosis. We review the results of the first large-scale randomized trial of this treatment. Recent findings The trial to assess chelation therapy was a $30 million National Institutes of Health-funded study of the safety and efficacy of EDTA-based chelation infusions in 1708 post-myocardial infarction (MI) patients. The trial to assess chelation therapy demonstrated a significant (P = 0.035) 18% reduction in a combined primary endpoint of death, MI, stroke, coronary revascularization, or hospitalization for angina. In diabetic patients the benefit was more extreme, with a 41% relative reduction in risk (P = 0.0002) and a 43% reduction in total mortality (P = 0.011). Safety data were favorable. A reduction of oxidative stress by chelation of toxic metals has been proposed as a possible mechanism of action. Summary Recent research suggests that EDTA chelation may be a well-tolerated and effective treatment for post-MI patients. Future replication and mechanistic studies are important prior to implementation in all post-MI patients. PMID:25023079

On the stability of a variety of organic photovoltaic devices by IPCE and in situ IPCE analyses: the ISOS-3 inter-laboratory collaboration

NARCIS (Netherlands)

Teran-Escobar, G.; Tanenbaum, D.M.; Voroshazi, E.; Hermenau, M.; Norrman, K.; Lloyd, M.T.; Galagan, Y.O.; Zimmermann, B.; Hösel, M.; Dam, H.F.; Jorgensen, M.; Gevorgyan, S.; Kudret, S.; Maes, W.; Lutsen, L.; Vanderzande, D.; Würfel, U.; Andriessen, H.A.J.M.; Rösch, R.; Hoppe, H.; Rivaton, A.; Uzunoglu, G.Y.; Germack, D.; Andreasen, B.; Madsen, M.V.; Bundgaard, E.; Krebs, F.C.; Lira-Cantu, M.

2012-01-01

This work is part of the inter-laboratory collaboration to study the stability of seven distinct sets of state-of-the-art organic photovoltaic (OPV) devices prepared by leading research laboratories. All devices have been shipped to and degraded at RISO-DTU up to 1830 hours in accordance with

The European cooperation for Acreditation of Laboratories interlaboratory comparison Pr3

International Nuclear Information System (INIS)

Liska, P.

1996-01-01

The Pr3 interlaboratory comparison has been organized in the gauge pressure mode, gas medium, for the range 0-5 MPa. It was planned at the Western European Calibration Cooperation expert group for pressure held at Laboratoire National d'Essais Paris on the nineteenth and twentieth of November 1992. The used transfer standard has been a Desgranges et Huot digital piston manometer. The manometer delivers a digital reading proportional to the input pressure. Thirty-seven accredited laboratories from fourteen countries participated in the comparison from January 1993 to July 1994. One of them was acreditation laboratory of Nuclear Power Plants Research Institute Trnava LTD. In the article the Nuclear Power Plants Research Institute Trnava LTD. laboratory results are discussed. The declared relative uncertainty of the standard pressure at 5 MPa were included between 0.4 and 3.10 -4 (most values between 0.5 and 1.10 -4 )

Interlaboratory survey for T3 and T4 assays in Italy: results from a two semester period

International Nuclear Information System (INIS)

Pilo, A.; Zucchelli, G.C.; Chiesa, M.R.; Piro, M.A.

1982-01-01

The usefulness of external quality control schemes (EQCS) is generally acknowledged in clinical chemistry; these schemes allow not only the evaluation of the between-laboratory variability of the assay under study, but also make it possible the improvement of the analytical performances of the participants laboratories. Recently interlaboratory surveys have been extended to radioimmunoassays. Starting from january 1980, a national EQCS hormone assays was organized in Italy; triiodothyronine (T3) and thyroxine (T4) have been the first assays considered due to their large diffusion

Rapid Analysis of Carbohydrates in Bioprocess Samples: An Evaluation of the CarboPac SA10 for HPAE-PAD Analysis by Interlaboratory Comparison

Energy Technology Data Exchange (ETDEWEB)

Sevcik, R. S.; Hyman, D. A.; Basumallich, L.; Scarlata, C. J.; Rohrer, J.; Chambliss, C. K.

2013-01-01

A technique for carbohydrate analysis for bioprocess samples has been developed, providing reduced analysis time compared to current practice in the biofuels R&D community. The Thermofisher CarboPac SA10 anion-exchange column enables isocratic separation of monosaccharides, sucrose and cellobiose in approximately 7 minutes. Additionally, use of a low-volume (0.2 mL) injection valve in combination with a high-volume detection cell minimizes the extent of sample dilution required to bring sugar concentrations into the linear range of the pulsed amperometric detector (PAD). Three laboratories, representing academia, industry, and government, participated in an interlaboratory study which analyzed twenty-one opportunistic samples representing biomass pretreatment, enzymatic saccharification, and fermentation samples. The technique's robustness, linearity, and interlaboratory reproducibility were evaluated and showed excellent-to-acceptable characteristics. Additionally, quantitation by the CarboPac SA10/PAD was compared with the current practice method utilizing a HPX-87P/RID. While these two methods showed good agreement a statistical comparison found significant quantitation difference between them, highlighting the difference between selective and universal detection modes.

[Interlaboratory Study on Evaporation Residue Test for Food Contact Products (Report 1)].

Science.gov (United States)

Ohno, Hiroyuki; Mutsuga, Motoh; Abe, Tomoyuki; Abe, Yutaka; Amano, Homare; Ishihara, Kinuyo; Ohsaka, Ikue; Ohno, Haruka; Ohno, Yuichiro; Ozaki, Asako; Kakihara, Yoshiteru; Kobayashi, Hisashi; Sakuragi, Hiroshi; Shibata, Hiroshi; Shirono, Katsuhiro; Sekido, Haruko; Takasaka, Noriko; Takenaka, Yu; Tajima, Yoshiyasu; Tanaka, Aoi; Tanaka, Hideyuki; Tonooka, Hiroyuki; Nakanishi, Toru; Nomura, Chie; Haneishi, Nahoko; Hayakawa, Masato; Miura, Toshihiko; Yamaguchi, Miku; Watanabe, Kazunari; Sato, Kyoko

2018-01-01

An interlaboratory study was performed to evaluate the equivalence between an official method and a modified method of evaporation residue test using three food-simulating solvents (water, 4% acetic acid and 20% ethanol), based on the Japanese Food Sanitation Law for food contact products. Twenty-three laboratories participated, and tested the evaporation residues of nine test solutions as blind duplicates. For evaporation, a water bath was used in the official method, and a hot plate in the modified method. In most laboratories, the test solutions were heated until just prior to evaporation to dryness, and then allowed to dry under residual heat. Statistical analysis revealed that there was no significant difference between the two methods, regardless of the heating equipment used. Accordingly, the modified method provides performance equal to the official method, and is available as an alternative method.

On the stability of a variety of organic photovoltaic devices by IPCE and in situ IPCE analyses – the ISOS-3 inter-laboratory collaboration

DEFF Research Database (Denmark)

Teran-Escobar, Gerardo; Tanenbaum, David; Voroshazi, Eszter

2012-01-01

This work is part of the inter-laboratory collaboration to study the stability of seven distinct sets of state-of-the-art organic photovoltaic (OPV) devices prepared by leading research laboratories. All devices have been shipped to and degraded at RISØ-DTU up to 1830 hours in accordance...

Bioassay battery interlaboratory investigation of emerging contaminants in spiked water extracts - Towards the implementation of bioanalytical monitoring tools in water quality assessment and monitoring.

Science.gov (United States)

Di Paolo, Carolina; Ottermanns, Richard; Keiter, Steffen; Ait-Aissa, Selim; Bluhm, Kerstin; Brack, Werner; Breitholtz, Magnus; Buchinger, Sebastian; Carere, Mario; Chalon, Carole; Cousin, Xavier; Dulio, Valeria; Escher, Beate I; Hamers, Timo; Hilscherová, Klára; Jarque, Sergio; Jonas, Adam; Maillot-Marechal, Emmanuelle; Marneffe, Yves; Nguyen, Mai Thao; Pandard, Pascal; Schifferli, Andrea; Schulze, Tobias; Seidensticker, Sven; Seiler, Thomas-Benjamin; Tang, Janet; van der Oost, Ron; Vermeirssen, Etienne; Zounková, Radka; Zwart, Nick; Hollert, Henner

2016-11-01

Bioassays are particularly useful tools to link the chemical and ecological assessments in water quality monitoring. Different methods cover a broad range of toxicity mechanisms in diverse organisms, and account for risks posed by non-target compounds and mixtures. Many tests are already applied in chemical and waste assessments, and stakeholders from the science-police interface have recommended their integration in regulatory water quality monitoring. Still, there is a need to address bioassay suitability to evaluate water samples containing emerging pollutants, which are a current priority in water quality monitoring. The presented interlaboratory study (ILS) verified whether a battery of miniaturized bioassays, conducted in 11 different laboratories following their own protocols, would produce comparable results when applied to evaluate blinded samples consisting of a pristine water extract spiked with four emerging pollutants as single chemicals or mixtures, i.e. triclosan, acridine, 17α-ethinylestradiol (EE2) and 3-nitrobenzanthrone (3-NBA). Assays evaluated effects on aquatic organisms from three different trophic levels (algae, daphnids, zebrafish embryos) and mechanism-specific effects using in vitro estrogenicity (ER-Luc, YES) and mutagenicity (Ames fluctuation) assays. The test battery presented complementary sensitivity and specificity to evaluate the different blinded water extract spikes. Aquatic organisms differed in terms of sensitivity to triclosan (algae > daphnids > fish) and acridine (fish > daphnids > algae) spikes, confirming the complementary role of the three taxa for water quality assessment. Estrogenicity and mutagenicity assays identified with high precision the respective mechanism-specific effects of spikes even when non-specific toxicity occurred in mixture. For estrogenicity, although differences were observed between assays and models, EE2 spike relative induction EC 50 values were comparable to the literature, and E2/EE2

An inter-laboratory comparison study on transfer, persistence and recovery of DNA from cable ties.

Science.gov (United States)

Steensma, Kristy; Ansell, Ricky; Clarisse, Lindy; Connolly, Edward; Kloosterman, Ate D; McKenna, Louise G; van Oorschot, Roland A H; Szkuta, Bianca; Kokshoorn, Bas

2017-11-01

To address questions on the activity that led to the deposition of biological traces in a particular case, general information on the probabilities of transfer, persistence and recovery of cellular material in relevant scenarios is necessary. These figures may be derived from experimental data described in forensic literature when conditions relevant to the case were included. The experimental methodology regarding sampling, DNA extraction, DNA typing and profile interpretation that were used to generate these published data may differ from those applied in the case and thus the applicability of the literature data may be questioned. To assess the level of variability that different laboratories obtain when similar exhibits are analysed, we performed an inter-laboratory study between four partner laboratories. Five sets of 20 cable ties bound by different volunteers were distributed to the participating laboratories and sampled and processed according to the in-house protocols. Differences were found for the amount of retrieved DNA, as well as for the reportability and composition of the DNA profiles. These differences also resulted in different probabilities of transfer, persistence and recovery for each laboratory. Nevertheless, when applied to a case example, these differences resulted in similar assignments of weight of evidence given activity-level propositions. Copyright © 2017 Elsevier B.V. All rights reserved.

An interlaboratory comparison exercise for organohalogens in marine mammal blubber

Energy Technology Data Exchange (ETDEWEB)

Kucklick, J.; Becker, P.; Pugh, R. [NIST, Hollings Marine Lab., Charleston (United States); Schantz, M.; Porter, B.; Wise, S. [NIST, Gaithersburg (United States); Rowles, T. [NOAA, Silversprings (United States)

2004-09-15

For analytical data generated on marine mammal tissues, such as blubber, harmonizing measurements of organohalogen compounds is very important. Often organohalogen data on marine mammal samples from different laboratories are combined to provide an indication of geographical trends or to help ascertain toxicological significance. In at least one study that combined data on organohalogen concentrations from marine mammal blubber to examine geographical trends, it was found that among laboratory variability contributed significantly to the observed data variability (Schwacke, personal communication). To help resolve such problems, NIST and the National Oceanic and Atmospheric Administration (NOAA) initiated an interlaboratory comparison exercise program patterned after the exercise described above but using marine mammal blubber as the exercise materials. The objective of this paper is to describe the exercises, summarize selected results, and discuss the value of these interterlaboratory comparison exercises. The exercises have been held on a small scale (<10 laboratories) starting in 1991 and on a larger scale (10 or more laboratories) starting in 1999. Twenty-four laboratories participated in the 2003 exercise.

Verification of Electromagnetic Field Measurements via Inter-laboratory Comparison Measurements

Directory of Open Access Journals (Sweden)

M. Mann

2005-01-01

Full Text Available An inter-laboratory comparison of field strength measurements was conducted in order to verify the comparability of high-frequency electromagnetic field measurements. For this purpose, 17 participating teams hosted by the working group "procedures of exposure determination" of the LAI (Länderausschuss für Immissionsschutz, state committee on immission control determined the field strength at given stations around a hospital situation. At those stations very different signals were generated, such as sine wave signals at 27MHz and 433MHz, signals from a diathermy device in Continuous-Wave (CW and Pulse-Width-Modulation (PWM mode, from a GSM base station at 900MHz and 1800MHz, from a UMTS base station, from a babyphone device and from a DECT cordless phone. This contribution describes the evaluation of the measured values and the approach to the computation of a reference value. Considering various sources of electromagnetic fields in the areas of personal safety at work and of immission control, the most important results are presented and the conclusions drawn are discussed.

Ejercicio interlaboratorio de bioensayos marinos para la evaluacion de la calidad ambiental de sedimentos costeros en Espana. II Ensayo de inhibicion dela bioluminiscencia para la evaluacion rapida de la toxicidad de sedimentos = Interlaboratory assessment of marine bioassays to evaluate the environmental quality of coastal sediments in Spain. II. Bioluminescence inhibition test for rapid sediment toxicity assessment

NARCIS (Netherlands)

Casado-Martinez, M.C.; Campisi, T.; Diaz, A.; Re, Lo R.; Obispo, R.; Postma, J.F.; Riba, I.; Sneekes, A.C.; Buceta, J.L.; DelValls, T.A.

2006-01-01

The Microtox (R) bioassay was tested in an interlaboratory study to evaluate the variability when using solid-phase samples. The exercise consisted of two consecutive phases each one carried out with six sediment samples from Spanish ports. Phase I included six laboratories that reported results for

REIMEP-22 inter-laboratory comparison: "U Age Dating - Determination of the production date of a uranium certified test sample"

OpenAIRE

VENCHIARUTTI CELIA; VARGA ZSOLT; RICHTER Stephan; JAKOPIC Rozle; MAYER Klaus; AREGBE Yetunde

2015-01-01

The REIMEP-22 inter-laboratory comparison aimed at determining the production date of a uranium certified test sample (i.e. the last chemical separation date of the material). Participants in REIMEP-22 on "U Age Dating - Determination of the production date of a uranium certified test sample" received one low-enriched 20 mg uranium sample for mass spectrometry measurements and/or one 50 mg uranium sample for D-spectrometry measurements, with an undisclosed value for the production date. They ...

Use of HOMA-IR to diagnose non-alcoholic fatty liver disease: a population-based and inter-laboratory study

OpenAIRE

Isokuortti, Elina; Zhou, You; Peltonen, Markku; Bugianesi, Elisabetta; Clement, Karine; Bonnefont-Rousselot, Dominique; Lacorte, Jean-Marc; Gastaldelli, Amalia; Schuppan, Detlef; Schattenberg, Jörn M.; Hakkarainen, Antti; Lundbom, Nina; Jousilahti, Pekka; Männistö, Satu; Keinänen-Kiukaanniemi, Sirkka

2017-01-01

Aims/hypothesis\\ud \\ud Recent European guidelines for non-alcoholic fatty liver disease (NAFLD) call for reference values for HOMA-IR. In this study, we aimed to determine: (1) the upper limit of normal HOMA-IR in two population-based cohorts; (2) the HOMA-IR corresponding to NAFLD; (3) the effect of sex and PNPLA3 genotype at rs738409 on HOMA-IR; and (4) inter-laboratory variations in HOMA-IR.\\ud \\ud Methods\\ud \\ud We identified healthy individuals in two population-based cohorts (FINRISK 20...

Interlaboratory test comparison among Environmental Radioactivity Laboratories using the ISO/IUPAC/AOAC Protocol

International Nuclear Information System (INIS)

Romero, L.; Ramos, L.; Salas, R.

1998-01-01

World-wide acceptance of results from radiochemical analyses requires reliable, traceable and comparable measurements to SI units, particularly when data sets generated by laboratories are to contribute to evaluation of data from environmental pollution research and monitoring programmes. The Spanish Nuclear Safety Council (CSN) organizes in collaboration with CIEMAT periodical interlaboratory test comparisons for environmental radioactivity laboratories aiming to provide them with the necessary means to asses the quality of their results. This paper presents data from the most recent exercise which, for the first time, was evaluated following the procedure recommended in the ISO/IUPAC/AOAC Harmonized Protocol for the proficiency testing of analytical laboratories (1). The test sample was a Reference Material provided by the IAEA-AQCS, a lake sediment containing the following radionuclides: k-40, Ra-226, Ac-228, Cs-137, Sr-90, Pu-(239+240). The results of the proficiency test were computed for the 28 participating laboratories using the z-score approach, the evaluation of the exercises is presented in the paper. The use of a z-score classification has demonstrated to provide laboratories with a more objective means of assessing and demonstrating the reliability of the data they are producing. Analytical proficiency of the participating laboratories has been found to be satisfactory in 57 to 100 percent of cases. (1)- The International harmonized protocol for the proficiency testing of (chemical) analytical laboratories. Pure and Appl. Chem. Vol. 65, n 9, pp. 2123-2144, 1993 IUPAC. GB (Author) 3 refs

Results of the Interlaboratory Exercise CNS/CIEMAT-2008 among Environmental Radioactivity Laboratories (Phosphogypsum)

International Nuclear Information System (INIS)

Romero, M. L.; Barrera, M.; Valino, F.

2010-01-01

The document describes the outcome of the CSN/CIEMAT-2008 interlaboratory test comparison among environmental radioactivity laboratories. The exercise was organised according to the ISO-43 and the ISO/IUPAC/AOAC. Aphosphogypsum material was used as a test sample, in an attempt to evaluate the performance of the laboratories analyzing NORM (Naturally-Occurring Radioactive Materials). The analysis required were: U-238, Th-234, U-234, Th-230, Ra-226, Pb-214, Bi-214, Pb-210, Po-210, Th-232 and U-235, and also gross alpha and gross beta activities. Reference values have been established according to the method of consensus of expert laboratories, with four international laboratories of credited experience: IAEA Seibersdorf, IAEA MEL, IRSN-Orsay and Sta.Teresa ENEA. The results of the exercise were computed for 34 answering laboratories and their analytical performance was assessed using the z-score. Robust statistics of the participants results was applied to obtain the median and standard deviation, to achieve a more complete and objective study of the laboratories performance. The exercise has shown an homogeneous behaviour of laboratories, being statistical parameters from the results close to the assigned Reference Values. Participant laboratories have demonstrated their ability to determine natural radionuclides in phosphogypsum samples (NORM material) with a satisfactory quality level. The scheme has also allowed examining the capability of laboratories to determine the activities of natural radionuclides at the equilibrium. (Author) 10 refs.

An European inter-laboratory validation of alternative endpoints of the murine local lymph node assay: 2nd round.

Science.gov (United States)

Ehling, G; Hecht, M; Heusener, A; Huesler, J; Gamer, A O; van Loveren, H; Maurer, Th; Riecke, K; Ullmann, L; Ulrich, P; Vandebriel, R; Vohr, H-W

2005-08-15

The original local lymph node assay (LLNA) is based on the use of radioactive labelling to measure cell proliferation. Other endpoints for the assessment of proliferation are also authorized by the OECD Guideline 429 provided there is appropriate scientific support, including full citations and description of the methodology (OECD, 2002. OECD Guideline for the Testing of Chemicals; Skin Sensitization: Local Lymph Node Assay, Guideline 429. Paris, adopted 24th April 2002.). Here, we describe the outcome of the second round of an inter-laboratory validation of alternative endpoints in the LLNA conducted in nine laboratories in Europe. The validation study was managed and supervised by the Swiss Agency for Therapeutic Products (Swissmedic) in Bern. Ear-draining lymph node (LN) weight and cell counts were used to assess LN cell proliferation instead of [3H]TdR incorporation. In addition, the acute inflammatory skin reaction was measured by ear weight determination of circular biopsies of the ears to identify skin irritation properties of the test items. The statistical analysis was performed in the department of statistics at the university of Bern. Similar to the EC(3) values defined for the radioactive method, threshold values were calculated for the endpoints measured in this modification of the LLNA. It was concluded that all parameters measured have to be taken into consideration for the categorisation of compounds due to their sensitising potencies. Therefore, an assessment scheme has been developed which turned out to be of great importance to consistently assess sensitisation versus irritancy based on the data of the different parameters. In contrast to the radioactive method, irritants have been picked up by all the laboratories applying this assessment scheme.

Harmonization of radiobiological assays: why and how?

International Nuclear Information System (INIS)

Prasanna, Pataje G.

2014-01-01

The International Atomic Energy Agency has made available a technical manual for cytogenetic biodosimetry assays (dicentric chromosome aberration (DCA) and cytokinesis-block micronucleus (CBMN) assays) used for radiation dose assessment in radiation accidents. The International Standardization Organization, which develops standards and guidelines, also provides an avenue for laboratory accreditation, has developed guidelines and recommendations for performing cytogenetic biodosimetry assays. Harmonization of DCA and CBMN assays, has improved their accuracy. Double-blinded inter-laboratory comparison studies involving several networks have further validated DCA and CBMN assays and improved the confidence in their potential use for radiation dose assessment in mass casualties. This kind of international harmonization is lacking for pre-clinical radiobiology assays. The widely used pre-clinical assays that are relatively important to set stage for clinical trials include clonogenic assays, flow-cytometry assays, apoptotic assays, and tumor regression and growth delay assays. However, significant inter-laboratory variations occur with respect to data among laboratories. This raises concerns on the reliability and reproducibility of preclinical data that drives further development and translation. Lack of reproducibility may stem from a variety of factors such as poor scientist training, less than optimal experimental design, inadequate description of methodology, and impulse to publish only the positive data etc. Availability of technical manuals, standard operating procedures, accreditation avenues for laboratories performing such assays, inter-laboratory comparisons, and use of standardized protocols are necessary to enhance reliability and reproducibility. Thus, it is important that radiobiological assays are harmonized for laboratory protocols to ensure successful translation of pre-clinical research on radiation effect modulators to help design clinic trials with

An Inter-Laboratory Comparison for the Urinary Acrolein Biomarker 3-Hydroxypropyl-Mercapturic Acid (3-HPMA

Directory of Open Access Journals (Sweden)

Scherer Gerhard

2017-01-01

Full Text Available An inter-laboratory comparison study on the acrolein biomarker of exposure 3-hydroxypropyl-mercapturic acid (3-HPMA with 12 laboratories from 7 globally distributed countries was performed. The laboratories received coded triplicates of 4 spiked and lyophilized urine samples (LU, 12 samples as well as 5 authentic urine pool samples (PU, 15 samples covering the 3-HPMA concentration range from background (non-smoking to heavy smoking levels for analysis by using their own (in-house analytical method. All laboratories applied liquid chromatography with tandem mass spectrometry (LC-MS/MS, with most of them (10 of 12 using solid phase extraction (SPE as sample work-up procedure. The intra-laboratory variation (indicating repeatability was determined by calculating the standard deviation (sr and the coefficient of variation (CVr of the triplicates, whereas the inter-laboratory variation (indicating reproducibility was determined by calculating the standard deviation between laboratories (sR and the corresponding coefficient of variation (CVR. After removal of outlier samples or laboratories, the mean CVr values for LU and PU test samples ranged from 2.1–3.6% (mean: 2.8% and 2.4–3.7% (mean: 3.3%, respectively, indicating good repeatability for the determination of 3-HPMA in both sample types. CVR for LU and PU test samples ranged from 9.1–31.9% (mean: 18.8% and 13.9–27.0% (mean: 18.5%, respectively, indicating limited reproducibility in 3-HPMA analysis for both sample types. Re-calculation of the PU results by applying an embedded calibration (EC, derived from the reported peak areas for the LU test samples, somewhat improved the CVR values (range: 9.6–28.8%, mean: 16.7%.

OECD validation study to assess intra- and inter-laboratory reproducibility of the zebrafish embryo toxicity test for acute aquatic toxicity testing.

Science.gov (United States)

Busquet, François; Strecker, Ruben; Rawlings, Jane M; Belanger, Scott E; Braunbeck, Thomas; Carr, Gregory J; Cenijn, Peter; Fochtman, Przemyslaw; Gourmelon, Anne; Hübler, Nicole; Kleensang, André; Knöbel, Melanie; Kussatz, Carola; Legler, Juliette; Lillicrap, Adam; Martínez-Jerónimo, Fernando; Polleichtner, Christian; Rzodeczko, Helena; Salinas, Edward; Schneider, Katharina E; Scholz, Stefan; van den Brandhof, Evert-Jan; van der Ven, Leo T M; Walter-Rohde, Susanne; Weigt, Stefan; Witters, Hilda; Halder, Marlies

2014-08-01

The OECD validation study of the zebrafish embryo acute toxicity test (ZFET) for acute aquatic toxicity testing evaluated the ZFET reproducibility by testing 20 chemicals at 5 different concentrations in 3 independent runs in at least 3 laboratories. Stock solutions and test concentrations were analytically confirmed for 11 chemicals. Newly fertilised zebrafish eggs (20/concentration and control) were exposed for 96h to chemicals. Four apical endpoints were recorded daily as indicators of acute lethality: coagulation of the embryo, lack of somite formation, non-detachment of the tail bud from the yolk sac and lack of heartbeat. Results (LC50 values for 48/96h exposure) show that the ZFET is a robust method with a good intra- and inter-laboratory reproducibility (CV30%) for some very toxic or volatile chemicals, and chemicals tested close to their limit of solubility. The ZFET is now available as OECD Test Guideline 236. Considering the high predictive capacity of the ZFET demonstrated by Belanger et al. (2013) in their retrospective analysis of acute fish toxicity and fish embryo acute toxicity data, the ZFET is ready to be considered for acute fish toxicity for regulatory purposes. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Initial Readability Assessment of Clinical Trial Eligibility Criteria

Science.gov (United States)

Kang, Tian; Elhadad, Noémie; Weng, Chunhua

2015-01-01

Various search engines are available to clinical trial seekers. However, it remains unknown how comprehensible clinical trial eligibility criteria used for recruitment are to a lay audience. This study initially investigated this problem. Readability of eligibility criteria was assessed according to (i) shallow and lexical characteristics through the use of an established, generic readability metric; (ii) syntactic characteristics through natural language processing techniques; and (iii) health terminological characteristics through an automated comparison to technical and lay health texts. We further stratified clinical trials according to various study characteristics (e.g., source country or study type) to understand potential factors influencing readability. Mainly caused by frequent use of technical jargons, a college reading level was found to be necessary to understand eligibility criteria text, a level much higher than the average literacy level of the general American population. The use of technical jargons should be minimized to simplify eligibility criteria text. PMID:26958204

Reimiep 87. An interlaboratory U-235 enrichment determination by gamma measurement on solid UF6 sample

International Nuclear Information System (INIS)

Aparo, M.; Cresti, P.

1988-01-01

Gamma spectroscopy technique, based on the measurement of U 235 186 KeV flux, is now currently used for the determination of Uranium enrichment in different material of nuclear fuel cycle, namely: Uranium metallic, UO 2 pellets, UF 6 liquid or solid. The present paper describes the use of such a technique and the obtained results in determining the U 235 /U atomic isotopic abundance on a certified UF 6 solid sample. The measurements have been carried out in the frame work of the partecipation to the ''UF 6 Interlaboratory Measurements Evaluation Programme'' organized by CBNM/Geel with the support of the ESARDA (European Safeguards Research and Development Association)

The AS-76 interlaboratory experiment on the alpha spectrometric determinaion of Pu-238. Part 3: Preparation and characterization of samples

International Nuclear Information System (INIS)

Bortels, G.; Broothaerts, J.; Bievre, P. de

1980-01-01

Four plutonium samples containing 0.2, 0.8, 1.6 and 0.9 atom % of 238 Pu have been prepared for the Interlaboratory Experiment AS-76. Of these three were input solutions from a reprocessing plant. The fourth sample was from a plutonium product solution. These samples have been characterized by two alpha spectrometry laboratories and two mass spectrometry laboratories to certify the ratio of alpha activities 238 Pu/( 239 Pu + 240 Pu) and the isotopic composition, respectively

Interlaboratory Reproducibility of Droplet Digital Polymerase Chain Reaction Using a New DNA Reference Material Format.

Science.gov (United States)

Pinheiro, Leonardo B; O'Brien, Helen; Druce, Julian; Do, Hongdo; Kay, Pippa; Daniels, Marissa; You, Jingjing; Burke, Daniel; Griffiths, Kate; Emslie, Kerry R

2017-11-07

Use of droplet digital PCR technology (ddPCR) is expanding rapidly in the diversity of applications and number of users around the world. Access to relatively simple and affordable commercial ddPCR technology has attracted wide interest in use of this technology as a molecular diagnostic tool. For ddPCR to effectively transition to a molecular diagnostic setting requires processes for method validation and verification and demonstration of reproducible instrument performance. In this study, we describe the development and characterization of a DNA reference material (NMI NA008 High GC reference material) comprising a challenging methylated GC-rich DNA template under a novel 96-well microplate format. A scalable process using high precision acoustic dispensing technology was validated to produce the DNA reference material with a certified reference value expressed in amount of DNA molecules per well. An interlaboratory study, conducted using blinded NA008 High GC reference material to assess reproducibility among seven independent laboratories demonstrated less than 4.5% reproducibility relative standard deviation. With the exclusion of one laboratory, laboratories had appropriate technical competency, fully functional instrumentation, and suitable reagents to perform accurate ddPCR based DNA quantification measurements at the time of the study. The study results confirmed that NA008 High GC reference material is fit for the purpose of being used for quality control of ddPCR systems, consumables, instrumentation, and workflow.

The assessment of field trials in GMO research around the world and their possible integration in field trials for variety registration.

Science.gov (United States)

Slot, M M; van de Wiel, C C M; Kleter, G A; Visser, R G F; Kok, E J

2018-05-04

Most regulations worldwide stipulate that a new genetically modified (GM) crop event has to be compared to its closest non-GM counterpart as a corner stone of the pre-market risk assessment. To this end the GM crop and its comparator should be grown in field trials for a phenotypic comparison as well as for subsequent detailed analysis of the composition of the two crop varieties. A more in-depth globally harmonised approach for the conduct of these field trials is lacking. Only a few countries have formulated detailed protocols for the set-up of GM field trials. In some countries, commercial non-GM reference varieties need to be included in a field study to compile reliable data that indicate the range of natural variation for the compounds tested at the specific location. Detailed analysis of pre-market assessment reports have so far not shown the added value of including these reference varieties in the field trials. In all cases where specific values were found to be outside of the range of the reference varieties, it proved possible to draw conclusions on the part of the pre-market risk assessment that relates to the compositional analysis, on the basis of already available compositional data. With the increasing quality of several databases on compositional data of a growing number of crop species, it seems unlikely that reference varieties will become more important on future occasions. It was furthermore investigated whether this part of the risk assessment can be related to field trial requirements for variety registration with the explicit intention of reducing the data burden on producers of new GM plant varieties. Field trials for variety registration so far include an assessment of phenotypic characteristics that do not cover safety aspects, with the exception of establishment of the glycoalkaloid content in potatoes in the Netherlands and Sweden. It may, however, under certain conditions be relatively easy to exchange data from compositional

Results of the Interlaboratory Exercise CNS/CIEMAT-04 Among Environmental Radioactivity Laboratories (Aqueous Solution)

International Nuclear Information System (INIS)

Romero Gonzalez, M. L.; Barrera Izquierdo, M.

2004-01-01

The document describes the outcome of the CSN/CIEMAT-04 interlaboratory test comparison among environmental radioactivity laboratories. The exercise was organised according to the ISO-43 and the ISO/IUPAC/AOAC Harmonised Protocol for the proficiency testing of analytical laboratories. Following the issue of the European Community Drinking Water Directive 98/83/EC concerning the quality of water for human consumption, the last inter-comparison exercise was organised by using a water sample, in an attempt to evaluate the performance of the laboratories analysing the required radioactivity parameters (H-3, gross alpha and beta activity and residual beta). The sample (a synthetic drinking water), was prepared at the National Laboratory for Ionising Radiation's Standards (CIEMAT), and contained the following radionuclides ''241 Am, ''239+240 Pu, ''90Sr, ''137 Cs, ''3 H y ''40 K. The results of the exercise were computed for 38 participating laboratories, and their analytical performance was assessed using the z-score approach. Robust statistics of the participant's results was applied to obtain the median and standard deviation, including suspected outliers. The exercise has revealed and homogeneous behaviour of laboratories, being statistical parameters from the results close to the reference values. A raised percentage os satisfactory laboratory performance has been obtained for gross alpha, gross beta and residual beta: 85, 97 and 87% respectively. The study has shown that participant laboratories perform radioactive determinations in drinking water samples with satisfactory quality levels. (Author) 16 refs

Interlaboratory comparison and accreditation in quality control testing of diagnostic X-ray equipment

International Nuclear Information System (INIS)

Kepler, K.; Vladimirov, A.; Servomaa, A.

2005-01-01

The Univ. of Tartu provides a quality control service to the majority of diagnostic X-ray departments in Estonia. Its methodology has been adopted from the IEC and other relevant standards. Recently the Testing Centre of the Univ. of Tartu was accredited on this methodology by ISO/IEC 17025. Besides the implementation of the quality management system, participation in interlaboratory comparison (ILC) was one of the prerequisites for the accreditation. Tests for estimating reproducibility of tube voltage and dose rate, accuracy of the voltage and accuracy of exposure time were carried out on a diagnostic X-ray unit in the Radiation and Nuclear Safety Authority in Helsinki. The measurement performance was judged by calculating deviation En normalised with respect to the stated uncertainties. En values for all tests were less than unity and by the common ILC criteria the testing performance could be considered as acceptable. (authors)

Comprehensive geriatric assessment for older adults admitted to hospital: meta-analysis of randomised controlled trials.

Science.gov (United States)

Ellis, Graham; Whitehead, Martin A; Robinson, David; O'Neill, Desmond; Langhorne, Peter

2011-10-27

To evaluate the effectiveness of comprehensive geriatric assessment in hospital for older adults admitted as an emergency. We searched the EPOC Register, Cochrane's Controlled Trials Register, the Database of Abstracts of Reviews of Effects (DARE), Medline, Embase, CINAHL, AARP Ageline, and handsearched high yield journals. Randomised controlled trials of comprehensive geriatric assessment (whether by mobile teams or in designated wards) compared with usual care. Comprehensive geriatric assessment is a multidimensional interdisciplinary diagnostic process used to determine the medical, psychological, and functional capabilities of a frail elderly person to develop a coordinated and integrated plan for treatment and long term follow-up. Three independent reviewers assessed eligibility and trial quality and extracted published data. Two additional reviewers moderated. Twenty two trials evaluating 10,315 participants in six countries were identified. For the primary outcome "living at home," patients who underwent comprehensive geriatric assessment were more likely to be alive and in their own homes at the end of scheduled follow-up (odds ratio 1.16 (95% confidence interval 1.05 to 1.28; P = 0.003; number needed to treat 33) at a median follow-up of 12 months versus 1.25 (1.11 to 1.42; P P P = 0.001) and were more likely to experience improved cognition (standardised mean difference 0.08, 0.01 to 0.15; P = 0.02) in the comprehensive geriatric assessment group. Comprehensive geriatric assessment increases patients' likelihood of being alive and in their own homes after an emergency admission to hospital. This seems to be especially true for trials of wards designated for comprehensive geriatric assessment and is associated with a potential cost reduction compared with general medical care.

[Evidence-based quality assessment of 10-year orthodontic clinical trials in 4 major dental journals].

Science.gov (United States)

Sun, Yan-nan; Lei, Fei-fei; Cao, Yan-li; Fu, Min-kui

2010-02-01

To assess the quality of orthodontic clinical trials published in 4 major dental journals in the past 10 years and establish the reference standard for orthodontic clinical trials and quality control of dental journals. All the clinical trials published in Chinese Journal of Stomatology, West China Journal of Stomatology, Journal of Practice Stomatology and Chinese Journal of Orthodontics from 1999 to 2008 were searched. The demographic information of the papers was extracted and the quality of the clinical trials according to the consolidated standards of reporting trials (CONSORT) was assessed. Four hundred and ninety-four clinical trials were retrieved, and 21.3% (105/494) of them were supported by grants. For the study design, only 26.1% (129/494) were prospective studies, and 3.8% (19/494) were randomized clinical trials. It was hard to evaluate precisely due to the lack of information about the details of the study designs. For the randomized clinical trials, the lack of details for randomization, allocation concealment, blinding and intention to treat compromised the quality. The general quality of clinical trials in orthodontics is poor. It needs to be improved both in the clinical study design and the paper writing.

Interlaboratory evaluation of the AOAC method and the A-1 procedure for recovery of fecal coliforms from foods.

Science.gov (United States)

Andrews, W H; Wilson, C R; Poelma, P L; Bullock, L K; McClure, F D; Gentile, D E

1981-09-01

An interlaboratory evaluation was made of the 96 h AOAC method and the 24 h A-1 procedure for the enumeration of fecal coliforms in samples of yellow corn meal, rye flour, mung beans, raw ground beef, and raw oyster homogenate. Results indicated that the efficiency of the A-1 procedure, measured in terms of recovery of fecal coliforms, and the reproducibility of that recovery were dependent on the particular food being analyzed. Accordingly, until its efficiency can be more fully demonstrated, the A-1 procedure is recommended only as a screening procedure for fecal coliforms in foods.

78 FR 33798 - Oral Rabies Vaccine Trial; Availability of a Supplemental Environmental Assessment

Science.gov (United States)

2013-06-05

... Inspection Service [Docket No. APHIS-2013-0046] Oral Rabies Vaccine Trial; Availability of a Supplemental... Inspection Service has prepared a supplemental environmental assessment (EA) relative to an oral rabies... analyzes expanding the field trial for an experimental oral rabies vaccine for wildlife to additional areas...

Inter-laboratory verification of European pharmacopoeia monograph on derivative spectrophotometry method and its application for chitosan hydrochloride.

Science.gov (United States)

Marković, Bojan; Ignjatović, Janko; Vujadinović, Mirjana; Savić, Vedrana; Vladimirov, Sote; Karljiković-Rajić, Katarina

2015-01-01

Inter-laboratory verification of European pharmacopoeia (EP) monograph on derivative spectrophotometry (DS) method and its application for chitosan hydrochloride was carried out on two generation of instruments (earlier GBC Cintra 20 and current technology TS Evolution 300). Instruments operate with different versions of Savitzky-Golay algorithm and modes of generating digital derivative spectra. For resolution power parameter, defined as the amplitude ratio A/B in DS method EP monograph, comparable results were obtained only with algorithm's parameters smoothing points (SP) 7 and the 2nd degree polynomial and those provided corresponding data with other two modes on TS Evolution 300 Medium digital indirect and Medium digital direct. Using quoted algorithm's parameters, the differences in percentages between the amplitude ratio A/B averages, were within accepted criteria (±3%) for assay of drug product for method transfer. The deviation of 1.76% for the degree of deacetylation assessment of chitosan hydrochloride, determined on two instruments, (amplitude (1)D202; the 2nd degree polynomial and SP 9 in Savitzky-Golay algorithm), was acceptable, since it was within allowed criteria (±2%) for assay deviation of drug substance, for method transfer in pharmaceutical analyses. Copyright © 2015 Elsevier B.V. All rights reserved.

Resource utilization implications of treatment were able to be assessed from appropriately reported clinical trial data

NARCIS (Netherlands)

Poole-Wilson, Philip A.; Kirwan, Bridget-Anne; Voko, Zoltan; de Brouwer, Sophie; Dunselman, Peter H. J. M.; van Dalen, Frederik J.; Lubsen, Jacobus

Background and Objective: Published clinical trial data rarely allow assessment of the health care resource utilization implications of treatment. We give an example of how these can be assessed given appropriate tabulation of data. Methods: Data from a trial comparing long-acting nifedipine

77 FR 49409 - Oral Rabies Vaccine Trial; Availability of an Environmental Assessment and Finding of No...

Science.gov (United States)

2012-08-16

...] Oral Rabies Vaccine Trial; Availability of an Environmental Assessment and Finding of No Significant... assessment and finding of no significant impact relative to an oral rabies vaccination field trial in New... be prepared. FOR FURTHER INFORMATION CONTACT: Mr. Richard Chipman, Rabies Program Coordinator...

Systematic literature review of clinical trials evaluating pharmacotherapy for overactive bladder in elderly patients: An assessment of trial quality.

Science.gov (United States)

Kistler, Kristin D; Xu, Yingxin; Zou, Kelly H; Ntanios, Fady; Chapman, Douglass S; Luo, Xuemei

2018-01-01

Overactive bladder (OAB) disproportionately affects older-aged adults, yet most randomized controlled trials (RCTs) underrepresent patients ≥65. This systematic literature review (SLR) identified RCTs evaluating β-3 adrenergic agonists or muscarinic antagonists in elderly patients with OAB, and compared study quality across trials. MEDLINE ® , Embase ® , and Cochrane Collaboration Central Register of Clinical Trials databases were searched from inception through April 28, 2015 to identify published, peer-reviewed RCT reports evaluating β-3 adrenergic agonists or muscarinic antagonists in elderly OAB patients (either ≥65 years or study-described as "elderly"). To assess study quality of RCT reports, we focused on internal/external validity, assessed via two scales: the validated Effective Public Health Practice Project [EPHPP]): Quality Assessment Tool for Quantitative Studies, and a tool commissioned by the Agency for Healthcare Research and Quality (AHRQ). Database searches yielded 1380 records that were then screened according to predefined inclusion/exclusion criteria. We included eight papers meeting study criteria. Despite scientific community efforts to improve RCT reporting standards, published reports still include incomplete and inconsistent reporting-of subject attrition, baseline patient characteristics, inclusion/exclusion criteria, and other important details. Only three of the eight OAB RCTs in this review received quality ratings of Strong (EPHPP) or Fair (AHRQ) and were multicenter with large samples. Despite the prevalence of OAB among older age individuals, relatively few RCTs evaluate OAB treatments explicitly among elderly subjects. The findings from this quality assessment suggest some areas for improvement in both conduct and reporting of future RCTs assessing OAB treatment in elderly. © 2017 Wiley Periodicals, Inc.

Inter-laboratory comparison of HITU power measurement methods and capabilities

International Nuclear Information System (INIS)

Jenderka, K V; Durando, G; Karaboece, B; Rajagopal, S; Shaw, A

2011-01-01

High Intensity Therapeutic Ultrasound (HITU) is gaining in importance among the spectrum of therapeutic options to combat cancer. HITU has already been approved and is in clinical use for the treatment of organs like the prostate, the liver and the uterus. Nevertheless, the metrology of the applied high power ultrasound fields, and in consequence, reliable treatment planning and monitoring, is still a challenge. As part of a European Metrology Research Programme project, the four National Metrology Institutes from the UK, Germany, Italy and Turkey conducted an inter-laboratory comparison of their power measurement capabilities at power levels of 5, 25, 75 and 150 W each at frequencies of 1.1, 1.5 and 3.3 MHz. The task was to measure the total, time-averaged ultrasonic output power, emitted by the circulated transducers under specified electrical excitation conditions into an anechoic water load, and the actual rms transducer input voltage. The output value to be reported was the electro-acoustic radiation conductance including the associated standard and expanded uncertainties. Several different measurement techniques were applied to gain further insight into HITU power measurement. The deviations from the calculated comparison reference value found for the different techniques are discussed and conclusions for the further improvement of measuring procedures are drawn.

Inter-laboratory comparison of HITU power measurement methods and capabilities

Energy Technology Data Exchange (ETDEWEB)

Jenderka, K V [Physikalisch-Technische Bundesanstalt (PTB), Bundesallee 100, 38116 Braunschweig (Germany); Durando, G [Istituto Nazionale di Ricerca Metrologica (INRIM), Strada delle Cacce 91, 10135 Torino (Italy); Karaboece, B [Tuebitak Ulusal Metroloji Enstituesue (UME), P.K. 54 41470 Gebze-Kocaeli (Turkey); Rajagopal, S; Shaw, A, E-mail: kvjend@ieee.org [National Physical Laboratory (NPL), Hampton Road, Teddington, TW11 0LW (United Kingdom)

2011-02-01

High Intensity Therapeutic Ultrasound (HITU) is gaining in importance among the spectrum of therapeutic options to combat cancer. HITU has already been approved and is in clinical use for the treatment of organs like the prostate, the liver and the uterus. Nevertheless, the metrology of the applied high power ultrasound fields, and in consequence, reliable treatment planning and monitoring, is still a challenge. As part of a European Metrology Research Programme project, the four National Metrology Institutes from the UK, Germany, Italy and Turkey conducted an inter-laboratory comparison of their power measurement capabilities at power levels of 5, 25, 75 and 150 W each at frequencies of 1.1, 1.5 and 3.3 MHz. The task was to measure the total, time-averaged ultrasonic output power, emitted by the circulated transducers under specified electrical excitation conditions into an anechoic water load, and the actual rms transducer input voltage. The output value to be reported was the electro-acoustic radiation conductance including the associated standard and expanded uncertainties. Several different measurement techniques were applied to gain further insight into HITU power measurement. The deviations from the calculated comparison reference value found for the different techniques are discussed and conclusions for the further improvement of measuring procedures are drawn.

Analytical quality control of neutron activation analysis by interlaboratory comparison and proficiency test

International Nuclear Information System (INIS)

Kim, S. H.; Moon, J. H.; Jeong, Y. S.

2002-01-01

Two air filters (V-50, P-50) artificially loaded with urban dust were provided from IAEA and trace elements to study inter-laboratory comparison and proficiency test were determined using instrumental neutron activation analysis non-destructively. Standard reference material(Urban Particulate Matter, NIST SRM 1648) of National Institute of Standard and Technology was used for internal analytical quality control. About 20 elements in each loaded filter sample were determined, respectively. Our analytical data were compared with statistical results using neutron activation analysis, particle induced X-ray emission spectrometry, inductively coupled plasma mass spectroscopy, etc., which were collected from 49 laboratories of 40 countries. From the results that were statistically re-treated with reported values, Z-scores of our analytical values are within ±2. In addition, the results of proficiency test are passed and accuracy and precision of the analytical values are reliable. Consequently, it was proved that analytical quality control for the analysis of air dust samples is reasonable

The interlaboratory experiment IDA-72 on mass spectrometric isotope dilution analysis. Vol. 2

International Nuclear Information System (INIS)

Beyrich, W.; Drosselmeyer, E.

1975-07-01

Volume II of the report on the IDA-72 experiment contains papers written by different authors on a number of special topics connected with the preparation, performance and evaluation of the interlaboratory test. In detail the sampling procedures for active samples of the reprocessing plant and the preparation of inactive reference and spike solution from standard material are described as well as new methods of sample conditioning by evaporation. An extra chapter is devoted to the chemical sample treatment as a preparation for mass spectrometric analysis of the U and Pu content of the solutions. Special topics are also methods for mass discrimination corrections, α-spectrometer measurements as a supplement for the determination of Pu-238 and the comparison of concentration determinations by mass spectrometric isotope dilution analysis with those performed by X-ray fluorescence spectrometry. The last part of this volume contains papers connected with the computerized statistical evaluation of the high number of data. (orig.) [de

Results of an interlaboratory comparison of analytical methods for contaminants of emerging concern in water.

Science.gov (United States)

Vanderford, Brett J; Drewes, Jörg E; Eaton, Andrew; Guo, Yingbo C; Haghani, Ali; Hoppe-Jones, Christiane; Schluesener, Michael P; Snyder, Shane A; Ternes, Thomas; Wood, Curtis J

2014-01-07

An evaluation of existing analytical methods used to measure contaminants of emerging concern (CECs) was performed through an interlaboratory comparison involving 25 research and commercial laboratories. In total, 52 methods were used in the single-blind study to determine method accuracy and comparability for 22 target compounds, including pharmaceuticals, personal care products, and steroid hormones, all at ng/L levels in surface and drinking water. Method biases ranged from caffeine, NP, OP, and triclosan had false positive rates >15%. In addition, some methods reported false positives for 17β-estradiol and 17α-ethynylestradiol in unspiked drinking water and deionized water, respectively, at levels higher than published predicted no-effect concentrations for these compounds in the environment. False negative rates were also generally contamination, misinterpretation of background interferences, and/or inappropriate setting of detection/quantification levels for analysis at low ng/L levels. The results of both comparisons were collectively assessed to identify parameters that resulted in the best overall method performance. Liquid chromatography-tandem mass spectrometry coupled with the calibration technique of isotope dilution were able to accurately quantify most compounds with an average bias of <10% for both matrixes. These findings suggest that this method of analysis is suitable at environmentally relevant levels for most of the compounds studied. This work underscores the need for robust, standardized analytical methods for CECs to improve data quality, increase comparability between studies, and help reduce false positive and false negative rates.

An European inter-laboratory validation of alternative endpoints of the murine local lymph node assay: first round.

Science.gov (United States)

Ehling, G; Hecht, M; Heusener, A; Huesler, J; Gamer, A O; van Loveren, H; Maurer, Th; Riecke, K; Ullmann, L; Ulrich, P; Vandebriel, R; Vohr, H-W

2005-08-15

The new OECD guideline 429 (skin sensitization: local lymph node assay) is based upon a protocol, which utilises the incorporation of radioactivity into DNA as a measure for cell proliferation in vivo. The guideline also enables the use of alternative endpoints in order to assess draining lymph node (LN) cell proliferation. Here we describe the first round of an inter-laboratory validation of alternative endpoints in the LLNA conducted in seven laboratories. The validation study was managed and supervised by the Swiss Agency for Therapeutic Products, Swissmedic. Statistical analyses of all data were performed by an independent centre at the University of Bern, Department of Statistics. Ear-draining, LN weight and cell count were used to assess proliferation instead of radioactive labeling of lymph node cells. In addition, the acute inflammatory skin reaction was measured by ear swelling and weight of circular biopsies of the ears to identify skin irritating properties of the test items. Hexylcinnamaldehyde (HCA) and three blinded test items were applied to female, 8--10 weeks old NMRI and BALB/c mice. Results were sent via the independent study coordinator to the statistician. The results of this first round showed that the alternative endpoints of the LLNA are sensitive and robust parameters. The use of ear weights added an important parameter assessing the skin irritation potential, which supports the differentiation of pure irritative from contact allergenic potential. There were absolute no discrepancies between the categorisation of the three test substances A--C determined by each single participating laboratories. The results highlighted also that many parameters do have an impact on the strength of the responses. Therefore, such parameters have to be taken into consideration for the categorisation of compounds due to their relative sensitizing potencies.

An European inter-laboratory validation of alternative endpoints of the murine local lymph node assay: First round

International Nuclear Information System (INIS)

Ehling, G.; Hecht, M.; Heusener, A.; Huesler, J.; Gamer, A.O.; Loveren, H. van; Maurer, Th.; Riecke, K.; Ullmann, L.; Ulrich, P.; Vandebriel, R.; Vohr, H.-W.

2005-01-01

The new OECD guideline 429 (skin sensitization: local lymph node assay) is based upon a protocol, which utilises the incorporation of radioactivity into DNA as a measure for cell proliferation in vivo. The guideline also enables the use of alternative endpoints in order to assess draining lymph node (LN) cell proliferation. Here we describe the first round of an inter-laboratory validation of alternative endpoints in the LLNA conducted in seven laboratories. The validation study was managed and supervised by the Swiss Agency for Therapeutic Products, Swissmedic. Statistical analyses of all data were performed by an independent centre at the University of Bern, Department of Statistics. Ear-draining, LN weight and cell count were used to assess proliferation instead of radioactive labeling of lymph node cells. In addition, the acute inflammatory skin reaction was measured by ear swelling and weight of circular biopsies of the ears to identify skin irritating properties of the test items. Hexylcinnamaldehyde (HCA) and three blinded test items were applied to female, 8-10 weeks old NMRI and BALB/c mice. Results were sent via the independent study coordinator to the statistician. The results of this first round showed that the alternative endpoints of the LLNA are sensitive and robust parameters. The use of ear weights added an important parameter assessing the skin irritation potential, which supports the differentiation of pure irritative from contact allergenic potential. There were absolute no discrepancies between the categorisation of the three test substances A-C determined by each single participating laboratories. The results highlighted also that many parameters do have an impact on the strength of the responses. Therefore, such parameters have to be taken into consideration for the categorisation of compounds due to their relative sensitizing potencies

Results of the Interlaboratory Exercise CNS/CIEMAT-05 among Environmental Radioactivity Laboratories (Vegetable Ash)

International Nuclear Information System (INIS)

Romero Gonzalez, M. L.; Barrera Izquierdo, M.; Valino Garcia, F.

2006-01-01

The document describes the outcome of the CSN/CIEMAT-05 interlaboratory test comparison among environmental radioactivity laboratories. The exercise was organised according to the ISO-43 and the IUPAC I nternational harmonised protocol for the proficiency testing of analytical chemistry laboratories . The exercise has been designed to evaluate the capability of national laboratories to determine environmental levels of radionuclides in vegetable ash samples. The sample has been prepared by the Environmental Radiation Laboratory, from the University of Barcelona, and it contains the following radionuclides: Sr-90, Pu-238, Am-241, Th-230, Pb-210, U-238, Ra-226, K-40, Ra-228, TI-208, Cs- 137 and Co-60. Reference values have been established TROUGH the kind collaboration of three international laboratories of recognized experience: IAEA MEL and IRSN-Orsay. The results of the exercise were computed for 35 participating laboratories and their analytical performance was assessed using the z-score approach. Robust statistics of the participant's results was applied to obtain the median and standard deviation, to achieve a more complete and objetiva study of the laboratories' performance. Some difficulties encountered to dissolve the test sample caused a lower response of analyses involving radiochemical separation, thus some laboratories couldn't apply their routine methods and no conclusions on PU-238, Am-241 and Th-230 performances have been obtained. The exercise has revealed an homogeneous behaviour of laboratories, being statistical parameters from the results close to the reference values. The study has shown that participant laboratories perform radioactive determinations in vegetable ash samples with satisfactory quality levels. (Author) 6 refs

Interlaboratory study of the ion source memory effect in 36Cl accelerator mass spectrometry

International Nuclear Information System (INIS)

Pavetich, Stefan; Akhmadaliev, Shavkat; Arnold, Maurice; Aumaître, Georges; Bourlès, Didier; Buchriegler, Josef; Golser, Robin; Keddadouche, Karim; Martschini, Martin; Merchel, Silke; Rugel, Georg; Steier, Peter

2014-01-01

Highlights: • Long-term memory effect in negative ion sources investigated for chlorine isotopes. • Interlaboratory comparison of four up-to date negative ion sources. • Ion source improvement at DREAMS for minimization of long-term memory effect. • Long-term memory effect is the limitation for precise AMS data of volatile elements. • Findings to be considered for samples with highly variable ratios of 36 Cl/Cl and 129 I/I. - Abstract: Understanding and minimization of contaminations in the ion source due to cross-contamination and long-term memory effect is one of the key issues for accurate accelerator mass spectrometry (AMS) measurements of volatile elements. The focus of this work is on the investigation of the long-term memory effect for the volatile element chlorine, and the minimization of this effect in the ion source of the Dresden accelerator mass spectrometry facility (DREAMS). For this purpose, one of the two original HVE ion sources at the DREAMS facility was modified, allowing the use of larger sample holders having individual target apertures. Additionally, a more open geometry was used to improve the vacuum level. To evaluate this improvement in comparison to other up-to-date ion sources, an interlaboratory comparison had been initiated. The long-term memory effect of the four Cs sputter ion sources at DREAMS (two sources: original and modified), ASTER (Accélérateur pour les Sciences de la Terre, Environnement, Risques) and VERA (Vienna Environmental Research Accelerator) had been investigated by measuring samples of natural 35 Cl/ 37 Cl-ratio and samples highly-enriched in 35 Cl ( 35 Cl/ 37 Cl ∼ 999). Besides investigating and comparing the individual levels of long-term memory, recovery time constants could be calculated. The tests show that all four sources suffer from long-term memory, but the modified DREAMS ion source showed the lowest level of contamination. The recovery times of the four ion sources were widely spread between

An inter-laboratory stability study of roll-to-roll coated flexible polymer solar modules

DEFF Research Database (Denmark)

Gevorgyan, Suren; Medford, Andrew James; Bundgaard, Eva

2011-01-01

A large number of flexible polymer solar modules comprising 16 serially connected individual cells was prepared at the experimental workshop at Risø DTU. The photoactive layer was prepared from several varieties of P3HT (Merck, Plextronics, BASF and Risø DTU) and two varieties of ZnO (nanoparticu......A large number of flexible polymer solar modules comprising 16 serially connected individual cells was prepared at the experimental workshop at Risø DTU. The photoactive layer was prepared from several varieties of P3HT (Merck, Plextronics, BASF and Risø DTU) and two varieties of Zn......O (nanoparticulate, thin film) were employed as electron transport layers. The devices were all tested at Risø DTU and the functional devices were subjected to an inter-laboratory study involving the performance and the stability of modules over time in the dark, under light soaking and outdoor conditions. 24...

Causal assessment of surrogacy in a meta-analysis of colorectal cancer trials

Science.gov (United States)

Li, Yun; Taylor, Jeremy M.G.; Elliott, Michael R.; Sargent, Daniel J.

2011-01-01

When the true end points (T) are difficult or costly to measure, surrogate markers (S) are often collected in clinical trials to help predict the effect of the treatment (Z). There is great interest in understanding the relationship among S, T, and Z. A principal stratification (PS) framework has been proposed by Frangakis and Rubin (2002) to study their causal associations. In this paper, we extend the framework to a multiple trial setting and propose a Bayesian hierarchical PS model to assess surrogacy. We apply the method to data from a large collection of colon cancer trials in which S and T are binary. We obtain the trial-specific causal measures among S, T, and Z, as well as their overall population-level counterparts that are invariant across trials. The method allows for information sharing across trials and reduces the nonidentifiability problem. We examine the frequentist properties of our model estimates and the impact of the monotonicity assumption using simulations. We also illustrate the challenges in evaluating surrogacy in the counterfactual framework that result from nonidentifiability. PMID:21252079

Patient-reported outcome (PRO assessment in clinical trials: a systematic review of guidance for trial protocol writers.

Directory of Open Access Journals (Sweden)

Melanie Calvert

Full Text Available Evidence suggests there are inconsistencies in patient-reported outcome (PRO assessment and reporting in clinical trials, which may limit the use of these data to inform patient care. For trials with a PRO endpoint, routine inclusion of key PRO information in the protocol may help improve trial conduct and the reporting and appraisal of PRO results; however, it is currently unclear exactly what PRO-specific information should be included. The aim of this review was to summarize the current PRO-specific guidance for clinical trial protocol developers.We searched the MEDLINE, EMBASE, CINHAL and Cochrane Library databases (inception to February 2013 for PRO-specific guidance regarding trial protocol development. Further guidance documents were identified via Google, Google scholar, requests to members of the UK Clinical Research Collaboration registered clinical trials units and international experts. Two independent investigators undertook title/abstract screening, full text review and data extraction, with a third involved in the event of disagreement. 21,175 citations were screened and 54 met the inclusion criteria. Guidance documents were difficult to access: electronic database searches identified just 8 documents, with the remaining 46 sourced elsewhere (5 from citation tracking, 27 from hand searching, 7 from the grey literature review and 7 from experts. 162 unique PRO-specific protocol recommendations were extracted from included documents. A further 10 PRO recommendations were identified relating to supporting trial documentation. Only 5/162 (3% recommendations appeared in ≥50% of guidance documents reviewed, indicating a lack of consistency.PRO-specific protocol guidelines were difficult to access, lacked consistency and may be challenging to implement in practice. There is a need to develop easily accessible consensus-driven PRO protocol guidance. Guidance should be aimed at ensuring key PRO information is routinely included in

REIMEP-22 U age dating - Determination of the production date of a uranium certified test sample Inter-laboratory comparison, Report to participants

OpenAIRE

VENCHIARUTTI CELIA; VARGA ZSOLT; RICHTER Stephan; NICHOLL Adrian; KRAJKO JUDIT; JAKOPIC Rozle; MAYER Klaus; AREGBE Yetunde

2015-01-01

The REIMEP-22 inter-laboratory comparison (ILC) "U Age Dating - Determination of the production date of a uranium certified test sample" was organised by JRC-IRMM as support to the Nuclear Forensics International Technical Working Group (ITWG) This ILC was organised prior to the release of the candidate certified reference material IRMM-1000, produced in cooperation with JRC-ITU. The aim of REIMEP-22 was to determine the production date of the uranium certified test sample (i.e. the last chem...

Comprehensive geriatric assessment for older adults admitted to hospital: meta-analysis of randomised controlled trials

OpenAIRE

Ellis, G.; Whitehead, M.A.; Robinson, D.; O'Neill, D.; Langhorne, P.

2011-01-01

Objective - To evaluate the effectiveness of comprehensive geriatric assessment in hospital for older adults admitted as an emergency.\\ud \\ud Search strategy - We searched the EPOC Register, Cochrane’s Controlled Trials Register, the Database of Abstracts of Reviews of Effects (DARE), Medline, Embase, CINAHL, AARP Ageline, and handsearched high yield journals.\\ud \\ud Selection criteria - Randomised controlled trials of comprehensive geriatric assessment (whether by mobile teams or in designat...

On the stability of a variety of organic photovoltaic devices by IPCE and in situ IPCE analyses - the ISOS-3 inter-laboratory collaboration

OpenAIRE

Terán-Escobar, Gerardo; Krebs, Frederik C.; Lira-Cantú, Mónica

2012-01-01

This work is part of the inter-laboratory collaboration to study the stability of seven distinct sets of state-of-the-art organic photovoltaic (OPV) devices prepared by leading research laboratories. All devices have been shipped to and degraded at RISempty set-DTU up to 1830 hours in accordance with established ISOS-3 protocols under defined illumination conditions. In this work, we apply the Incident Photon-to-Electron Conversion Efficiency (IPCE) and the in situ IPCE techniques to determin...

Sample requirements and design of an inter-laboratory trial for radiocarbon laboratories

NARCIS (Netherlands)

Bryant, C; Carmi, [No Value; Cook, G; Gulliksen, S; Harkness, D; Heinemeier, J; McGee, E; Naysmith, P; Possnert, G; van der Plicht, H; van Strydonck, M; Carmi, Israel

2000-01-01

An on-going inter-comparison programme which is focused on assessing and establishing consensus protocols to be applied in the identification, selection and sub-sampling of materials for subsequent C-14 analysis is described. The outcome of the programme will provide a detailed quantification of the

PhysioDirect: Supporting physiotherapists to deliver telephone assessment and advice services within the context of a randomised trial

Science.gov (United States)

Bishop, Annette; Gamlin, Jill; Hall, Jeanette; Hopper, Cherida; Foster, Nadine E.

2013-01-01

Physiotherapy-led telephone assessment and advice services for patients with musculoskeletal problems have been developed in many services in the UK, but high quality trial data on clinical and cost effectiveness has been lacking. In order to address this ‘The PhysioDirect trial’ (ISRCTN55666618), was a pragmatic randomised trial of a PhysioDirect telephone assessment and advice service. This paper describes the PhysioDirect system used in the trial and how physiotherapists were trained and supported to use the system and deliver the PhysioDirect service. The PhysioDirect system used in the trial was developed in Huntingdon and now serves a population of 350,000 people. When initiating or providing physiotherapy-led telephone assessment and advice services training and support for physiotherapists delivering care in this way is essential. An enhanced skill set is required for telephone assessment and advice particularly in listening and communication skills. In addition to an initial training programme, even experienced physiotherapists benefit from a period of skill consolidation to become proficient and confident in assessing patients and delivering care using the telephone. A computer-based system assists the delivery of a physiotherapy-led musculoskeletal assessment and advice service. Clinical Trials Registration Number (ISRCTN55666618). PMID:23219629

Design and Methodology of the Trial to Assess Chelation Therapy (TACT)

Science.gov (United States)

Lamas, Gervasio A.; Goertz, Christine; Boineau, Robin; Mark, Daniel B.; Rozema, Theodore; Nahin, Richard L.; Drisko, Jeanne A.; Lee, Kerry L.

2011-01-01

The Trial to Assess Chelation Therapy (TACT) is an NIH-sponsored, randomized, double blind, placebo-controlled, 2×2 factorial clinical trial testing the benefits and risks of 40 infusions of a multi-component Na2EDTA-chelation solution compared with placebo, and of an oral, high-dose multivitamin and mineral supplement. TACT has randomized and will follow 1708 patients for an average of approximately 4 years. The primary endpoint is a composite of all cause mortality, myocardial infarction, stroke, coronary revascularization, and hospitalization for angina. A 900 patient substudy will examine quality of life outcomes. The trial is designed to have >85% power to detect a 25% relative reduction in the primary endpoint for each treatment factor. Enrollment began in September 2003 and completed in October 2010. PMID:22172430

Interlaboratory comparison for the measurement of particle size and zeta potential of silica nanoparticles in an aqueous suspension

Science.gov (United States)

Lamberty, Andrée; Franks, Katrin; Braun, Adelina; Kestens, Vikram; Roebben, Gert; Linsinger, Thomas P. J.

2011-12-01

The Institute for Reference Materials and Measurements has organised an interlaboratory comparison (ILC) to allow the participating laboratories to demonstrate their proficiency in particle size and zeta potential measurements on monomodal aqueous suspensions of silica nanoparticles in the 10-100 nm size range. The main goal of this ILC was to identify competent collaborators for the production of certified nanoparticle reference materials. 38 laboratories from four different continents participated in the ILC with different methods for particle sizing and determination of zeta potential. Most of the laboratories submitted particle size results obtained with centrifugal liquid sedimentation (CLS), dynamic light scattering (DLS) or electron microscopy (EM), or zeta potential values obtained via electrophoretic light scattering (ELS). The results of the laboratories were evaluated using method-specific z scores, calculated on the basis of consensus values from the ILC. For CLS (13 results) and EM (13 results), all reported values were within the ±2 | z| interval. For DLS, 25 of the 27 results reported were within the ±2 | z| interval, the two other results were within the ±3 | z| interval. The standard deviations of the corresponding laboratory mean values varied between 3.7 and 6.5%, which demonstrates satisfactory interlaboratory comparability of CLS, DLS and EM particle size values. From the received test reports, a large discrepancy was observed in terms of the laboratory's quality assurance systems, which are equally important for the selection of collaborators in reference material certification projects. Only a minority of the participating laboratories is aware of all the items that are mandatory in test reports compliant to ISO/IEC 17025 (ISO General requirements for the competence of testing and calibration laboratories. International Organisation for Standardization, Geneva, 2005b). The absence of measurement uncertainty values in the reports, for

Clinical trials radiotherapy treatment plan review software : is this the first quantified assessment

International Nuclear Information System (INIS)

Hatton, J.A.; Cornes, D.A.

2011-01-01

Full text: Clinical trials require robust quality assurance (QA) procedures to ensure commonality of all treatments, with independent reviews to assess compliance with trial protocols. All clinical trials tools, including QA software, require testing for validity and reliability. enabling inter- and intra-trial comparison. Unlike clinical radiotherapy treatment planning (RTP) systems, review software has no published guidelines. This study describes the design and development of a test suite to quantify the performance of review software in TROG clinical trials. Test areas are image handling and reconstruction; geometric accuracy; dosimetric accuracy; dose-volume histogram (DVH) calculation; display of plan parameters. TROG have developed tests for commissioning plan review software, assessed with SWAN 2.3, and CMS Elekta FocalPro. While image handling tests were based on published guidelines for RTP systems, dosimetric tests used the TROG QA case review requirements. Treatment plans represented systems of all manufacturers (Pinnacle, Eclipse, Xio and Oncentra) used in Australasian centres. The test suite identified areas for SW A software development, including the DVH algorithm, changed to reduce calculation time. Results, in Fig. I, for known volumes of varying shapes and sizes, demonstrate differences between SWAN 2.1 and 2.3 when compared with Eclipse. Liaison with SWAN programmers enabled re-instatement of 2.1 algorithm. The test suite has quantified the RTP review software, prioritised areas for development with the programmers, and improved the user experience.

Variability in P-Glycoprotein Inhibitory Potency (IC50) Using Various in Vitro Experimental Systems: Implications for Universal Digoxin Drug- Drug Interaction Risk Assessment Decision Criterias

NARCIS (Netherlands)

Bentz, J.; O'Connor, M.P.; Bednarczyk, D.; Coleman, J.; Lee, C.; Palm, J.; Pak, Y.A.; Perloff, E.S.; Reyner, E.; Balimane, P.; Brännström, M.; Chu, X.; Funk, C.; Guo, A.; Hanna, I.; Herédi-Szabó, K.; Hillgren, K.; Li, L.; Hollnack-Pusch, E.; Jamei, M.; Lin, X.; Mason, A.K.; Neuhoff, S.; Patel, A.; Podila, L.; Plise, E.; Rajaraman, G.; Salphati, L.; Sands, E.; Taub, M.E.; Taur, J.-S.; Weitz, D.; Wortelboer, H.M.; Xia, C.Q.; Xiao, G.; Yabut, J.; Yamagata, T.; Zhang, L.; Ellens, H.

2013-01-01

A P-glycoprotein (P-gp) IC50 working group was established with 23 participating pharmaceutical and contract research laboratories and one academic institution to assess interlaboratory variability in P-gp IC 50 determinations. Each laboratory followed its in-house protocol to determine in vitro

Assessing and reporting heterogeneity in treatment effects in clinical trials: a proposal

Directory of Open Access Journals (Sweden)

Kent David M

2010-08-01

Full Text Available Abstract Mounting evidence suggests that there is frequently considerable variation in the risk of the outcome of interest in clinical trial populations. These differences in risk will often cause clinically important heterogeneity in treatment effects (HTE across the trial population, such that the balance between treatment risks and benefits may differ substantially between large identifiable patient subgroups; the "average" benefit observed in the summary result may even be non-representative of the treatment effect for a typical patient in the trial. Conventional subgroup analyses, which examine whether specific patient characteristics modify the effects of treatment, are usually unable to detect even large variations in treatment benefit (and harm across risk groups because they do not account for the fact that patients have multiple characteristics simultaneously that affect the likelihood of treatment benefit. Based upon recent evidence on optimal statistical approaches to assessing HTE, we propose a framework that prioritizes the analysis and reporting of multivariate risk-based HTE and suggests that other subgroup analyses should be explicitly labeled either as primary subgroup analyses (well-motivated by prior evidence and intended to produce clinically actionable results or secondary (exploratory subgroup analyses (performed to inform future research. A standardized and transparent approach to HTE assessment and reporting could substantially improve clinical trial utility and interpretability.

Interlaboratory study of the ion source memory effect in {sup 36}Cl accelerator mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Pavetich, Stefan, E-mail: s.pavetich@hzdr.de [Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstraße 400, 01314 Dresden (Germany); Akhmadaliev, Shavkat [Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstraße 400, 01314 Dresden (Germany); Arnold, Maurice; Aumaître, Georges; Bourlès, Didier [Aix-Marseille Université, CEREGE CNRS-IRD, F-13545 Aix-en-Provence (France); Buchriegler, Josef [Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstraße 400, 01314 Dresden (Germany); University of Vienna, Faculty of Physics, VERA Laboratory, Währingerstraße 17, 1090 Vienna (Austria); Golser, Robin [University of Vienna, Faculty of Physics, VERA Laboratory, Währingerstraße 17, 1090 Vienna (Austria); Keddadouche, Karim [Aix-Marseille Université, CEREGE CNRS-IRD, F-13545 Aix-en-Provence (France); Martschini, Martin [University of Vienna, Faculty of Physics, VERA Laboratory, Währingerstraße 17, 1090 Vienna (Austria); Merchel, Silke; Rugel, Georg [Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstraße 400, 01314 Dresden (Germany); Steier, Peter [University of Vienna, Faculty of Physics, VERA Laboratory, Währingerstraße 17, 1090 Vienna (Austria)

2014-06-01

Highlights: • Long-term memory effect in negative ion sources investigated for chlorine isotopes. • Interlaboratory comparison of four up-to date negative ion sources. • Ion source improvement at DREAMS for minimization of long-term memory effect. • Long-term memory effect is the limitation for precise AMS data of volatile elements. • Findings to be considered for samples with highly variable ratios of {sup 36}Cl/Cl and {sup 129}I/I. - Abstract: Understanding and minimization of contaminations in the ion source due to cross-contamination and long-term memory effect is one of the key issues for accurate accelerator mass spectrometry (AMS) measurements of volatile elements. The focus of this work is on the investigation of the long-term memory effect for the volatile element chlorine, and the minimization of this effect in the ion source of the Dresden accelerator mass spectrometry facility (DREAMS). For this purpose, one of the two original HVE ion sources at the DREAMS facility was modified, allowing the use of larger sample holders having individual target apertures. Additionally, a more open geometry was used to improve the vacuum level. To evaluate this improvement in comparison to other up-to-date ion sources, an interlaboratory comparison had been initiated. The long-term memory effect of the four Cs sputter ion sources at DREAMS (two sources: original and modified), ASTER (Accélérateur pour les Sciences de la Terre, Environnement, Risques) and VERA (Vienna Environmental Research Accelerator) had been investigated by measuring samples of natural {sup 35}Cl/{sup 37}Cl-ratio and samples highly-enriched in {sup 35}Cl ({sup 35}Cl/{sup 37}Cl ∼ 999). Besides investigating and comparing the individual levels of long-term memory, recovery time constants could be calculated. The tests show that all four sources suffer from long-term memory, but the modified DREAMS ion source showed the lowest level of contamination. The recovery times of the four ion

Variability in physical contamination assessment of source segregated biodegradable municipal waste derived composts.

Science.gov (United States)

Echavarri-Bravo, Virginia; Thygesen, Helene H; Aspray, Thomas J

2017-01-01

Physical contaminants (glass, metal, plastic and 'other') and stones were isolated and categorised from three finished commercial composts derived from source segregated biodegradable municipal waste (BMW). A subset of the identified physical contaminant fragments were subsequently reintroduced into the cleaned compost samples and sent to three commercial laboratories for testing in an inter-laboratory trial using the current PAS100:2011 method (AfOR MT PC&S). The trial showed that the 'other' category caused difficulty for all three laboratories with under reporting, particularly of the most common 'other' contaminants (paper and cardboard) and, over-reporting of non-man-made fragments. One laboratory underreported metal contaminant fragments (spiked as silver foil) in three samples. Glass, plastic and stones were variably underreported due to miss-classification or over reported due to contamination with compost (organic) fragments. The results are discussed in the context of global physical contaminant test methods and compost quality assurance schemes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Methodical principles of assessment of financial compensation for clinical trial volunteer participants

Directory of Open Access Journals (Sweden)

V. Ye. Dobrova

2013-10-01

participation in clinical trials by patients and healthy volunteers has been rationalized, whereas methods of calculating monetary compensation for such participation have been suggested. The two methods of calculating of the financial compensation were proposed: first - hourly compensation for the time which was spent on clinical trials, the second - hourly-bonus compensation for the possible discomfort and inconvenience of participation in clinical trials in accordance with the ethical rules for research involving people as objects of observation. Conclusion. Achievement of the organizational and financial constituent ensuring participation of volunteers in a clinical trial on the one hand should assure the appropriate experimental foundation for reliable research conducting and on other hand should focus attention on the fulfillment of mental and ethical rules for investigations involving human as a studied object. Basing on the results of an analysis and the survey performed which involved qualified experts regarding aspects affecting volunteers enrollment in a clinical trial, the scientifically substantiated system of the volunteers discomfort and inconvenience assessment in a clinical trial has been proposed, which includes criteria: study duration, adverse events/adverse reactions possibility, blood sampling during study, discomfort caused by study design, inconvenience to participate in a clinical trial. Two techniques for calculation of the financial compensation for healthy volunteers participation in a clinical trial have been proposed: the first one is the payment by the hour spent for participation in a study, and the second one is the hourly pay with bonus for possible discomfort caused by involvement in a clinical trial. In the further study authors plan to research the aspects of risk assessment associated with volunteers participation in a clinical trial and its considering as an additional constituent in the process of the calculation of financial incentives

[Inter-laboratory reproducibility of pulsed-field electrophoresis for the study of 12 types of Pseudomonas aeruginosa].

Science.gov (United States)

Foissaud, V; Puyhardy, J M; Chapalain, J C; Salord, H; Depina, J J; Morillon, M; Nicolas, P; Perrier-Gros-Claude, J D

1999-12-01

The increasing hospital-to-hospital transmission of multiple drug-resistant bacteria is a major concern for bacteriology laboratories involved in nosocomial infection control. The interlaboratory reproducibility of pulsed-field gel electrophoresis (PFGE) for Pseudomonas aeruginosa typing was evaluated by asking four hospital laboratories (two in Lyon, one in Brest, and one in Marseille) to study 11 P. aeruginosa isolates, some of which were epidemiologically related, and the reference strain ATCC 27853. Two laboratories used the Genepath system, one the Chef DR II, system, and one the Chef Mapper system, Bio-Rad, restriction/Spe I. Profiles were read visually and by computerized comparison of restriction band molecular weights (Taxotron, software, PAD Grimont, Pasteur Institute, Paris, France). These two methods led to similar epidemiological conclusions. However, centralization of the data showed poor center-to-center reproducibility due to inadequate standardization of the procedure.

Investigation of the Intra- and Interlaboratory Reproducibility of a Small Scale Standardized Supersaturation and Precipitation Method

DEFF Research Database (Denmark)

Plum, Jakob; Madsen, Cecilie M; Teleki, Alexandra

2017-01-01

order for the three model compounds using the SSPM (aprepitant > felodipine ≈ fenofibrate). The α-value is dependent on the experimental setup and can be used as a parameter to evaluate the uniformity of the data set. This study indicated that the SSPM was able to obtain the same rank order of the β...... compound available for absorption. However, due to the stochastic nature of nucleation, supersaturating drug delivery systems may lead to inter- and intrapersonal variability. The ability to define a feasible range with respect to the supersaturation level is a crucial factor for a successful formulation...... reproducibility study of felodipine was conducted, after which seven partners contributed with data for three model compounds; aprepitant, felodipine, and fenofibrate, to determine the interlaboratory reproducibility of the SSPM. The first part of the SSPM determines the apparent degrees of supersaturation (a...

Results of an interlaboratory method performance study for the size determination and quantification of silver nanoparticles in chicken meat by single-particle inductively coupled plasma mass spectrometry (sp-ICP-MS).

Science.gov (United States)

Weigel, Stefan; Peters, Ruud; Loeschner, Katrin; Grombe, Ringo; Linsinger, Thomas P J

2017-08-01

Single-particle inductively coupled plasma mass spectrometry (sp-ICP-MS) promises fast and selective determination of nanoparticle size and number concentrations. While several studies on practical applications have been published, data on formal, especially interlaboratory validation of sp-ICP-MS, is sparse. An international interlaboratory study was organized to determine repeatability and reproducibility of the determination of the median particle size and particle number concentration of Ag nanoparticles (AgNPs) in chicken meat. Ten laboratories from the European Union, the USA, and Canada determined particle size and particle number concentration of two chicken meat homogenates spiked with polyvinylpyrrolidone (PVP)-stabilized AgNPs. For the determination of the median particle diameter, repeatability standard deviations of 2 and 5% were determined, and reproducibility standard deviations were 15 and 25%, respectively. The equivalent median diameter itself was approximately 60% larger than the diameter of the particles in the spiking solution. Determination of the particle number concentration was significantly less precise, with repeatability standard deviations of 7 and 18% and reproducibility standard deviations of 70 and 90%.

Continuous Analytical Performances Monitoring at the On-Site Laboratory through Proficiency, Inter-Laboratory Testing and Inter-Comparison Analytical Methods

International Nuclear Information System (INIS)

Duhamel, G.; Decaillon, J.-G.; Dashdondog, S.; Kim, C.-K.; Toervenyi, A.; Hara, S.; Kato, S.; Kawaguchi, T.; Matsuzawa, K.

2015-01-01

Since 2008, as one measure to strengthen its quality management system, the On-Site Laboratory for nuclear safeguards at the Rokkasho Reprocessing Plant, has increased its participation in domestic and international proficiency and inter-laboratory testing for the purpose of determining analytical method accuracy, precision and robustness but also to support method development and improvement. This paper provides a description of the testing and its scheduling. It presents the way the testing was optimized to cover most of the analytical methods at the OSL. The paper presents the methodology used for the evaluation of the obtained results based on Analysis of variance (ANOVA). Results are discussed with respect to random, systematic and long term systematic error. (author)

An interlaboratory comparison of methods for measuring rock matrix porosity

International Nuclear Information System (INIS)

Rasilainen, K.; Hellmuth, K.H.; Kivekaes, L.; Ruskeeniemi, T.; Melamed, A.; Siitari-Kauppi, M.

1996-09-01

An interlaboratory comparison study was conducted for the available Finnish methods of rock matrix porosity measurements. The aim was first to compare different experimental methods for future applications, and second to obtain quality assured data for the needs of matrix diffusion modelling. Three different versions of water immersion techniques, a tracer elution method, a helium gas through-diffusion method, and a C-14-PMMA method were tested. All methods selected for this study were established experimental tools in the respective laboratories, and they had already been individually tested. Rock samples for the study were obtained from a homogeneous granitic drill core section from the natural analogue site at Palmottu. The drill core section was cut into slabs that were expected to be practically identical. The subsamples were then circulated between the different laboratories using a round robin approach. The circulation was possible because all methods were non-destructive, except the C-14-PMMA method, which was always the last method to be applied. The possible effect of drying temperature on the measured porosity was also preliminarily tested. These measurements were done in the order of increasing drying temperature. Based on the study, it can be concluded that all methods are comparable in their accuracy. The selection of methods for future applications can therefore be based on practical considerations. Drying temperature seemed to have very little effect on the measured porosity, but a more detailed study is needed for definite conclusions. (author) (4 refs.)

Trial to assess the utility of genetic sequencing to improve patient outcomes

Science.gov (United States)

A pilot trial to assess whether assigning treatment based on specific gene mutations can provide benefit to patients with metastatic solid tumors is being launched this month by the NCI. The Molecular Profiling based Assignment of Cancer Therapeutics, or

Interlaboratory comparison of environmental relevant nuclides with spinach powder as sample medium; Vergleichspruefung mit Spinatpulver als Probenart fuer umweltrelevante Nuklide

Energy Technology Data Exchange (ETDEWEB)

Roos, N.; Tait, D. [Max Rubner-Institut, Kiel (Germany). Leitstelle fuer Boden, Bewuchs, Futtermittel und Nahrungsmittel pflanzlicher und tierischer Herkunft

2014-01-20

Spinach is cited as a representative medium for leafy vegetables in the Integrated Measurement and Information System for the surveillance of environmental radioactivity (IMIS) in Germany. Fresh spinach, however, is not suitable in interlaboratory comparisons on the determination of spiked radionuclides because of the difficulties in homogeneously distributing the radionuclides and attaining a known specific activity in the samples. In contrast, spinach powder is finely milled, so that homogeneous distribution and known specific activities of the nuclides are more readily achievable. For this interlaboratory comparison spinach powder was mixed with the pure beta emitter Sr-90 and the gamma-emitting nuclides I-131, Cs-134 and Cs-137. After homogenization samples were dispatched to 77 laboratories from Germany and other European countries (59 in Germany, 5 in Switzerland, 4 each in the UK and Austria, and one each in France, Italy, the Netherlands, Ireland and Luxembourg). In addition to the added nuclides participants had to determine the natural radionuclide K-40. The participants were instructed to use a fast method for the determination of dry matter (DM). To check the homogeneity of the nuclide distribution 14 samples of the labeled spinach powder were randomly selected and analyzed in the Coordinating Laboratory for the Surveillance of Radioactivity in the Environment of the Max Rubner-Institute (MRI). According to DIN 13528:2005 the samples showed sufficient homogeneity of the added nuclides. For the evaluation of the interlaboratory comparison the Physikalisch-Technische Bundesanstalt (PTB) determined reference values for the the specific activities (Bq per kg DM) of the gamma emitters. The values with the expanded uncertainties (k = 2) were as follows: I-131: 181 ± 6 Bq/kg; Cs-134: 34.4 ± 1.1 Bq/kg; Cs-137: 11.1 ± 0.4 Bq/kg; K-40: 1240 ± 40 Bq/kg. Since a reference value of the PTB for the specific activity of Sr-90 was not available the general average

76 FR 56731 - Oral Rabies Vaccine Trial; Availability of an Environmental Assessment and Finding of No...

Science.gov (United States)

2011-09-14

...] Oral Rabies Vaccine Trial; Availability of an Environmental Assessment and Finding of No Significant... the Animal and Plant Health Inspection Service relative to an oral rabies vaccination field trial in... INFORMATION CONTACT: Dr. Dennis Slate, Rabies Program Coordinator, Wildlife Services, APHIS, 59 Chennell Drive...

The third international interlaboratory study on brominated flame retardants

Energy Technology Data Exchange (ETDEWEB)

Boer, J. de [Netherlands Institute for Fisheries Research, IJmuiden (Netherlands); Wells, D. [FRS Marine Laboratory, Aberdeen (United Kingdom)

2004-09-15

Polybrominated diphenyl ethers (PBDEs) have been produced as brominated flame retardants (BFRs) since the early 1970s and have been found in the aquatic environment since the late 1970s. However, as a result of their detection in sperm whales from deeper Atlantic waters and in human milk, many laboratories are now measuring PBDEs in environmental samples. A first international interlaboratory study (ILS) on the analysis of PBDEs, organised by the Bromine Science and Environmental Forum (BSEF), Brussels, Belgium, in collaboration with the Netherlands Institute for Fisheries Research (RIVO) was conducted in 1999-2000. The results showed that the 18 participating laboratories produced comparable results for BDE 47 in various matrices but had analytical difficulties for other BDEs, in particular for the BDEs 99 and 209. A second study was organised in 2001-2002 by BSEF, QUASIMEME and RIVO. That study showed improvement in comparability of the participating laboratories for BDE99 and some other BDEs. However, there was no improvement for BDE209. Hexabromocyclododecane (HBCD), tetrabromobisphenol-A (TBBP-A) and the dimethyl derivative of TBBP-A (dimethyl TBBP-A) were included in the second study. However, it appeared that only two or three laboratories were able to analyse these determinands. Others laboratories were still in the development phase with their methods for these BFRs. This third study was organised as a development exercise by QUASIMEME, in collaboration with RIVO between September and December 2003. The BFRs selected were the same as in the second study. Two biota test materials, a harbor sediment, a sewage sludge, and two standard solutions were dispatched to the participants.

Comparison of the effectiveness of various procedures for the rejection of outlying results and assigning consensus values in interlaboratory programs involving determination of trace elements or radionuclides

International Nuclear Information System (INIS)

Dybczynski, R.

1980-01-01

Rejection of outlying results is usually necessary in the evaluation of interlaboratory comparisons, especially those involving trace elements and low-level activity measurements. The performance of several criteria (Dixon's test, Grubbs' test, coefficient of skewness test, and coefficient of kurtosis test) is described; authentic data sets from intercomparison runs on trace element or radionuclide determinations in spiked samples are used. The existence of 'masking effects' in certain cases is demonstrated. It is shown that concurrent use of all four criteria at small (0.01) or moderate (0.05) significance levels gives better results than the use of any single test. The use of all four criteria at α = 0.05 followed by calculation of overall mean and pertinent confidence limits is suggested as a general method of data handling in interlaboratory comparison. This method normally ensures good selectivity of outlier rejection while avoiding excessive rejections, and results in generally good agreement between the 'true' value and the final overall mean. The use of this approach for the establishment of recommended values in candidate reference materials is demonstrated and its advantages and limitations are discussed. The results are further compared with those obtained by other methods of data evaluation (Student's test, dominant cluster mode and gamma transformation). (Auth.)

Assessing validity of observational intervention studies - the Benchmarking Controlled Trials.

Science.gov (United States)

Malmivaara, Antti

2016-09-01

Benchmarking Controlled Trial (BCT) is a concept which covers all observational studies aiming to assess impact of interventions or health care system features to patients and populations. To create and pilot test a checklist for appraising methodological validity of a BCT. The checklist was created by extracting the most essential elements from the comprehensive set of criteria in the previous paper on BCTs. Also checklists and scientific papers on observational studies and respective systematic reviews were utilized. Ten BCTs published in the Lancet and in the New England Journal of Medicine were used to assess feasibility of the created checklist. The appraised studies seem to have several methodological limitations, some of which could be avoided in planning, conducting and reporting phases of the studies. The checklist can be used for planning, conducting, reporting, reviewing, and critical reading of observational intervention studies. However, the piloted checklist should be validated in further studies. Key messages Benchmarking Controlled Trial (BCT) is a concept which covers all observational studies aiming to assess impact of interventions or health care system features to patients and populations. This paper presents a checklist for appraising methodological validity of BCTs and pilot-tests the checklist with ten BCTs published in leading medical journals. The appraised studies seem to have several methodological limitations, some of which could be avoided in planning, conducting and reporting phases of the studies. The checklist can be used for planning, conducting, reporting, reviewing, and critical reading of observational intervention studies.

Clinical trial transparency update: an assessment of the disclosure of results of company-sponsored trials associated with new medicines approved in Europe in 2014.

Science.gov (United States)

Deane, Bryan R; Porkess, Sheuli

2018-07-01

The objective of this study was to assess the timely disclosure of results of company-sponsored clinical trials related to all new medicines approved by the European Medicines Agency (EMA) during 2014. This is the final extension of three previously reported studies of trials related to all new medicines approved in Europe in 2009, 2010 and 2011, and in 2012 and 2013. The original study found that over a three-year period over three-quarters of all trials were disclosed within 12 months and almost 90% were disclosed by the end of the study (31 January 2013). The extension studies (2012 and 2013 approvals) both showed an improvement in results disclosure within 12 months to 90%, and an overall disclosure rate of 92% and 93% respectively by the end of the studies. The methodology used was exactly as previously reported. Various publicly available information sources were searched for both clinical trial registration and disclosure of results. All completed company-sponsored trials related to each new medicine approved for marketing by the EMA in 2014, carried out in patients and recorded on a clinical trials registry and/or included in an EMA European Public Assessment Report (EPAR), were included. Information sources were searched between 1 May and 31 July 2016. The main outcome measure was the proportion of trials for which results had been disclosed on a registry or in the scientific literature either within 12 months of the later of either first regulatory approval or trial completion, or by 31 July 2016 (end of survey). Of the completed trials associated with 32 new medicines licensed to 22 different companies in 2014, results of 93% (505/542) had been disclosed within 12 months, and results of 96% (518/542) had been disclosed by 31 July 2016. The disclosure rate within 12 months of 93% suggests that industry is continuing to achieve disclosure in a timely manner. The overall disclosure rate at study end of 96% indicates that the improvement in transparency

Use of HOMA-IR to diagnose non-alcoholic fatty liver disease: a population-based and inter-laboratory study.

Science.gov (United States)

Isokuortti, Elina; Zhou, You; Peltonen, Markku; Bugianesi, Elisabetta; Clement, Karine; Bonnefont-Rousselot, Dominique; Lacorte, Jean-Marc; Gastaldelli, Amalia; Schuppan, Detlef; Schattenberg, Jörn M; Hakkarainen, Antti; Lundbom, Nina; Jousilahti, Pekka; Männistö, Satu; Keinänen-Kiukaanniemi, Sirkka; Saltevo, Juha; Anstee, Quentin M; Yki-Järvinen, Hannele

2017-10-01

Recent European guidelines for non-alcoholic fatty liver disease (NAFLD) call for reference values for HOMA-IR. In this study, we aimed to determine: (1) the upper limit of normal HOMA-IR in two population-based cohorts; (2) the HOMA-IR corresponding to NAFLD; (3) the effect of sex and PNPLA3 genotype at rs738409 on HOMA-IR; and (4) inter-laboratory variations in HOMA-IR. We identified healthy individuals in two population-based cohorts (FINRISK 2007 [n = 5024] and the Programme for Prevention of Type 2 Diabetes in Finland [FIN-D2D; n = 2849]) to define the upper 95th percentile of HOMA-IR. Non-obese individuals with normal fasting glucose levels, no excessive alcohol use, no known diseases and no use of any drugs were considered healthy. The optimal HOMA-IR cut-off for NAFLD (liver fat ≥5.56%, based on the Dallas Heart Study) was determined in 368 non-diabetic individuals (35% with NAFLD), whose liver fat was measured using proton magnetic resonance spectroscopy ( 1 H-MRS). Samples from ten individuals were simultaneously analysed for HOMA-IR in seven European laboratories. The upper 95th percentiles of HOMA-IR were 1.9 and 2.0 in healthy individuals in the FINRISK (n = 1167) and FIN-D2D (n = 459) cohorts. Sex or PNPLA3 genotype did not influence these values. The optimal HOMA-IR cut-off for NAFLD was 1.9 (sensitivity 87%, specificity 79%). A HOMA-IR of 2.0 corresponded to normal liver fat (HOMA-IR measured in Helsinki corresponded to 1.3, 1.6, 1.8, 1.8, 2.0 and 2.1 in six other laboratories. The inter-laboratory CV% of HOMA-IR was 25% due to inter-assay variation in insulin (25%) rather than glucose (5%) measurements. The upper limit of HOMA-IR in population-based cohorts closely corresponds to that of normal liver fat. Standardisation of insulin assays would be the first step towards definition of normal values for HOMA-IR.

Pressure ulcers: effectiveness of risk-assessment tools. A randomised controlled trial (the ULCER trial).

Science.gov (United States)

Webster, Joan; Coleman, Kerrie; Mudge, Alison; Marquart, Louise; Gardner, Glenn; Stankiewicz, Monica; Kirby, Julie; Vellacott, Catherine; Horton-Breshears, Margaret; McClymont, Alice

2011-04-01

To evaluate the effectiveness of two pressure-ulcer screening tools against clinical judgement in preventing pressure ulcers. A single blind randomised controlled trial. A large metropolitan tertiary hospital. 1231 patients admitted to internal medicine or oncology wards. Patients were excluded if their hospital stay was expected to be 2 days or less. Participants allocated to either a Waterlow (n=410) or Ramstadius (n=411) screening tool group or to a clinical judgement group (n=410) where no formal risk screening instrument was used. Incidence of hospital acquired pressure ulcers ascertained by regular direct observation. Use of any devices for the prevention of pressure ulcers, documentation of a pressure plan and any dietetic or specialist skin integrity review were recorded. On admission, 71 (5.8%) patients had an existing pressure ulcer. The incidence of hospital-acquired pressure ulcers was similar between groups (clinical judgement 28/410 (6.8%); Waterlow 31/411 (7.5%); Ramstadius 22/410 (5.4%), p=0.44). Significant associations with pressure injury in regression modelling included requiring a dietetic referral, being admitted from a location other than home and age over 65 years. The authors found no evidence to show that two common pressure-ulcer risk-assessment tools are superior to clinical judgement to prevent pressure injury. Resources associated with use of these tools might be better spent on careful daily skin inspection and improving management targetted at specific risks. The trial was registered with the Australian and New Zealand Clinicat Trials Registry (ACTRN 12608000541303).

Collaborative ring trial of the papaya endogenous reference gene and its polymerase chain reaction assays for genetically modified organism analysis.

Science.gov (United States)

Wei, Jiaojun; Li, Feiwu; Guo, Jinchao; Li, Xiang; Xu, Junfeng; Wu, Gang; Zhang, Dabing; Yang, Litao

2013-11-27

The papaya (Carica papaya L.) Chymopapain (CHY) gene has been reported as a suitable endogenous reference gene for genetically modified (GM) papaya detection in previous studies. Herein, we further validated the use of the CHY gene and its qualitative and quantitative polymerase chain reaction (PCR) assays through an interlaboratory collaborative ring trial. A total of 12 laboratories working on detection of genetically modified organisms participated in the ring trial and returned test results. Statistical analysis of the returned results confirmed the species specificity, low heterogeneity, and single-copy number of the CHY gene among different papaya varieties. The limit of detection of the CHY qualitative PCR assay was 0.1%, while the limit of quantification of the quantitative PCR assay was ∼25 copies of haploid papaya genome with acceptable PCR efficiency and linearity. The differences between the tested and true values of papaya content in 10 blind samples ranged from 0.84 to 6.58%. These results indicated that the CHY gene was suitable as an endogenous reference gene for the identification and quantification of GM papaya.

Designing clinical trials to assess antiepileptic drugs as monotherapy : difficulties and solutions.

Science.gov (United States)

Perucca, Emilio

2008-01-01

Designing monotherapy trials in epilepsy is fraught with many hurdles, including diagnostic and classification difficulties, sparse information regarding the natural history of the disorder, and ethical objections to the use of placebo or a suboptimal comparator in a condition where the consequences of therapeutic failure can be serious. These issues are further complicated by regulatory differences between the US and the EU.In the US, the FDA considers that evidence of efficacy requires demonstration of superiority to a comparator. Because available antiepileptic drugs possess relatively high efficacy, in most settings it is unrealistic to expect that a new treatment will be superior to a standard treatment used at optimized dosages. To circumvent this problem, trial designs have been developed whereby patients in the control group are assigned to receive a suboptimal comparator and are required to exit from the trial if seizure deterioration occurs. This allows demonstration of a between-group difference in efficacy endpoints, such as time to exit or time to first seizure. Although these trials have come under increasing criticism because of ethical concerns, extensive information is now available on the outcome of patients with chronic epilepsy randomized to suboptimal treatment in similarly designed conversion to monotherapy trials. This has allowed the construction of a dataset of historical controls against which response to a fully active treatment can be compared. A number of studies using this novel approach are now in progress.In the EU, in addition to requiring data on conversion to monotherapy in refractory patients, the European Medicines Agency stipulates that a monotherapy indication in newly diagnosed epilepsy can only be granted if a candidate drug has shown at least a similar benefit/risk balance compared with an acknowledged standard at its optimal use during an assessment period of no less than 1 year. This has led to the implementation of

Multicenter evaluation of molecular and culture-dependent diagnostics for Shigella species and Entero-invasive Escherichia coli in the Netherlands

NARCIS (Netherlands)

van den Beld, Maaike J. C.; Friedrich, Alexander W.; van Zanten, Evert; Reubsaet, Frans A. G.; Kooistra-Smid, Mirjam A. M. D.; Rossen, John W. A.

2016-01-01

An inter-laboratory collaborative trial for the evaluation of diagnostics for detection and identification of Shigella species and Entero-invasive Escherichia coil (EIEC) was performed. Sixteen Medical Microbiological Laboratories (MMLs) participated. MMLs were interviewed about their diagnostic

A quality assessment of randomized controlled trial reports in endodontics.

Science.gov (United States)

Lucena, C; Souza, E M; Voinea, G C; Pulgar, R; Valderrama, M J; De-Deus, G

2017-03-01

To assess the quality of the randomized clinical trial (RCT) reports published in Endodontics between 1997 and 2012. Retrieval of RCTs in Endodontics was based on a search of the Thomson Reuters Web of Science (WoS) database (March 2013). Quality evaluation was performed using a checklist based on the Jadad criteria, CONSORT (Consolidated Standards of Reporting Trials) statement and SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials). Descriptive statistics were used for frequency distribution of data. Student's t-test and Welch test were used to identify the influence of certain trial characteristics upon report quality (α = 0.05). A total of 89 RCTs were evaluated, and several methodological flaws were found: only 45% had random sequence generation at low risk of bias, 75% did not provide information on allocation concealment, and 19% were nonblinded designs. Regarding statistics, only 55% of the RCTs performed adequate sample size estimations, only 16% presented confidence intervals, and 25% did not provide the exact P-value. Also, 2% of the articles used no statistical tests, and in 87% of the RCTs, the information provided was insufficient to determine whether the statistical methodology applied was appropriate or not. Significantly higher scores were observed for multicentre trials (P = 0.023), RCTs signed by more than 5 authors (P = 0.03), articles belonging to journals ranked above the JCR median (P = 0.03), and articles complying with the CONSORT guidelines (P = 0.000). The quality of RCT reports in key areas for internal validity of the study was poor. Several measures, such as compliance with the CONSORT guidelines, are important in order to raise the quality of RCTs in Endodontics. © 2016 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Assessing the treatment effect in a randomized controlled trial with extensive non-adherence: the EVOLVE trial.

Science.gov (United States)

Kubo, Yumi; Sterling, Lulu Ren; Parfrey, Patrick S; Gill, Karminder; Mahaffey, Kenneth W; Gioni, Ioanna; Trotman, Marie-Louise; Dehmel, Bastian; Chertow, Glenn M

2015-01-01

Intention-to-treat (ITT) analysis is widely used to establish efficacy in randomized clinical trials. However, in a long-term outcomes study where non-adherence to study drug is substantial, the on-treatment effect of the study drug may be underestimated using the ITT analysis. The analyses presented herein are from the EVOLVE trial, a double-blind, placebo-controlled, event-driven cardiovascular outcomes study conducted to assess whether a treatment regimen including cinacalcet compared with placebo in addition to other conventional therapies reduces the risk of mortality and major cardiovascular events in patients receiving hemodialysis with secondary hyperparathyroidism. Pre-specified sensitivity analyses were performed to assess the impact of non-adherence on the estimated effect of cinacalcet. These analyses included lag-censoring, inverse probability of censoring weights (IPCW), rank preserving structural failure time model (RPSFTM) and iterative parameter estimation (IPE). The relative hazard (cinacalcet versus placebo) of mortality and major cardiovascular events was 0.93 (95% confidence interval 0.85, 1.02) using the ITT analysis; 0.85 (0.76, 0.95) using lag-censoring analysis; 0.81 (0.70, 0.92) using IPCW; 0.85 (0.66, 1.04) using RPSFTM and 0.85 (0.75, 0.96) using IPE. These analyses, while not providing definitive evidence, suggest that the intervention may have an effect while subjects are receiving treatment. The ITT method remains the established method to evaluate efficacy of a new treatment; however, additional analyses should be considered to assess the on-treatment effect when substantial non-adherence to study drug is expected or observed. Copyright © 2015 John Wiley & Sons, Ltd.

Beyond the checklist: assessing understanding for HIV vaccine trial participation in South Africa.

Science.gov (United States)

Lindegger, Graham; Milford, Cecilia; Slack, Catherine; Quayle, Michael; Xaba, Xolani; Vardas, Eftyhia

2006-12-15

Informed consent and understanding are essential ethical requirements for clinical trial participation. Traditional binary measures of understanding may be limited and not be the best measures of level of understanding. This study designed and compared 4 measures of understanding for potential participants being prepared for enrollment in South African HIV vaccine trials, using detailed operational scoring criteria. Assessment of understanding of 7 key trial components was compared via self-report, checklist, vignettes, and narrative measures. Fifty-nine participants, including members of vaccine preparedness groups and 1 HIV vaccine trial, took part. There were significant differences across the measures for understanding of 5 components and for overall understanding. Highest scores were obtained on self-report and checklist measures, and lowest scores were obtained for vignettes and narrative descriptions. The findings suggest that levels of measured understanding are dependent on the tools used. Forced-choice measures like checklists tend to yield higher scores than open-ended measures like narratives or vignettes. Consideration should be given to complementing checklists and self-reports with open-ended measures, particularly for critical trial concepts, where the consequences of misunderstanding are potentially severe.

An interlaboratory comparison programme on radio frequency electromagnetic field measurements: the second round of the scheme

International Nuclear Information System (INIS)

Nicolopoulou, E.P.; Ztoupis, I.N.; Gonos, I.F.; Stathopulos, I.A.; Karabetsos, E.

2015-01-01

The second round of an interlaboratory comparison scheme on radio frequency electromagnetic field measurements has been conducted in order to evaluate the overall performance of laboratories that perform measurements in the vicinity of mobile phone base stations and broadcast antenna facilities. The participants recorded the electric field strength produced by two high frequency signal generators inside an anechoic chamber in three measurement scenarios with the antennas transmitting each time different signals at the FM, VHF, UHF and GSM frequency bands. In each measurement scenario, the participants also used their measurements in order to calculate the relative exposure ratios. The results were evaluated in each test level calculating performance statistics (z-scores and E n numbers). Subsequently, possible sources of errors for each participating laboratory were discussed, and the overall evaluation of their performances was determined by using an aggregated performance statistic. A comparison between the two rounds proves the necessity of the scheme. (authors)

Assessment of Sexual Desire for Clinical Trials of Women With Hypoactive Sexual Desire Disorder: Measures, Desire-Related Behavior, and Assessment of Clinical Significance.

Science.gov (United States)

Pyke, Robert E; Clayton, Anita H

2018-01-19

The Female Sexual Function Index-desire subscale is the standard measure for clinical trials of hypoactive sexual desire disorder (HSDD), but lacks items assessing sexually related behaviors and attitudes toward partner. Counting satisfying sexual events is criticized, but sexual behavior remains important. Mean treatment differences cannot define clinical significance; responder and remitter analyses help. We reviewed measures on sexual desire and sexual behavior relevant to HSDD, and how to assess clinical significance. We conducted a literature review of measures of sexual desire comparing expert-proposed criteria for dysfunctional desire, expert-developed scales, and scales from patient input. Commonly recognized symptoms of HSDD were identified. Results of HSDD trials and scale validation studies were evaluated to extract responder and remitter values. The utility of distribution-based measures of responders and remitters was assessed. Symptom relevance was evaluated as the proportion of symptom sets that included the item; responder and remitter cut points were determined by distribution-based methods. 12 Validated rating scales, 5 scales primarily derived from expert recommendations and 7 scales initially from patient input, and 5 sets of diagnostic criteria for conditions like HSDD were compared. Content varied highly between scales despite compliance with U.S. Food and Drug Administration recommendations for patient-reported outcomes. This disunity favors an expert-recommended scale such as the Elements of Desire Questionnaire with each of the common items, plus a measure of frequency of sexual activity, eg, item in the Patient Reported Outcomes Measurement Information System. Registrational drug trials, but not psychological treatment trials, usually give responder/remitter analyses, using dichotomized global impressions or anchor-based definitions. Distribution-based methods are more uniformly applicable to define responder and remitter status. The

Inter-laboratory and inter-assay comparison on two real-time PCR techniques for quantification of PCV2 nucleic acid extracted from field samples

DEFF Research Database (Denmark)

Hjulsager, Charlotte Kristiane; Grau-Roma, L.; Sibila, M.

2009-01-01

Several real-time PCR assays for quantification of PCV2 DNA (qPCR) have been described in the literature. and different in-house assays are being used by laboratories around the world. A general threshold of it copies of PCV2 per millilitre serum for postweaning multisystemic wasting syndrome (PMWS......) diagnosis has been suggested. However, neither inter-laboratory nor inter-assay comparisons have been published so far. In the present study two different qPCR probe assays Used routinely in two laboratories were compared on DNA extracted From serum, nasal and rectal swabs. Results showed a significant...

Methods of blinding in reports of randomized controlled trials assessing pharmacologic treatments: a systematic review.

Directory of Open Access Journals (Sweden)

Isabelle Boutron

2006-10-01

Full Text Available BACKGROUND: Blinding is a cornerstone of therapeutic evaluation because lack of blinding can bias treatment effect estimates. An inventory of the blinding methods would help trialists conduct high-quality clinical trials and readers appraise the quality of results of published trials. We aimed to systematically classify and describe methods to establish and maintain blinding of patients and health care providers and methods to obtain blinding of outcome assessors in randomized controlled trials of pharmacologic treatments. METHODS AND FINDINGS: We undertook a systematic review of all reports of randomized controlled trials assessing pharmacologic treatments with blinding published in 2004 in high impact-factor journals from Medline and the Cochrane Methodology Register. We used a standardized data collection form to extract data. The blinding methods were classified according to whether they primarily (1 established blinding of patients or health care providers, (2 maintained the blinding of patients or health care providers, and (3 obtained blinding of assessors of the main outcomes. We identified 819 articles, with 472 (58% describing the method of blinding. Methods to establish blinding of patients and/or health care providers concerned mainly treatments provided in identical form, specific methods to mask some characteristics of the treatments (e.g., added flavor or opaque coverage, or use of double dummy procedures or simulation of an injection. Methods to avoid unblinding of patients and/or health care providers involved use of active placebo, centralized assessment of side effects, patients informed only in part about the potential side effects of each treatment, centralized adapted dosage, or provision of sham results of complementary investigations. The methods reported for blinding outcome assessors mainly relied on a centralized assessment of complementary investigations, clinical examination (i.e., use of video, audiotape, or

Cardiovascular risk assessment in the treatment of nonalcoholic steatohepatitis: a secondary analysis of the MOZART trial.

Science.gov (United States)

Lin, Steven C; Ang, Brandon; Hernandez, Carolyn; Bettencourt, Ricki; Jain, Rashmi; Salotti, Joanie; Richards, Lisa; Kono, Yuko; Bhatt, Archana; Aryafar, Hamed; Lin, Grace Y; Valasek, Mark A; Sirlin, Claude B; Brouha, Sharon; Loomba, Rohit

2016-03-01

Nonalcoholic steatohepatitis (NASH) is associated with increased cardiovascular risk and mortality. No US Food and Drug Administration (FDA) approved therapies for NASH are available; clinical trials to date have not yet systematically assessed for changes in cardiovascular risk. This study examines the prospective utility of cardiovascular risk assessments, the Framingham risk score (FRS) and coronary artery calcium (CAC) score, as endpoints in a NASH randomized clinical trial, and assesses whether histologic improvements lead to lower cardiovascular risk. Secondary analysis of a 24-week randomized, double-blind, placebo-controlled trial (MOZART) in which 50 biopsy-proven NASH patients received oral ezetimibe 10 mg daily (n = 25) versus placebo (n = 25). Biochemical profiling, FRS, CAC scores, liver biopsies were obtained at baseline and endpoint. Ezetimibe improved FRS whereas placebo did not (4.4 ± 6.2 to 2.9 ± 4.8, p = 0.038; 3.0 ± 4.4 to 2.9 ± 4.2, p = 0.794). CAC scores did not change with ezetimibe or placebo (180.4 ± 577.2 to 194.1 ± 623.9, p = 0.293; 151.4 ± 448.9 to 183.3 ± 555.7, p = 0.256). Ezetimibe improved FRS and CAC scores in more patients than placebo (48% versus 23%, p = 0.079, and 21% versus 0%, p = 0.090, respectively), though not significantly. No differences were noted in cardiovascular risk scores among histologic responders versus nonresponders. Ezetimibe improved FRS whereas placebo did not. FRS and CAC scores improved in a greater proportion of patients with ezetimibe; this trend did not reach significance. These findings indicate the utility and feasibility of monitoring cardiovascular risk in a NASH trial. The utility of CAC scores may be higher in trials of longer duration (⩾52 weeks) and with older patients (age ⩾45). ClinicalTrials.gov registration: NCT01766713.

Randomized trial of two swallowing assessment approaches in patients with acquired brain injury

DEFF Research Database (Denmark)

Kjaersgaard, Annette; Nielsen, Lars Hedemann; Sjölund, Bengt H.

2014-01-01

trial. SETTING: Specialized, national neurorehabilitation centre. SUBJECTS: Adult patients with acquired brain injury. Six hundred and seventy-nine patients were assessed for eligibility and 138 were randomly allocated between June 2009 and April 2011. INTERVENTIONS: Assessment by Facial-Oral Tract....... Seven patients were left for analysis, 4 of whom developed aspiration pneumonia within 10 days after initiating oral intake (1 control/3 interventions). CONCLUSION: In the presence of a structured clinical assessment with the Facial-Oral Tract Therapy approach, it is unnecessary to undertake...

Quantity and quality assessment of randomized controlled trials on orthodontic practice in PubMed.

Science.gov (United States)

Shimada, Tatsuo; Takayama, Hisako; Nakamura, Yoshiki

2010-07-01

To find current high-quality evidence for orthodontic practice within a reasonable time, we tested the performance of a PubMed search. PubMed was searched using publication type randomized controlled trial and medical subject heading term "orthodontics" for articles published between 2003 and 2007. The PubMed search results were compared with those from a hand search of four orthodontic journals to determine the sensitivity of PubMed search. We evaluated the precision of the PubMed search result and assessed the quality of individual randomized controlled trials using the Jadad scale. Sensitivity and precision were 97.46% and 58.12%, respectively. In PubMed, of the 277 articles retrieved, 161 (58.12%) were randomized controlled trials on orthodontic practice, and 115 of the 161 articles (71.42%) were published in four orthodontic journals: American Journal of Orthodontics and Dentofacial Orthopedics, The Angle Orthodontist, the European Journal of Orthodontics, and the Journal of Orthodontics. Assessment by the Jadad scale revealed 60 high-quality randomized controlled trials on orthodontic practice, of which 45 (75%) were published in these four journals. PubMed is a highly desirable search engine for evidence-based orthodontic practice. To stay current and get high-quality evidence, it is reasonable to look through four orthodontic journals: American Journal of Orthodontics and Dentofacial Orthopedics, The Angle Orthodontist, the European Journal of Orthodontics, and the Journal of Orthodontics.

Interlaboratory comparison of the determination of 137Cs and 90Sr in water, food and soil: preparation and characterization of test materials

International Nuclear Information System (INIS)

Fuks, L.; Polkowska-Motrenko, H.

2006-01-01

Only reliable analytical results can serve as a basis of meaningful evaluation and protection of the environment against radioactive contaminants. So, laboratories dealing with the environmental radioactivity determinations should regularly demonstrate their ability to produce acceptable results. Since 2002, every two years organization of national interlaboratory comparisons (ILC) on the determination of different radionuclides in food and environmental samples is required by the Polish law. The aim of the paper is presentation how test materials applied in the Institute of Nuclear Chemistry and Technology (INCT, Warsaw, Poland) for the 2004 ILC on the determination of 137 Cs and 90 Sr in water, food and soil were prepared. (author)

Inter-laboratory validation of an inexpensive streamlined method to measure inorganic arsenic in rice grain.

Science.gov (United States)

Chaney, Rufus L; Green, Carrie E; Lehotay, Steven J

2018-05-04

With the establishment by CODEX of a 200 ng/g limit of inorganic arsenic (iAs) in polished rice grain, more analyses of iAs will be necessary to ensure compliance in regulatory and trade applications, to assess quality control in commercial rice production, and to conduct research involving iAs in rice crops. Although analytical methods using high-performance liquid chromatography-inductively coupled plasma-mass spectrometry (HPLC-ICP-MS) have been demonstrated for full speciation of As, this expensive and time-consuming approach is excessive when regulations are based only on iAs. We report a streamlined sample preparation and analysis of iAs in powdered rice based on heated extraction with 0.28 M HNO 3 followed by hydride generation (HG) under control of acidity and other simple conditions. Analysis of iAs is then conducted using flow-injection HG and inexpensive ICP-atomic emission spectroscopy (AES) or other detection means. A key innovation compared with previous methods was to increase the acidity of the reagent solution with 4 M HCl (prior to reduction of As 5+ to As 3+ ), which minimized interferences from dimethylarsinic acid. An inter-laboratory method validation was conducted among 12 laboratories worldwide in the analysis of six shared blind duplicates and a NIST Standard Reference Material involving different types of rice and iAs levels. Also, four laboratories used the standard HPLC-ICP-MS method to analyze the samples. The results between the methods were not significantly different, and the Horwitz ratio averaged 0.52 for the new method, which meets official method validation criteria. Thus, the simpler, more versatile, and less expensive method may be used by laboratories for several purposes to accurately determine iAs in rice grain. Graphical abstract Comparison of iAs results from new and FDA methods.

Evaluation of an interlaboratory comparison of the chemical assay of U, Th, oxide coated particles

International Nuclear Information System (INIS)

Tamberg, T.; Thiele, D.; Brodda, B.G.

1981-09-01

The prototype reactor THTR in Schmehausen (Germany, F.R.) burns a (Th,U)O 2 nuclear fuel using 93% enriched uranium. This material is particularly Safeguards sensitive. It was therefore desirable for the Safeguards Analytical Laboratory (SAL) and other laboratories of the Agency Network to collect experience and test their performance in the analysis of such materials. Support was requested from the ''Joint Programme between the IAEA and the Federal Republic of Germany for the Development of Safeguards Techniques'' to perform, as a first step, an interlaboratory comparison of the chemical assay of U and Th in pyrocarbon-coated BISO-type fuel particles. Such an intercomparison was organized under the auspices of the Institut fuer Chemische Technologie (ICT) of the Kernforschungsanlage Juelich GmbH (KFA). SAL prepared a statistical evaluation of the results which was discussed in Vienna in June 1980. The objective of the project was to define the state of the art in the chemical assay of U-Th fuels and the analytical requirements for the sampling of materials of major interest to Agency Safeguards at present

Experience of an inter-laboratory exercise for the determination of Carbon-14 in biological samples

International Nuclear Information System (INIS)

Baburajan, A.; Rajaram, S.; D'Souza, Renita Shiny; Nayak, Rasmi; Karunakara, N.; Ravi, P.M.; Tripathi, R.M.

2018-01-01

Carbon-14 is one of the naturally occurring cosmogenic nuclide with long half life of 5730 y and beta energy, E max : 156 keV produced continuously in the outer atmosphere. It is also produced by the anthropogenic activities like nuclear weapon test, nuclear power plant etc. contributing to the atmospheric inventory. The 14 CO 2 gets incorporated with the plant species during photosynthesis and ultimately reaches to man through food chain. It is important to accurately quantify the level of 14 C in different biological matrices for the computation of radiation dose due to ingestion. There are different methods available for the determination of 14 C in biological samples. The oxidation of the dried sample is one of the methods used for liberating the 14 CO 2 and which in turn re-absorbed using Carbo Sorb and subjected to Liquid scintillation analyses with Permaflour scintillator solution. The paper deals with the quality assurance programme initiated by ESL, Tarapur along with ESL, Kalpakkam and CARER, Mangalore University and share the experience of the inter-laboratory comparison exercise

Degradation in PV Encapsulation Strength of Attachment: An Interlaboratory Study Towards a Climate-Specific Test

Energy Technology Data Exchange (ETDEWEB)

Miller, David; Annigoni, Eleonora; Ballion, Amal; Bokria, Jayesh G.; Bruckman, Laura S.; Burns, David M.; Chen, Xinxin; Feng, Jiangtao; French, Roger H.; Fowler, Sean; Honeker, Christian C.; Kempe, Michael; Khonkar, Hussam; Kohl, Michael; Perret-Aebi, Laure-Emmanuelle; Phillips, Nancy H.; Scott, Kurt P.; Sculati-Meillaud, Fanny; Wohlgemuth, John

2016-06-06

Reduced strength of attachment of the encapsulant resulting from the outdoor environment, including ultraviolet (UV) radiation, may decrease photovoltaic (PV) module lifetime by enabling widespread corrosion of internal components. To date, few studies exist showing how the adhesion of PV components varies with environmental stress. We have conducted an interlaboratory experiment to provide an understanding that will be used to develop climatic specific module tests. Factors examined in the study included the UV light source (lamp type), temperature, and humidity to be proposed for use in accelerated aging tests. A poly (ethylene-co-vinyl acetate) (EVA) formulation often used in veteran PV installations was studied using a compressive shear test - to quantify the strength of attachment at the EVA/glass interface. Replicate laminated glass/polymer/glass coupon specimens were weathered at 12 institutions using a variety of indoor chambers or field aging. Shear strength, shear strain, and toughness were measured using a mechanical load-frame for the compressive shear test, with subsequent optical imaging and electron microscopy of the separated surfaces.

Interlaboratory reproducibility of DiversiLab rep-PCR typing and clustering of Acinetobacter baumannii isolates.

Science.gov (United States)

Higgins, Paul G; Hujer, Andrea M; Hujer, Kristine M; Bonomo, Robert A; Seifert, Harald

2012-01-01

We have investigated the reproducibility of DiversiLab rep-PCR fingerprints between two laboratories with the aim of determining if the fingerprints and clustering are laboratory-specific or portable. One-hundred non-duplicate Acinetobacter baumannii isolates were used in this study. DNA isolation and rep-PCR were each performed separately in two laboratories and rep-PCR patterns generated in laboratory A were compared with those from laboratory B. Twelve A. baumannii isolates processed in laboratory A showed ≥98 % pattern similarity with the corresponding 12 isolates tested in laboratory B and were considered identical. Sixty-four isolates showed 95-97.9 % similarity with their corresponding isolates. Twenty-three isolates showed 90-94 % similarity with the corresponding isolates, while one isolate showed only 87.4 % similarity. However, intra-laboratory clustering was conserved: isolates that clustered in laboratory A also clustered in laboratory B. While clustering was conserved and reproducible at two different laboratories, demonstrating the robustness of rep-PCR, interlaboratory comparison of individual isolate fingerprints showed more variability. This comparison allows conclusions regarding clonality to be reached independent of the laboratory where the analysis is performed.

Tendency for interlaboratory precision in the GMO analysis method based on real-time PCR.

Science.gov (United States)

Kodama, Takashi; Kurosawa, Yasunori; Kitta, Kazumi; Naito, Shigehiro

2010-01-01

The Horwitz curve estimates interlaboratory precision as a function only of concentration, and is frequently used as a method performance criterion in food analysis with chemical methods. The quantitative biochemical methods based on real-time PCR require an analogous criterion to progressively promote method validation. We analyzed the tendency of precision using a simplex real-time PCR technique in 53 collaborative studies of seven genetically modified (GM) crops. Reproducibility standard deviation (SR) and repeatability standard deviation (Sr) of the genetically modified organism (GMO) amount (%) was more or less independent of GM crops (i.e., maize, soybean, cotton, oilseed rape, potato, sugar beet, and rice) and evaluation procedure steps. Some studies evaluated whole steps consisting of DNA extraction and PCR quantitation, whereas others focused only on the PCR quantitation step by using DNA extraction solutions. Therefore, SR and Sr for GMO amount (%) are functions only of concentration similar to the Horwitz curve. We proposed S(R) = 0.1971C 0.8685 and S(r) = 0.1478C 0.8424, where C is the GMO amount (%). We also proposed a method performance index in GMO quantitative methods that is analogous to the Horwitz Ratio.

Degradation in PV Encapsulation Transmittance: An Interlaboratory Study Toward a Climate-Specific Test

Energy Technology Data Exchange (ETDEWEB)

Miller, David C.; Hacke, Peter L.; Kempe, Michael D.; Wohlgemuth, John H.; Annigoni, Eleonora; Sculati-Meillaud, Fanny; Ballion, Amal; Kohl, Michael; Bokria, Jayesh G.; Bruckman, Laura S.; French, Roger H.; Burns, David; Phillips, Nancy H.; Feng; Jiangtao; Elliott, Lamont; Scott, Kurt P.; Fowler, Sean; Gu, Xiaohong; Honeker, Christian C.; Khonkar, Hussam; Perret-Aebi, Laure-Emmanuelle; Shioda, Tsy

2015-06-14

Reduced optical transmittance of encapsulation resulting from ultraviolet (UV) degradation has frequently been identified as a cause of decreased PV module performance through the life of installations in the field. The present module safety and qualification standards, however, apply short UV doses only capable of examining design robustness or 'infant mortality' failures. Essential information that might be used to screen encapsulation through product lifetime remains unknown. For example, the relative efficacy of xenon-arc and UVA-340 fluorescent sources or the typical range of activation energy for degradation is not quantified. We have conducted an interlaboratory experiment to provide the understanding that will be used towards developing a climate- and configuration-specific (UV) weathering test. Five representative, known formulations of EVA were studied in addition to one TPU material. Replicate laminated silica/polymer/silica specimens are being examined at 14 institutions using a variety of indoor chambers (including Xe, UVA-340, and metal-halide light sources) or field aging. The solar-weighted transmittance, yellowness index, and the UV cut-off wavelength, determined from the measured hemispherical transmittance, are examined to provide understanding and guidance for the UV light source (lamp type) and temperature used in accelerated UV aging tests. Index Terms -- reliability, durability, thermal activation.

Quality assurance trials for Ki67 assessment in pathology.

Science.gov (United States)

Raap, M; Ließem, S; Rüschoff, J; Fisseler-Eckhoff, A; Reiner, A; Dirnhofer, S; von Wasielewski, R; Kreipe, H

2017-10-01

Ki67 is a broadly used proliferation marker in surgical pathology with an obvious need for standardization to improve reproducibility of assessment. Here, we present results of the so far only existing round robin tests on Ki67, organized annually in Germany, Austria, and Switzerland from 2010 to 2015 with up to 160 participating laboratories (QuIP). In each quality assessment trial, eight probes from each breast cancer, neuroendocrine tumor, and malignant lymphoma were compiled on a tissue microarray (TMA). TMAs were stained in the participants' laboratories with antibodies and procedures also applied in their daily routine. Participating pathologists were expected to assign Ki67 values to one of four different categories for each tumor type. All local stainings and evaluations were reassessed by the organizing panel and compared to a preset standard. On average, 95% of participants reached the benchmark of over 80% concordance rates with the Ki67 category pre-established by the panel. Automatization and type of antibody did not affect the success rate. Concordance rates differed between tumor entities being highest in each tumor type with either very high or very low labeling indices. Lower rates were seen for intermediate Ki67 levels. Staining quality improved during the observation period as did inter-observer concordance with 85% of participants achieving excellent agreement (kappa > 0.8) in the first year and over 95% in 2015. In conclusion, regular external quality assurance trials have been established as a tool to improve the reproducibility and reliability of the prognostic and predictive proliferation marker Ki67.

OARSI Clinical Trials Recommendations: Soluble biomarker assessments in clinical trials in osteoarthritis.

Science.gov (United States)

Kraus, V B; Blanco, F J; Englund, M; Henrotin, Y; Lohmander, L S; Losina, E; Önnerfjord, P; Persiani, S

2015-05-01

The objective of this work was to describe requirements for inclusion of soluble biomarkers in osteoarthritis (OA) clinical trials and progress toward OA-related biomarker qualification. The Guidelines for Biomarkers Working Group, representing experts in the field of OA biomarker research from both academia and industry, convened to discuss issues related to soluble biomarkers and to make recommendations for their use in OA clinical trials based on current knowledge and anticipated benefits. This document summarizes current guidance on use of biomarkers in OA clinical trials and their utility at five stages, including preclinical development and phase I to phase IV trials. As demonstrated by this summary, biomarkers can provide value at all stages of therapeutics development. When resources permit, we recommend collection of biospecimens in all OA clinical trials for a wide variety of reasons but in particular, to determine whether biomarkers are useful in identifying those individuals most likely to receive clinically important benefits from an intervention; and to determine whether biomarkers are useful for identifying individuals at earlier stages of OA in order to institute treatment at a time more amenable to disease modification. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Bias from two analytical laboratories involved in a long-term air monitoring program measuring organic pollutants in the Arctic: a quality assurance/quality control assessment.

Science.gov (United States)

Su, Yushan; Hung, Hayley; Stern, Gary; Sverko, Ed; Lao, Randy; Barresi, Enzo; Rosenberg, Bruno; Fellin, Phil; Li, Henrik; Xiao, Hang

2011-11-01

Initiated in 1992, air monitoring of organic pollutants in the Canadian Arctic provided spatial and temporal trends in support of Canada's participation in the Stockholm Convention of Persistent Organic Pollutants. The specific analytical laboratory charged with this task was changed in 2002 while field sampling protocols remained unchanged. Three rounds of intensive comparison studies were conducted in 2004, 2005, and 2008 to assess data comparability between the two laboratories. Analysis was compared for organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) in standards, blind samples of mixed standards and extracts of real air samples. Good measurement accuracy was achieved for both laboratories when standards were analyzed. Variation of measurement accuracy over time was found for some OCPs and PCBs in standards on a random and non-systematic manner. Relatively low accuracy in analyzing blind samples was likely related to the process of sample purification. Inter-laboratory measurement differences for standards (<30%) and samples (<70%) were generally less than or comparable to those reported in a previous inter-laboratory study with 21 participating laboratories. Regression analysis showed inconsistent data comparability between the two laboratories during the initial stages of the study. These inter-laboratory differences can complicate abilities to discern long-term trends of pollutants in a given sampling site. It is advisable to maintain long-term measurements with minimal changes in sample analysis.

78 FR 49444 - Oral Rabies Vaccine Trial; Availability of a Supplement to an Environmental Assessment and...

Science.gov (United States)

2013-08-14

...] Oral Rabies Vaccine Trial; Availability of a Supplement to an Environmental Assessment and Finding of... supplement to an environmental assessment and finding of no significant impact relative to an oral rabies.... Richard Chipman, Rabies Program Coordinator, Wildlife Services, APHIS, 59 Chennell Drive, Suite 7, Concord...

How many research nurses for how many clinical trials in an oncology setting? Definition of the Nursing Time Required by Clinical Trial-Assessment Tool (NTRCT-AT).

Science.gov (United States)

Milani, Alessandra; Mazzocco, Ketti; Stucchi, Sara; Magon, Giorgio; Pravettoni, Gabriella; Passoni, Claudia; Ciccarelli, Chiara; Tonali, Alessandra; Profeta, Teresa; Saiani, Luisa

2017-02-01

Few resources are available to quantify clinical trial-associated workload, needed to guide staffing and budgetary planning. The aim of the study is to describe a tool to measure clinical trials nurses' workload expressed in time spent to complete core activities. Clinical trials nurses drew up a list of nursing core activities, integrating results from literature searches with personal experience. The final 30 core activities were timed for each research nurse by an outside observer during daily practice in May and June 2014. Average times spent by nurses for each activity were calculated. The "Nursing Time Required by Clinical Trial-Assessment Tool" was created as an electronic sheet that combines the average times per specified activities and mathematic functions to return the total estimated time required by a research nurse for each specific trial. The tool was tested retrospectively on 141 clinical trials. The increasing complexity of clinical research requires structured approaches to determine workforce requirements. This study provides a tool to describe the activities of a clinical trials nurse and to estimate the associated time required to deliver individual trials. The application of the proposed tool in clinical research practice could provide a consistent structure for clinical trials nursing workload estimation internationally. © 2016 John Wiley & Sons Australia, Ltd.

Student Experience of Oral Communication Assessment Tasks Online from a Multi-Disciplinary Trial

Science.gov (United States)

McBain, Bonnie; Drew, Antony; James, Carole; Phelan, Liam; Harris, Keith M; Archer, Jennifer

2016-01-01

Purpose: The purpose of this paper is to evaluate the experiences of tertiary students learning oral presentation skills in a range of online and blended learning contexts across diverse disciplines. Design/methodology/approach: The research was designed as a "federation" of trials of diverse online oral communications assessment tasks…

Assessing subject privacy and data confidentiality in an emerging region for clinical trials: United Arab Emirates.

Science.gov (United States)

Nair, Satish Chandrasekhar; Ibrahim, Halah

2015-01-01

Pharmaceutical sponsored clinical trials, formerly conducted predominantly in the United States and Europe, have expanded to emerging regions, including the Middle East. Our study explores factors influencing clinical trial privacy and confidentiality in the United Arab Emirates. Factors including concept familiarity, informed consent compliance, data access, and preservation, were analyzed to assess current practices in the Arab world. As the UAE is an emerging region for clinical trials, there is a growing need for regulations related to data confidentiality and subject privacy. Informational and decisional privacy should be viewed within the realms of Arab culture and religious background.

Status Report of the Inter-Laboratory Task Force on Remote Operation

Energy Technology Data Exchange (ETDEWEB)

Phinney, Nan

2001-12-13

The next generation of particle accelerators will be major projects which may require a new mode of international and inter-laboratory collaboration. They are likely to be too costly to be funded by a single nation and too large to be built by a single laboratory. The tremendous technical challenge of a new facility requires a critical mass of highly qualified and experienced physicists and engineers. These experts are presently distributed among the major accelerator centers around the world and it is believed important to maintain and develop this broad base of expertise. The successful accelerator technology development of recent decades depended on extensive exchange of people with complementary technical skills. Therefore, it is desirable and probably necessary that several accelerator laboratories will participate in any future project. A consequence of a multi-laboratory project is that the accelerator will be located a considerable distance from most of the contributing institutions which design, build and operate it. These considerations led the International Committee for Future Accelerators to initiate a study on the general and technical implications of such a collaboration. Two task forces were formed in February 2000 to conduct this study and they were asked to prepare a report on a time scale of one year. The task force on Remote Operation included members from most of the major accelerator laboratories around the world with expertise on accelerator operation, controls software, communication technologies, hardware design and maintenance. The task force members gathered information from the experts at their own institutions and from available experience in other fields, particularly astronomy.

Assessment of the performance of containment and surveillance equipment part 2: trial application

International Nuclear Information System (INIS)

Rezniczek, A.; Richter, B.; Jussofie, A.

2009-01-01

The adopted methodological approach for assessing the performance of Containment and Surveillance (C/S) equipment resulted from an account of work performed for and in cooperation with the ESARDA Working Group on C/S. It was applied on a trial basis to a dry storage facility for spent nuclear fuel and consisted of the following steps: (1) Acquisition and analysis of design information and operational characteristics of the facility under consideration, (2) assumptions on diversion and misuse scenarios, (3) assumptions on safeguards approach and definition of safeguards requirements, (4) compilation and characterisation of candidate C/S equipment, (5) performance assessment of C/S equipment. The candidate equipment taken into account was routinely used by the IAEA: DCM14-type camera, Type E capand- wire seal, COBRA fibre optic seal, and VACOSS electronic seal. Four applications were considered: camera mounted in the reception area, seal on secondary lid of transport and storage cask, seal on protective lid, and seal on group of casks. For these applications, requirements were defined and requirement levels were attributed. The assignment of performance levels was carried out by using the technical specifications and design basis tolerances provided by the equipment manufacturers. The results were entered into four performance assessment tables. Although the assessment methodology was not yet fully developed, its trial application yielded promising results with regard to the selection of appropriate C/S equipment.

The assessment of field trials in GMO research around the world and their possible integration in field trials for variety registration

NARCIS (Netherlands)

Slot, M.M.; Wiel, van de C.C.M.; Kleter, G.A.; Visser, R.G.F.; Kok, E.J.

2018-01-01

Most regulations worldwide stipulate that a new genetically modified (GM) crop event has to be compared to its closest non-GM counterpart as a corner stone of the pre-market risk assessment. To this end the GM crop and its comparator should be grown in field trials for a phenotypic comparison as

The Harmonising Outcome Measures for Eczema (HOME) statement to assess clinical signs of atopic eczema in trials.

Science.gov (United States)

Schmitt, Jochen; Spuls, Phyllis I; Thomas, Kim S; Simpson, Eric; Furue, Masutaka; Deckert, Stefanie; Dohil, Magdalene; Apfelbacher, Christian; Singh, Jasvinder A; Chalmers, Joanne; Williams, Hywel C

2014-10-01

The lack of core outcome sets for atopic eczema (AE) is a major obstacle for advancing evidence-based treatment. The global Harmonising Outcome Measures for Eczema (HOME) initiative has already defined clinical signs, symptoms, quality of life, and long-term control of flares as core outcome domains for AE trials. This article deals with the standardization of measurement instruments to assess clinical signs of AE. To resolve the current lack of standardization of the assessment of clinical signs of AE, we followed a structured process of systematic reviews and international consensus sessions to identify 1 core outcome measurement instrument for assessment of clinical signs in all future AE trials. Systematic reviews indicated that from 16 different instruments identified to assess clinical signs of AE, only the Eczema Area and Severity Index (EASI) and the objective Scoring Atopic Dermatitis (SCORAD) index were identified as extensively validated. The EASI has adequate validity, responsiveness, internal consistency, and intraobserver reliability. The objective SCORAD index has adequate validity, responsiveness, and interobserver reliability but unclear intraobserver reliability to measure clinical signs of AE. In an international consensus study, patients, physicians, nurses, methodologists, and pharmaceutical industry representatives agreed that the EASI is the preferred core instrument to measure clinical signs in all future AE trials. All stakeholders involved in designing, reporting, and using clinical trials on AE are asked to comply with this consensus to enable better evidence-based decision making, clearer scientific communication, and improved patient care. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Comprehensive Geriatric Assessment for Prevention of Delirium After Hip Fracture: A Systematic Review of Randomized Controlled Trials.

Science.gov (United States)

Shields, Lynn; Henderson, Victoria; Caslake, Robert

2017-07-01

To assess the efficacy of comprehensive geriatric assessment (CGA) in prevention of delirium after hip fracture. Systematic review and metaanalysis. Ward based models on geriatrics wards and visiting team based models on orthopaedics wards were included. Four trials (three European, one U.S.; 973 participants) were identified. Two assessed ward-based, and two assessed team-based interventions. MEDLINE, EMBASE, CINAHL and PsycINFO databases; Clinicaltrials.gov; and the Central Register of Controlled Trials were searched. Reference lists from full-text articles were reviewed. Incidence of delirium was the primary outcome. Length of stay, delirium severity, institutionalization, long-term cognition and mortality were predefined secondary outcomes. Duration of delirium was included as a post hoc outcome. There was a significant reduction in delirium overall (relative risk (RR) = 0.81, 95% confidence interval (CI) = 0.69-0.94) in the intervention group. Post hoc subgroup analysis found this effect to be preserved in the team-based intervention group (RR = 0.77, 95% CI = 0.61-0.98) but not the ward-based group. No significant effect was observed on any secondary outcome. There was a reduction in the incidence of delirium after hip fracture with CGA. This is in keeping with results of non-randomized controlled trials and trials in other populations. Team-based interventions appeared superior in contrast to the Ellis CGA paper, but it is likely that heterogeneity in interventions and population studied affected this. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

UK Dermatology Clinical Trials Network's STOP GAP trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum): protocol for a randomised controlled trial.

Science.gov (United States)

Craig, Fiona F; Thomas, Kim S; Mitchell, Eleanor J; Williams, Hywel C; Norrie, John; Mason, James M; Ormerod, Anthony D

2012-04-28

Pyoderma gangrenosum (PG) is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment. A systematic review published in 2005 found no randomised controlled trials (RCTs) relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. The UK Dermatology Clinical Trials Network's STOP GAP Trial has been designed to address this lack of trial evidence. The objective is to assess whether oral ciclosporin is more effective than oral prednisolone for the treatment of PG. The trial design is a two-arm, observer-blind, parallel-group, randomised controlled trial comparing ciclosporin (4 mg/kg/day) to prednisolone (0.75 mg/kg/day). A total of 140 participants are to be recruited over a period of 4 years, from up to 50 hospitals in the UK and Eire. Primary outcome of velocity of healing at 6 weeks is assessed blinded to treatment allocation (using digital images of the ulcers). Secondary outcomes include: (i) time to healing; (ii) global assessment of improvement; (iii) PG inflammation assessment scale score; (iv) self-reported pain; (v) health-related quality of life; (vi) time to recurrence; (vii) treatment failures; (viii) adverse reactions to study medications; and (ix) cost effectiveness/utility. Patients with a clinical diagnosis of PG (excluding granulomatous PG); measurable ulceration (that is, not pustular PG); and patients aged over 18 years old who are able to give informed consent are included in the trial. Randomisation is by computer generated code using permuted blocks of randomly varying size, stratified by lesion size, and

Evaluation of the analytic performance of laboratories: inter-laboratorial study of the spectroscopy of atomic absorption

International Nuclear Information System (INIS)

Wong Wong, S. M.

1996-01-01

The author made an inter-laboratorial study, with the participation of 18 national laboratories, that have spectrophotometer of atomic absorption. To evaluate the methods of analysis of lead, sodium, potasium, calcium, magnesium, zinc, copper, manganese, and iron, in the ambit of mg/l. The samples, distributed in four rounds to the laboratories, were prepared from primary patterns, deionized and distilled water. The study evaluated the homogeneity and stability, and verified its concentration, using as a reference method, the spectrometry method of Inductively Coupled Plasma emission (1CP). To obtain the characteristics of analytic performance, it applied the norm ASTM E 691. To evaluated the analytic performance, it used harmonized protocol of the International Union of Pure and applied chemistry (IUPAC). The study obtained the 29% of the laboratories had a satisfactory analytic performance, 9% had a questionable performance and 62% made an unsatisfactory analytic performance, according to the IUPAC norm. The results of the values of the characteristic performance method, show that there is no intercomparability between the laboratories, which is attributed to the different methodologies of analysis. (S. Grainger)

Interlaboratory validation of quantitative duplex real-time PCR method for screening analysis of genetically modified maize.

Science.gov (United States)

Takabatake, Reona; Koiwa, Tomohiro; Kasahara, Masaki; Takashima, Kaori; Futo, Satoshi; Minegishi, Yasutaka; Akiyama, Hiroshi; Teshima, Reiko; Oguchi, Taichi; Mano, Junichi; Furui, Satoshi; Kitta, Kazumi

2011-01-01

To reduce the cost and time required to routinely perform the genetically modified organism (GMO) test, we developed a duplex quantitative real-time PCR method for a screening analysis simultaneously targeting an event-specific segment for GA21 and Cauliflower Mosaic Virus 35S promoter (P35S) segment [Oguchi et al., J. Food Hyg. Soc. Japan, 50, 117-125 (2009)]. To confirm the validity of the method, an interlaboratory collaborative study was conducted. In the collaborative study, conversion factors (Cfs), which are required to calculate the GMO amount (%), were first determined for two real-time PCR instruments, the ABI PRISM 7900HT and the ABI PRISM 7500. A blind test was then conducted. The limit of quantitation for both GA21 and P35S was estimated to be 0.5% or less. The trueness and precision were evaluated as the bias and reproducibility of the relative standard deviation (RSD(R)). The determined bias and RSD(R) were each less than 25%. We believe the developed method would be useful for the practical screening analysis of GM maize.

Methodology for Speech Assessment in the Scandcleft Project-An International Randomized Clinical Trial on Palatal Surgery

DEFF Research Database (Denmark)

Willadsen, Elisabeth

2009-01-01

Objective: To present the methodology for speech assessment in the Scandcleft project and discuss issues from a pilot study. Design: Description of methodology and blinded test for speech assessment. Speech samples and instructions for data collection and analysis for comparisons of speech outcomes...... across five included languages were developed and tested. Participants and Materials: Randomly selected video recordings of 10 5-year-old children from each language (n = 50) were included in the project. Speech material consisted of test consonants in single words, connected speech, and syllable chains......-sum and the overall rating of VPC was 78%. Conclusions: Pooling data of speakers of different languages in the same trial and comparing speech outcome across trials seems possible if the assessment of speech concerns consonants and is confined to speech units that are phonetically similar across languages. Agreed...

Assessing validity of observational intervention studies – the Benchmarking Controlled Trials

Science.gov (United States)

Malmivaara, Antti

2016-01-01

Abstract Background: Benchmarking Controlled Trial (BCT) is a concept which covers all observational studies aiming to assess impact of interventions or health care system features to patients and populations. Aims: To create and pilot test a checklist for appraising methodological validity of a BCT. Methods: The checklist was created by extracting the most essential elements from the comprehensive set of criteria in the previous paper on BCTs. Also checklists and scientific papers on observational studies and respective systematic reviews were utilized. Ten BCTs published in the Lancet and in the New England Journal of Medicine were used to assess feasibility of the created checklist. Results: The appraised studies seem to have several methodological limitations, some of which could be avoided in planning, conducting and reporting phases of the studies. Conclusions: The checklist can be used for planning, conducting, reporting, reviewing, and critical reading of observational intervention studies. However, the piloted checklist should be validated in further studies.Key messagesBenchmarking Controlled Trial (BCT) is a concept which covers all observational studies aiming to assess impact of interventions or health care system features to patients and populations.This paper presents a checklist for appraising methodological validity of BCTs and pilot-tests the checklist with ten BCTs published in leading medical journals. The appraised studies seem to have several methodological limitations, some of which could be avoided in planning, conducting and reporting phases of the studies.The checklist can be used for planning, conducting, reporting, reviewing, and critical reading of observational intervention studies. PMID:27238631

Information flow to assess cardiorespiratory interactions in patients on weaning trials.

Science.gov (United States)

Vallverdú, M; Tibaduisa, O; Clariá, F; Hoyer, D; Giraldo, B; Benito, S; Caminal, P

2006-01-01

Nonlinear processes of the autonomic nervous system (ANS) can produce breath-to-breath variability in the pattern of breathing. In order to provide assess to these nonlinear processes, nonlinear statistical dependencies between heart rate variability and respiratory pattern variability are analyzed. In this way, auto-mutual information and cross-mutual information concepts are applied. This information flow analysis is presented as a short-term non linear analysis method to investigate the information flow interactions in patients on weaning trials. 78 patients from mechanical ventilation were studied: Group A of 28 patients that failed to maintain spontaneous breathing and were reconnected; Group B of 50 patients with successful trials. The results show lower complexity with an increase of information flow in group A than in group B. Furthermore, a more (weakly) coupled nonlinear oscillator behavior is observed in the series of group A than in B.

Linking quantitative microbial risk assessment and epidemiological data: informing safe drinking water trials in developing countries.

Science.gov (United States)

Enger, Kyle S; Nelson, Kara L; Clasen, Thomas; Rose, Joan B; Eisenberg, Joseph N S

2012-05-01

Intervention trials are used extensively to assess household water treatment (HWT) device efficacy against diarrheal disease in developing countries. Using these data for policy, however, requires addressing issues of generalizability (relevance of one trial in other contexts) and systematic bias associated with design and conduct of a study. To illustrate how quantitative microbial risk assessment (QMRA) can address water safety and health issues, we analyzed a published randomized controlled trial (RCT) of the LifeStraw Family Filter in the Congo. The model accounted for bias due to (1) incomplete compliance with filtration, (2) unexpected antimicrobial activity by the placebo device, and (3) incomplete recall of diarrheal disease. Effectiveness was measured using the longitudinal prevalence ratio (LPR) of reported diarrhea. The Congo RCT observed an LPR of 0.84 (95% CI: 0.61, 1.14). Our model predicted LPRs, assuming a perfect placebo, ranging from 0.50 (2.5-97.5 percentile: 0.33, 0.77) to 0.86 (2.5-97.5 percentile: 0.68, 1.09) for high (but not perfect) and low (but not zero) compliance, respectively. The calibration step provided estimates of the concentrations of three pathogen types (modeled as diarrheagenic E. coli, Giardia, and rotavirus) in drinking water, consistent with the longitudinal prevalence of reported diarrhea measured in the trial, and constrained by epidemiological data from the trial. Use of a QMRA model demonstrated the importance of compliance in HWT efficacy, the need for pathogen data from source waters, the effect of quantifying biases associated with epidemiological data, and the usefulness of generalizing the effectiveness of HWT trials to other contexts. © 2012 American Chemical Society

Conformity Assessment in Nuclear Material and Environmental Sample Analysis

International Nuclear Information System (INIS)

Aregbe, Y.; Jakopic, R.; Richter, S.; Venchiarutti, C.

2015-01-01

Safeguards conclusions are based to a large extent on comparison of measurement results between operator and safeguards laboratories. Measurement results must state traceability and uncertainties to be comparable. Recent workshops held at the IAEA and in the frame of the European Safeguards Research and Development Association (ESARDA), reviewed different approaches for Nuclear Material Balance Evaluation (MBE). Among those, the ''bottom-up'' approach requires assessment of operators and safeguards laboratories measurement systems and capabilities. Therefore, inter-laboratory comparisons (ILCs) with independent reference values provided for decades by JRC-IRMM, CEA/CETAMA and US DOE are instrumental to shed light on the current state of practice in measurements of nuclear material and environmental swipe samples. Participating laboratories are requested to report the measurement results with associated uncertainties, and have the possibility to benchmark those results against independent and traceable reference values. The measurement capability of both the IAEA Network of Analytical Laboratories (NWAL) and the nuclear operator's analytical services participating in ILCs can be assessed against the independent reference values as well as against internationally agreed quality goals, in compliance with ISO 13528:2005. The quality goals for nuclear material analysis are the relative combined standard uncertainties listed in the ITV2010. Concerning environmental swipe sample analysis, the IAEA defined measurement quality goals applied in conformity assessment. The paper reports examples from relevant inter-laboratory comparisons, looking at laboratory performance according to the purpose of the measurement and the possible use of the result in line with the IUPAC International Harmonized Protocol. Tendencies of laboratories to either overestimate and/or underestimate uncertainties are discussed using straightforward graphical tools to evaluate

Interlaboratory study of a method for determining nonvolatile organic carbon in aquifer materials

Science.gov (United States)

Caughey, M.E.; Barcelona, M.J.; Powell, R.M.; Cahill, R.A.; Gron, C.; Lawrenz, D.; Meschi, P.L.

1995-01-01

The organic carbon fraction in aquifer materials exerts a major influence on the subsurface mobilities of organic and organic-associated contaminants. The spatial distribution of total organic carbon (TOC) in aquifer materials must be determined before the transport of hydrophobic organic pollutants in aquifers can be modeled accurately. Previous interlaboratory studies showed that it is difficult to measure TOC concentrations 1%. We have tested a new analytical method designed to improve the accuracy and precision of nonvolatile TOC quantitation in geologic materials that also contain carbonate minerals. Four authentic aquifer materials and one NIST standard reference material were selected as test materials for a blind collaborative study. Nonvolatile TOC in these materials ranged from 0.05 to 1.4%, while TIC ranged from 0.46 to 12.6%. Sample replicates were digested with sulfurous acid, dried at 40??C, and then combusted at 950??C using LECO or UIC instruments. For the three test materials that contained >2% TIC, incomplete acidification resulted in a systematic positive bias of TOC values reported by five of the six laboratories that used the test method. Participants did not have enough time to become proficient with the new method before they analyzed the test materials. A seventh laboratory successfully used an alternative method that analyzed separate liquid and solid fractions of the acidified sample residues. ?? 1995 Springer-Verlag.

Cartographic Mapping and Travel Burden to Assess and Develop Strategies to Improve Minority Access to National Cancer Clinical Trials

International Nuclear Information System (INIS)

Bruner, Deborah Watkins; Pugh, Stephanie L.; Yeager, Katherine A.; Bruner, Jesse; Curran, Walter

2015-01-01

Purpose: To assess how accrual to clinical trials is related to US minority population density relative to clinical trial site location and distance traveled to Radiation Therapy Oncology Group (RTOG) clinical trial sites. Methods and Materials: Data included member site address and ZIP codes, patient accrual, and patient race or ethnicity and ZIP code. Geographic Information System maps were developed for overall, Latino, and African American accrual to trials by population density. The Kruskal-Wallis test was used to assess differences in distance traveled by site, type of trial, and race or ethnicity. Results: From 2006 to 2009, 6168 patients enrolled on RTOG trials. The RTOG US site distribution is generally concordant with overall population density. Sites with highest accrual are located throughout the United States and parts of Canada and do not cluster, nor does highest minority accrual cluster in areas of highest US minority population density. Of the 4913 US patients with complete data, patients traveled a median of 11.6 miles to participate in clinical trials. Whites traveled statistically longer distances (12.9 miles; P<.0001) to participate, followed by Latinos (8.22 miles) and African Americans (5.85 miles). Patients were willing to drive longer distances to academic sites than community sites, and there was a trend toward significantly longer median travel for therapeutic versus cancer control or metastatic trials. Conclusions: Location matters, but only to a degree, for minority compared with nonminority participation in clinical trials. Geographic Information System tools help identify gaps in geographic access and travel burden for clinical trials participation. Strategies that emerged using these tools are discussed.

Cartographic Mapping and Travel Burden to Assess and Develop Strategies to Improve Minority Access to National Cancer Clinical Trials

Science.gov (United States)

Bruner, Deborah Watkins; Pugh, Stephanie L.; Yeager, Katherine A.; Bruner, Jesse; Curran, Walter

2015-01-01

Purpose To assess how accrual to clinical trials is related to U.S. minority population density relative to clinical trial site location and distance traveled to Radiation Therapy Oncology Group (RTOG) clinical trials sites. Methods Data included member site address and zip codes, patient accrual, and patient race/ethnicity and zip code. Geographic Information System (GIS) maps were developed for overall, Latino and African American accrual to trials by population density. The Kruskal-Wallis test was used to assess differences in distance traveled by site, type of trial and race/ethnicity. Results From 2006–2009, 6168 patients enrolled on RTOG trials. RTOG U.S. site distribution is generally concordant with overall population density. Sites with highest accrual are located throughout the U.S. and parts of Canada and do not cluster, nor does highest minority accrual cluster in areas of highest U.S. minority population density. Of the 4913 U.S. patients with complete data, patients traveled a median of 11.6 miles to participate in clinical trials. Whites traveled statistically longer distances (12.9 miles; p<0.0001) to participate followed by Latinos (8.22 miles), and African Americans (5.85 miles). Patients were willing to drive longer distances to academic sites than community sites and there was a trend toward significantly longer median travel for therapeutic vs cancer control or metastatic trials. Conclusions Location matters, but only to a degree, for minority compared to non-minority participation in clinical trials. GIS tools help identify gaps in geographic access and travel burden for clinical trials participation. Strategies that emerged using these tools are discussed. PMID:26281827

Cartographic Mapping and Travel Burden to Assess and Develop Strategies to Improve Minority Access to National Cancer Clinical Trials

Energy Technology Data Exchange (ETDEWEB)

Bruner, Deborah Watkins, E-mail: deborah.w.bruner@emory.edu [Emory University, Atlanta, Georgia (United States); Pugh, Stephanie L. [NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States); Yeager, Katherine A.; Bruner, Jesse; Curran, Walter [Emory University, Atlanta, Georgia (United States)

2015-11-01

Purpose: To assess how accrual to clinical trials is related to US minority population density relative to clinical trial site location and distance traveled to Radiation Therapy Oncology Group (RTOG) clinical trial sites. Methods and Materials: Data included member site address and ZIP codes, patient accrual, and patient race or ethnicity and ZIP code. Geographic Information System maps were developed for overall, Latino, and African American accrual to trials by population density. The Kruskal-Wallis test was used to assess differences in distance traveled by site, type of trial, and race or ethnicity. Results: From 2006 to 2009, 6168 patients enrolled on RTOG trials. The RTOG US site distribution is generally concordant with overall population density. Sites with highest accrual are located throughout the United States and parts of Canada and do not cluster, nor does highest minority accrual cluster in areas of highest US minority population density. Of the 4913 US patients with complete data, patients traveled a median of 11.6 miles to participate in clinical trials. Whites traveled statistically longer distances (12.9 miles; P<.0001) to participate, followed by Latinos (8.22 miles) and African Americans (5.85 miles). Patients were willing to drive longer distances to academic sites than community sites, and there was a trend toward significantly longer median travel for therapeutic versus cancer control or metastatic trials. Conclusions: Location matters, but only to a degree, for minority compared with nonminority participation in clinical trials. Geographic Information System tools help identify gaps in geographic access and travel burden for clinical trials participation. Strategies that emerged using these tools are discussed.

Cartographic Mapping and Travel Burden to Assess and Develop Strategies to Improve Minority Access to National Cancer Clinical Trials.

Science.gov (United States)

Bruner, Deborah Watkins; Pugh, Stephanie L; Yeager, Katherine A; Bruner, Jesse; Curran, Walter

2015-11-01

To assess how accrual to clinical trials is related to US minority population density relative to clinical trial site location and distance traveled to Radiation Therapy Oncology Group (RTOG) clinical trial sites. Data included member site address and ZIP codes, patient accrual, and patient race or ethnicity and ZIP code. Geographic Information System maps were developed for overall, Latino, and African American accrual to trials by population density. The Kruskal-Wallis test was used to assess differences in distance traveled by site, type of trial, and race or ethnicity. From 2006 to 2009, 6168 patients enrolled on RTOG trials. The RTOG US site distribution is generally concordant with overall population density. Sites with highest accrual are located throughout the United States and parts of Canada and do not cluster, nor does highest minority accrual cluster in areas of highest US minority population density. Of the 4913 US patients with complete data, patients traveled a median of 11.6 miles to participate in clinical trials. Whites traveled statistically longer distances (12.9 miles; P<.0001) to participate, followed by Latinos (8.22 miles) and African Americans (5.85 miles). Patients were willing to drive longer distances to academic sites than community sites, and there was a trend toward significantly longer median travel for therapeutic versus cancer control or metastatic trials. Location matters, but only to a degree, for minority compared with nonminority participation in clinical trials. Geographic Information System tools help identify gaps in geographic access and travel burden for clinical trials participation. Strategies that emerged using these tools are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Type 1 Diabetes TrialNet--an international collaborative clinical trials network.

Science.gov (United States)

Skyler, Jay S; Greenbaum, Carla J; Lachin, John M; Leschek, Ellen; Rafkin-Mervis, Lisa; Savage, Peter; Spain, Lisa

2008-12-01

Type 1 Diabetes TrialNet is an international consortium of clinical research centers aimed at the prevention or delay of type 1 diabetes (T1D). The fundamental goal of TrialNet is to counter the T1D disease process by immune modulation and/or enhancement of beta cell proliferation and regeneration. To achieve this goal, TrialNet researchers are working to better understand the natural history of the disease, to identify persons at risk, and to clinically evaluate novel therapies that balance potential risks and benefits. The particular focus is on studies of preventive measures. In addition, TrialNet evaluates therapies in individuals with newly diagnosed T1D with preserved beta cell function to help determine the risk/benefit profile and gain an initial assessment of potential efficacy in preservation of beta cell function, so that promising agents can be studied in prevention trials. In addition, TrialNet evaluates methodologies that enhance the conduct of its clinical trials, which includes tests of outcome assessment methodology, the evaluation of surrogate markers, and mechanistic studies laying the foundation for future clinical trials.

UK Dermatology Clinical Trials Network’s STOP GAP trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum: protocol for a randomised controlled trial

Directory of Open Access Journals (Sweden)

Craig Fiona F

2012-04-01

Full Text Available Abstract Background Pyoderma gangrenosum (PG is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment. A systematic review published in 2005 found no randomised controlled trials (RCTs relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. The UK Dermatology Clinical Trials Network’s STOP GAP Trial has been designed to address this lack of trial evidence. Methods The objective is to assess whether oral ciclosporin is more effective than oral prednisolone for the treatment of PG. The trial design is a two-arm, observer-blind, parallel-group, randomised controlled trial comparing ciclosporin (4 mg/kg/day to prednisolone (0.75 mg/kg/day. A total of 140 participants are to be recruited over a period of 4 years, from up to 50 hospitals in the UK and Eire. Primary outcome of velocity of healing at 6 weeks is assessed blinded to treatment allocation (using digital images of the ulcers. Secondary outcomes include: (i time to healing; (ii global assessment of improvement; (iii PG inflammation assessment scale score; (iv self-reported pain; (v health-related quality of life; (vi time to recurrence; (vii treatment failures; (viii adverse reactions to study medications; and (ix cost effectiveness/utility. Patients with a clinical diagnosis of PG (excluding granulomatous PG; measurable ulceration (that is, not pustular PG; and patients aged over 18 years old who are able to give informed consent are included in the trial. Randomisation is by computer generated code using permuted blocks of randomly varying size

Assessing the Eventual Publication of Clinical Trial Abstracts Submitted to a Large Annual Oncology Meeting.

Science.gov (United States)

Massey, Paul R; Wang, Ruibin; Prasad, Vinay; Bates, Susan E; Fojo, Tito

2016-03-01

Despite the ethical imperative to publish clinical trials when human subjects are involved, such data frequently remain unpublished. The objectives were to tabulate the rate and ascertain factors associated with eventual publication of clinical trial results reported as abstracts in the Proceedings of the American Society of Clinical Oncology (American Society of Clinical Oncology). Abstracts describing clinical trials for patients with breast, lung, colorectal, ovarian, and prostate cancer from 2009 to 2011 were identified by using a comprehensive online database (http://meetinglibrary.asco.org/abstracts). Abstracts included reported results of a treatment or intervention assessed in a discrete, prospective clinical trial. Publication status at 4-6 years was determined by using a standardized search of PubMed. Primary outcomes were the rate of publication for abstracts of randomized and nonrandomized clinical trials. Secondary outcomes included factors influencing the publication of results. A total of 1,075 abstracts describing 378 randomized and 697 nonrandomized clinical trials were evaluated. Across all years, 75% of randomized and 54% of nonrandomized trials were published, with an overall publication rate of 61%. Sample size was a statistically significant predictor of publication for both randomized and nonrandomized trials (odds ratio [OR] per increase of 100 participants = 1.23 [1.11-1.36], p publication (OR 2.37, p = .013; and 2.21, p = .01, respectively). Among nonrandomized studies, phase II trials were more likely to be published than phase I (p publication in randomized (OR 0.76 [0.38-1.52]; p = .441) or nonrandomized trials (OR 0.89 [0.61-1.29]; p = .532). This is the largest reported study examining why oncology trials are not published. The data show that 4-6 years after appearing as abstracts, 39% of oncology clinical trials remain unpublished. Larger sample size and advanced trial phase were associated with eventual publication; among randomized

Guidelines for time-to-event end point definitions in breast cancer trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†.

Science.gov (United States)

Gourgou-Bourgade, S; Cameron, D; Poortmans, P; Asselain, B; Azria, D; Cardoso, F; A'Hern, R; Bliss, J; Bogaerts, J; Bonnefoi, H; Brain, E; Cardoso, M J; Chibaudel, B; Coleman, R; Cufer, T; Dal Lago, L; Dalenc, F; De Azambuja, E; Debled, M; Delaloge, S; Filleron, T; Gligorov, J; Gutowski, M; Jacot, W; Kirkove, C; MacGrogan, G; Michiels, S; Negreiros, I; Offersen, B V; Penault Llorca, F; Pruneri, G; Roche, H; Russell, N S; Schmitt, F; Servent, V; Thürlimann, B; Untch, M; van der Hage, J A; van Tienhoven, G; Wildiers, H; Yarnold, J; Bonnetain, F; Mathoulin-Pélissier, S; Bellera, C; Dabakuyo-Yonli, T S

2015-05-01

Using surrogate end points for overall survival, such as disease-free survival, is increasingly common in randomized controlled trials. However, the definitions of several of these time-to-event (TTE) end points are imprecisely which limits interpretation and cross-trial comparisons. The estimation of treatment effects may be directly affected by the definitions of end points. The DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for randomized cancer clinical trials (RCTs) in breast cancer. A literature review was carried out to identify TTE end points (primary or secondary) reported in publications of randomized trials or guidelines. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points based on a validated consensus method that formalize the degree of agreement among experts. Recommended guidelines for the definitions of TTE end points commonly used in RCTs for breast cancer are provided for non-metastatic and metastatic settings. The use of standardized definitions should facilitate comparisons of trial results and improve the quality of trial design and reporting. These guidelines could be of particular interest to those involved in the design, conducting, reporting, or assessment of RCT. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Assessing methods for dealing with treatment crossover in clinical trials: A follow-up simulation study

OpenAIRE

Latimer, N.R.; Abrams, K.R.; Lambert, P.C.; Crowther, M.J.; Morden, J.P.

2014-01-01

Background: Treatment switching commonly occurs in clinical trials of novel interventions, particularly in the advanced or metastatic cancer setting, which causes important problems for health technology assessment. Previous research has demonstrated which adjustment methods are suitable in specific scenarios, but scenarios considered have been limited. \\ud Objectives: We aimed to assess statistical approaches for adjusting survival estimates in the presence of treatment switching in order to...

PErineal Assessment and Repair Longitudinal Study (PEARLS: protocol for a matched pair cluster trial

Directory of Open Access Journals (Sweden)

Thomas Peter W

2010-02-01

Full Text Available Abstract Background The Perineal Assessment and Repair Longitudinal Study (PEARLS is a national clinical quality improvement initiative designed to improve the assessment and management of perineal trauma. Perineal trauma affects around 85% of women who have a vaginal birth in the UK each year and millions more world-wide. Continuous suturing techniques compared with traditional interrupted methods are more effective in reducing pain and postnatal morbidity, however they are not widely used by clinicians despite recommendations of evidence based national clinical guidelines. Perineal suturing skills and postnatal management of trauma remain highly variable within and between maternity units in the UK as well as worldwide. Implementation of a standardised training package to support effective perineal management practices could reduce perineal pain and other related postnatal morbidity for a substantial number of women. Methods/Design PEARLS is a matched pair cluster trial, which is being conducted in maternity units across the UK. Units within a matched pair will be randomised to implement the study intervention either early or late in the study period. The intervention will include the cascading of a multi-professional training package to enhance midwifery and obstetric skills in the assessment, repair and postnatal management of perineal trauma. Women who have had an episiotomy or second degree perineal tear will be eligible for recruitment. Prior to developing the intervention and deciding on study outcomes, a Delphi survey and a consensus conference were held to identify what women, who previously suffered perineal trauma during childbirth, considered to be important outcomes for them. Findings from this preliminary work (which will be reported elsewhere and other outcomes including women's experiences of perineal pain and pain on activity, breastfeeding uptake and duration and psychological well-being as assessed using the Edinburgh

The use of importance sampling in a trial assessment to obtain converged estimates of radiological risk

International Nuclear Information System (INIS)

Johnson, K.; Lucas, R.

1986-12-01

In developing a methodology for assessing potential sites for the disposal of radioactive wastes, the Department of the Environment has conducted a series of trial assessment exercises. In order to produce converged estimates of radiological risk using the SYVAC A/C simulation system an efficient sampling procedure is required. Previous work has demonstrated that importance sampling can substantially increase sampling efficiency. This study used importance sampling to produce converged estimates of risk for the first DoE trial assessment. Four major nuclide chains were analysed. In each case importance sampling produced converged risk estimates with between 10 and 170 times fewer runs of the SYVAC A/C model. This increase in sampling efficiency can reduce the total elapsed time required to obtain a converged estimate of risk from one nuclide chain by a factor of 20. The results of this study suggests that the use of importance sampling could reduce the elapsed time required to perform a risk assessment of a potential site by a factor of ten. (author)

The design and development of a complex multifactorial falls assessment intervention for falls prevention: The Prevention of Falls Injury Trial (PreFIT).

Science.gov (United States)

Bruce, Julie; Ralhan, Shvaita; Sheridan, Ray; Westacott, Katharine; Withers, Emma; Finnegan, Susanne; Davison, John; Martin, Finbarr C; Lamb, Sarah E

2017-06-01

This paper describes the design and development of a complex multifactorial falls prevention (MFFP) intervention for implementation and testing within the framework of a large UK-based falls prevention randomised controlled trial (RCT). A complex intervention was developed for inclusion within the Prevention of Falls Injury Trial (PreFIT), a multicentre pragmatic RCT. PreFIT aims to compare the clinical and cost-effectiveness of three alternative primary care falls prevention interventions (advice, exercise and MFFP), on outcomes of fractures and falls. Community-dwelling adults, aged 70 years and older, were recruited from primary care in the National Health Service (NHS), England. Development of the PreFIT MFFP intervention was informed by the existing evidence base and clinical guidelines for the assessment and management of falls in older adults. After piloting and modification, the final MFFP intervention includes seven falls risk factors: a detailed falls history interview with consideration of 'red flags'; assessment of balance and gait; vision; medication screen; cardiac screen; feet and footwear screen and home environment assessment. This complex intervention has been fully manualised with clear, documented assessment and treatment pathways for each risk factor. Each risk factor is assessed in every trial participant referred for MFFP. Referral for assessment is based upon a screening survey to identify those with a history of falling or balance problems. Intervention delivery can be adapted to the local setting. This complex falls prevention intervention is currently being tested within the framework of a large clinical trial. This paper adheres to TIDieR and CONSORT recommendations for the comprehensive and explicit reporting of trial interventions. Results from the PreFIT study will be published in due course. The effectiveness and cost-effectiveness of the PreFIT MFFP intervention, compared to advice and exercise, on the prevention of falls and

Developing an OMERACT Core Outcome Set for Assessing Safety Components in Rheumatology Trials

DEFF Research Database (Denmark)

Klokker, Louise; Tugwell, Peter; Furst, Daniel E

2016-01-01

in such COS. The Outcome Measures in Rheumatology (OMERACT) Filter 2.0 emphasizes the importance of measuring harms. The Safety Working Group was reestablished at the OMERACT 2016 with the objective to develop a COS for assessing safety components in trials across rheumatologic conditions. METHODS: The safety......OBJECTIVE: Failure to report harmful outcomes in clinical research can introduce bias favoring a potentially harmful intervention. While core outcome sets (COS) are available for benefits in randomized controlled trials in many rheumatic conditions, less attention has been paid to safety...... that patients consider relevant so that they will be able to make informed decisions. CONCLUSION: The OMERACT Safety Working Group will advance the work previously done within OMERACT using a new patient-driven approach....

Post hoc interlaboratory comparison of single particle ICP-MS size measurements of NIST gold nanoparticle reference materials.

Science.gov (United States)

Montoro Bustos, Antonio R; Petersen, Elijah J; Possolo, Antonio; Winchester, Michael R

2015-09-01

Single particle inductively coupled plasma-mass spectrometry (spICP-MS) is an emerging technique that enables simultaneous measurement of nanoparticle size and number quantification of metal-containing nanoparticles at realistic environmental exposure concentrations. Such measurements are needed to understand the potential environmental and human health risks of nanoparticles. Before spICP-MS can be considered a mature methodology, additional work is needed to standardize this technique including an assessment of the reliability and variability of size distribution measurements and the transferability of the technique among laboratories. This paper presents the first post hoc interlaboratory comparison study of the spICP-MS technique. Measurement results provided by six expert laboratories for two National Institute of Standards and Technology (NIST) gold nanoparticle reference materials (RM 8012 and RM 8013) were employed. The general agreement in particle size between spICP-MS measurements and measurements by six reference techniques demonstrates the reliability of spICP-MS and validates its sizing capability. However, the precision of the spICP-MS measurement was better for the larger 60 nm gold nanoparticles and evaluation of spICP-MS precision indicates substantial variability among laboratories, with lower variability between operators within laboratories. Global particle number concentration and Au mass concentration recovery were quantitative for RM 8013 but significantly lower and with a greater variability for RM 8012. Statistical analysis did not suggest an optimal dwell time, because this parameter did not significantly affect either the measured mean particle size or the ability to count nanoparticles. Finally, the spICP-MS data were often best fit with several single non-Gaussian distributions or mixtures of Gaussian distributions, rather than the more frequently used normal or log-normal distributions.

International interlaboratory study comparing single organism 16S rRNA gene sequencing data: Beyond consensus sequence comparisons

Science.gov (United States)

Olson, Nathan D.; Lund, Steven P.; Zook, Justin M.; Rojas-Cornejo, Fabiola; Beck, Brian; Foy, Carole; Huggett, Jim; Whale, Alexandra S.; Sui, Zhiwei; Baoutina, Anna; Dobeson, Michael; Partis, Lina; Morrow, Jayne B.

2015-01-01

This study presents the results from an interlaboratory sequencing study for which we developed a novel high-resolution method for comparing data from different sequencing platforms for a multi-copy, paralogous gene. The combination of PCR amplification and 16S ribosomal RNA gene (16S rRNA) sequencing has revolutionized bacteriology by enabling rapid identification, frequently without the need for culture. To assess variability between laboratories in sequencing 16S rRNA, six laboratories sequenced the gene encoding the 16S rRNA from Escherichia coli O157:H7 strain EDL933 and Listeria monocytogenes serovar 4b strain NCTC11994. Participants performed sequencing methods and protocols available in their laboratories: Sanger sequencing, Roche 454 pyrosequencing®, or Ion Torrent PGM®. The sequencing data were evaluated on three levels: (1) identity of biologically conserved position, (2) ratio of 16S rRNA gene copies featuring identified variants, and (3) the collection of variant combinations in a set of 16S rRNA gene copies. The same set of biologically conserved positions was identified for each sequencing method. Analytical methods using Bayesian and maximum likelihood statistics were developed to estimate variant copy ratios, which describe the ratio of nucleotides at each identified biologically variable position, as well as the likely set of variant combinations present in 16S rRNA gene copies. Our results indicate that estimated variant copy ratios at biologically variable positions were only reproducible for high throughput sequencing methods. Furthermore, the likely variant combination set was only reproducible with increased sequencing depth and longer read lengths. We also demonstrate novel methods for evaluating variable positions when comparing multi-copy gene sequence data from multiple laboratories generated using multiple sequencing technologies. PMID:27077030

International interlaboratory study comparing single organism 16S rRNA gene sequencing data: Beyond consensus sequence comparisons

Directory of Open Access Journals (Sweden)

Nathan D. Olson

2015-03-01

Full Text Available This study presents the results from an interlaboratory sequencing study for which we developed a novel high-resolution method for comparing data from different sequencing platforms for a multi-copy, paralogous gene. The combination of PCR amplification and 16S ribosomal RNA gene (16S rRNA sequencing has revolutionized bacteriology by enabling rapid identification, frequently without the need for culture. To assess variability between laboratories in sequencing 16S rRNA, six laboratories sequenced the gene encoding the 16S rRNA from Escherichia coli O157:H7 strain EDL933 and Listeria monocytogenes serovar 4b strain NCTC11994. Participants performed sequencing methods and protocols available in their laboratories: Sanger sequencing, Roche 454 pyrosequencing®, or Ion Torrent PGM®. The sequencing data were evaluated on three levels: (1 identity of biologically conserved position, (2 ratio of 16S rRNA gene copies featuring identified variants, and (3 the collection of variant combinations in a set of 16S rRNA gene copies. The same set of biologically conserved positions was identified for each sequencing method. Analytical methods using Bayesian and maximum likelihood statistics were developed to estimate variant copy ratios, which describe the ratio of nucleotides at each identified biologically variable position, as well as the likely set of variant combinations present in 16S rRNA gene copies. Our results indicate that estimated variant copy ratios at biologically variable positions were only reproducible for high throughput sequencing methods. Furthermore, the likely variant combination set was only reproducible with increased sequencing depth and longer read lengths. We also demonstrate novel methods for evaluating variable positions when comparing multi-copy gene sequence data from multiple laboratories generated using multiple sequencing technologies.

The Nation's Report Card: A First Look--2013 Mathematics and Reading Trial Urban District Assessment. NCES 2014-466

Science.gov (United States)

National Center for Education Statistics, 2013

2013-01-01

The National Assessment of Educational Progress (NAEP), in partnership with the National Assessment Governing Board and the Council of the Great City Schools (CGCS), created the Trial Urban District Assessment (TUDA) in 2002 to support the improvement of student achievement in the nation's large urban districts. The TUDA focuses attention on urban…

Quality of reporting in oncology phase II trials: A 5-year assessment through systematic review.

Science.gov (United States)

Langrand-Escure, Julien; Rivoirard, Romain; Oriol, Mathieu; Tinquaut, Fabien; Rancoule, Chloé; Chauvin, Frank; Magné, Nicolas; Bourmaud, Aurélie

2017-01-01

Phase II clinical trials are a cornerstone of the development in experimental treatments They work as a "filter" for phase III trials confirmation. Surprisingly the attrition ratio in Phase III trials in oncology is significantly higher than in any other medical specialty. This suggests phase II trials in oncology fail to achieve their goal. Objective The present study aims at estimating the quality of reporting in published oncology phase II clinical trials. A literature review was conducted among all phase II and phase II/III clinical trials published during a 5-year period (2010-2015). All articles electronically published by three randomly-selected oncology journals with Impact-Factors>4 were included: Journal of Clinical Oncology, Annals of Oncology and British Journal of Cancer. Quality of reporting was assessed using the Key Methodological Score. 557 articles were included. 315 trials were single-arm studies (56.6%), 193 (34.6%) were randomized and 49 (8.8%) were non-randomized multiple-arm studies. The Methodological Score was equal to 0 (lowest level), 1, 2, 3 (highest level) respectively for 22 (3.9%), 119 (21.4%), 270 (48.5%) and 146 (26.2%) articles. The primary end point is almost systematically reported (90.5%), while sample size calculation is missing in 66% of the articles. 3 variables were independently associated with reporting of a high standard: presence of statistical design (p-value <0.001), multicenter trial (p-value = 0.012), per-protocol analysis (p-value <0.001). Screening was mainly performed by a sole author. The Key Methodological Score was based on only 3 items, making grey zones difficult to translate. This literature review highlights the existence of gaps concerning the quality of reporting. It therefore raised the question of the suitability of the methodology as well as the quality of these trials, reporting being incomplete in the corresponding articles.

Recruitment to publicly funded trials--are surgical trials really different?

Science.gov (United States)

Cook, Jonathan A; Ramsay, Craig R; Norrie, John

2008-09-01

Good recruitment is integral to the conduct of a high-quality randomised controlled trial. It has been suggested that recruitment is particularly difficult for evaluations of surgical interventions, a field in which there is a dearth of evidence from randomised comparisons. While there is anecdotal speculation to support the inference that recruitment to surgical trials is more challenging than for medical trials we are unaware of any formal assessment of this. In this paper, we compare recruitment to surgical and medical trials using a cohort of publicly funded trials. Overall recruitment to trials was assessed using of a cohort of publicly funded trials (n=114). Comparisons were made by using the Recruitment Index, a simple measure of recruitment activity for multicentre randomised controlled trials. Recruitment at the centre level was also investigated through three example surgical trials. The Recruitment Index was found to be higher, though not statistically significantly, in the surgical group (n=18, median=38.0 IQR (10.7, 77.4)) versus (n=81, median=34.8 IQR (11.7, 98.0)) days per recruit for the medical group (median difference 1.7 (-19.2, 25.1); p=0.828). For the trials where the comparison was between a surgical and a medical intervention, the Recruitment Index was substantially higher (n=6, 68.3 (23.5, 294.8)) versus (n=93, 34.6 (11.7, 90.0); median difference 25.9 (-35.5, 221.8); p=0.291) for the other trials. There was no clear evidence that surgical trials differ from medical trials in terms of recruitment activity. There was, however, support for the inference that medical versus surgical trials are more difficult to recruit to. Formal exploration of the recruitment data through a modelling approach may go some way to tease out where important differences exist.

Assessing barriers to a rational chemoprevention trial design in young patients with familial adenomatous polyposis.

Science.gov (United States)

Wood, Joanna P; Howells, Lynne M; Brown, Karen; Thomas, Anne L

2017-07-01

Familial adenomatous polyposis coli (FAP) is an autosomal dominant condition caused by a germline mutation in the adenomatous polyposis coli gene. Colonic adenomas form and almost all patients will develop colorectal cancer if they are not managed at an early stage. The safest preventive strategy is surgical resection of the colon, most commonly performed in late teenage years. There is a paucity of trials investigating the use of primary chemoprevention to delay polyp formation in paediatric FAP. There are extensive preclinical and early clinical data demonstrating that curcumin may be a safe and effective chemotherapeutic agent in reducing the polyp burden in this disease. We ultimately proposed to design and conduct a clinical study to assess whether curcumin treatment delays the need for surgery and/or prevents cancer in young patients with FAP. Research into clinical trial protocols has demonstrated that assessing patients' perceptions at the initial stage leads to better outcomes. We therefore conducted a questionnaire study of patients and parents of children affected by FAP to gain information to aid the protocol design. Results demonstrated that there are some FAP patients for whom this study is relevant and desirable. Those with a personal history of curcumin use reported that it was well tolerated. However, the response rate was poor (25%), indicating that there are potential difficulties ensuring adequate recruitment to the proposed trial. This report draws on lessons learnt from prior trials and the findings from the questionnaire to outline the challenges faced in designing such a study.

Assessing quality of reports on randomized clinical trials in nursing journals.

Science.gov (United States)

Parent, Nicole; Hanley, James A

2009-01-01

Several surveys have presented the quality of reports on randomized clinical trials (RCTs) published in general and specialty medical journals. The aim of these surveys was to raise scientific consciousness on methodological aspects pertaining to internal and external validity. These reviews have suggested that the methodological quality could be improved. We conducted a survey of reports on RCTs published in nursing journals to assess their methodological quality. The features we considered included sample size, flow of participants, assessment of baseline comparability, randomization, blinding, and statistical analysis. We collected data from all reports of RCTs published between January 1994 and December 1997 in Applied Nursing Research, Heart & Lung and Nursing Research. We hand-searched the journals and included all 54 articles in which authors reported that individuals have been randomly allocated to distinct groups. We collected data using a condensed form of the Consolidated Standards of Reporting Trials (CONSORT) statement for structured reporting of RCTs (Begg et al., 1996). Sample size calculations were included in only 22% of the reports. Only 48% of the reports provided information about the type of randomization, and a mere 22% described blinding strategies. Comparisons of baseline characteristics using hypothesis tests were abusively produced in more than 76% of the reports. Excessive use and unstructured reports of significance testing were common (59%), and all reports failed to provide magnitude of treatment differences with confidence intervals. Better methodological quality in reports of RCTs will contribute to increase the standards of nursing research.

Interlaboratory comparison of the determination of 137Cs and 90Sr in water, food and soil

International Nuclear Information System (INIS)

Fuks, L.; Polkowska-Motrenko, H.; Merta, A.

2006-01-01

Reliable measurements of radioisotope concentrations are of primary importance for the laboratories dealing with radioactivity determinations. According to the Polish regulations, since 2002 it is obligatory to organize every two years national interlaboratory comparisons (ILC) on the determination of various radionuclides in food and environmental samples. First such ILC on the determination of 137 Cs and 90 Sr in water, food and soil was organized by the National Atomic Energy Agency of Poland in 2004 with the participation of fourteen laboratories from Polish research institutes and universities. The ILC was conducted by the Institute of Nuclear Chemistry and Technology. Two types of water (surface and potable; six samples), wheat flour and soil (four samples) were spiked with 137 Cs and 90 Sr. From the results obtained in all participating laboratories it can be concluded that the procedures of assigning value and preparation of homogeneous material have been done properly and the majority of the determinations remain in good agreement with the assigned values and with the results obtained by other laboratories. Such agreement means that the performance of the laboratories is good and also that the samples are equivalent

ParaMED Home: A protocol for a randomised controlled trial of paramedic assessment and referral to access medical care at home

Directory of Open Access Journals (Sweden)

Johnston Steven

2011-06-01

Full Text Available Abstract Background In Australia approximately 25% of Emergency Department (ED attendances are via ambulance. ED overcrowding in Australia, as in many countries, is common. Measures to reduce overcrowding include the provision of enhanced timely primary care in the community for appropriate low risk injury and illness. Therefore paramedic assessment and referral to a community home hospital service, in preference to transfer to ED, may confer clinical and cost benefit. Methods/Design A randomised controlled trial. Consenting adult patients that call an ambulance and are assessed by paramedics as having an eligible low risk problem will be randomised to referral to ED via ambulance transfer or referral to a rapid response service that will assess and treat the patient in their own residence. The primary outcome measure is requirement for unplanned medical attention (in or out of hospital in the first 48 hours. Secondary outcomes will include a number of other clinical endpoints. A cost effectiveness analysis will be conducted. Discussion If this trial demonstrates clinical non-inferiority and cost savings associated with the primary assessment service, it will provide one means to safely address ED overcrowding. Trial Registration Australian and New Zealand Clinical Trials Registry Number 12610001064099

The Nation's Report Card: Mathematics 2011. Trial Urban District Assessment Results at Grades 4 and 8. NCES 2012-452

Science.gov (United States)

National Center for Education Statistics, 2011

2011-01-01

Representative samples of fourth- and eighth-grade public school students from 21 urban districts participated in the 2011 National Assessment of Educational Progress (NAEP) in mathematics. Eighteen of the districts participating in the 2011 NAEP Trial Urban District Assessment (TUDA) participated in earlier assessment years, while three districts…

EC static high-temperature leach test. Summary report of an European Community interlaboratory round robin

International Nuclear Information System (INIS)

Koennecke, R.; Kirsch, J.

1985-01-01

The results of an interlaboratory static high-temperature leach test conducted by the Commission of the European Communities in 1983 over a period of 9 months are compiled and statistically evaluated. A total of 12 laboratories - 10 from Member States of the EC and one from Finland and the USA - provided information concerning the test method and the analytical test results in the frame of a round robin test (RRT). All together these laboratories tested 366 waste from specimens of the borosilicate glass UK 209 containing simulated high-level radioactive waste. Leach tests were performed on the basis of the ''Document on the EC static high-temperature leach test method'' in autoclaves at leaching temperatures of 90 0 C, 110 0 C, 150 0 C, and 190 0 C over time periods of 3,7,14,28 and 56 days using dionized water as leachant. The resulting leachates were analysed for the elemental concentrations of Si,B,Sr,Nd and Cs by all laboratories and for the concentrations of the optional elements Na, Al,Ce,Mo,Cr,Fe,Li,Mg and Zn by some of the participating laboratories. Additionally, the F content of the blank leachates was analysed by all laboratories

Interlaboratory comparison of fig (Ficus carica L. microsatellite genotyping data and determination of reference alleles

Directory of Open Access Journals (Sweden)

Matjaž HLADNIK

2018-04-01

Full Text Available Microsatellites have been identified as the marker of choice in plant genotyping projects. However, due to length discrepancies obtained between different laboratories for the same allele, interlaboratory comparison of fingerprinting results is often a difficult task. The objectives of this study were to compare genotyping results of two laboratories, to evaluate genetic parameters of microsatellite markers and to determine reference allele sizes for fig cultivars from the Istrian peninsula.Genotyping results of ninety fig (Ficus carica L. accessions were comparable between the laboratories despite differences observed when comparing electropherograms of different capillary electrophoresis systems. Differences in lengths of the same alleles were detected due to different PCR methods and laboratory equipment, but the distances between alleles of the same locus were preserved. However, locus FSYC01 exhibited one allele dropout which led to misidentification of 28 heterozygotes as homozygote individuals suggesting this locus as unreliable. Allele dropout was assigned to the tail PCR technology or to a touchdown PCR protocol.Genotypes of twenty-four reference cultivars from the Istrian peninsula were confirmed by both laboratories. These results will contribute to the usage of markers with greater reliability, discrimination power and consequently, to more reliable standardization with other fig genotyping projects.

Advances in Interlaboratory Testing and Evaluation of Bituminous Materials State-of-the-Art Report of the RILEM Technical Committee 206-ATB

CERN Document Server

Bahia, Hussain; Canestrari, Francesco; Roche, Chantal; Benedetto, Hervé; Piber, Herald; Sybilski, Dariusz

2013-01-01

This STAR on asphalt materials presents the achievements of RILEM TC 206 ATB, acquired over many years of interlaboratory tests and international knowledge exchange. It covers experimental aspects of bituminous binder fatigue testing; the background on compaction methods and imaging techniques for characterizing asphalt mixtures including validation of a new imaging software; it focuses on experimental questions and analysis tools regarding mechanical wheel tracking tests, comparing results from different labs and using finite element techniques. Furthermore, long-term rutting prediction and evaluation for an Austrian road are discussed, followed by an extensive analysis and test program on interlayer bond testing of three different test sections which were specifically constructed for this purpose. Finally, the key issue of manufacturing reclaimed hot mix asphalt in the laboratory is studied and recommendations for laboratory ageing of bituminous mixtures are given.

Results of the Interlaboratory Exercise CSN/CIEMAT-02 Among Environmental Radioactivity Laboratories (Sea Fish); Resultados del Ejercicio Interlaboratorios de Radiactividad Ambiental CSN/CIEMAT-02 (Fauna Marina)

Energy Technology Data Exchange (ETDEWEB)

Romero gonzalez, M. L.

2003-07-01

The document describes the outcome of the CSN/CIEMAT-02 interlaboratory test comparison among environmental radioactivity laboratories. The exercise was organised according to the ISO-43 and the ISO/IUPAC/AOAC Harmonized Protocol for the proficiency testing of analytical laboratories. The test sample was a reference materials provided by the IAEA-MEL (IAE Marine Environmental Laboratory, Monaco), a sea fish containing environmental levels of U-238, U-234, K-40, Pb-210, Ra-226, Sr-90, Cs-137, Co-60, Pu-(239+240), Am-241 and Tc-99. The results of the exercise were computed for 32 participating laboratories, and their analytical performance was assessed using the z-score approach. A raised percentage of satisfactory laboratory performance has been obtained for all the analysis, being the best performance in gamma measurements. The laboratories have made an effort to calculate the combined uncertainty of the radiochemical determinations. Most of the laboratories have demonstrated its competence in performing the study analysis and also the adequate measuring capability of their detection equipment even in conditions close to detection limits. The study has shown the capacity of participant laboratories to perform radioactive determinations in environmental sea fish samples with satisfactory quality levels. (Author) 6 refs.

Assessing clinically meaningful treatment effects in controlled trials: chronic migraine as an example.

Science.gov (United States)

Dodick, David W; Turkel, Catherine C; DeGryse, Ronald E; Diener, Hans-Christoph; Lipton, Richard B; Aurora, Sheena K; Nolan, Marissa E; Silberstein, Stephen D

2015-02-01

In addition to headache, persons with chronic migraine (CM) experience multiple symptoms, both ictal and interictal, that may contribute to their suffering. Translating clinical trial results into practice requires assessment of the results' clinical meaningfulness. When examining treatment benefit in this disabled patient population, multiple headache-symptom measures should be considered to fully reflect clinical relevance. Currently, only onabotulinumtoxinA is approved specifically for headache prophylaxis in adults with CM. Topiramate is the only other therapeutic agent with double-blind, placebo-controlled evidence in this population. Herein we evaluate the clinical meaningfulness of onabotulinumtoxinA and topiramate as headache prophylaxis in CM by comparing primary endpoints from the placebo-controlled, double-blind phase of the Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program and the topiramate clinical trial (frequency of headache days [primary endpoint in PREEMPT; secondary in topiramate trial] and migraine/migrainous days [primary in topiramate trial, or "migraine/probable-migraine days"; secondary in PREEMPT]). Additionally, outcome measures such as responder rates, health-related quality of life, discontinuation rates, safety, and tolerability profiles are important clinical considerations. The clinical data indicate that statistically significant, clinically relevant treatment benefits exist for both onabotulinumtoxinA and topiramate. These data support these treatments as meaningful headache prophylaxis in adults with CM. CM is a chronic pain condition. We sought to determine the clinical relevance of recent trials in this disabled population. Clinical data indicate that statistically significant, clinically relevant treatment benefits exist for both onabotulinumtoxinA and topiramate, and support use of these treatments as meaningful headache prophylaxis in CM. Copyright © 2015 American Pain Society. Published

Preoperative airway assessment - experience gained from a multicentre cluster randomised trial and the Danish Anaesthesia Database

DEFF Research Database (Denmark)

Nørskov, Anders Kehlet

2016-01-01

difficult intubation compared with usual care for airway assessment. This thesis is based on data from the Danish Anaesthesia Database (DAD). Paper 1 presents an observational cohort study on 188,064 patients who underwent tracheal intubation from 2008 to 2011. Data on the anaesthesiologists' preoperative...... to the DIFFICAIR trial described in Paper 4. The trial was designed to randomise anaesthesia department to either thorough education in, and subsequent use of the SARI for preoperative airway assessment or to continue usual care. Registration of the SARI in DAD was made mandatory in SARI departments and impossible...... unanticipated. Furthermore, 94% of all difficult mask ventilations were unanticipated. In Paper 4, 59,514 patients were included in the primary analyses. The proportion of unanticipated difficult intubations was 2.38% (696/29,209) in SARI departments and 2.39% (723/30,305) in usual care departments...

Sample requirements and design of an inter-laboratory trial for radiocarbon laboratories

International Nuclear Information System (INIS)

Bryant, Charlotte; Carmi, Israel; Cook, Gordon; Gulliksen, Steinar; Harkness, Doug; Heinemeier, Jan; McGee, Edward; Naysmith, Philip; Possnert, Goran; Scott, Marian; Plicht, Hans van der; Strydonck, Mark van

2000-01-01

An on-going inter-comparison programme which is focused on assessing and establishing consensus protocols to be applied in the identification, selection and sub-sampling of materials for subsequent 14 C analysis is described. The outcome of the programme will provide a detailed quantification of the uncertainties associated with 14 C measurements including the issues of accuracy and precision. Such projects have become recognised as a fundamental aspect of continuing laboratory quality assurance schemes, providing a mechanism for the harmonisation of measurements and for demonstrating the traceability of results. The design of this study and its rationale are described. In summary, a suite of core samples has been defined which will be made available to both AMS and radiometric laboratories. These core materials are representative of routinely dated material and their ages span the full range of the applied 14 C time-scale. Two of the samples are of wood from the German and Irish dendrochronologies, thus providing a direct connection to the master dendrochronological calibration curve. Further samples link this new inter-comparison to past studies. Sample size and precision have been identified as being of paramount importance in defining dating confidence, and so several core samples have been identified for more in-depth study of these practical issues. In addition to the core samples, optional samples have been identified and prepared specifically for either AMS and/or radiometric laboratories. For AMS laboratories, these include bone, textile, leather and parchment samples. Participation in the study requires a commitment to a minimum of 10 core analyses, with results to be returned within a year

A multi-center ring trial for the identification of anaerobic bacteria using MALDI-TOF MS

DEFF Research Database (Denmark)

Veloo, A; Jean-Pierre, H; Justesen, U S

2017-01-01

Inter-laboratory reproducibility of Matrix Assisted Laser Desorption Time-of-Flight Mass Spectrometry (MALDI-TOF MS) of anaerobic bacteria has not been shown before. Therefore, ten anonymized anaerobic strains were sent to seven participating laboratories, an initiative of the European Network...

Seizure control as a new metric in assessing efficacy of tumor treatment in low-grade glioma trials

Science.gov (United States)

Chamberlain, Marc; Schiff, David; Reijneveld, Jaap C.; Armstrong, Terri S.; Ruda, Roberta; Wen, Patrick Y.; Weller, Michael; Koekkoek, Johan A. F.; Mittal, Sandeep; Arakawa, Yoshiki; Choucair, Ali; Gonzalez-Martinez, Jorge; MacDonald, David R.; Nishikawa, Ryo; Shah, Aashit; Vecht, Charles J.; Warren, Paula; van den Bent, Martin J.; DeAngelis, Lisa M.

2017-01-01

Patients with low-grade glioma frequently have brain tumor–related epilepsy, which is more common than in patients with high-grade glioma. Treatment for tumor-associated epilepsy usually comprises a combination of surgery, anti-epileptic drugs (AEDs), chemotherapy, and radiotherapy. Response to tumor-directed treatment is measured primarily by overall survival and progression-free survival. However, seizure frequency has been observed to respond to tumor-directed treatment with chemotherapy or radiotherapy. A review of the current literature regarding seizure assessment for low-grade glioma patients reveals a heterogeneous manner in which seizure response has been reported. There is a need for a systematic approach to seizure assessment and its influence on health-related quality-of-life outcomes in patients enrolled in low-grade glioma therapeutic trials. In view of the need to have an adjunctive metric of tumor response in these patients, a method of seizure assessment as a metric in brain tumor treatment trials is proposed. PMID:27651472

Physical activity and trial-by-trial adjustments of response conflict.

Science.gov (United States)

Kamijo, Keita; Takeda, Yuji

2013-08-01

The relationship of physical activity to trial-by-trial adjustments of response conflict was assessed using behavioral task performance, the N2 event-related brain potential component, and phase-locking values (PLVs) in a lower gamma band during a perceptual conflict task. Nineteen physically active and 19 inactive young adults (mean age = 21.3 years) performed a Navon task, using a global letter made up of local letters of either the same kind (congruent trials) or a different kind (incongruent trials). Findings revealed that active individuals exhibited smaller N2 amplitudes and greater PLVs on incongruent trials that were preceded by incongruent trials compared with those preceded by congruent trials. Such phenomena were not observed for inactive individuals. These results suggest that greater physical activity is associated with larger trial-by-trial adjustments of response conflict, which we attribute to upregulation of top-down cognitive control and reductions in response conflict.

Interlaboratory comparison of techniques for measuring lung burdens of low-energy X-ray emitters. Part of a coordinated programme on the calibration of burdens of inhaled plutonium by external counting

International Nuclear Information System (INIS)

Newton, D.; Fry, F.A.; Taylor, B.T.; Eagle, M.C.; Sharma, R.C.

1978-02-01

An interlaboratory exercise has been conducted to assess techniques of detection and calibration in the direct measurement of lung contamination with plutonium and other nuclides emitting only low-energy X-rays. Three volunteers, of small, intermediate and large physique, inhaled an aerosol incorporating Pd-103, a 20-keV X-ray emitter, and visited 13 other laboratories in the UK, Europe and North America. Participants in the exercise were asked to estimate each subject's lung content, using their procedures for assessing burdens of plutonium, and their estimates were compared with values derived independently from measurements of Cr-51, also incorporated in the inhaled particles, by gamma-ray spectrometry. Laboratories' calibration procedures were in most cases based on elaborate thorax phantoms, and these generally led to underestimates of the subjects' contents, in some instances by a factor of three or more; only one such laboratory produced estimates in satisfactory agreement with the independently-known values. The ''phoswich'' detectors, employed by most participants, appeared to be more sensitive than gas counters. If a standard configuration were required, offering the highest sensitivity in most situations, the choice would be a pair of 12-cm diameter phoswich detectors viewing the left and right anterior surfaces of the upper thorax. No improvement in sensitivity would result from increasing the size, although larger units may offer other advantages

Reactivity to smartphone-based ecological momentary assessment of depressive symptoms (MoodMonitor: protocol of a randomised controlled trial

Directory of Open Access Journals (Sweden)

Wouter van Ballegooijen

2016-10-01

Full Text Available Abstract Background Ecological momentary assessment (EMA of mental health symptoms may influence the symptoms that it measures, i.e. assessment reactivity. In the field of depression, EMA reactivity has received little attention. We aim to investigate whether EMA of depressive symptoms induces assessment reactivity. Reactivity will be operationalised as an effect of EMA on depressive symptoms measured by a retrospective questionnaire, and, secondly, as a change in response rate and variance of the EMA ratings. Methods This study is a 12-week randomised controlled trial comprising three groups: group 1 carries out EMA of mood and completes a retrospective questionnaire, group 2 carries out EMA of how energetic they feel and completes a retrospective questionnaire, group 3 is the control group, which completes only the retrospective questionnaire. The retrospective questionnaire (Centre for Epidemiologic Studies Depression scale; CES-D assesses depressive symptoms and is administered at baseline, 6 weeks after baseline and 12 weeks after baseline. We aim to recruit 160 participants who experience mild to moderate depressive symptoms, defined as a Patient Health Questionnaire (PHQ-9 score of 5 to 15. This study is powered to detect a small between-groups effect, where no clinically relevant effect is defined as the effect size margin −0.25< d <0.25. Discussion To our knowledge, this is the first study to investigate whether self-rated EMA of depressive symptoms could induce assessment reactivity among mildly depressed individuals. Trial registration Netherlands Trial Register NTR5803. Registered 12 April 2016. http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5803 .

Mixture effects in samples of multiple contaminants - An inter-laboratory study with manifold bioassays.

Science.gov (United States)

Altenburger, Rolf; Scholze, Martin; Busch, Wibke; Escher, Beate I; Jakobs, Gianina; Krauss, Martin; Krüger, Janet; Neale, Peta A; Ait-Aissa, Selim; Almeida, Ana Catarina; Seiler, Thomas-Benjamin; Brion, François; Hilscherová, Klára; Hollert, Henner; Novák, Jiří; Schlichting, Rita; Serra, Hélène; Shao, Ying; Tindall, Andrew; Tolefsen, Knut-Erik; Umbuzeiro, Gisela; Williams, Tim D; Kortenkamp, Andreas

2018-05-01

Chemicals in the environment occur in mixtures rather than as individual entities. Environmental quality monitoring thus faces the challenge to comprehensively assess a multitude of contaminants and potential adverse effects. Effect-based methods have been suggested as complements to chemical analytical characterisation of complex pollution patterns. The regularly observed discrepancy between chemical and biological assessments of adverse effects due to contaminants in the field may be either due to unidentified contaminants or result from interactions of compounds in mixtures. Here, we present an interlaboratory study where individual compounds and their mixtures were investigated by extensive concentration-effect analysis using 19 different bioassays. The assay panel consisted of 5 whole organism assays measuring apical effects and 14 cell- and organism-based bioassays with more specific effect observations. Twelve organic water pollutants of diverse structure and unique known modes of action were studied individually and as mixtures mirroring exposure scenarios in freshwaters. We compared the observed mixture effects against component-based mixture effect predictions derived from additivity expectations (assumption of non-interaction). Most of the assays detected the mixture response of the active components as predicted even against a background of other inactive contaminants. When none of the mixture components showed any activity by themselves then the mixture also was without effects. The mixture effects observed using apical endpoints fell in the middle of a prediction window defined by the additivity predictions for concentration addition and independent action, reflecting well the diversity of the anticipated modes of action. In one case, an unexpectedly reduced solubility of one of the mixture components led to mixture responses that fell short of the predictions of both additivity mixture models. The majority of the specific cell- and organism

Multifactorial assessment and targeted intervention to reduce falls among the oldest-old: a randomized controlled trial

NARCIS (Netherlands)

Ferrer, A.; Formiga, F.; Sanz, H.; de Vries, O.J.; Badia, T.; Pujol, R.

2014-01-01

Background: The purpose of this study was to assess the effectiveness of a multifactorial intervention to reduce falls among the oldest-old people, including individuals with cognitive impairment or comorbidities. Methods: A randomized, single-blind, parallel-group clinical trial was conducted from

Study of the precision and trueness of the Brazilian method for ethanol and gasoline determination; Estudo da precisao e exatidao do metodo brasileiro para determinacao de etanol e gasolina

Energy Technology Data Exchange (ETDEWEB)

Zucchini, Ricardo R.; Hinata, Patricia [Instituto de Pesquisas Tecnologicas (IPT), Sao Paulo, SP (Brazil); Gioseffi, Carla S.; Franco, Joao B.S. [Instituto Brasileiro de Petroleo, Gas e Biocombustiveis (IBP), Rio de Janeiro, RJ (Brazil); Nascimento, Cristina R.; Torres, Eduardo S. [Agencia Nacional do Petroleo, Gas Natural e Biocombustiveis (ANP), Rio de Janeiro, RJ (Brazil)

2008-07-01

The determination of repeatability and reproducibility standard deviations of an analytical method, s{sub r} and s{sub R}, obtained by Interlaboratory program, makes it possible to calculate many kinds of precision limits of the method, which are needed in every laboratory's routine result comparisons and also in between-laboratories comparisons. This paper presents the results of the first interlaboratory trial, accomplished in the Brazilian petroleum sector, performed to define the trueness and precision of the Brazilian standard method for the determination of fuel anhydrous ethylic alcohol content in gasoline, that was performed by 34 experienced laboratories. The r and R values were 0,7 and 2,3 and main factors that would improve and optimize the method are presented. (author)

Using the web for recruitment, screen, tracking, data management, and quality control in a dietary assessment clinical validation trial.

Science.gov (United States)

Arab, Lenore; Hahn, Harry; Henry, Judith; Chacko, Sara; Winter, Ashley; Cambou, Mary C

2010-03-01

Screening and tracking subjects and data management in clinical trials require significant investments in manpower that can be reduced through the use of web-based systems. To support a validation trial of various dietary assessment tools that required multiple clinic visits and eight repeats of online assessments, we developed an interactive web-based system to automate all levels of management of a biomarker-based clinical trial. The "Energetics System" was developed to support 1) the work of the study coordinator in recruiting, screening and tracking subject flow, 2) the need of the principal investigator to review study progress, and 3) continuous data analysis. The system was designed to automate web-based self-screening into the trial. It supported scheduling tasks and triggered tailored messaging for late and non-responders. For the investigators, it provided real-time status overviews on all subjects, created electronic case reports, supported data queries and prepared analytic data files. Encryption and multi-level password protection were used to insure data privacy. The system was programmed iteratively and required six months of a web programmer's time along with active team engagement. In this study the enhancement in speed and efficiency of recruitment and quality of data collection as a result of this system outweighed the initial investment. Web-based systems have the potential to streamline the process of recruitment and day-to-day management of clinical trials in addition to improving efficiency and quality. Because of their added value they should be considered for trials of moderate size or complexity. Copyright 2009 Elsevier Inc. All rights reserved.

An interlaboratory comparison of the performance of ethanol-producing micro-organisms in a xylose-rich acid hydrolysate

Energy Technology Data Exchange (ETDEWEB)

Hahn-Haegerdal, B. (Dept. of Applied Microbiology, Lund Inst. of Technology/Univ. of Lund (Sweden)); Jeppsson, H. (Dept. of Applied Microbiology, Lund Inst. of Technology/Univ. of Lund (Sweden)); Olsson, L. (Dept. of Applied Microbiology, Lund Inst. of Technology/Univ. of Lund (Sweden)); Mohagheghi, A. (Bioprocess and Fuels Engineering Research Branch, National Renewable Energy Lab., Golden, CO (United States))

1994-03-01

A xylose-rich, dilute-acid-pretreated corn-cob hydrolysate was fermented by Escherichia coli ATCC 11303, recombinant (rec) E. coli B (pLOI 297 and KO11), Pichia stipitis (CBS 5773, 6054 and R), Saccharomyces cerevisiae isolate 3 in combination with xylose isomerase, rec S. cerevisiae (TJ1, H550 and H477) and Fusarium oxysporum VTT-D-80134 in an interlaboratory comparison. The micro-organisms were studied according to three different options: (A) fermentation under consistent conditions. (B) fermentation under optimal conditions for the organism, and (C) fermentation under optimal conditions for the organism with detoxification of the hydrolysate. The highest yields of ethanol, 0.24 g/g (A), 0.36 g/g (B) and 0.54 g/g (C), were obtained from rec E. coli B, KO11. P. stipitis and F. oxysporum were sensitive to the inhibitors present in the hydrolysate and produced a maximum yield of 0.34 g/g (C) and 0.04 g/g (B), respectively. The analysis of the corn-cob hydrolysate and aspects of process economy of the different fermentation options (pH, sterilization, nutrient supplementation, adaptation, detoxification) are discussed. (orig.)

Atlas-based liver segmentation and hepatic fat-fraction assessment for clinical trials.

Science.gov (United States)

Yan, Zhennan; Zhang, Shaoting; Tan, Chaowei; Qin, Hongxing; Belaroussi, Boubakeur; Yu, Hui Jing; Miller, Colin; Metaxas, Dimitris N

2015-04-01

Automated assessment of hepatic fat-fraction is clinically important. A robust and precise segmentation would enable accurate, objective and consistent measurement of hepatic fat-fraction for disease quantification, therapy monitoring and drug development. However, segmenting the liver in clinical trials is a challenging task due to the variability of liver anatomy as well as the diverse sources the images were acquired from. In this paper, we propose an automated and robust framework for liver segmentation and assessment. It uses single statistical atlas registration to initialize a robust deformable model to obtain fine segmentation. Fat-fraction map is computed by using chemical shift based method in the delineated region of liver. This proposed method is validated on 14 abdominal magnetic resonance (MR) volumetric scans. The qualitative and quantitative comparisons show that our proposed method can achieve better segmentation accuracy with less variance comparing with two other atlas-based methods. Experimental results demonstrate the promises of our assessment framework. Copyright © 2014 Elsevier Ltd. All rights reserved.

REIMEP-22 inter-laboratory comparison. ''U Age Dating - determination of the production date of a uranium certified test sample''

Energy Technology Data Exchange (ETDEWEB)

Venchiarutti, Celia; Richter, Stephan; Jakopic, Rozle; Aregbe, Yetunde [European Commission, Joint Research Centre (JRC), Geel (Belgium). Institute for Reference Materials and Measurements (IRMM); Varga, Zsolt; Mayer, Klaus [European Commission, Joint Research Centre (JRC), Karlsruhe (Germany). Institute for Transuranium Elements (ITU)

2015-07-01

The REIMEP-22 inter-laboratory comparison aimed at determining the production date of a uranium certified test sample (i.e. the last chemical separation date of the material). Participants in REIMEP-22 on ''U Age Dating - Determination of the production date of a uranium certified test sample'' received one low-enriched 20 mg uranium sample for mass spectrometry measurements and/or one 50 mg uranium sample for a-spectrometry measurements, with an undisclosed value for the production date. They were asked to report the isotope amount ratios n({sup 230}Th)/n({sup 234}U) for the 20 mg uranium sample and/or the activity ratios A({sup 230}Th)/A({sup 234}U) for the 50 mg uranium sample in addition to the calculated production date of the certified test samples with its uncertainty. Reporting of the {sup 231}Pa/{sup 235}U ratio and the respective calculated production date was optional. Eleven laboratories reported results in REIMEP-22. Two of them reported results for both the 20 mg and 50 mg uranium certified test samples. The measurement capability of the participants was assessed against the independent REIMEP-22 reference value by means of z- and zeta-scores in compliance with ISO 13528:2005. Furthermore a performance assessment criterion for acceptable uncertainty was applied to evaluate the participants' results. In general, the REIMEP-22 participants' results were satisfactory. This confirms the analytical capabilities of laboratories to determine accurately the age of uranium materials with low amount of ingrown thorium (young certified test sample). The Joint Research Centre of the European Commission (EC-JRC) organised REIMEP-22 in parallel to the preparation and certification of a uranium reference material certified for the production date (IRMM-1000a and IRMM-1000b).

Falls Assessment Clinical Trial (FACT: design, interventions, recruitment strategies and participant characteristics

Directory of Open Access Journals (Sweden)

Lawton Beverley

2007-07-01

Full Text Available Abstract Background Guidelines recommend multifactorial intervention programmes to prevent falls in older adults but there are few randomised controlled trials in a real life health care setting. We describe the rationale, intervention, study design, recruitment strategies and baseline characteristics of participants in a randomised controlled trial of a multifactorial falls prevention programme in primary health care. Methods Participants are patients from 19 primary care practices in Hutt Valley, New Zealand aged 75 years and over who have fallen in the past year and live independently. Two recruitment strategies were used – waiting room screening and practice mail-out. Intervention participants receive a community based nurse assessment of falls and fracture risk factors, home hazards, referral to appropriate community interventions, and strength and balance exercise programme. Control participants receive usual care and social visits. Outcome measures include number of falls and injuries over 12 months, balance, strength, falls efficacy, activities of daily living, quality of life, and physical activity levels. Results 312 participants were recruited (69% women. Of those who had fallen, 58% of people screened in the practice waiting rooms and 40% when screened by practice letter were willing to participate. Characteristics of participants recruited using the two methods are similar (p > 0.05. Mean age of all participants was 81 years (SD 5. On average participants have 7 medical conditions, take 5.5 medications (29% on psychotropics with a median of 2 falls (interquartile range 1, 3 in the previous year. Conclusion The two recruitment strategies and the community based intervention delivery were feasible and successful, identifying a high risk group with multiple falls. Recruitment in the waiting room gave higher response rates but was less efficient than practice mail-out. Testing the effectiveness of an evidence based intervention in a

Assessing Cognitive Function in Bipolar Disorder: Challenges and Recommendations for Clinical Trial Design

Science.gov (United States)

Burdick, Katherine E.; Ketter, Terence A.; Goldberg, Joseph F.; Calabrese, Joseph R.

2015-01-01

provided here as a preliminary guide for future trial design. Recommendations comprise exclusion of certain syndromal level comorbid diagnoses and current affective instability, restrictions on numbers and types of medications, and use of pre-screening assessment to ensure enrollment of subjects with adequate objective evidence of baseline cognitive impairment. CONCLUSIONS Clinical trials to address cognitive deficits in bipolar disorder face distinctive design challenges. As such trials move from proof-of-concept to confirmation of clinical efficacy, it will be important to incorporate distinctive design modifications to adequately address these challenges and increase the likelihood of demonstrating cognitive remediation effects. The field is now primed to address these challenges and a comprehensive effort to formalize best practice guidelines will be a critically important next step. PMID:25830456

Measuring Compositions in Organic Depth Profiling: Results from a VAMAS Interlaboratory Study

Energy Technology Data Exchange (ETDEWEB)

Shard, A. G.; Havelund, Rasmus; Spencer, Steve J.; Gilmore, I. S.; Alexander, Morgan R.; Angerer, Tina B.; Aoyagi, Satoka; Barnes, Jean P.; Benayad, Anass; Bernasik, Andrzej; Ceccone, Giacomo; Counsell, Jonathan D.; Deeks, Christopher; Fletcher, John S.; Graham, Daniel J.; Heuser, Christian; Lee, Tae G.; Marie, Camille; Marzec, Mateusz M.; Mishra, Gautam; Rading, Derk; Renault, Oliver; Scurr, David J.; Shon, Hyun K.; Spampinato, Valentina; Tian, Hua; Wang, Fuyi; Winograd, Nicholas; Wu, Kui; Wucher, Andreas; Zhou, Yufan; Zhu, Zihua

2015-07-23

We report the results of a VAMAS (Versailles Project on Advanced Materials and Standards) interlaboratory study on the measurement of composition in organic depth profiling. Layered samples with known binary compositions of Irganox 1010 and either Irganox 1098 or Fmoc-pentafluoro-L-phenylalanine in each layer were manufactured in a single batch and distributed to more than 20 participating laboratories. The samples were analyzed using argon cluster ion sputtering and either X-ray Photoelectron Spectroscopy (XPS) or Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) to generate depth profiles. Participants were asked to estimate the volume fractions in two of the layers and were provided with the compositions of all other layers. Participants using XPS provided volume fractions within 0.03 of the nominal values. Participants using ToF-SIMS either made no attempt, or used various methods that gave results ranging in error from 0.02 to over 0.10 in volume fraction, the latter representing a 50% relative error for a nominal volume fraction of 0.2. Error was predominantly caused by inadequacy in the ability to compensate for primary ion intensity variations and the matrix effect in SIMS. Matrix effects in these materials appear to be more pronounced as the number of atoms in both the primary analytical ion and the secondary ion increase. Using the participants’ data we show that organic SIMS matrix effects can be measured and are remarkably consistent between instruments. We provide recommendations for identifying and compensating for matrix effects. Finally we demonstrate, using a simple normalization method, that virtually all ToF-SIMS participants could have obtained estimates of volume fraction that were at least as accurate and consistent as XPS.

Clinical trials in dentistry in India: Analysis from trial registry.

Science.gov (United States)

Gowri, S; Kannan, Sridharan

2017-01-01

Evidence-based practice requires clinical trials to be performed. In India, if any clinical trial has to be performed, it has to be registered with clinical trial registry of India. Studies have shown that the report of clinical trials is poor in dentistry. Hence, the present study has been conducted to assess the type and trends of clinical trials being undertaken in dentistry in India over a span of 6 years. All the clinical trials which were registered with the Central Trial Registry of India (CTRI) (www.ctri.nic.in) from January 1, 2007 to March 3, 2014 were evaluated using the keyword "dental." Following information were collected for each of the clinical trials obtained from the search; number of centres (single center/multicentric), type of the institution undertaking the research (government/private/combined), study (observational/interventional), study design (randomized/single blinded/double-blinded), type of health condition, type of participants (healthy/patients), sponsors (academia/commercial), phase of clinical trial (Phase 1/2/3/4), publication details (published/not published), whether it was a postgraduate thesis or not and prospective or retrospective registration of clinical trials, methodological quality (method of randomization, allocation concealment). Descriptive statistics was used for analysis of various categories. Trend analysis was done to assess the changes over a period of time. The search yielded a total of 84 trials of which majority of them were single centered. Considering the study design more than half of the registered clinical trials were double-blinded (47/84 [56%]). With regard to the place of conducting a trial, most of the trials were planned to be performed in private hospitals (56/84 [66.7%]). Most (79/84, 94.1%) of the clinical trials were interventional while only 5/84 (5.9%) were observational. Majority (65/84, 77.4%) of the registered clinical trials were recruiting patients while the rest were being done in healthy

Randomized controlled trial in rural Ethiopia to assess a portable water treatment device.

Science.gov (United States)

Boisson, Sophie; Schmidt, Wolf-Peter; Berhanu, Tsegahiwot; Gezahegn, Henock; Clasen, Thomas

2009-08-01

We conducted a randomized controlled trial to assess the Lifestraw Personal pipe-style water treatment device among a rural population in Ethiopia. A total of 313 households (including 1516 persons) were randomly assigned either to an intervention group in which each householder received a Lifestraw Personal or a control. Households were visited fortnightly over a five-month intervention period and asked to report any episode of diarrhea during the previous week. A random sample of 160 devices was tested each month to assess the presence of thermotolerant coliforms (TTC) and residual iodine in treated water and to measure flow rate under simulated use. Members of the intervention group had 25% fewer weeks with diarrhea than those of the control group (longitudinal prevalence ratio = 0.75; 95% CI 0.60; 0.95). All 718 filtered water samples were free of TTC, were free of detectable iodine disinfectant, and showed a constant flow rate over time. After the five-month intervention period, 34% of participants reported use of device in the preceding week and 13% reported consistent use. While the device was associated with a 25% reduction in longitudinal prevalence of diarrhea, low levels of use suggest that much of this effect is likely to be attributable to reporting bias that is common in open trials with nonobjective outcomes.

Results of the eurofoods trial on between-laboratory variation in the analysis of macronutrients in foods

NARCIS (Netherlands)

Hollman, Peter C. H.; Katan, M.B.

1987-01-01

In order to determine the influence of laboratory procedures on nutrient values in different food tables and data banks, an interlaboratory study was set up. Nineteen laboratories participated, and received well-homogenized samples of egg powder, full-fat milk powder, whole rye and wheat meal,

Results of the Eurofood trials on between-laboratory variation in the analysis of macronutrient in foods.

NARCIS (Netherlands)

Hollman, P.C.H.; Katan, M.B.

1987-01-01

In order to determine the influence of laboratory procedures on nutrient values in different food tables and data banks, an interlaboratory study was set up. Nineteen laboratories participated, and received well-homogenized samples of egg powder, full-fat milk powder, whole rye and wheat meal,

Epizone: Interlaboratory Ring Trial to Compare Dna Transfection Efficiencies

DEFF Research Database (Denmark)

Dory, Daniel; Albina, Emmanuel; Kwiatek, Olivier

Chemical-based transfection of DNA into cultured cells is routinely used to study for example viral or cellular gene functions involved in virus replication, to analyse cellular defence mechanisms or develop specific strategies to interfere with virus replication. Other applications include rescu...

Radiometric method for the determination of uranium in soil and air: single-laboratory evaluation and interlaboratory collaborative study

International Nuclear Information System (INIS)

Casella, V.R.; Bishop, C.T.; Glosby, A.A.

1980-02-01

Results of a single-laboratory evaluation and an interlaboratory collaborative study of a method for determining uranium isotopes in soil and air samples are presented. The method is applicable to 10-gram soil samples and to both glass fiber and polystyrene (Microsorban) air filter samples. Sample decomposition is accomplished with a nitric-hydrofluoric acid dissolution. After a solvent extraction step to remove most of the iron present, the uranium is isolated by anion exchange chromatography and electrodeposition. Alpha spectrometry is used to measure the uranium isotopes. Two soil samples, a glass fiber air filter sample, and a polystyrene air filter sample were used to evaluate the method for uranium concentrations ranging from a few tenths to about one hundred disintegrations per minute per sample. Tracer recoveries for the single-laboratory evaluation averaged 78%, while the tracer recoveries for the collaborative study averaged 66%. Although the precision of the collaborative study results did not approach counting statistics errors, the measured uranium concentrations for these samples agreed to within 5% of the reference concentrations when the uranium concentration was greater than one disintegration per minute per gram of soil or one disintegration per minute per air filter

Instruments to measure radon activity concentration or exposure to radon. Interlaboratory comparison 2011

International Nuclear Information System (INIS)

Foerster, Elisabeth; Beck, Thomas; Buchroeder, Helmut; Doering, Joachim; Schmidt, Volkmar

2011-10-01

According to the Directive 96/29/EURATOM the monitoring of occupational radiation exposures shall base on individual measurements carried out by an approved dosimetric service. Pursuant to the European Directive an approved dosimetric service is a body responsible for the calibration, reading or interpretation of individual monitoring devices.., whose capacity to act in this respect is recognized by the competent authorities. This concept will also be applied to radon services issuing passive radon measurement devices. Passive radon measurement devices 1 using solid state nuclear track detectors or electrets are recommended for individual monitoring of exposures to radon. German regulations lay down that radon measuring devices are appropriate for purposes of occupational radiation monitoring if the devices are issued by recognized radon measurement services, and the measurement service submits devices of the same type issued for radon monitoring to regular intercomparisons conducted by BfS. A radon measuring service is recognized by the competent authority if it proves its organizational and technical competence, e. g. by accreditation. These regulations have been introduced in the area of occupational radiation exposures. Nevertheless, it is recommended that radon measuring services which carry out radon measurements in other areas (e.g. dwellings) should subject themselves to these measures voluntarily. The interlaboratory comparisons comprise the organization, exposure, and evaluation of measurements of radon activity concentration or exposure to radon. The comparisons only concern radon-222; radon-220 is not in the scope. Radon services being interested can get further information from the website www.bfs.de/de/ion/radon/fachinfomessung/vergleichspruefungen.html and from the European Information System on Proficiency Testing Schemes (eptis) available in the internet. (orig.)

Multicenter validation of PCR-based method for detection of Salmonella in chicken and pig samples

DEFF Research Database (Denmark)

Malorny, B.; Cook, N.; D'Agostino, M.

2004-01-01

As part of a standardization project, an interlaboratory trial including 15 laboratories from 13 European countries was conducted to evaluate the performance of a noproprietary polymerase chain reaction (PCR)-based method for the detection of Salmonella on artificially contaminated chicken rinse...... or positive. Outlier results caused, for example, by gross departures from the experimental protocol, were omitted from the analysis. For both the chicken rinse and the pig swab samples, the diagnostic sensitivity was 100%, with 100% accordance (repeatability) and concordance (reproducibility). The diagnostic...... specificity was 80.1% (with 85.7% accordance and 67.5% concordance) for chicken rinse, and 91.7% (with 100% accordance and 83.3% concordance) for pig swab. Thus, the interlaboratory variation due to personnel, reagents, thermal cyclers, etc., did not affect the performance of the method, which...

New scoring methodology improves the sensitivity of the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) in clinical trials.

Science.gov (United States)

Verma, Nishant; Beretvas, S Natasha; Pascual, Belen; Masdeu, Joseph C; Markey, Mia K

2015-11-12

As currently used, the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) has low sensitivity for measuring Alzheimer's disease progression in clinical trials. A major reason behind the low sensitivity is its sub-optimal scoring methodology, which can be improved to obtain better sensitivity. Using item response theory, we developed a new scoring methodology (ADAS-CogIRT) for the ADAS-Cog, which addresses several major limitations of the current scoring methodology. The sensitivity of the ADAS-CogIRT methodology was evaluated using clinical trial simulations as well as a negative clinical trial, which had shown an evidence of a treatment effect. The ADAS-Cog was found to measure impairment in three cognitive domains of memory, language, and praxis. The ADAS-CogIRT methodology required significantly fewer patients and shorter trial durations as compared to the current scoring methodology when both were evaluated in simulated clinical trials. When validated on data from a real clinical trial, the ADAS-CogIRT methodology had higher sensitivity than the current scoring methodology in detecting the treatment effect. The proposed scoring methodology significantly improves the sensitivity of the ADAS-Cog in measuring progression of cognitive impairment in clinical trials focused in the mild-to-moderate Alzheimer's disease stage. This provides a boost to the efficiency of clinical trials requiring fewer patients and shorter durations for investigating disease-modifying treatments.

HElmet therapy Assessment in infants with Deformed Skulls (HEADS: protocol for a randomised controlled trial

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van Wijk Renske M

2012-07-01

Full Text Available Abstract Background In The Netherlands, helmet therapy is a commonly used treatment in infants with skull deformation (deformational plagiocephaly or deformational brachycephaly. However, evidence of the effectiveness of this treatment remains lacking. The HEADS study (HElmet therapy Assessment in Deformed Skulls aims to determine the effects and costs of helmet therapy compared to no helmet therapy in infants with moderate to severe skull deformation. Methods/design Pragmatic randomised controlled trial (RCT nested in a cohort study. The cohort study included infants with a positional preference and/or skull deformation at two to four months (first assessment. At 5 months of age, all children were assessed again and infants meeting the criteria for helmet therapy were asked to participate in the RCT. Participants were randomly allocated to either helmet therapy or no helmet therapy. Parents of eligible infants that do not agree with enrolment in the RCT were invited to stay enrolled for follow up in a non-randomisedrandomised controlled trial (nRCT; they were then free to make the decision to start helmet therapy or not. Follow-up assessments took place at 8, 12 and 24 months of age. The main outcome will be head shape at 24 months that is measured using plagiocephalometry. Secondary outcomes will be satisfaction of parents and professionals with the appearance of the child, parental concerns about the future, anxiety level and satisfaction with the treatment, motor development and quality of life of the infant. Finally, compliance and costs will also be determined. Discussion HEADS will be the first study presenting data from an RCT on the effectiveness of helmet therapy. Outcomes will be important for affected children and their parents, health care professionals and future treatment policies. Our findings are likely to influence the reimbursement policies of health insurance companies. Besides these health outcomes, we will be able to

Applicability of the DPPH assay for evaluating the antioxidant capacity of food additives - inter-laboratory evaluation study -.

Science.gov (United States)

Shimamura, Tomoko; Sumikura, Yoshihiro; Yamazaki, Takeshi; Tada, Atsuko; Kashiwagi, Takehiro; Ishikawa, Hiroya; Matsui, Toshiro; Sugimoto, Naoki; Akiyama, Hiroshi; Ukeda, Hiroyuki

2014-01-01

An inter-laboratory evaluation study was conducted in order to evaluate the antioxidant capacity of food additives by using a 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Four antioxidants used as existing food additives (i.e., tea extract, grape seed extract, enju extract, and d-α-tocopherol) and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) were used as analytical samples, and 14 laboratories participated in this study. The repeatability relative standard deviation (RSD(r)) of the IC50 of Trolox, four antioxidants, and the Trolox equivalent antioxidant capacity (TEAC) were 1.8-2.2%, 2.2-2.9%, and 2.1-2.5%, respectively. Thus, the proposed DPPH assay showed good performance within the same laboratory. The reproducibility relative standard deviation (RSD(R)) of IC50 of Trolox, four antioxidants, and TEAC were 4.0-7.9%, 6.0-11%, and 3.7-9.3%, respectively. The RSD(R)/RSD(r) values of TEAC were lower than, or nearly equal to, those of IC50 of the four antioxidants, suggesting that the use of TEAC was effective for reducing the variance among the laboratories. These results showed that the proposed DPPH assay could be used as a standard method to evaluate the antioxidant capacity of food additives.

'PhysioDirect' telephone assessment and advice services for physiotherapy: protocol for a pragmatic randomised controlled trial

Directory of Open Access Journals (Sweden)

Hopper Cherida

2009-08-01

Full Text Available Abstract Background Providing timely access to physiotherapy has long been a problem for the National Health Service in the United Kingdom. In an attempt to improve access some physiotherapy services have introduced a new treatment pathway known as PhysioDirect. Physiotherapists offer initial assessment and advice by telephone, supported by computerised algorithms, and patients are sent written self-management and exercise advice by post. They are invited for face-to-face treatment only when necessary. Although several such services have been developed, there is no robust evidence regarding clinical and cost-effectiveness, nor the acceptability of PhysioDirect. Methods/Design This protocol describes a multi-centre pragmatic individually randomised trial, with nested qualitative research. The aim is to determine the effectiveness, cost-effectiveness, and acceptability of PhysioDirect compared with usual models of physiotherapy based on patients going onto a waiting list and receiving face-to-face care. PhysioDirect services will be established in four areas in England. Adult patients in these areas with musculoskeletal problems who refer themselves or are referred by a primary care practitioner for physiotherapy will be invited to participate in the trial. About 1875 consenting patients will be randomised in a 2:1 ratio to PhysioDirect or usual care. Data about outcome measures will be collected at baseline and 6 weeks and 6 months after randomisation. The primary outcome is clinical improvement at 6 months; secondary outcomes include cost, waiting times, time lost from work and usual activities, patient satisfaction and preference. The impact of PhysioDirect on patients in different age-groups and with different conditions will also be examined. Incremental cost-effectiveness will be assessed in terms of quality adjusted life years in relation to cost. Qualitative methods will be used to explore factors associated with the success or failure of

US Food and Drug Administration Pooled Analysis to Assess the Impact of Bone-Only Metastatic Breast Cancer on Clinical Trial Outcomes and Radiographic Assessments.

Science.gov (United States)

Wedam, Suparna B; Beaver, Julia A; Amiri-Kordestani, Laleh; Bloomquist, Erik; Tang, Shenghui; Goldberg, Kirsten B; Sridhara, Rajeshwari; Ibrahim, Amna; Kim, Geoffrey; Kluetz, Paul; McKee, Amy; Pazdur, Richard

2018-04-20

Purpose The outcome and proportion of patients with bone-only (BO) metastatic breast cancer (MBC) has not been well described. We sought to describe the differential outcomes of patients with BO MBC in clinical trials and explore whether there was a discrepancy in radiographic reads between investigator and blinded independent central review. Methods We pooled and analyzed data on 10,521 patients from 13 prospective trials submitted for MBC treatment in initial or supplemental New Drug or Biologics License Applications from 2005. Three subsets were evaluated: BO, bone with other metastases (BWO), and no bone metastases (NBM). Early discordance rate and late discordance rate were calculated from 3,733 and 2,813 patients subject to a blinded independent central review, respectively. Results Bone metastases were identified in 49% (range: 42% to 73%) of patients across trials. BO disease was present in 12.5% (range: 4% to 26%), dependent on subtype. Investigator-assessed progression-free survival (PFS) and overall survival (OS) for the pooled trials demonstrated improved outcomes for the BO subgroup compared with other subgroups (BO v BWO PFS hazard ratio [HR], 0.64; 95% CI, 0.591 to 0.696; BO v NBM PFS HR, 0.70; 95% CI, 0.65 to 0.76; BO v BWO OS HR, 0.56; 95% CI, 0.50 to 0.61; BO v NBM OS HR, 0.68; 95% CI, 0.61 to 0.76). The BO subgroup has a higher early discordance rate and lower late discordance rate than the BWO and NBM subgroups. Conclusion To our knowledge, this review is the largest analysis to date of the BO subgroup of MBC and suggests this subgroup may have a distinct natural history. There also seems to be a difference in how the local investigators assessed progression events in the BO subgroup when compared with the other two groups.

(60)Co in cast steel matrix: A European interlaboratory comparison for the characterisation of new activity standards for calibration of gamma-ray spectrometers in metallurgy.

Science.gov (United States)

Tzika, Faidra; Burda, Oleksiy; Hult, Mikael; Arnold, Dirk; Marroyo, Belén Caro; Dryák, Pavel; Fazio, Aldo; Ferreux, Laurent; García-Toraño, Eduardo; Javornik, Andrej; Klemola, Seppo; Luca, Aurelian; Moser, Hannah; Nečemer, Marijan; Peyrés, Virginia; Reis, Mario; Silva, Lidia; Šolc, Jaroslav; Svec, Anton; Tyminski, Zbigniew; Vodenik, Branko; Wätjen, Uwe

2016-08-01

Two series of activity standards of (60)Co in cast steel matrix, developed for the calibration of gamma-ray spectrometry systems in the metallurgical sector, were characterised using a European interlaboratory comparison among twelve National Metrology Institutes and one international organisation. The first standard, consisting of 14 disc shaped samples, was cast from steel contaminated during production ("originally"), and the second, consisting of 15 similar discs, from artificially-contaminated ("spiked") steel. The reference activity concentrations of (60)Co in the cast steel standards were (1.077±0.019) Bqg(-1) on 1 January 2013 12h00 UT and (1.483±0.022) Bqg(-1) on 1 June 2013 12h00 UT, respectively. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Primary pulmonary non-small cell carcinomas: the College of American Pathologists Interlaboratory Comparison Program confirms a significant trend toward subcategorization based upon fine-needle aspiration cytomorphology alone.

Science.gov (United States)

Yildiz-Aktas, Isil Z; Sturgis, Charles D; Barkan, Guliz A; Souers, Rhona J; Fraig, Mostafa M; Laucirica, Rodolfo; Khalbuss, Walid E; Moriarty, Ann T

2014-01-01

Context.-Subtyping of non-small cell lung carcinomas (NSCLCs) is necessary for optimal patient management with specific diagnoses triggering specific molecular tests and affecting therapy. Objective.-To assess the accuracy of the participants of the College of American Pathologists Interlaboratory Comparison Program in diagnosing and subtyping NSCLC fine-needle aspiration (FNA) slides, based on morphology alone, considering preparation and participant type and trends over time. Design.-The performance of program participants was reviewed for the 5-year period spanning 2007-2011. Lung FNA challenges with reference diagnoses of adenocarcinoma and squamous cell carcinoma (SCC) were evaluated for diagnostic concordance by using a nonlinear mixed model analysis. Results.-There were 10 493 pathologist and 6378 cytotechnologist responses with concordance rates of 97.4% and 97.9% for malignancy, respectively. Overall concordance rates for subcategorization were 54.6% for adenocarcinoma and 74.9% for SCC. For the exact reference diagnoses, pathologists performed better for adenocarcinoma and cytotechnologists performed better for SCC. Accurate subcategorization of adenocarcinomas significantly increased over time with 31.5% of adenocarcinomas classified as NSCLC in 2007 and 25.5% of adenocarcinomas classified as NSCLC in 2011 (P alone. During the study period, a statistically significant trend was confirmed toward greater accuracy of subcategorization of adenocarcinomas, suggesting that participants are cognizant of the impact that more specific cytomorphologic interpretations have in directing molecular triage and therapy.

Assessing the feasibility of the Effectiveness of Discontinuing Bisphosphonates trial: a pilot study.

Science.gov (United States)

Wright, N C; Foster, P J; Mudano, A S; Melnick, J A; Lewiecki, M E; Shergy, W J; Curtis, J R; Cutter, G R; Danila, M I; Kilgore, M L; Lewis, E C; Morgan, S L; Redden, D T; Warriner, A H; Saag, K G

2017-08-01

The Effectiveness of Discontinuing Bisphosphonates (EDGE) study is a planned pragmatic clinical trial to guide "drug holiday" clinical decision making. This pilot study assessed work flow and feasibility of such a study. While participant recruitment and treatment adherence were suboptimal, administrative procedures were generally feasible and minimally disrupted clinic flow. The comparative effectiveness of continuing or discontinuing long-term alendronate (ALN) on fractures is unknown. A large pragmatic ALN discontinuation study has potential to answer this question. We conducted a 6-month pilot study of the planned the EDGE study among current long-term ALN users (women aged ≥65 with ≥3 years of ALN use) to determine study work flow and feasibility including evaluating the administrative aspects of trial conduct (e.g., time to contract, institutional review board (IRB) approval), assessing rates of site and participant recruitment, and evaluating post-randomization outcomes, including adherence, bisphosphonate-associated adverse events, and participant and site satisfaction. We assessed outcomes 1 and 6 months after randomization. Nine sites participated, including seven community-based medical practices and two academic medical centers. On average (SD), contract execution took 3.4 (2.3) months and IRB approval took 13.9 (4.1) days. Sites recruited 27 participants (13 to continue ALN and 14 to discontinue ALN). Over follow-up, 22% of participants did not adhere to their randomization assignment: 30.8% in the continuation arm and 14.3% in the discontinuation arm. No fractures or adverse events were reported. Sites reported no issues regarding work flow, and participants were highly satisfied with the study. Administrative procedures of the EDGE study were generally feasible, with minimal disruption to clinic flow. In this convenience sample, participant recruitment was suboptimal across most practice sites. Accounting for low treatment arm adherence, a

A counterfactual p-value approach for benefit-risk assessment in clinical trials.

Science.gov (United States)

Zeng, Donglin; Chen, Ming-Hui; Ibrahim, Joseph G; Wei, Rachel; Ding, Beiying; Ke, Chunlei; Jiang, Qi

2015-01-01

Clinical trials generally allow various efficacy and safety outcomes to be collected for health interventions. Benefit-risk assessment is an important issue when evaluating a new drug. Currently, there is a lack of standardized and validated benefit-risk assessment approaches in drug development due to various challenges. To quantify benefits and risks, we propose a counterfactual p-value (CP) approach. Our approach considers a spectrum of weights for weighting benefit-risk values and computes the extreme probabilities of observing the weighted benefit-risk value in one treatment group as if patients were treated in the other treatment group. The proposed approach is applicable to single benefit and single risk outcome as well as multiple benefit and risk outcomes assessment. In addition, the prior information in the weight schemes relevant to the importance of outcomes can be incorporated in the approach. The proposed CPs plot is intuitive with a visualized weight pattern. The average area under CP and preferred probability over time are used for overall treatment comparison and a bootstrap approach is applied for statistical inference. We assess the proposed approach using simulated data with multiple efficacy and safety endpoints and compare its performance with a stochastic multi-criteria acceptability analysis approach.

Study of the trial subjects’ protection aspects in Phase I clinical trials and bioequivalence studies

Directory of Open Access Journals (Sweden)

K. O. Zupanets

2016-03-01

Full Text Available Protection of rights, health and well-being of persons who are taking the drug during the trial (trial subjects is one of the basic principles of clinical trials (CT management. Aim. In order to study key aspects of volunteer protection, determine factors that influence these indicators and estimate the importance of ensuring their proper implementation on the clinical site (CS three survey of 135 trial subjects were carried out to evaluate the importance of assessing the impact of factors such as the procedure of signing the informed consent (IC at the CS and testing procedures for HIV / AIDS, hepatitis and others. Assessment of the quality of life of trial subjects as indirect indicator of the quality of clinical trials that ensures the proper protection of their life was the subject of the third survey. Methods and results. The general model of the relationship between the key aspects of the trial subjects protection and the factors which are providing them during the clinical trials of drugs management was substantiated, which included the main aspects of the trial subjects’ protection, protective factors and basic CT management procedures, the impact of the above factors on the possibility of providing protection aspects depends on their implementation quality. It was found that trial subjects’ protection improvement can be achieved during the IC signing process. It is necessary to ensure a higher level of volunteers understanding of the terms that could be used in the IC form. Regarding the procedure of compulsory testing for HIV/AIDS in the course of screening, we can conclude that the majority of the trial subjects believe that this procedure is an additional factor in their health protection and do not consider it as an excessive psychological pressure on them. Conclusion. Assessing the quality of life during the bioequivalence study at the CS makes possible to reach a conclusion on general well-being and satisfaction with those

Toward Semi-automated Assessment of Target Volume Delineation in Radiotherapy Trials: The SCOPE 1 Pretrial Test Case

Energy Technology Data Exchange (ETDEWEB)

Gwynne, Sarah, E-mail: Sarah.Gwynne2@wales.nhs.uk [Department of Clinical Oncology, Velindre Cancer Centre, Cardiff, Wales (United Kingdom); Spezi, Emiliano; Wills, Lucy [Department of Medical Physics, Velindre Cancer Centre, Cardiff, Wales (United Kingdom); Nixon, Lisette; Hurt, Chris [Wales Cancer Trials Unit, School of Medicine, Cardiff University, Cardiff, Wales (United Kingdom); Joseph, George [Department of Diagnostic Radiology, Velindre Cancer Centre, Cardiff, Wales (United Kingdom); Evans, Mererid [Department of Clinical Oncology, Velindre Cancer Centre, Cardiff, Wales (United Kingdom); Griffiths, Gareth [Wales Cancer Trials Unit, School of Medicine, Cardiff University, Cardiff, Wales (United Kingdom); Crosby, Tom [Department of Clinical Oncology, Velindre Cancer Centre, Cardiff, Wales (United Kingdom); Staffurth, John [Division of Cancer, School of Medicine, Cardiff University, Cardiff, Wales (United Kingdom)

2012-11-15

Purpose: To evaluate different conformity indices (CIs) for use in the analysis of outlining consistency within the pretrial quality assurance (Radiotherapy Trials Quality Assurance [RTTQA]) program of a multicenter chemoradiation trial of esophageal cancer and to make recommendations for their use in future trials. Methods and Materials: The National Cancer Research Institute SCOPE 1 trial is an ongoing Cancer Research UK-funded phase II/III randomized controlled trial of chemoradiation with capecitabine and cisplatin with or without cetuximab for esophageal cancer. The pretrial RTTQA program included a detailed radiotherapy protocol, an educational package, and a single mid-esophageal tumor test case that were sent to each investigator to outline. Investigator gross tumor volumes (GTVs) were received from 50 investigators in 34 UK centers, and CERR (Computational Environment for Radiotherapy Research) was used to perform an assessment of each investigator GTV against a predefined gold-standard GTV using different CIs. A new metric, the local conformity index (l-CI), that can localize areas of maximal discordance was developed. Results: The median Jaccard conformity index (JCI) was 0.69 (interquartile range, 0.62-0.70), with 14 of 50 investigators (28%) achieving a JCI of 0.7 or greater. The median geographical miss index was 0.09 (interquartile range, 0.06-0.16), and the mean discordance index was 0.27 (95% confidence interval, 0.25-0.30). The l-CI was highest in the middle section of the volume, where the tumor was bulky and more easily definable, and identified 4 slices where fewer than 20% of investigators achieved an l-CI of 0.7 or greater. Conclusions: The available CIs analyze different aspects of a gold standard-observer variation, with JCI being the most useful as a single metric. Additional information is provided by the l-CI and can focus the efforts of the RTTQA team in these areas, possibly leading to semi-automated outlining assessment.

Toward Semi-automated Assessment of Target Volume Delineation in Radiotherapy Trials: The SCOPE 1 Pretrial Test Case

International Nuclear Information System (INIS)

Gwynne, Sarah; Spezi, Emiliano; Wills, Lucy; Nixon, Lisette; Hurt, Chris; Joseph, George; Evans, Mererid; Griffiths, Gareth; Crosby, Tom; Staffurth, John

2012-01-01

Purpose: To evaluate different conformity indices (CIs) for use in the analysis of outlining consistency within the pretrial quality assurance (Radiotherapy Trials Quality Assurance [RTTQA]) program of a multicenter chemoradiation trial of esophageal cancer and to make recommendations for their use in future trials. Methods and Materials: The National Cancer Research Institute SCOPE 1 trial is an ongoing Cancer Research UK-funded phase II/III randomized controlled trial of chemoradiation with capecitabine and cisplatin with or without cetuximab for esophageal cancer. The pretrial RTTQA program included a detailed radiotherapy protocol, an educational package, and a single mid-esophageal tumor test case that were sent to each investigator to outline. Investigator gross tumor volumes (GTVs) were received from 50 investigators in 34 UK centers, and CERR (Computational Environment for Radiotherapy Research) was used to perform an assessment of each investigator GTV against a predefined gold-standard GTV using different CIs. A new metric, the local conformity index (l-CI), that can localize areas of maximal discordance was developed. Results: The median Jaccard conformity index (JCI) was 0.69 (interquartile range, 0.62-0.70), with 14 of 50 investigators (28%) achieving a JCI of 0.7 or greater. The median geographical miss index was 0.09 (interquartile range, 0.06-0.16), and the mean discordance index was 0.27 (95% confidence interval, 0.25-0.30). The l-CI was highest in the middle section of the volume, where the tumor was bulky and more easily definable, and identified 4 slices where fewer than 20% of investigators achieved an l-CI of 0.7 or greater. Conclusions: The available CIs analyze different aspects of a gold standard–observer variation, with JCI being the most useful as a single metric. Additional information is provided by the l-CI and can focus the efforts of the RTTQA team in these areas, possibly leading to semi-automated outlining assessment.

Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) Trial: Baseline Characteristics

Science.gov (United States)

Diamond, Michael P.; Legro, Richard S.; Coutifaris, Christos; Alvero, Ruben; Robinson, Randal D.; Casson, Peter; Christman, Gregory M.; Ager, Joel; Huang, Hao; Hansen, Karl R.; Baker, Valerie; Usadi, Rebecca; Seungdamrong, Aimee; Bates, G. Wright; Rosen, R. Mitchell; Haisonleder, Daniell; Krawetz, Stephen A.; Barnhart, Kurt; Trussell, J.C.; Jin, Yufeng; Santoro, Nanette; Eisenberg, Esther; Zhang, Heping

2015-01-01

Objective To identify baseline characteristics of women with unexplained infertility to determine whether treatment with an aromatase inhibitor will result in a lower rate of multiple gestations than current standard ovulation induction medications. Design Randomized, prospective clinical trial Patients 900 couples with unexplained infertility Interventions: Ovarian stimulation with gonadotropins, clomiphene citrate, or letrozole in conjunction with intrauterine insemination. Setting Multicenter University based clinical practices. Main Outcome Measures Demographic, laboratory, imaging, and survey characteristics. Interventions Collection of baseline demographics, blood samples, and ultrasonographic assessments. Results Demographic characteristics of women receiving clomiphene citrate, letrozole, or gonadotropins for ovarian stimulation were very consistent. Their mean age was 32.2 ± 4.4 years and infertility duration was 34.7± 25.7 months, with 59% primary infertility. More than 1/3 of the women were current or past smokers. The mean BMI was 27 and mean AMH level was 2.6; only 11 women (1.3%) had antral follicle counts of less than 5. Similar observations were identified for hormonal profiles, ultrasound characterization of the ovaries, semen parameters, and quality of life assessments in both male and female partners. Conclusion The cause of infertility in the couples recruited to this treatment trial is elusive, as the women were regularly ovulating and had evidence of good ovarian reserve both by basal FSH, AMH levels, and antral follicle counts; the male partners had normal semen parameters. The three treatment subgroups have common baseline characteristics, thereby providing comparable patient populations for testing the hypothesis that use of letrozole for ovarian stimulation can reduce the rates of multiples from that observed with gonadotropin and clomiphene citrate treatment. PMID:25707331

Guidelines for time-to-event end point definitions in sarcomas and gastrointestinal stromal tumors (GIST) trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†.

Science.gov (United States)

Bellera, C A; Penel, N; Ouali, M; Bonvalot, S; Casali, P G; Nielsen, O S; Delannes, M; Litière, S; Bonnetain, F; Dabakuyo, T S; Benjamin, R S; Blay, J-Y; Bui, B N; Collin, F; Delaney, T F; Duffaud, F; Filleron, T; Fiore, M; Gelderblom, H; George, S; Grimer, R; Grosclaude, P; Gronchi, A; Haas, R; Hohenberger, P; Issels, R; Italiano, A; Jooste, V; Krarup-Hansen, A; Le Péchoux, C; Mussi, C; Oberlin, O; Patel, S; Piperno-Neumann, S; Raut, C; Ray-Coquard, I; Rutkowski, P; Schuetze, S; Sleijfer, S; Stoeckle, E; Van Glabbeke, M; Woll, P; Gourgou-Bourgade, S; Mathoulin-Pélissier, S

2015-05-01

The use of potential surrogate end points for overall survival, such as disease-free survival (DFS) or time-to-treatment failure (TTF) is increasingly common in randomized controlled trials (RCTs) in cancer. However, the definition of time-to-event (TTE) end points is rarely precise and lacks uniformity across trials. End point definition can impact trial results by affecting estimation of treatment effect and statistical power. The DATECAN initiative (Definition for the Assessment of Time-to-event End points in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for RCT in sarcomas and gastrointestinal stromal tumors (GIST). We first carried out a literature review to identify TTE end points (primary or secondary) reported in publications of RCT. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points. Recommendations were developed through a validated consensus method formalizing the degree of agreement among experts. Recommended guidelines for the definition of TTE end points commonly used in RCT for sarcomas and GIST are provided for adjuvant and metastatic settings, including DFS, TTF, time to progression and others. Use of standardized definitions should facilitate comparison of trials' results, and improve the quality of trial design and reporting. These guidelines could be of particular interest to research scientists involved in the design, conduct, reporting or assessment of RCT such as investigators, statisticians, reviewers, editors or regulatory authorities. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Juvenile offenders: competence to stand trial.

Science.gov (United States)

Soulier, Matthew

2012-12-01

This article details the legal background and assists the reader in the preparation and practical conduct of evaluations regarding juvenile adjudicative competency. The material is presented to be useful as a guide to direct questions of competency and covers aspects of evaluation that include: legal standard for competency to stand trial, developmental immaturity, current practice in juvenile competency to stand trial, forensic evaluation of juvenile competency to stand trial, organizing the evaluation, collateral sources of information, psychiatric evaluation of juvenile adjudicative competency, assessment of mental disorder and intellectual disability, assessment of developmental status, assessment of functional abilities for adjudicative competence, and reaching the forensic opinion. Copyright © 2012 Elsevier Inc. All rights reserved.

A Randomized Trial of Genetic and Environmental Risk Assessment (GERA) for Colorectal Cancer Risk in Primary Care: Trial Design and Baseline Findings

Science.gov (United States)

Myers, Ronald E.; Manne, Sharon L.; Wilfond, Benjamin; Sifri, Randa; Ziring, Barry; Wolf, Thomas A.; Cocroft, James; Ueland, Amy; Petrich, Anett; Swan, Heidi; DiCarlo, Melissa; Weinberg, David S.

2010-01-01

Purpose This paper describes an ongoing randomized controlled trial designed to assess the impact of genetic and environmental risk assessment (GERA) on colorectal cancer (CRC) screening. Methods The trial includes asymptomatic patients who are 50-79 years and are not up-to-date with CRC screening guidelines. Patients who responded to a baseline telephone survey are randomized to a GERA or Control group. GERA Group participants meet with a nurse, decide whether to have a GERA blood test (a combination of genetic polymorphism and folate), and, if tested, receive GERA feedback. Follow-up telephone surveys are conducted at one and six months. A chart audit is performed at six months. Results Of 2,223 eligible patients, 562 (25%) have enrolled. Patients who enrolled in the study were significantly younger than those who did not (p<0.001). Participants tended to be 50-59 years (64%), female (58%), white (52%), married (51%), and have more than a high school education (67%). At baseline, most participants had some knowledge of CRC screening and GERA, viewed CRC screening favorably, and reported that they had decided to do screening. Almost half had worries and concerns about CRC. Conclusions One in four eligible primary care patients enrolled in the study. Age was negatively associated with enrollment. Prospective analyses using data for all participants will provide more definitive information on GERA uptake and the impact of GERA feedback. PMID:20828635

Assessment of clinical trial participant patient satisfaction: a call to action.

Science.gov (United States)

Pflugeisen, Bethann Mangel; Rebar, Stacie; Reedy, Anne; Pierce, Roslyn; Amoroso, Paul J

2016-10-06

As patient satisfaction scores become increasingly relevant in today's health care market, we sought to evaluate satisfaction of the unique subset of patients enrolling in clinical trials in a research facility embedded within a community hospital system. We developed and deployed a patient satisfaction survey tailored to clinical trial patients who consented to and/or completed a clinical trial in our research institute in the prior year. The survey was distributed to 222 patients. Likert scale responses were analyzed using top box and percentile rank procedures. Correlation analysis was used to evaluate associations between the clinical trial experience and intent to return to our system for routine care. Ninety surveys were returned in the 6 months following the mailing for a 41 % response rate; the bulk of these (N = 81) were returned within 6 weeks of the mailing. The questions with the highest ranking responses were related to interactions with staff (84th percentile or higher). Fifty-one point one percent of patients (64th percentile) strongly agreed that they would seek future care in our system. Patient intent to return to the provider seen during the clinical trial was most highly correlated with intent to seek future care within our system (r = 0.54, p system-based clinical trials and the relationship between clinical trial participation and perception of the healthcare system as a desirable resource for routine medical care. We argue that this work is invaluable to the research community and submit a call to action to our peers to begin systematic evaluation of clinical trial patient satisfaction.

A Virtual Clinical Trial of FDG-PET Imaging of Breast Cancer: Effect of Variability on Response Assessment1

OpenAIRE

Harrison, Robert L; Elston, Brian F; Doot, Robert K; Lewellen, Thomas K; Mankoff, David A; Kinahan, Paul E

2014-01-01

INTRODUCTION: There is growing interest in using positron emission tomography (PET) standardized uptake values (SUVs) to assess tumor response to therapy. However, many error sources compromise the ability to detect SUV changes. We explore relationships between these errors and overall SUV variability. METHODS: We used simulations in a virtual clinical trial framework to study impacts of error sources from scanning and analysis effects on assessment of SUV changes. We varied tumor diameter, s...

Novel assessment tools to evaluate clinical and laboratory responses in a subset of patients enrolled in the Rituximab in Myositis trial.

Science.gov (United States)

Rider, Lisa G; Yip, Adrienne L; Horkayne-Szakaly, Iren; Volochayev, Rita; Shrader, Joseph A; Turner, Maria L; Kong, Heidi H; Jain, Minal S; Jansen, Anna V; Oddis, Chester V; Fleisher, Thomas A; Miller, Frederick W

2014-01-01

We aimed to assess changes in myositis core set measures and ancillary clinical and laboratory data from the National Institutes of Health's subset of patients enrolled in the Rituximab in Myositis trial. Eighteen patients (5 dermatomyositis, 8 polymyositis, 5 juvenile dermatomyositis) completed more in-depth testing of muscle strength and cutaneous assessments, patient-reported outcomes, and laboratory tests before and after administration of rituximab. Percentage change in individual measures and in the definitions of improvement (DOIs) and standardized response means were examined over 44 weeks. Core set activity measures improved by 18-70% from weeks 0-44 and were sensitive to change. Fifteen patients met the DOI at week 44, 9 patients met a DOI 50% response, and 4 met a DOI 70% response. Muscle strength and function measures were more sensitive to change than cutaneous assessments. Constitutional, gastrointestinal, and pulmonary systems improved 44-70%. Patient-reported outcomes improved up to 28%. CD20+ B cells were depleted in the periphery, but B cell depletion was not associated with clinical improvement at week 16. This subset of patients had high rates of clinical response to rituximab, similar to patients in the overall trial. Most measures were responsive, and muscle strength had a greater degree of change than cutaneous assessments. Several novel assessment tools, including measures of strength and function, extra-muscular organ activity, fatigue, and health-related quality of life, are promising for use in future myositis trials. Further study of B cell-depleting therapies in myositis, particularly in treatment-naïve patients, is warranted.

Safety and nutritional assessment of GM plants and derived food and feed: The role of animal feeding trials

NARCIS (Netherlands)

Haver, van E.; Alink, G.M.; Cockburn, A.; Kuiper, H.A.; Peijnenburg, A.A.C.M.

2008-01-01

In this report the various elements of the safety and nutritional assessment procedure for genetically modified (GM) plant derived food and feed are discussed, in particular the potential and limitations of animal feeding trials for the safety and nutritional testing of whole GM food and feed. The

Statins but not aspirin reduce thrombotic risk assessed by thrombin generation in diabetic patients without cardiovascular events: the RATIONAL trial.

Directory of Open Access Journals (Sweden)

Alejandro Macchia

Full Text Available The systematic use of aspirin and statins in patients with diabetes and no previous cardiovascular events is controversial. We sought to assess the effects of aspirin and statins on the thrombotic risk assessed by thrombin generation (TG among patients with type II diabetes mellitus and no previous cardiovascular events.Prospective, randomized, open, blinded to events evaluation, controlled, 2×2 factorial clinical trial including 30 patients randomly allocated to aspirin 100 mg/d, atorvastatin 40 mg/d, both or none. Outcome measurements included changes in TG levels after treatment (8 to 10 weeks, assessed by a calibrated automated thrombogram. At baseline all groups had similar clinical and biochemical profiles, including TG levels. There was no interaction between aspirin and atorvastatin. Atorvastatin significantly reduced TG measured as peak TG with saline (85.09±55.34 nmol vs 153.26±75.55 nmol for atorvastatin and control groups, respectively; p = 0.018. On the other hand, aspirin had no effect on TG (121.51±81.83 nmol vs 116.85±67.66 nmol, for aspirin and control groups, respectively; p = 0.716. The effects of treatments on measurements of TG using other agonists were consistent.While waiting for data from ongoing large clinical randomized trials to definitively outline the role of aspirin in primary prevention, our study shows that among diabetic patients without previous vascular events, statins but not aspirin reduce thrombotic risk assessed by TG.ClinicalTrials.gov NCT00793754.

Nuclear Nonproliferation Ontology Assessment Team Final Report

Energy Technology Data Exchange (ETDEWEB)

Strasburg, Jana D.; Hohimer, Ryan E.

2012-01-01

Final Report for the NA22 Simulations, Algorithm and Modeling (SAM) Ontology Assessment Team's efforts from FY09-FY11. The Ontology Assessment Team began in May 2009 and concluded in September 2011. During this two-year time frame, the Ontology Assessment team had two objectives: (1) Assessing the utility of knowledge representation and semantic technologies for addressing nuclear nonproliferation challenges; and (2) Developing ontological support tools that would provide a framework for integrating across the Simulation, Algorithm and Modeling (SAM) program. The SAM Program was going through a large assessment and strategic planning effort during this time and as a result, the relative importance of these two objectives changed, altering the focus of the Ontology Assessment Team. In the end, the team conducted an assessment of the state of art, created an annotated bibliography, and developed a series of ontological support tools, demonstrations and presentations. A total of more than 35 individuals from 12 different research institutions participated in the Ontology Assessment Team. These included subject matter experts in several nuclear nonproliferation-related domains as well as experts in semantic technologies. Despite the diverse backgrounds and perspectives, the Ontology Assessment team functioned very well together and aspects could serve as a model for future inter-laboratory collaborations and working groups. While the team encountered several challenges and learned many lessons along the way, the Ontology Assessment effort was ultimately a success that led to several multi-lab research projects and opened up a new area of scientific exploration within the Office of Nuclear Nonproliferation and Verification.

A standardized conjugation protocol to assess antibiotic resistance transfer between lactococcal species

NARCIS (Netherlands)

Lampkowska, J.; Feld, L.; Monaghan, A.; Toomey, N.; Schjørring, S.; Jacobsen, B.; Voet, van der H.; Andersen, S.R.; Bolton, D.; Aarts, H.J.M.; Krogfelt, K.A.; Wilcks, A.; Bardowski, J.K.

2008-01-01

Optimal conditions and a standardized method for conjugation between two model lactococcal strains, Lactococcus lactis SH4174 (pAMbeta1-containing, erythromycin resistant donor) and L. lactis Bu2-60 (plasmid-free, erythromycin sensitive recipient), were developed and tested in a inter-laboratory

Fundamentals of clinical trials

CERN Document Server

Friedman, Lawrence M; DeMets, David L; Reboussin, David M; Granger, Christopher B

2015-01-01

This is the fifth edition of a very successful textbook on clinical trials methodology, written by recognized leaders who have long and extensive experience in all areas of clinical trials. The three authors of the first four editions have been joined by two others who add great expertise.  Most chapters have been revised considerably from the fourth edition.  A chapter on regulatory issues has been included and the chapter on data monitoring has been split into two and expanded.  Many contemporary clinical trial examples have been added.  There is much new material on adverse events, adherence, issues in analysis, electronic data, data sharing, and international trials.  This book is intended for the clinical researcher who is interested in designing a clinical trial and developing a protocol. It is also of value to researchers and practitioners who must critically evaluate the literature of published clinical trials and assess the merits of each trial and the implications for the care and treatment of ...

Trial application of the candidate root cause categorization scheme and preliminary assessment of selected data bases for the root causes of component failures program

International Nuclear Information System (INIS)

Bruske, S.Z.; Cadwallader, L.C.; Stepina, P.L.

1985-04-01

The objective of the Nuclear Regulatory Commission's (NRC) Root Causes of Component Failures Program is to develop and apply a categorization scheme for identifying root causes of failures for components that comprise safety and safety support systems of nuclear power plants. Results from this program will provide valuable input in the areas of probabilistic risk assessment, reliability assurance, and application of risk assessments in the inspection program. This report presents the trial application and assessment of the candidate root cause categorization scheme to three failure data bases: the In-Plant Reliability Data System (IPRDS), the Licensee Event Report (LER) data base, and the Nuclear Plant Reliability Data System (NPRDS). Results of the trial application/assessment show that significant root cause information can be obtained from these failure data bases

Results of the Interlaboratory Exercise CNS/CIEMAT-2008 among Environmental Radioactivity Laboratories (Phosphogypsum); Evaluacion de la Intercomparacion CSN/CIEMAT-2008 entre Laboratorios Nacionales de Radiactividad Ambiental (Fosfoyeso)

Energy Technology Data Exchange (ETDEWEB)

Romero, M L; Barrera, M; Valino, F

2010-05-27

The document describes the outcome of the CSN/CIEMAT-2008 interlaboratory test comparison among environmental radioactivity laboratories. The exercise was organised according to the ISO-43 and the ISO/IUPAC/AOAC. Aphosphogypsum material was used as a test sample, in an attempt to evaluate the performance of the laboratories analyzing NORM (Naturally-Occurring Radioactive Materials). The analysis required were: U-238, Th-234, U-234, Th-230, Ra-226, Pb-214, Bi-214, Pb-210, Po-210, Th-232 and U-235, and also gross alpha and gross beta activities. Reference values have been established according to the method of consensus of expert laboratories, with four international laboratories of credited experience: IAEA Seibersdorf, IAEA MEL, IRSN-Orsay and Sta.Teresa ENEA. The results of the exercise were computed for 34 answering laboratories and their analytical performance was assessed using the z-score. Robust statistics of the participants results was applied to obtain the median and standard deviation, to achieve a more complete and objective study of the laboratories performance. The exercise has shown an homogeneous behaviour of laboratories, being statistical parameters from the results close to the assigned Reference Values. Participant laboratories have demonstrated their ability to determine natural radionuclides in phosphogypsum samples (NORM material) with a satisfactory quality level. The scheme has also allowed examining the capability of laboratories to determine the activities of natural radionuclides at the equilibrium. (Author) 10 refs.

Liver safety assessment in special populations (hepatitis B, C, and oncology trials).

Science.gov (United States)

Kullak-Ublick, Gerd A; Merz, Michael; Griffel, Louis; Kaplowitz, Neil; Watkins, Paul B

2014-11-01

The FDA guidance for industry in the premarketing clinical evaluation of drug-induced liver injury (DILI) is the most specific regulatory guidance currently available and has been useful in setting standards for the great majority of clinical indications involving subjects with a low risk of liver disorders. However, liver safety assessment faces challenges in populations with underlying liver disease, such as viral hepatitis or metastatic cancer. This is an important issue because there are currently many promising anti-viral and oncologic therapies in clinical development, with a trend toward oral therapies with reduced side effects. Without clearer guidelines, questions regarding liver safety may become a major factor in regulatory approval and ultimately physician uptake of the new treatments. The lack of consensus in defining stopping rules based on serum alanine aminotransferase (ALT) levels underscores the need for precompetitive data sharing to improve our understanding of DILI in these populations and to allow evidence-based rather than empirical definition of stopping rules. A workshop was convened to discuss best practices for the assessment of drug-induced liver injury (DILI) in clinical trials.

Clinical trials of homoeopathy.

Science.gov (United States)

Kleijnen, J; Knipschild, P; ter Riet, G

1991-01-01

OBJECTIVE--To establish whether there is evidence of the efficacy of homoeopathy from controlled trials in humans. DESIGN--Criteria based meta-analysis. Assessment of the methodological quality of 107 controlled trials in 96 published reports found after an extensive search. Trials were scored using a list of predefined criteria of good methodology, and the outcome of the trials was interpreted in relation to their quality. SETTING--Controlled trials published world wide. MAIN OUTCOME MEASURES--Results of the trials with the best methodological quality. Trials of classical homoeopathy and several modern varieties were considered separately. RESULTS--In 14 trials some form of classical homoeopathy was tested and in 58 trials the same single homoeopathic treatment was given to patients with comparable conventional diagnosis. Combinations of several homoeopathic treatments were tested in 26 trials; isopathy was tested in nine trials. Most trials seemed to be of very low quality, but there were many exceptions. The results showed a positive trend regardless of the quality of the trial or the variety of homeopathy used. Overall, of the 105 trials with interpretable results, 81 trials indicated positive results whereas in 24 trials no positive effects of homoeopathy were found. The results of the review may be complicated by publication bias, especially in such a controversial subject as homoeopathy. CONCLUSIONS--At the moment the evidence of clinical trials is positive but not sufficient to draw definitive conclusions because most trials are of low methodological quality and because of the unknown role of publication bias. This indicates that there is a legitimate case for further evaluation of homoeopathy, but only by means of well performed trials. PMID:1825800

Are pilot trials useful for predicting randomisation and attrition rates in definitive studies: A review of publicly funded trials

Science.gov (United States)

Whitehead, Amy; Pottrill, Edward; Julious, Steven A; Walters, Stephen J

2018-01-01

Background/aims: External pilot trials are recommended for testing the feasibility of main or confirmatory trials. However, there is little evidence that progress in external pilot trials actually predicts randomisation and attrition rates in the main trial. To assess the use of external pilot trials in trial design, we compared randomisation and attrition rates in publicly funded randomised controlled trials with rates in their pilots. Methods: Randomised controlled trials for which there was an external pilot trial were identified from reports published between 2004 and 2013 in the Health Technology Assessment Journal. Data were extracted from published papers, protocols and reports. Bland–Altman plots and descriptive statistics were used to investigate the agreement of randomisation and attrition rates between the full and external pilot trials. Results: Of 561 reports, 41 were randomised controlled trials with pilot trials and 16 met criteria for a pilot trial with sufficient data. Mean attrition and randomisation rates were 21.1% and 50.4%, respectively, in the pilot trials and 16.8% and 65.2% in the main. There was minimal bias in the pilot trial when predicting the main trial attrition and randomisation rate. However, the variation was large: the mean difference in the attrition rate between the pilot and main trial was −4.4% with limits of agreement of −37.1% to 28.2%. Limits of agreement for randomisation rates were −47.8% to 77.5%. Conclusion: Results from external pilot trials to estimate randomisation and attrition rates should be used with caution as comparison of the difference in the rates between pilots and their associated full trial demonstrates high variability. We suggest using internal pilot trials wherever appropriate. PMID:29361833

Assessment of complementary feeding of Canadian infants: effects on microbiome & oxidative stress, a randomized controlled trial.

Science.gov (United States)

Qasem, Wafaa; Azad, Meghan B; Hossain, Zakir; Azad, Elnaz; Jorgensen, Sarah; Castillo San Juan, Sandra; Cai, Chenxi; Khafipour, Ehsan; Beta, Trust; Roberts, L Jackson; Friel, James

2017-02-14

The World Health Organization recommends exclusive breastfeeding until 6 months followed by introduction of iron-rich complementary foods (CFs). The aim of this study was to determine the impact of different iron-rich CFs on infant gut inflammation and microbiota. Eighty-seven exclusively breastfed infants were randomly assigned to receive one of the following as their first CF: iron-fortified cereal (Cer), iron-fortified cereal with fruit (Cer + Fr), or meat (M). Urine and stool samples were collected to assess reactive oxygen species (ROS) generation, gut microbiota and inflammation. Fecal iron differed across feeding groups (p microbiota richness increased after introduction of M or Cer + Fr. Regardless of feeding group, Coriobacteriaceae were positively correlated with ROS and Staphylococcaceae were negatively correlated with calprotectin. Choice of first CF may influence gut inflammation and microbiota, potentially due to variations in iron absorption from different foods. Further research is warranted to fully characterize these associations and to establish implications for infant health. This study was registered in the ClinicalTrial.gov registry (Identifier No. NCT01790542 ). This study was registered in the ClinicalTrial.gov registry under the name "Assessment of Complementary Feeding of Canadian Infants" (Identifier No. NCT01790542 ) February 6, 2013.

Validity of randomized clinical trials in gastroenterology from 1964-2000

DEFF Research Database (Denmark)

Kjaergard, Lise L; Frederiksen, Sarah L; Gluud, Christian

2002-01-01

The internal validity of clinical trials depends on the adequacy of the reported methodological quality. We assessed the methodological quality of all 383 randomized clinical trials published in GASTROENTEROLOGY as original articles from 1964 to 2000.......The internal validity of clinical trials depends on the adequacy of the reported methodological quality. We assessed the methodological quality of all 383 randomized clinical trials published in GASTROENTEROLOGY as original articles from 1964 to 2000....

Inter-laboratory comparison of turkey in ovo carcinogenicity assessment (IOCA) of hepatocarcinogens.

Science.gov (United States)

Enzmann, H; Brunnemann, K; Iatropoulos, M; Shpyleva, S; Lukyanova, N; Todor, I; Moore, M; Spicher, K; Chekhun, V; Tsuda, H; Williams, G

2013-09-01

In three independent laboratories carcinogens (diethylnitrosamine, DEN, 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone, NNK) and non-carcinogens (N-nitrosoproline, nicotine) were evaluated in turkey eggs for in ovo carcinogenicity assessment (IOCA). Compounds were injected into aseptic fertilized eggs. After incubation for 24 days, foci of altered hepatocytes (FAH), some with a pseudoglandular structure and/or signs of compression of the surrounding tissue were observed in the fetal liver. All laboratories were able to distinguish unequivocally the hepatocarcinogen-exposed groups from those exposed to non-carcinogens or the vehicle controls, based on the pre-specified evaluation parameters: tumor-like lesions, pseudoglandular areas and FAH. In addition to focal changes, only the carcinogens induced hepatocellular karyomegaly. Lower doses of the carcinogens, which did not induce FAH, were sufficient to induce hepatocellular karyomegaly. After exposure to 4 mg DEN, gall bladder agenesis was observed in all fetuses. The IOCA may be a valuable tool for early investigative studies on carcinogenicity and since it does not use rodents may complement chronic rat or mouse bioassays. Test substances that are positive in both rodents and fertilized turkey eggs are most probably trans-species carcinogens with particular significance for humans. The good concordance observed among the three laboratories demonstrates that the IOCA is a reliable and robust method. Copyright © 2012 Elsevier GmbH. All rights reserved.

Measuring the glycemic index of foods: interlaboratory study.

Science.gov (United States)

Wolever, Thomas M S; Brand-Miller, Jennie C; Abernethy, John; Astrup, Arne; Atkinson, Fiona; Axelsen, Mette; Björck, Inger; Brighenti, Furio; Brown, Rachel; Brynes, Audrey; Casiraghi, M Cristina; Cazaubiel, Murielle; Dahlqvist, Linda; Delport, Elizabeth; Denyer, Gareth S; Erba, Daniela; Frost, Gary; Granfeldt, Yvonne; Hampton, Shelagh; Hart, Valerie A; Hätönen, Katja A; Henry, C Jeya; Hertzler, Steve; Hull, Sarah; Jerling, Johann; Johnston, Kelly L; Lightowler, Helen; Mann, Neil; Morgan, Linda; Panlasigui, Leonora N; Pelkman, Christine; Perry, Tracy; Pfeiffer, Andreas F H; Pieters, Marlien; Ramdath, D Dan; Ramsingh, Rayna T; Robert, S Daniel; Robinson, Carol; Sarkkinen, Essi; Scazzina, Francesca; Sison, Dave Clark D; Sloth, Birgitte; Staniforth, Jane; Tapola, Niina; Valsta, Liisa M; Verkooijen, Inge; Weickert, Martin O; Weseler, Antje R; Wilkie, Paul; Zhang, Jian

2008-01-01

Many laboratories offer glycemic index (GI) services. We assessed the performance of the method used to measure GI. The GI of cheese-puffs and fruit-leather (centrally provided) was measured in 28 laboratories (n=311 subjects) by using the FAO/WHO method. The laboratories reported the results of their calculations and sent the raw data for recalculation centrally. Values for the incremental area under the curve (AUC) reported by 54% of the laboratories differed from central calculations. Because of this and other differences in data analysis, 19% of reported food GI values differed by >5 units from those calculated centrally. GI values in individual subjects were unrelated to age, sex, ethnicity, body mass index, or AUC but were negatively related to within-individual variation (P=0.033) expressed as the CV of the AUC for repeated reference food tests (refCV). The between-laboratory GI values (mean+/-SD) for cheese-puffs and fruit-leather were 74.3+/-10.5 and 33.2+/-7.2, respectively. The mean laboratory GI was related to refCV (P=0.003) and the type of restrictions on alcohol consumption before the test (P=0.006, r2=0.509 for model). The within-laboratory SD of GI was related to refCV (P<0.001), the glucose analysis method (P=0.010), whether glucose measures were duplicated (P=0.008), and restrictions on dinner the night before (P=0.013, r2=0.810 for model). The between-laboratory SD of the GI values is approximately 9. Standardized data analysis and low within-subject variation (refCV<30%) are required for accuracy. The results suggest that common misconceptions exist about which factors do and do not need to be controlled to improve precision. Controlled studies and cost-benefit analyses are needed to optimize GI methodology. The trial was registered at clinicaltrials.gov as NCT00260858.

Transparency and public accessibility of clinical trial information in Croatia: how it affects patient participation in clinical trials.

Science.gov (United States)

Šolić, Ivana; Stipčić, Ana; Pavličević, Ivančica; Marušić, Ana

2017-06-15

Despite increased visibility of clinical trials through international trial registries, patients often remain uninformed of their existence, especially if they do not have access to adequate information about clinical research, including the language of the information. The aim of this study was to describe the context for transparency of clinical trials in Croatia in relation to countries in Central and Eastern Europe, and to assess how informed Croatian patients are about clinical trials and their accessibility. We assessed the transparency of clinical trials from the data available in the public domain. We also conducted an anonymous survey on a convenience sample of 257 patients visiting two family medicine offices or an oncology department in south Croatia, and members of national patients' associations. Despite legal provisions for transparency of clinical trials in Croatia, they are still not sufficiently visible in the public domain. Among countries from Central and Eastern Europe, Croatia has the fewest number of registered trials in the EU Clinical Trials Registry. 66% of the patients in the survey were aware of the existence of clinical trials but only 15% were informed about possibilities of participating in a trial. Although 58% of the respondents were willing to try new treatments, only 6% actually participated in a clinical trial. Only 2% of the respondents were aware of publicly available trial registries. Our study demonstrates that there is low transparency of clinical trials in Croatia, and that Croatian patients are not fully aware of clinical trials and the possibilities of participating in them, despite reported availability of Internet resources and good communication with their physicians. There is a need for active policy measures to increase the awareness of and access to clinical trials to patients in Croatia, particularly in their own language.

Preliminary evaluation of factors associated with premature trial closure and feasibility of accrual benchmarks in phase III oncology trials.

Science.gov (United States)

Schroen, Anneke T; Petroni, Gina R; Wang, Hongkun; Gray, Robert; Wang, Xiaofei F; Cronin, Walter; Sargent, Daniel J; Benedetti, Jacqueline; Wickerham, Donald L; Djulbegovic, Benjamin; Slingluff, Craig L

2010-08-01

A major challenge for randomized phase III oncology trials is the frequent low rates of patient enrollment, resulting in high rates of premature closure due to insufficient accrual. We conducted a pilot study to determine the extent of trial closure due to poor accrual, feasibility of identifying trial factors associated with sufficient accrual, impact of redesign strategies on trial accrual, and accrual benchmarks designating high failure risk in the clinical trials cooperative group (CTCG) setting. A subset of phase III trials opened by five CTCGs between August 1991 and March 2004 was evaluated. Design elements, experimental agents, redesign strategies, and pretrial accrual assessment supporting accrual predictions were abstracted from CTCG documents. Percent actual/predicted accrual rate averaged per month was calculated. Trials were categorized as having sufficient or insufficient accrual based on reason for trial termination. Analyses included univariate and bivariate summaries to identify potential trial factors associated with accrual sufficiency. Among 40 trials from one CTCG, 21 (52.5%) trials closed due to insufficient accrual. In 82 trials from five CTCGs, therapeutic trials accrued sufficiently more often than nontherapeutic trials (59% vs 27%, p = 0.05). Trials including pretrial accrual assessment more often achieved sufficient accrual than those without (67% vs 47%, p = 0.08). Fewer exclusion criteria, shorter consent forms, other CTCG participation, and trial design simplicity were not associated with achieving sufficient accrual. Trials accruing at a rate much lower than predicted (accrual rate) were consistently closed due to insufficient accrual. This trial subset under-represents certain experimental modalities. Data sources do not allow accounting for all factors potentially related to accrual success. Trial closure due to insufficient accrual is common. Certain trial design factors appear associated with attaining sufficient accrual. Defining

Measurement, simulation and uncertainty assessment of implant heating during MRI

International Nuclear Information System (INIS)

Neufeld, E; Kuehn, S; Kuster, N; Szekely, G

2009-01-01

The heating of tissues around implants during MRI can pose severe health risks, and careful evaluation is required for leads to be labeled as MR conditionally safe. A recent interlaboratory comparison study has shown that different groups can produce widely varying results (sometimes with more than a factor of 5 difference) when performing measurements according to current guidelines. To determine the related difficulties and to derive optimized procedures, two different generic lead structures have been investigated in this study by using state-of-the-art temperature and dosimetric probes, as well as simulations for which detailed uncertainty budgets have been determined. The agreement between simulations and measurements is well within the combined uncertainty. The study revealed that the uncertainty can be kept below 17% if appropriate instrumentation and procedures are applied. Optimized experimental assessment techniques can be derived from the findings presented herein.

Measurement, simulation and uncertainty assessment of implant heating during MRI

Energy Technology Data Exchange (ETDEWEB)

Neufeld, E; Kuehn, S; Kuster, N [Foundation for Research on Information Technologies in Society (IT' IS), Zeughausstr. 43, 8004 Zurich (Switzerland); Szekely, G [Computer Vision Laboratory, Swiss Federal Institute of Technology (ETHZ), Sternwartstr 7, ETH Zentrum, 8092 Zurich (Switzerland)], E-mail: neufeld@itis.ethz.ch

2009-07-07

The heating of tissues around implants during MRI can pose severe health risks, and careful evaluation is required for leads to be labeled as MR conditionally safe. A recent interlaboratory comparison study has shown that different groups can produce widely varying results (sometimes with more than a factor of 5 difference) when performing measurements according to current guidelines. To determine the related difficulties and to derive optimized procedures, two different generic lead structures have been investigated in this study by using state-of-the-art temperature and dosimetric probes, as well as simulations for which detailed uncertainty budgets have been determined. The agreement between simulations and measurements is well within the combined uncertainty. The study revealed that the uncertainty can be kept below 17% if appropriate instrumentation and procedures are applied. Optimized experimental assessment techniques can be derived from the findings presented herein.

OARSI Clinical Trials Recommendations: Design and conduct of clinical trials for hand osteoarthritis.

Science.gov (United States)

Kloppenburg, M; Maheu, E; Kraus, V B; Cicuttini, F; Doherty, M; Dreiser, R-L; Henrotin, Y; Jiang, G-L; Mandl, L; Martel-Pelletier, J; Nelson, A E; Neogi, T; Pelletier, J-P; Punzi, L; Ramonda, R; Simon, L S; Wang, S

2015-05-01

Hand osteoarthritis (OA) is a very frequent disease, but yet understudied. However, a lot of works have been published in the past 10 years, and much has been done to better understand its clinical course and structural progression. Despite this new knowledge, few therapeutic trials have been conducted in hand OA. The last OARSI recommendations for the conduct of clinical trials in hand OA dates back to 2006. The present recommendations aimed at updating previous recommendations, by incorporating new data. The purpose of this expert opinion, consensus driven exercise is to provide evidence-based guidance on the design, execution and analysis of clinical trials in hand OA, where published evidence is available, supplemented by expert opinion, where evidence is lacking, to perform clinical trials in hand OA, both for symptom and for structure-modification. They indicate core outcome measurement sets for studies in hand OA, and list the methods and instruments that should be used to measure symptoms or structure. For both symptom- and structure-modification, at least pain, physical function, patient global assessment, HR-QoL, joint activity and hand strength should be assessed. In addition, for structure-modification trials, structural progression should be measured by radiographic changes. We also provide a research agenda listing many unsolved issues that seem to most urgently need to be addressed from the perspective of performing "good" clinical trials in hand OA. These updated OARSI recommendations should allow for better standardizing the conduct of clinical trials in hand OA in the next future. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Risk of bias assessment of randomised controlled trials in high-impact ophthalmology journals and general medical journals: a systematic review.

Science.gov (United States)

Joksimovic, Lazar; Koucheki, Robert; Popovic, Marko; Ahmed, Yusuf; Schlenker, Matthew B; Ahmed, Iqbal Ike K

2017-10-01

Evidence-based treatments in ophthalmology are often based on the results of randomised controlled trials. Biased conclusions from randomised controlled trials may lead to inappropriate management recommendations. This systematic review investigates the prevalence of bias risk in randomised controlled trials published in high-impact ophthalmology journals and ophthalmology trials from general medical journals. Using Ovid MEDLINE, randomised controlled trials in the top 10 high-impact ophthalmology journals in 2015 were systematically identified and critically appraised for the prevalence of bias risk. Included randomised controlled trials were assessed in all domains of bias as defined by the Cochrane Collaboration. In addition, the prevalence of conflict of interest and industry sponsorship was investigated. A comparison with ophthalmology articles from high-impact general medical journals was performed. Of the 259 records that were screened from ophthalmology-specific journals, 119 trials met all inclusion criteria and were critically appraised. In total, 29.4% of domains had an unclear risk, 13.8% had a high risk and 56.8% had a low risk of bias. In comparison, ophthalmology articles from general medical journals had a lower prevalence of unclear risk (17.1%), higher prevalence of high risk (21.9%) and a higher prevalence of low risk domains (61.9%). Furthermore, 64.7% of critically appraised trials from ophthalmology-specific journals did not report any conflicts of interest, while 70.6% did not report an industry sponsor of their trial. In closing, it is essential that authors, peer reviewers and readers closely follow published risk of bias guidelines. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Blinded trials taken to the test

DEFF Research Database (Denmark)

Hróbjartsson, A; Forfang, E; Haahr, M T

2007-01-01

Blinding can reduce bias in randomized clinical trials, but blinding procedures may be unsuccessful. Our aim was to assess how often randomized clinical trials test the success of blinding, the methods involved and how often blinding is reported as being successful....

Does suprascapular nerve block reduce shoulder pain following stroke: a double-blind randomised controlled trial with masked outcome assessment

Directory of Open Access Journals (Sweden)

Crotty Maria

2010-09-01

Full Text Available Abstract Background Shoulder pain is a common complication of a stroke which can impede participation in rehabilitation programs and has been associated with poorer outcomes. The evidence base for current medical and therapeutic management options of hemiplegic shoulder pain is limited. This study will evaluate the use of suprascapular nerve block injection as part of an interdisciplinary approach to the treatment of shoulder pain following stroke. The technique has previously been proven safe and effective in the treatment of shoulder pain associated with rheumatoid arthritis and degenerative shoulder conditions but its usefulness in a stroke population is unclear. Methods/Design A double blind randomised placebo controlled trial will assess the effect of a suprascapular nerve block compared with placebo in a population of 66 stroke patients. The trial will measure effect of injection on the primary outcome of pain, and secondary outcomes of function and quality of life. Measurements will take place at baseline, and 1, 4 and 12 weeks post intervention. Both groups will continue to receive routine physiotherapy and standard ward care. Discussion The results of this study could reduce pain symptoms in persons with mechanical shoulder pain post stroke and provide improvement in upper limb function. Trial Registration This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR - ACTRN12609000621213.

Results of the Interlaboratory Exercise CNS/CIEMAT-04 Among Environmental Radioactivity Laboratories (Aqueous Solution); Resultados del Ejercicio Interlaboratorios de Radiactividad Ambiental CSN/CIEMAT-04 (Solucion Acuosa)

Energy Technology Data Exchange (ETDEWEB)

Romero Gonzalez, M. L.; Barrera Izquierdo, M.

2004-07-01

The document describes the outcome of the CSN/CIEMAT-04 interlaboratory test comparison among environmental radioactivity laboratories. The exercise was organised according to the ISO-43 and the ISO/IUPAC/AOAC Harmonised Protocol for the proficiency testing of analytical laboratories. Following the issue of the European Community Drinking Water Directive 98/83/EC concerning the quality of water for human consumption, the last inter-comparison exercise was organised by using a water sample, in an attempt to evaluate the performance of the laboratories analysing the required radioactivity parameters (H-3, gross alpha and beta activity and residual beta). The sample (a synthetic drinking water), was prepared at the National Laboratory for Ionising Radiation's Standards (CIEMAT), and contained the following radionuclides ''241 Am, ''239+240 Pu, ''90Sr, ''137 Cs, ''3 H y ''40 K. The results of the exercise were computed for 38 participating laboratories, and their analytical performance was assessed using the z-score approach. Robust statistics of the participant's results was applied to obtain the median and standard deviation, including suspected outliers. The exercise has revealed and homogeneous behaviour of laboratories, being statistical parameters from the results close to the reference values. A raised percentage os satisfactory laboratory performance has been obtained for gross alpha, gross beta and residual beta: 85, 97 and 87% respectively. The study has shown that participant laboratories perform radioactive determinations in drinking water samples with satisfactory quality levels. (Author) 16 refs.

Subjective and objective outcomes in randomized clinical trials

DEFF Research Database (Denmark)

Moustgaard, Helene; Bello, Segun; Miller, Franklin G

2014-01-01

explicitly defined the terms. CONCLUSION: The terms "subjective" and "objective" are ambiguous when used to describe outcomes in randomized clinical trials. We suggest that the terms should be defined explicitly when used in connection with the assessment of risk of bias in a clinical trial......OBJECTIVES: The degree of bias in randomized clinical trials varies depending on whether the outcome is subjective or objective. Assessment of the risk of bias in a clinical trial will therefore often involve categorization of the type of outcome. Our primary aim was to examine how the concepts...... "subjective outcome" and "objective outcome" are defined in methodological publications and clinical trial reports. To put this examination into perspective, we also provide an overview of how outcomes are classified more broadly. STUDY DESIGN AND SETTING: A systematic review of methodological publications...

OARSI Clinical Trials Recommendations: Hand imaging in clinical trials in osteoarthritis.

Science.gov (United States)

Hunter, D J; Arden, N; Cicuttini, F; Crema, M D; Dardzinski, B; Duryea, J; Guermazi, A; Haugen, I K; Kloppenburg, M; Maheu, E; Miller, C G; Martel-Pelletier, J; Ochoa-Albíztegui, R E; Pelletier, J-P; Peterfy, C; Roemer, F; Gold, G E

2015-05-01

Tremendous advances have occurred in our understanding of the pathogenesis of hand osteoarthritis (OA) and these are beginning to be applied to trials targeted at modification of the disease course. The purpose of this expert opinion, consensus driven exercise is to provide detail on how one might use and apply hand imaging assessments in disease modifying clinical trials. It includes information on acquisition methods/techniques (including guidance on positioning for radiography, sequence/protocol recommendations/hardware for MRI); commonly encountered problems (including positioning, hardware and coil failures, sequences artifacts); quality assurance/control procedures; measurement methods; measurement performance (reliability, responsiveness, validity); recommendations for trials; and research recommendations. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Blinding in randomized control trials: the enigma unraveled.

Directory of Open Access Journals (Sweden)

Vartika Saxena

2016-03-01

Full Text Available The search for new treatments and testing of new ideas begins in the laboratory and then established in clinical research settings. Studies addressing the same therapeutic problem may produce conflicting results hence Randomised Clinical Trial is regarded as the most valid method for assessing the benefits and harms of healthcare interventions. The next challenge face by the medical community is the validity of such trials as theses tend to deviate from the truth because of various biases. For the avoidance of the same it has been suggested that the validity or quality of primary trials should be assessed under blind conditions. Thus blinding, is a crucial method for reducing bias in randomized clinical trials. Blinding can be defined as withholding information about the assigned interventions from people involved in the trial who may potentially be prejudiced by this knowledge. In this article we make an effort to define blinding, explain its chronology, hierarchy and discuss methods of blinding, its assessment, its possibility, un-blinding and finally the latest guidelines.

An inter-laboratory study to test the ability of amendments to reduce the availability of Cd, Pb, and Zn in situ

International Nuclear Information System (INIS)

Brown, Sally; Christensen, Barbara; Lombi, Enzo; McLaughlin, Mike; McGrath, Steve; Colpaert, Jan; Vangronsveld, Jaco

2005-01-01

An international inter-laboratory research program investigated the effectiveness of in situ remediation of soils contaminated by cadmium, lead and zinc, measuring changes in soil and soil solution chemistry, plants and soil microbiota. A common soil, from mine wastes in Jasper County MO, was used. The soil was pH 5.9, had low organic matter (1.2 g kg -1 C) and total Cd, Pb, and Zn concentrations of 92, 5022, and 18 532 mg kg -1 , respectively. Amendments included lime, phosphorus (P), red mud (RM), cyclonic ashes (CA), biosolids (BIO), and water treatment residuals (WTR). Both soil solution and NH 4 NO 3 extractable metals were decreased by all treatments. Phytotoxicity of metals was reduced, with plants grown in P treatments having the highest yields and lowest metal concentration (0.5, 7.2 and 406 mg kg -1 Cd, Pb, and Zn). Response of soil micro-organisms was similar to plant responses. Phosphorus addition reduced the physiologically based extraction test Pb from 84% of total Pb extracted in the untreated soil to 34.1%. - Addition of phosphorus to Pb, Zn and Cd contaminated mine waste was able to reduce metal toxicity for a range of biological endpoints

Trials by Juries: Suggested Practices for Database Trials

Science.gov (United States)

Ritterbush, Jon

2012-01-01

Librarians frequently utilize product trials to assess the content and usability of a database prior to committing funds to a new subscription or purchase. At the 2012 Electronic Resources and Libraries Conference in Austin, Texas, three librarians presented a panel discussion on their institutions' policies and practices regarding database…

A trial burn of rape straw and whole crops harvested for energy use to assess efficiency implications

Energy Technology Data Exchange (ETDEWEB)

Newman, R.

2003-11-01

Increased biomass utilisation and alternatives to cereal straw such as oil seed rape (OSR) straw will be necessary to achieve the Government's renewable energy targets. This report describes the results of a study to investigate the technical and economic feasibility of burning OSR straw and whole crops in an existing biomass power plant operated by EPR Ely Ltd in comparison with conventional cereal straw. Suitable quantities of bales of each fuel were provided for the combustion trials by Anglian Straw Ltd. Three trials were conducted: one using wheat-based cereal straw; one using 92% OSR; and one using 65% whole crop fuel. The availability of OSR straw and whole crop in Eastern England for use as fuel was also determined. Plant performance and stack emissions were evaluated and samples of delivered crop samples, bottom ash and fly ash from each trial were analysed. The parameters against which performance was assessed included: ease of handling and conveying; ease of chopping; ease of entry into the combustion chamber; furnace temperature profile; steam and electricity production rate; plant chimney emissions; ash collection and removal; operating stability; sustainability; and fuel availability.

Smartphone-based ecological momentary assessment and intervention in a coping-focused intervention for hearing voices (SAVVy): study protocol for a pilot randomised controlled trial.

Science.gov (United States)

Bell, Imogen H; Fielding-Smith, Sarah F; Hayward, Mark; Rossell, Susan L; Lim, Michelle H; Farhall, John; Thomas, Neil

2018-05-02

Smartphone-based ecological momentary assessment and intervention (EMA/I) show promise for enhancing psychological treatments for psychosis. EMA has the potential to improve assessment and formulation of experiences which fluctuate day-to-day, and EMI may be used to prompt use of therapeutic strategies in daily life. The current study is an examination of these capabilities in the context of a brief, coping-focused intervention for distressing voice hearing experiences. This is a rater-blinded, pilot randomised controlled trial comparing a four-session intervention in conjunction with use of smartphone EMA/I between sessions, versus treatment-as-usual. The recruitment target is 34 participants with persisting and distressing voice hearing experiences, recruited through a Voices Clinic based in Melbourne, Australia, and via wider advertising. Allocation will be made using minimisation procedure, balancing of the frequency of voices between groups. Assessments are completed at baseline and 8 weeks post-baseline. The primary outcomes of this trial will focus on feasibility and acceptability of the intervention and trial methodology, with secondary outcomes examining preliminary clinical effects related to overall voice severity, the emotional and functional impact of the voices, and emotional distress. This study offers a highly novel examination of specific smartphone capabilities and their integration with traditional psychological treatment for distressing voices. Such technology has potential to enhance psychological interventions and promote adaptation to distressing experiences. Australian New Zealand Clinical Trial Registry, ACTRN12617000348358 . Registered on 7 March 2017.

GC-MS determination of creatinine in human biological fluids as pentafluorobenzyl derivative in clinical studies and biomonitoring: Inter-laboratory comparison in urine with Jaffé, HPLC and enzymatic assays.

Science.gov (United States)

Tsikas, Dimitrios; Wolf, Alexander; Mitschke, Anja; Gutzki, Frank-Mathias; Will, Wolfgang; Bader, Michael

2010-10-01

In consideration of its relatively constant urinary excretion rate, creatinine in urine is a useful biochemical parameter to correct the urinary excretion rate of endogenous and exogenous biomolecules. Assays based on the reaction of creatinine and picric acid first reported by Jaffé in 1886 still belong to the most frequently used laboratory approaches for creatinine measurement in urine. Further analytical methods for creatinine include HPLC-UV, GC-MS, and LC-MS and LC-MS/MS approaches. In the present article we report on the development, validation and biomedical application of a new GC-MS method for the reliable quantitative determination of creatinine in human urine, plasma and serum. This method is based on the derivatization of creatinine (d(0)-Crea) and the internal standard [methyl-trideutero]creatinine (d(3)-Crea) with pentafluorobenzyl (PFB) bromide in the biological sample directly or after dilution with phosphate buffered saline, extraction of the reaction products with toluene and quantification in 1-μl aliquots of the toluene extract by selected-ion monitoring of m/z 112 for d(0)-Crea-PFB and m/z 115 for d(3)-Crea-PFB in the electron-capture negative-ion chemical ionization mode. The limit of detection of the method is 100 amol of creatinine. In an inter-laboratory study on urine samples from 100 healthy subjects, the GC-MS method was used to test the reliability of currently used Jaffé, enzymatic and HPLC assays in clinical and occupational studies. The results of the inter-laboratory study indicate that all three tested methods allow for satisfactory quantification of creatinine in human urine. The GC-MS method is suitable for use as a reference method for urinary creatinine in humans. In serum, creatine was found to contribute to creatinine up to 20% when measured by the present GC-MS method. The application of the GC-MS method can be extended to other biological samples such as saliva. Copyright © 2010 Elsevier B.V. All rights reserved.

Electronic Cigarette Trial and Use among Young Adults: Reasons for Trial and Cessation of Vaping

OpenAIRE

Lois Biener; Eunyoung Song; Erin L. Sutfin; John Spangler; Mark Wolfson

2015-01-01

This paper identifies predictors of trial and current use, and reasons for trying and ceasing use of electronic cigarettes (e-cigarettes) among young adults, with particular attention to former and never smokers. Data are from a mail survey of a population-based sample of adults aged 18 to 35 (N = 4740) in three U.S. metropolitan areas. Survey items assessed trial and use of e-cigarettes, cigarette smoking status, and reasons for trial and for ceasing use of e-cigarettes. Almost 23% reported ...

Interlaboratory toxicology data base

International Nuclear Information System (INIS)

Watson, C.R.

1988-01-01

The goal of this project is to provide investigators with the capability to assess experimentally derived dose-effect data from many laboratories for evaluating potential insults to human health. Initial efforts, reported here, concentrate on the beagle dog life span health-effects studies supported by DOE at five laboratories. Significant steps include standardization of the medical observation glossary, development of an independent off site data tape archive, and preliminary design of a registry to contain common-format dosimetric estimates and histopathologic observations for each major tissue in the more than 5000 dogs under study

Analysis of a provider of proficiency testing by interlaboratory comparisons for dosimetry in function of guides ISO/IEC 43 and ILAC G13

International Nuclear Information System (INIS)

Lohr, J.; Zaretzky, Alba; Stefanic, Amalia M.; Saravi, M.

2009-01-01

The Ionising Radiation Dosimetry Group (CNEA) has participated of the last intercomparison scheme organized by EUROMET. This intercomparison was held starting 2005 until 2008.The objective of this paper is to analyze this Association as a proficiency test provider according to the ISO/IEC Guide 43 (1997) 'Proficiency testing by interlaboratory comparisons' and ILAC G13 Guide (2007) 'Guidelines for the Requirements for the Competence of Providers of Proficiency Testing Schemes'. The analysis of EURAMET (so called since 2007) as the provider of this dosimetric comparison was made taking into account the following sections of the ILAC G13 Guide: Conduct of proficiency testing schemes; Statistical design, Communication with participants and Reports, taking them as essential parameters of the compliance of a proficiency test provider with the general requirements set by the Guides. This intercomparison had special characteristics coming from the participants and the primary objective of the scheme. It is remarkable the important degree of agreement of the organization with Guides ISO/IEC 43 and ILAC G13. (author)

Developing an OMERACT Core Outcome Set for Assessing Safety Components in Rheumatology Trials: The OMERACT Safety Working Group.

Science.gov (United States)

Klokker, Louise; Tugwell, Peter; Furst, Daniel E; Devoe, Dan; Williamson, Paula; Terwee, Caroline B; Suarez-Almazor, Maria E; Strand, Vibeke; Woodworth, Thasia; Leong, Amye L; Goel, Niti; Boers, Maarten; Brooks, Peter M; Simon, Lee S; Christensen, Robin

2017-12-01

Failure to report harmful outcomes in clinical research can introduce bias favoring a potentially harmful intervention. While core outcome sets (COS) are available for benefits in randomized controlled trials in many rheumatic conditions, less attention has been paid to safety in such COS. The Outcome Measures in Rheumatology (OMERACT) Filter 2.0 emphasizes the importance of measuring harms. The Safety Working Group was reestablished at the OMERACT 2016 with the objective to develop a COS for assessing safety components in trials across rheumatologic conditions. The safety issue has previously been discussed at OMERACT, but without a consistent approach to ensure harms were included in COS. Our methods include (1) identifying harmful outcomes in trials of interventions studied in patients with rheumatic diseases by a systematic literature review, (2) identifying components of safety that should be measured in such trials by use of a patient-driven approach including qualitative data collection and statistical organization of data, and (3) developing a COS through consensus processes including everyone involved. Members of OMERACT including patients, clinicians, researchers, methodologists, and industry representatives reached consensus on the need to continue the efforts on developing a COS for safety in rheumatology trials. There was a general agreement about the need to identify safety-related outcomes that are meaningful to patients, framed in terms that patients consider relevant so that they will be able to make informed decisions. The OMERACT Safety Working Group will advance the work previously done within OMERACT using a new patient-driven approach.

Use of 'sham' radiotherapy in randomized clinical trials

International Nuclear Information System (INIS)

Schwarz, F.; Christie, D.

2008-01-01

The objective of this systematic review was to identify quality trials that use sham radiotherapy in their design and review them to determine its potential value. The Cochrane Library, Pubmed and a Reference Search served as data sources. Trials were included if they met a minimum quality score of 3 on a validated assessment instrument (which assesses randomization, control and blinding) and if they compared sham radiotherapy to active treatment. External beam therapy and brachytherapy trials were considered. Twenty-six trials were identified, collectively including 2663 participants in the period of 1970-2004. All the trials studied the value of radiotherapy for treatment or prevention of benign diseases, including multiple sclerosis, coronary artery restenosis, age-related macular degeneration and Graves' ophthalmopathy. There were no trials relating to the use of radiotherapy in the treatment of malignancy. This review showed that it is possible to carry out sham radiotherapy with due regard for ethical concerns, with effective blinding and high levels of patient acceptance. Large sample sizes with multicentre trial designs were achievable. Although the statistical philosophy for using sham radiotherapy in trials is legitimate, it is no longer routinely used.

Assessment and reduction of comet assay variation in relation to DNA damage: studies from the European Comet Assay Validation Group

DEFF Research Database (Denmark)

Møller, Peter; Möller, Lennart; Godschalk, Roger W L

2010-01-01

The alkaline single cell gel electrophoresis (comet) assay has become a widely used method for the detection of DNA damage and repair in cells and tissues. Still, it has been difficult to compare results from different investigators because of differences in assay conditions and because the data...... are reported in different units. The European Comet Assay Validation Group (ECVAG) was established for the purpose of validation of the comet assay with respect to measures of DNA damage formation and its repair. The results from this inter-laboratory validation trail showed a large variation in measured level...... reliability for the measurement of DNA damage by the comet assay but there is still a need for further validation to reduce both assay and inter-laboratory variation....

Skin sensitisation: the Colipa strategy for developing and evaluating non-animal test methods for risk assessment.

Science.gov (United States)

Maxwell, Gavin; Aeby, Pierre; Ashikaga, Takao; Bessou-Touya, Sandrine; Diembeck, Walter; Gerberick, Frank; Kern, Petra; Marrec-Fairley, Monique; Ovigne, Jean-Marc; Sakaguchi, Hitoshi; Schroeder, Klaus; Tailhardat, Magali; Teissier, Silvia; Winkler, Petra

2011-01-01

Allergic contact dermatitis is a delayed-type hypersensitivity reaction induced by small reactive chemicals (haptens). Currently, the sensitising potential and potency of new chemicals is usually characterised using data generated via animal studies, such as the local lymph node assay (LLNA). There are, however, increasing public and political concerns regarding the use of animals for the testing of new chemicals. Consequently, the development of in vitro, in chemico or in silico models for predicting the sensitising potential and/or potency of new chemicals is receiving widespread interest. The Colipa Skin Tolerance task force currently collaborates with and/or funds several academic research groups to expand our understanding of the molecular and cellular events occurring during the acquisition of skin sensitisation. Knowledge gained from this research is being used to support the development and evaluation of novel alternative approaches for the identification and characterisation of skin sensitizing chemicals. At present three non-animal test methods (Direct Peptide Reactivity Assay (DPRA), Myeloid U937 Skin Sensitisation Test (MUSST) and human Cell Line Activation Test (hCLAT)) have been evaluated in Colipa interlaboratory ring trials for their potential to predict skin sensitisation potential and were recently submitted to ECVAM for formal pre-validation. Data from all three test methods will now be used to support the study and development of testing strategy approaches for skin sensitiser potency prediction. This publication represents the current viewpoint of the cosmetics industry on the feasibility of replacing the need for animal test data for informing skin sensitisation risk assessment decisions.

Hepatitis C - Assessment to Treatment Trial (HepCATT) in primary care: study protocol for a cluster randomised controlled trial.

Science.gov (United States)

Roberts, Kirsty; Macleod, John; Metcalfe, Chris; Simon, Joanne; Horwood, Jeremy; Hollingworth, William; Marlowe, Sharon; Gordon, Fiona H; Muir, Peter; Coleman, Barbara; Vickerman, Peter; Harrison, Graham I; Waldron, Cherry-Ann; Irving, William; Hickman, Matthew

2016-07-29

Public Health England (PHE) estimates that there are upwards of 160,000 individuals in England and Wales with chronic hepatitis C virus (HCV) infection, but until now only around 100,000 laboratory diagnoses have been reported to PHE and of these 28,000 have been treated. Targeted case-finding in primary care is estimated to be cost-effective; however, there has been no robust randomised controlled trial evidence available of specific interventions. Therefore, this study aims to develop and conduct a complex intervention within primary care and to evaluate this approach using a cluster randomised controlled trial. A total of 46 general practices in South West England will be randomised in a 1:1 ratio to receive either a complex intervention comprising: educational training on HCV for the practice; poster and leaflet display in the practice waiting rooms to raise awareness and encourage opportunistic testing; a HCV risk prediction algorithm based on information on possible risk markers in the electronic patient record run using Audit + software (BMJ Informatica). The audit will then be used to recall and offer patients a HCV test. Control practices will follow usual care. The effectiveness of the intervention will be measured by comparing number and rates of HCV testing, the number and proportion of patients testing positive, onward referral, rates of specialist assessment and treatment in control and intervention practices. Intervention costs and health service utilisation will be recorded to estimate the NHS cost per new HCV diagnosis and new HCV patient initiating treatment. Longer-term cost-effectiveness of the intervention in improving quality-adjusted life years (QALYs) will be extrapolated using a pre-existing dynamic health economic model. Patients' and health care workers' experiences and acceptability of the intervention will be explored through semi-structured qualitative interviews. This trial has the potential to make an important impact on patient

Characterization of human lymphoid cell lines GM9947 and GM9948 as intra- and interlaboratory reference standards for DNA typing

Energy Technology Data Exchange (ETDEWEB)

Fregeau, C.J.; Elliott, J.C.; Fourney, R.M. [RCMP Central Forensic Laboratory, Ottawa, Ontario (Canada)] [and others

1995-07-20

The incorporation of reference DNA is crucial to the validation of any DNA typing protocol. Currently, reference DNA standards are restricted to molecular size DNA ladders and/or tumor cell line DNA. Either of these, however, presents some limitations. We have rigorously characterized two Epstein-Barr virus (EBV)-immortalized human lymphoid cell lines-GM9947 (female) and GM9948 (male)-to determine their suitability as alternative in-line standards for three widely employed allele profiling strategies. Twenty-one highly polymorphic VNTR-based allelic systems (7 RFLPs, 2 AmpFLPs, and 12 STRs) distributed over 12 chromosomes were scrutinized along with 3 gender-based discriminatory systems. The genetic stability of each locus was confirmed over a period of 225 in vitro population doublings. Allele size estimates and degree of informativeness for each of the 21 VNTR systems were compiled. The reproducibility of allele scoring by traditional RFLP analyses, using both cell lines as reference standards, was also verified by an interlaboratory validation study involving 13 analysts from two geographically distinct forensic laboratories. Taken together, our data indicate that GM9947 and GM9948 genomic DNAs could be adopted as reliable reference standards for DNA typing. 82 refs., 3 figs., 8 tabs.

Cancer clinical trials

International Nuclear Information System (INIS)

Scheurlen, A.; Kay, R.; Baum, M.

1988-01-01

This book contains the proceedings on Cancer clinical trials: A critical appraisal. Topics covered include: Scientific fundamentals; Heterogeneous treatment effects; On combining information: Historical controls, overviews, and comprehensive cohort studies; and assessment of quality of life

Classroom Application of a Trial-Based Functional Analysis

Science.gov (United States)

Bloom, Sarah E.; Iwata, Brian A.; Fritz, Jennifer N.; Roscoe, Eileen M.; Carreau, Abbey B.

2011-01-01

We evaluated a trial-based approach to conducting functional analyses in classroom settings. Ten students referred for problem behavior were exposed to a series of assessment trials, which were interspersed among classroom activities throughout the day. Results of these trial-based functional analyses were compared to those of more traditional…

Initiating change locally in bullying and aggression through the school environment (INCLUSIVE) trial: update to cluster randomised controlled trial protocol.

Science.gov (United States)

Bonell, Chris; Mathiot, Anne; Allen, Elizabeth; Bevilacqua, Leonardo; Christie, Deborah; Elbourne, Diana; Fletcher, Adam; Grieve, Richard; Legood, Rosa; Scott, Stephen; Warren, Emily; Wiggins, Meg; Viner, Russell M

2017-05-25

Systematic reviews suggest that multi-component interventions are effective in reducing bullying victimisation and perpetration. We are undertaking a phase III randomised trial of the INCLUSIVE multi-component intervention. This trial aims to assess the effectiveness and cost-effectiveness of the INCLUSIVE intervention in reducing aggression and bullying victimisation in English secondary schools. This paper updates the original trial protocol published in 2014 (Trials 15:381, 2014) and presents the changes in the process evaluation protocol and the secondary outcome data collection. The methods are summarised as follows. cluster randomised trial. 40 state secondary schools. Outcomes assessed among the cohort of students at the end of year 7 (n = 6667) at baseline. INCLUSIVE is a multi-component school intervention including a social and emotional learning curriculum, changes to school environment (an action group comprising staff and students reviews local data on needs to review rules and policies and determine other local actions) and staff training in restorative practice. The intervention will be delivered by schools supported in the first two years by educational facilitators independent of the research team, with a third intervention year involving no external facilitation but all other elements. Comparator: normal practice. Primary: Two primary outcomes at student level assessed at baseline and at 36 months: 1. Aggressive behaviours in school: Edinburgh Study of Youth Transitions and Crime school misbehaviour subscale (ESYTC) 2. Bullying and victimisation: Gatehouse Bullying Scale (GBS) Secondary outcomes assessed at baseline, 24 and 36 months will include measures relating to the economic evaluation, psychosocial outcomes in students and staff and school-level truancy and exclusion rates. 20 schools per arm will provide 90% power to identify an effect size of 0.25 SD with a 5% significance level. Randomisation: eligible consenting schools were

Motor outcome measures in Huntington disease clinical trials.

Science.gov (United States)

Reilmann, Ralf; Schubert, Robin

2017-01-01

Deficits in motor function are a hallmark of Huntington disease (HD). The Unified Huntington's Disease Rating Scale Total Motor Score (UHDRS-TMS) is a categoric clinical rating scale assessing multiple domains of motor disability in HD. The UHDRS-TMS or subsets of its items have served as primary or secondary endpoints in numerous clinical trials. In spite of a well-established video-based annual online certification system, intra- and interrater variability, subjective error, and rater-induced placebo effects remain a concern. In addition, the UHDRS-TMS was designed to primarily assess motor symptoms in manifest HD. Recently, advancement of technology resulted in the introduction of the objective Q-Motor (i.e., Quantitative-Motor) assessments in biomarker studies and clinical trials in HD. Q-Motor measures detected motor signs in blinded cross-sectional and longitudinal analyses of manifest, prodromal, and premanifest HD cohorts up to two decades before clinical diagnosis. In a multicenter clinical trial in HD, Q-Motor measures were more sensitive than the UHDRS-TMS and exhibited no placebo effects. Thus, Q-Motor measures are currently explored in several multicenter trials targeting both symptomatic and disease-modifying mechanisms. They may supplement the UHDRS-TMS, increase the sensitivity and reliability in proof-of-concept studies, and open the door for phenotype assessments in clinical trials in prodromal and premanifest HD. Copyright © 2017 Elsevier B.V. All rights reserved.

Assessment and model guided cancer screening promotion by village doctors in China: a randomized controlled trial protocol.

Science.gov (United States)

Feng, Rui; Shen, Xingrong; Chai, Jing; Chen, Penglai; Cheng, Jing; Liang, Han; Zhao, Ting; Sha, Rui; Li, Kaichun; Wang, Debin

2015-10-12

Proven cost-effectiveness contrasted by low uptake of cancer screening (CS) calls for new methodologies promoting the service. Contemporary interventions in this regard relies primarily on strategies targeting general or specific groups with limited attention being paid to individualized approaches. This trial tests a novel package promoting CS utilization via continuous and tailored counseling delivered by primary caregivers. It aims at demonstrating that high risk individuals in the intervention arm will, compared to those in the delayed intervention condition, show increased use of CS service. The trial adopts a quasi-randomized controlled trial design and involves 2160 high risk individuals selected, via rapid and detailed risk assessments, from about 72,000 farmers aged 35+ in 36 administrative villages randomized into equal intervention and delayed intervention arms. The CS intervention package uses: a) village doctors and village clinics to deliver personalized and thus relatively sophisticated CS counseling; b) two-stage risk assessment models in identifying high risk individuals to focus the intervention on the most needed; c) standardized operation procedures to guide conduct of counseling; d) real-time effectiveness and quality monitoring to leverage continuous improvement; e) web-based electronic system to enable prioritizing complex determinants of CS uptake and tailoring counseling sessions to the changing needs of individual farmers. The intervention arm receives baseline and semiannual follow up evaluations plus CS counseling for 5 years; while the delayed intervention arm, only the same baseline and follow-up evaluations for the first 5 years and CS counseling starting from the 6th year if the intervention proved effective. Evaluation measures include: CS uptake by high risk farmers and changes in their knowledge, perceptions and self-efficacy about CS. Given the complexity and heterogeneity in the determinant system of individual CS service

Background rates of adverse pregnancy outcomes for assessing the safety of maternal vaccine trials in sub-Saharan Africa.

Directory of Open Access Journals (Sweden)

Lauren A V Orenstein

Full Text Available Maternal immunization has gained traction as a strategy to diminish maternal and young infant mortality attributable to infectious diseases. Background rates of adverse pregnancy outcomes are crucial to interpret results of clinical trials in Sub-Saharan Africa.We developed a mathematical model that calculates a clinical trial's expected number of neonatal and maternal deaths at an interim safety assessment based on the person-time observed during different risk windows. This model was compared to crude multiplication of the maternal mortality ratio and neonatal mortality rate by the number of live births. Systematic reviews of severe acute maternal morbidity (SAMM, low birth weight (LBW, prematurity, and major congenital malformations (MCM in Sub-Saharan African countries were also performed.Accounting for the person-time observed during different risk periods yields lower, more conservative estimates of expected maternal and neonatal deaths, particularly at an interim safety evaluation soon after a large number of deliveries. Median incidence of SAMM in 16 reports was 40.7 (IQR: 10.6-73.3 per 1,000 total births, and the most common causes were hemorrhage (34%, dystocia (22%, and severe hypertensive disorders of pregnancy (22%. Proportions of liveborn infants who were LBW (median 13.3%, IQR: 9.9-16.4 or premature (median 15.4%, IQR: 10.6-19.1 were similar across geographic region, study design, and institutional setting. The median incidence of MCM per 1,000 live births was 14.4 (IQR: 5.5-17.6, with the musculoskeletal system comprising 30%.Some clinical trials assessing whether maternal immunization can improve pregnancy and young infant outcomes in the developing world have made ethics-based decisions not to use a pure placebo control. Consequently, reliable background rates of adverse pregnancy outcomes are necessary to distinguish between vaccine benefits and safety concerns. Local studies that quantify population-based background rates of

Interlaboratory study for the validation of an ecotoxicological procedure to monitor the quality of septic sludge received at a wastewater treatment plant.

Science.gov (United States)

Robidoux, P Y; Choucri, A; Bastien, C; Sunahara, G I; López-Gastey, J

2001-01-01

Septic tank sludge is regularly hauled to the Montreal Urban Community (MUC) wastewater treatment plant. It is then discharged and mixed with the wastewater inflow before entering the primary chemical treatment process. An ecotoxicological procedure integrating chemical and toxicological analyses has been recently developed and applied to screen for the illicit discharge of toxic substances in septic sludge. The toxicity tests used were the Microtox, the bacterial-respiration, and the lettuce (Lactuca sativa) root elongation tests. In order to validate the applicability of the proposed procedure, a two-year interlaboratory study was carried out. In general, the results obtained by two independent laboratories (MUC and the Centre d'expertise en analyse environnementale du Quebec) were comparable and reproducible. Some differences were found using the Microtox test. Organic (e.g., phenol and formaldehyde) and inorganic (e.g., nickel and cyanide) spiked septic sludge were detected with good reliability and high efficiency. The relative efficiency to detect spiked substances was > 70% and confirms the results of previous studies. In addition, the respiration test was the most efficient toxicological tool to detect spiked substances, whereas the Microtox was the least efficient (septic sludge.

Effect of in-hospital comprehensive geriatric assessment (CGA in older people with hip fracture. The protocol of the Trondheim Hip Fracture Trial

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Taraldsen Kristin

2011-04-01

Full Text Available Abstract Background Hip fractures in older people are associated with high morbidity, mortality, disability and reduction in quality of life. Traditionally people with hip fracture are cared for in orthopaedic departments without additional geriatric assessment. However, studies of postoperative rehabilitation indicate improved efficiency of multidisciplinary geriatric rehabilitation as compared to traditional care. This randomized controlled trial (RCT aims to investigate whether an additional comprehensive geriatric assessment of hip fracture patients in a special orthogeriatric unit during the acute in-hospital phase may improve outcomes as compared to treatment as usual in an orthopaedic unit. Methods/design The intervention of interest, a comprehensive geriatric assessment is compared with traditional care in an orthopaedic ward. The study includes 401 home-dwelling older persons >70 years of age, previously able to walk 10 meters and now treated for hip fracture at St. Olav Hospital, Trondheim, Norway. The participants are enrolled and randomised during the stay in the Emergency Department. Primary outcome measure is mobility measured by the Short Physical Performance Battery (SPPB at 4 months after surgery. Secondary outcomes measured at 1, 4 and 12 months postoperatively are place of residence, activities of daily living, balance and gait, falls and fear of falling, quality of life and depressive symptoms, as well as use of health care resources and survival. Discussion We believe that the design of the study, the randomisation procedure and outcome measurements will be of sufficient strength and quality to evaluate the impact of comprehensive geriatric assessment on mobility and other relevant outcomes in hip fracture patients. Trials registration ClinicalTrials.gov, NCT00667914

Methodology Series Module 4: Clinical Trials.

Science.gov (United States)

Setia, Maninder Singh

2016-01-01

In a clinical trial, study participants are (usually) divided into two groups. One group is then given the intervention and the other group is not given the intervention (or may be given some existing standard of care). We compare the outcomes in these groups and assess the role of intervention. Some of the trial designs are (1) parallel study design, (2) cross-over design, (3) factorial design, and (4) withdrawal group design. The trials can also be classified according to the stage of the trial (Phase I, II, III, and IV) or the nature of the trial (efficacy vs. effectiveness trials, superiority vs. equivalence trials). Randomization is one of the procedures by which we allocate different interventions to the groups. It ensures that all the included participants have a specified probability of being allocated to either of the groups in the intervention study. If participants and the investigator know about the allocation of the intervention, then it is called an "open trial." However, many of the trials are not open - they are blinded. Blinding is useful to minimize bias in clinical trials. The researcher should familiarize themselves with the CONSORT statement and the appropriate Clinical Trials Registry of India.

The Virtual Anemia Trial: An Assessment of Model‐Based In Silico Clinical Trials of Anemia Treatment Algorithms in Patients With Hemodialysis

Science.gov (United States)

Topping, Alice; Kappel, Franz; Thijssen, Stephan; Kotanko, Peter

2018-01-01

In silico approaches have been proposed as a novel strategy to increase the repertoire of clinical trial designs. Realistic simulations of clinical trials can provide valuable information regarding safety and limitations of treatment protocols and have been shown to assist in the cost‐effective planning of clinical studies. In this report, we present a blueprint for the stepwise integration of internal, external, and ecological validity considerations in virtual clinical trials (VCTs). We exemplify this approach in the context of a model‐based in silico clinical trial aimed at anemia treatment in patients undergoing hemodialysis (HD). Hemoglobin levels and subsequent anemia treatment were simulated on a per patient level over the course of a year and compared to real‐life clinical data of 79,426 patients undergoing HD. The novel strategies presented here, aimed to improve external and ecological validity of a VCT, significantly increased the predictive power of the discussed in silico trial. PMID:29368434

A randomised controlled trial to assess the efficacy of Laparoscopic Uterosacral Nerve Ablation (LUNA) in the treatment of chronic pelvic pain: The trial protocol [ISRCTN41196151].

Science.gov (United States)

2003-12-08

BACKGROUND: Chronic pelvic pain is a common condition with a major impact on health-related quality of life, work productivity and health care utilisation. The cause of the pain is not always obvious as no pathology is seen in 40-60% of the cases. In the absence of pathology there is no established treatment. The Lee-Frankenhauser sensory nerve plexuses and parasympathetic ganglia in the uterosacral ligaments carry pain from the uterus, cervix and other pelvic structures. Interruption of these nerve trunks by laparoscopic uterosacral nerve ablation (LUNA) may alleviate pain. However, the balance of benefits and risks of this intervention have not been reliably assessed. LUNA has, nevertheless, been introduced into practice, although there remains controversy regarding indications for LUNA. Hence, there is an urgent need for a randomised controlled trial to confirm, or refute, any worthwhile effectiveness. The principal hypothesis is that, in women with chronic pelvic pain in whom diagnostic laparoscopy reveals either no pathology or mild endometriosis (AFS score life quality at 12 months. METHODS/DESIGN: The principal objective is to test the hypothesis that in women with chronic pelvic pain in whom diagnostic laparoscopy reveals either no pathology or mild endometriosis (AFS score life quality at 12 months. A multi-centre, prospective, randomised-controlled-trial will be carried out with blind assessment of outcomes in eligible consenting patients randomised at diagnostic laparoscopy to LUNA (experimental group) or to no pelvic denervation (control group). Postal questionnaires including visual analogue scale for pain (primary outcome), an index of sexual satisfaction and the EuroQoL 5D-EQ instrument (secondary outcomes) will be administered at 3, 6 and 12 months. The primary assessment of the effectiveness of LUNA will be from comparison of outcomes at the one-year follow-up, although the medium-term and longer-term risks and benefits of LUNA will also be

A randomised controlled trial to assess the efficacy of Laparoscopic Uterosacral Nerve Ablation (LUNA in the treatment of chronic pelvic pain: The trial protocol [ISRCTN41196151

Directory of Open Access Journals (Sweden)

2003-12-01

Full Text Available Abstract Background Chronic pelvic pain is a common condition with a major impact on health-related quality of life, work productivity and health care utilisation. The cause of the pain is not always obvious as no pathology is seen in 40–60% of the cases. In the absence of pathology there is no established treatment. The Lee-Frankenhauser sensory nerve plexuses and parasympathetic ganglia in the uterosacral ligaments carry pain from the uterus, cervix and other pelvic structures. Interruption of these nerve trunks by laparoscopic uterosacral nerve ablation (LUNA may alleviate pain. However, the balance of benefits and risks of this intervention have not been reliably assessed. LUNA has, nevertheless, been introduced into practice, although there remains controversy regarding indications for LUNA. Hence, there is an urgent need for a randomised controlled trial to confirm, or refute, any worthwhile effectiveness. The principal hypothesis is that, in women with chronic pelvic pain in whom diagnostic laparoscopy reveals either no pathology or mild endometriosis (AFS score ≤ 5 LUNA alleviates pain and improves life quality at 12 months. Methods/Design The principal objective is to test the hypothesis that in women with chronic pelvic pain in whom diagnostic laparoscopy reveals either no pathology or mild endometriosis (AFS score ≤ 5 LUNA alleviates pain and improves life quality at 12 months. A multi-centre, prospective, randomised-controlled-trial will be carried out with blind assessment of outcomes in eligible consenting patients randomised at diagnostic laparoscopy to LUNA (experimental group or to no pelvic denervation (control group. Postal questionnaires including visual analogue scale for pain (primary outcome, an index of sexual satisfaction and the EuroQoL 5D-EQ instrument (secondary outcomes will be administered at 3, 6 and 12 months. The primary assessment of the effectiveness of LUNA will be from comparison of outcomes at the one

Assessing methods for dealing with treatment switching in randomised controlled trials: a simulation study

Directory of Open Access Journals (Sweden)

Latimer Nicholas

2011-01-01

Full Text Available Abstract Background We investigate methods used to analyse the results of clinical trials with survival outcomes in which some patients switch from their allocated treatment to another trial treatment. These included simple methods which are commonly used in medical literature and may be subject to selection bias if patients switching are not typical of the population as a whole. Methods which attempt to adjust the estimated treatment effect, either through adjustment to the hazard ratio or via accelerated failure time models, were also considered. A simulation study was conducted to assess the performance of each method in a number of different scenarios. Results 16 different scenarios were identified which differed by the proportion of patients switching, underlying prognosis of switchers and the size of true treatment effect. 1000 datasets were simulated for each of these and all methods applied. Selection bias was observed in simple methods when the difference in survival between switchers and non-switchers were large. A number of methods, particularly the AFT method of Branson and Whitehead were found to give less biased estimates of the true treatment effect in these situations. Conclusions Simple methods are often not appropriate to deal with treatment switching. Alternative approaches such as the Branson & Whitehead method to adjust for switching should be considered.

Therapeutic assessment promotes treatment readiness but does not affect symptom change in patients with personality disorders: Findings from a randomized clinical trial

NARCIS (Netherlands)

de Saeger, H.; Kamphuis, J.H.; Finn, S.E.; Smith, J.D.; Verheul, R.; van Busschbach, J.J.; Feenstra, D.J.; Dine, J.; Horn, E.K.

2014-01-01

The field of clinical personality assessment is lacking in published empirical evidence regarding its treatment and clinical utility. This article reports on a randomized controlled clinical trial (N = 74) allocating patients awaiting treatment in a specialized clinic for personality disorders to

The ecologic validity of fructose feeding trials: Supraphysiological feeding of fructose in human trials requires careful consideration when drawing conclusions on cardiometabolic risk

OpenAIRE

Vivian L Choo; Vivian L Choo; John L Sievenpiper; John L Sievenpiper; John L Sievenpiper

2015-01-01

Background: Select trials of fructose overfeeding have been used to implicate fructose as a driver of cardiometabolic risk.Objective: We examined temporal trends of fructose dose in human controlled feeding trials of fructose and cardiometabolic risk.Methods: We combined studies from eight meta-analyses on fructose and cardiometabolic risk to assess the average fructose dose used in these trials. Two types of trials were identified: 1) substitution trials, in which energy from fructose was e...

The Ecologic Validity of Fructose Feeding Trials: Supraphysiological Feeding of Fructose in Human Trials Requires Careful Consideration When Drawing Conclusions on Cardiometabolic Risk

OpenAIRE

Choo, Vivian L.; Sievenpiper, John L.

2015-01-01

Background Select trials of fructose overfeeding have been used to implicate fructose as a driver of cardiometabolic risk. Objective We examined temporal trends of fructose dose in human controlled feeding trials of fructose and cardiometabolic risk. Methods We combined studies from eight meta-analyses on fructose and cardiometabolic risk to assess the average fructose dose used in these trials. Two types of trials were identified: (1) substitution trials, in which energy f...

Do clinical trials conducted in India match its healthcare needs? An audit of the Clinical Trials Registry of India

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Mansi Chaturvedi

2017-01-01

Full Text Available Background: India continues to contribute disproportionately to the global burden of disease and public health research output from India is also known to be not commensurate with her healthcare needs. We carried out the present study to assess if clinical trials were in line with the health care needs of the country by auditing the clinical trials registry of India. Materials and Methods: All the clinical studies registered in CTRI between July 20, 2007 and December 31, 2015 were searched in the “Trial Search” section. The total number of studies, their phases of development, and therapeutic areas were assessed. Trials in each therapeutic area was compared with the disease burden (DALYs in that area taken from Global Health Estimates [2014] Summary Tables of the WHO. The number of trials conducted per state in India was also compared with the population of that state [Census 2011]. Results: A total of 6474 studies were registered of which 3325 (51.4% were clinical trials. The state of Maharashtra had the highest number trials [16.4%] followed by Karnataka ( 11.6% and Tamil Nadu (10%. Populous states like Uttar Pradesh (5.3% and Bihar (1.4% had far fewer trials. The largest number of trials was in the area of cancer (16.4%, followed by diabetes (12.1% and cardiovascular diseases (10.1%. Infectious and parasitic diseases had the highest DALYs (82,681 and ranked first in disease burden but accounted for only 5% of the total trials and ranked 7th according to number of trials. Cancer ranked first in the number of trials (16.4%, but ranked 6th based on DALYs. Conclusion: Clinical trials conducted in India are not in consonance with her health care needs. Strengthening the capacity for conducting trials in the populous states and the north-eastern part of the country is necessary to allow a more equitable selection of participants. The government should introduce policies to encourage new drug development in areas where needed the most.

Assessing social risks prior to commencement of a clinical trial: due diligence or ethical inflation?

Science.gov (United States)

Burris, Scott; Davis, Corey

2009-11-01

Assessing social risks has proven difficult for IRBs. We undertook a novel effort to empirically investigate social risks before an HIV prevention trial among drug users in Thailand and China. The assessment investigated whether law, policies and enforcement strategies would place research subjects at significantly elevated risk of arrest, incarceration, physical harm, breach of confidentiality, or loss of access to health care relative to drug users not participating in the research. The study validated the investigator's concern that drug users were subject to serious social risks in the site localities, but also suggested that participation in research posed little or no marginal increase in risk and might even have a protective effect. Our experience shows that it is feasible to inform IRB deliberations with actual data on social risks, but also raises the question of whether and when such research is an appropriate use of scare research resources.

Systematic review of clinical trials assessing the therapeutic efficacy of visceral leishmaniasis treatments: A first step to assess the feasibility of establishing an individual patient data sharing platform.

Directory of Open Access Journals (Sweden)

Jacob T Bush

2017-09-01

Full Text Available There are an estimated 200,000 to 400,000 cases of visceral leishmaniasis (VL annually. A variety of factors are taken into account when considering the best therapeutic options to cure a patient and reduce the risk of resistance, including geographical area, malnourishment and HIV coinfection. Pooled analyses combine data from many studies to answer specific scientific questions that cannot be answered with individual studies alone. However, the heterogeneity of study design, data collection, and analysis often makes direct comparison difficult. Individual Participant Data (IPD files can be standardised and analysed, allowing detailed analysis of this merged larger pool, but only a small fraction of systematic reviews and meta-analyses currently employ pooled analysis of IPD. We conducted a systematic literature review to identify published studies and studies reported in clinical trial registries to assess the feasibility of developing a VL data sharing platform to facilitate an IPD-based analysis of clinical trial data. Studies conducted between 1983 to 2015 that reported treatment outcome were eligible.From the 2,271 documents screened, 145 published VL clinical trials were identified, with data from 26,986 patients. Methodologies varied for diagnosis and treatment outcomes, but overall the volume of data potentially available on different drugs and dose regimens identified hundreds or possibly thousands of patients per arm suitable for IPD pooled meta-analyses.A VL data sharing platform would provide an opportunity to maximise scientific use of available data to enable assessment of treatment efficacy, contribute to evidence-based clinical management and guide optimal prospective data collection.

Protocol of the Definition for the Assessment of Time-to-event Endpoints in CANcer trials (DATECAN) project: formal consensus method for the development of guidelines for standardised time-to-event endpoints' definitions in cancer clinical trials.

Science.gov (United States)

Bellera, Carine A; Pulido, Marina; Gourgou, Sophie; Collette, Laurence; Doussau, Adélaïde; Kramar, Andrew; Dabakuyo, Tienhan Sandrine; Ouali, Monia; Auperin, Anne; Filleron, Thomas; Fortpied, Catherine; Le Tourneau, Christophe; Paoletti, Xavier; Mauer, Murielle; Mathoulin-Pélissier, Simone; Bonnetain, Franck

2013-03-01

In randomised phase III cancer clinical trials, the most objectively defined and only validated time-to-event endpoint is overall survival (OS). The appearance of new types of treatments and the multiplication of lines of treatment have resulted in the use of surrogate endpoints for overall survival such as progression-free survival (PFS), or time-to-treatment failure. Their development is strongly influenced by the necessity of reducing clinical trial duration, cost and number of patients. However, while these endpoints are frequently used, they are often poorly defined and definitions can differ between trials which may limit their use as primary endpoints. Moreover, this variability of definitions can impact on the trial's results by affecting estimation of treatments' effects. The aim of the Definition for the Assessment of Time-to-event Endpoints in CANcer trials (DATECAN) project is to provide recommendations for standardised definitions of time-to-event endpoints in randomised cancer clinical trials. We will use a formal consensus methodology based on experts' opinions which will be obtained in a systematic manner. Definitions will be independently developed for several cancer sites, including pancreatic, breast, head and neck and colon cancer, as well as sarcomas and gastrointestinal stromal tumours (GISTs). The DATECAN project should lead to the elaboration of recommendations that can then be used as guidelines by researchers participating in clinical trials. This process should lead to a standardisation of the definitions of commonly used time-to-event endpoints, enabling appropriate comparisons of future trials' results. Copyright © 2012 Elsevier Ltd. All rights reserved.

An inter-laboratory study to test the ability of amendments to reduce the availability of Cd, Pb, and Zn in situ

Energy Technology Data Exchange (ETDEWEB)

Brown, Sally [Box 352100 University of Washington, Seattle, WA 98195 (United States)]. E-mail: slb@u.washington.edu; Christensen, Barbara [Box 352100 University of Washington, Seattle, WA 98195 (United States); Lombi, Enzo [CSIRO Land and Water PMB, 2 Glen Osmond, Adelaide, South Australia (Australia)]. E-mail: enzo.lombi@csiro.au; McLaughlin, Mike [CSIRO Land and Water PMB, 2 Glen Osmond, Adelaide, South Australia (Australia)]. E-mail: mike.mclaughlin@csiro.au; McGrath, Steve [Rothamsted Research, Harpenden, Herts AL5 2JQ (United Kingdom)]. E-mail: steve.mcgrath@bbsrc.ac.uk; Colpaert, Jan [Limburgs Universitair, Centrum Universitaire Campus, Building D, BE 3590 Diepenbeek (Belgium); Vangronsveld, Jaco [Limburgs Universitair, Centrum Universitaire Campus, Building D, BE 3590 Diepenbeek (Belgium)]. E-mail: jvangron@luc.ac.be

2005-11-15

An international inter-laboratory research program investigated the effectiveness of in situ remediation of soils contaminated by cadmium, lead and zinc, measuring changes in soil and soil solution chemistry, plants and soil microbiota. A common soil, from mine wastes in Jasper County MO, was used. The soil was pH 5.9, had low organic matter (1.2 g kg{sup -1} C) and total Cd, Pb, and Zn concentrations of 92, 5022, and 18 532 mg kg{sup -1}, respectively. Amendments included lime, phosphorus (P), red mud (RM), cyclonic ashes (CA), biosolids (BIO), and water treatment residuals (WTR). Both soil solution and NH{sub 4}NO{sub 3} extractable metals were decreased by all treatments. Phytotoxicity of metals was reduced, with plants grown in P treatments having the highest yields and lowest metal concentration (0.5, 7.2 and 406 mg kg{sup -1} Cd, Pb, and Zn). Response of soil micro-organisms was similar to plant responses. Phosphorus addition reduced the physiologically based extraction test Pb from 84% of total Pb extracted in the untreated soil to 34.1%. - Addition of phosphorus to Pb, Zn and Cd contaminated mine waste was able to reduce metal toxicity for a range of biological endpoints.

Further Development and Validation of the Frog Embryo Teratogenesis Assay - Xenopus (FETAX). Phase III

National Research Council Canada - National Science Library

Bantle, John

1996-01-01

This interlaboratory study of the Frog Embryo Teratogenesis Assay (FETAX) was undertaken in order to assess the repeatability and reliability of data collected under the guide published by the American Society for Testing and Materials...

The Virtual Anemia Trial: An Assessment of Model-Based In Silico Clinical Trials of Anemia Treatment Algorithms in Patients With Hemodialysis.

Science.gov (United States)

Fuertinger, Doris H; Topping, Alice; Kappel, Franz; Thijssen, Stephan; Kotanko, Peter

2018-04-01

In silico approaches have been proposed as a novel strategy to increase the repertoire of clinical trial designs. Realistic simulations of clinical trials can provide valuable information regarding safety and limitations of treatment protocols and have been shown to assist in the cost-effective planning of clinical studies. In this report, we present a blueprint for the stepwise integration of internal, external, and ecological validity considerations in virtual clinical trials (VCTs). We exemplify this approach in the context of a model-based in silico clinical trial aimed at anemia treatment in patients undergoing hemodialysis (HD). Hemoglobin levels and subsequent anemia treatment were simulated on a per patient level over the course of a year and compared to real-life clinical data of 79,426 patients undergoing HD. The novel strategies presented here, aimed to improve external and ecological validity of a VCT, significantly increased the predictive power of the discussed in silico trial. © 2018 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Blinded trials taken to the test: an analysis of randomized clinical trials that report tests for the success of blinding

DEFF Research Database (Denmark)

Hróbjartsson, A; Forfang, E; Haahr, M T

2007-01-01

Blinding can reduce bias in randomized clinical trials, but blinding procedures may be unsuccessful. Our aim was to assess how often randomized clinical trials test the success of blinding, the methods involved and how often blinding is reported as being successful....

MRI and MRE for non-invasive quantitative assessment of hepatic steatosis and fibrosis in NAFLD and NASH: Clinical trials to clinical practice

Science.gov (United States)

Dulai, Parambir S.; Sirlin, Claude B.; Loomba, Rohit

2016-01-01

Nonalcoholic fatty liver disease (NAFLD) represents one of the most common causes of chronic liver disease, and its prevalence is rising worldwide. The occurrence of nonalcoholic steatohepatitis (NASH) is associated with a substantial increase in disease related morbidity and mortality. Accordingly, there has been a surge of innovation surrounding drug development in an effort to off-set the natural progression and long-term risks of this disease. Disease assessment within clinical trials and clinical practice for NAFLD is currently done with liver biopsies. Liver biopsy-based assessments, however, remain imprecise and are not without cost or risk. This carries significant implications for the feasibility and costs of bringing therapeutic interventions to market. A need therefore arises for reliable and highly accurate surrogate end-points that can be used in phase 2 and 3 clinical trials to reduce trial size requirements and costs, while improving feasibility and ease of implementation in clinical practice. Significant advances have now been made in magnetic resonance technology, and magnetic resonance imaging (MRI) and elastrography (MRE) have been demonstrated to be highly accurate diagnostic tools for the detection of hepatic steatosis and fibrosis. In this review article, we will summarize the currently available evidence regarding the use of MRI and MRE among NAFLD patients, and the evolving role these surrogate biomarkers will play in the rapidly advancing arena of clinical trials in NASH and hepatic fibrosis. Furthermore, we will highlight how these tools can be readily applied to routine clinical practice, where the growing burden of NAFLD will need to be met with enhanced monitoring algorithms. PMID:27312947

Summary and recommendations of the NRC/INEL Activated Carbon Testing Program

International Nuclear Information System (INIS)

Scarpellino, C.D.; Sill, C.W.

1986-01-01

The Committee on Nuclear Air and Gas Treatment (CONAGT) of the American Society of Mechanical Engineers (ASME) sponsored an interlaboratory testing program, round-robin, of nuclear-grade activated carbon. The results of this round-robin revealed gross differences in penetration of radio-labeled methyl iodide as measured by the various laboratories when using Method A of the ASTM D-3803-79 Standard. These differences prompted the Nuclear Regulatory Commission (NRC) to establish the NRC/INEL Activated Carbon Testing Program to determine the causes of these discrepancies and to provide recommendations that could lead to an accurate and reliable testing procedure that would ensure an adequate method for assessing the capability of activated carbon to remove radioiodine from gas streams within commercial nuclear power plants. The NRC/INEL Activated Carbon Testing Program has conducted formal and informal interlaboratory comparisons to identify problems with the test method and its application and to assess the effectiveness of changes to procedures and equipment voluntarily implemented by commercial laboratories to mitigate the disparity of test results. The results of the first formal NRC/INEL Interlaboratory Comparison (IC) essentially verified the CONAGT round-robin results despite the use of a detailed test protocol. This data indicated that many of the participating laboratories probably had been operating outside the ASTM specifications for relative humidity (RH) and flow. In addition, this process provided information which was used to modify the testing protocol employed for the second NRC/INEL Interlaboratory Comparison (IC-2) to make it more rugged and reliable. These changes to the protocol together with the results of INEL sensitivity testing are the basis for the recommendations presented

Challenges in conducting clinical trials in nephrology

DEFF Research Database (Denmark)

Baigent, Colin; Herrington, William G; Coresh, Josef

2017-01-01

Despite the high costs of treatment of people with kidney disease and associated comorbid conditions, the amount of reliable information available to guide the care of such patients is very limited. Some treatments have been assessed in randomized trials, but most such trials have been too small ...

Methodology series module 4: Clinical trials

Directory of Open Access Journals (Sweden)

Maninder Singh Setia

2016-01-01

Full Text Available In a clinical trial, study participants are (usually divided into two groups. One group is then given the intervention and the other group is not given the intervention (or may be given some existing standard of care. We compare the outcomes in these groups and assess the role of intervention. Some of the trial designs are (1 parallel study design, (2 cross-over design, (3 factorial design, and (4 withdrawal group design. The trials can also be classified according to the stage of the trial (Phase I, II, III, and IV or the nature of the trial (efficacy vs. effectiveness trials, superiority vs. equivalence trials. Randomization is one of the procedures by which we allocate different interventions to the groups. It ensures that all the included participants have a specified probability of being allocated to either of the groups in the intervention study. If participants and the investigator know about the allocation of the intervention, then it is called an "open trial." However, many of the trials are not open - they are blinded. Blinding is useful to minimize bias in clinical trials. The researcher should familiarize themselves with the CONSORT statement and the appropriate Clinical Trials Registry of India.

Conducting feasibilities in clinical trials: An investment to ensure a good study

Directory of Open Access Journals (Sweden)

Viraj Rajadhyaksha

2010-01-01

Full Text Available Conducting clinical trial feasibility is one of the first steps in clinical trial conduct. This process includes assessing internal and environmental capacity, alignment of the clinical trial in terms of study design, dose of investigational product, comparator, patient type, with the local environment and assessing potential of conducting clinical trial in a specific country. A robust feasibility also ensures a realistic assessment and capability to conduct the clinical trial. For local affiliates of pharmaceutical organizations, and contract research organizations, this is a precursor to study placement and influences the decision of study placement. This article provides details on different types of feasibilities, information which is to be included and relevance of each. The article also aims to provide practical hands-on suggestions to make feasibilities more realistic and informative.

Conducting feasibilities in clinical trials: an investment to ensure a good study.

Science.gov (United States)

Rajadhyaksha, Viraj

2010-07-01

Conducting clinical trial feasibility is one of the first steps in clinical trial conduct. This process includes assessing internal and environmental capacity, alignment of the clinical trial in terms of study design, dose of investigational product, comparator, patient type, with the local environment and assessing potential of conducting clinical trial in a specific country. A robust feasibility also ensures a realistic assessment and capability to conduct the clinical trial. For local affiliates of pharmaceutical organizations, and contract research organizations, this is a precursor to study placement and influences the decision of study placement. This article provides details on different types of feasibilities, information which is to be included and relevance of each. The article also aims to provide practical hands-on suggestions to make feasibilities more realistic and informative.

A Bayesian approach to assess data from radionuclide activity analyses in environmental samples

International Nuclear Information System (INIS)

Barrera, Manuel; Lourdes Romero, M.; Nunez-Lagos, Rafael; Bernardo, Jose M.

2007-01-01

A Bayesian statistical approach is introduced to assess experimental data from the analyses of radionuclide activity concentration in environmental samples (low activities). A theoretical model has been developed that allows the use of known prior information about the value of the measurand (activity), together with the experimental value determined through the measurement. The model has been applied to data of the Inter-laboratory Proficiency Test organised periodically among Spanish environmental radioactivity laboratories that are producing the radiochemical results for the Spanish radioactive monitoring network. A global improvement of laboratories performance is produced when this prior information is taken into account. The prior information used in this methodology is an interval within which the activity is known to be contained, but it could be extended to any other experimental quantity with a different type of prior information available

Is one trial enough for repeated testing? Same-day assessments of walking, mobility and fine hand use in people with myotonic dystrophy type 1.

Science.gov (United States)

Kierkegaard, Marie; Petitclerc, Emilie; Hébert, Luc J; Gagnon, Cynthia

2017-02-01

Performance-based assessments of physical function are essential in people with myotonic dystrophy type 1 (DM1) to monitor disease progression and evaluate interventions. Commonly used are the six-minute walk test, the 10 m-walk test, the timed up-and-go test, the timed-stands test, grip strength tests and the nine-hole peg test. The number of trials needed on a same-day test occasion and whether the first, best or average of trials should be reported as result is unknown. Thus, the aim was to describe and explore differences between trials in these measures of walking, mobility and fine hand use in 70 adults with DM1. Three trials were performed for each test except for the six-minute walk test where two trials were allowed. There were statistical significant differences over trials in all tests except for the 10 m-walk test and grip strength tests. Pair-wise comparisons showed that the second and third trials were in general better than the first, although effect sizes were small. At which trial the individuals performed their best differed between individuals and tests. People with severe muscular impairment had difficulties to perform repeated trials. Intraclass correlation coefficients were all high in analyses exploring how to report results. The conclusion and clinical implication is that, for a same-day test occasion, one trial is sufficient for the 10 m-walk test and grip strength tests, and that repeated trials should be allowed in the timed up-and-go test, timed-stands test and nine-hole peg tests. We recommend that two trials are performed for these latter tests as such a protocol could accommodate people with various levels of impairments and physical limitations. Copyright © 2016 Elsevier B.V. All rights reserved.

Impact of clinical trials on neurosurgical practice: an assessment of case volume.

Science.gov (United States)

Simon, Scott D; Koyama, Tatsuki; Zacharia, Brad E; Schirmer, Clemens M; Cheng, Joseph S

2015-04-01

To evaluate the effect of important trials on the practice of neurosurgery. We hypothesized that evidence from trials addressing the management of intracranial aneurysms (International Subarachnoid Aneurysm Trial [ISAT]) and nontraumatic intracerebral hemorrhages (Surgical Trial in Intracerebral Hemorrhage [STICH]) and vertebral augmentation for osteoporotic vertebral body fractures had a significant impact on the frequency of the corresponding neurosurgical procedures. A Medicare administrative database was queried for corresponding Common Procedural Terminology codes and units billed per calendar year. The effects of ISAT and STICH were evaluated using a generalized linear model. The effect of the vertebral augmentation study was evaluated using a t test. After publication of ISAT in 2002, the rate of increase in proportion of cerebral aneurysms that were treated with embolization (Common Procedural Terminology code 61624) per year increased from 3.9% to 5.5% (P = 0.01). After publication of STICH in 2005, the number of craniotomies performed for intracerebral hematoma decreased from 2341 in 2002 to 1646 in 2011 (P = 0.03). After 2 publications in 2009, performance of vertebral augmentation decreased from a high of 99,961 in 2009 per year to 77,108 in 2013 (P = 0.002). Randomized clinical trials remain the gold standard in the medical community to demonstrate efficacy, but their true impact relies on rapid and extensive assimilation into everyday medical practice. However, the described methodology establishes a temporal relationship only and does not prove causation. Nonetheless, trends in procedural volume suggest that the results of these select randomized clinical trials had a significant effect on neurosurgical practice affecting Medicare patients within an interval of a few years. Copyright © 2015 Elsevier Inc. All rights reserved.

The development by means of trial assessments, of a procedure for radiological risk assessment of underground disposal of low and intermediate level radioactive wastes

International Nuclear Information System (INIS)

Thompson, B.G.J.

1987-01-01

Seven trials are outlined showing the development and testing of a procedure based upon pra using Monte Carlo simulators, to assess post closure risks from the underground disposal of low and intermediate level radioactive wastes. The PRA method is found to be more justifiable than the use of 'best estimates'. Problems of accounting for long-term environmental changes and of future human intrusions are discussed. The importance of achieving statistical convergence within practical time scales and resources and of accounting for the influence of different sources of systematic bias is emphasised. (orig.)

Disproportionate Intrauterine Growth Intervention Trial At Term: DIGITAT

Directory of Open Access Journals (Sweden)

Huisjes Anjoke JM

2007-07-01

Full Text Available Abstract Background Around 80% of intrauterine growth restricted (IUGR infants are born at term. They have an increase in perinatal mortality and morbidity including behavioral problems, minor developmental delay and spastic cerebral palsy. Management is controversial, in particular the decision whether to induce labour or await spontaneous delivery with strict fetal and maternal surveillance. We propose a randomised trial to compare effectiveness, costs and maternal quality of life for induction of labour versus expectant management in women with a suspected IUGR fetus at term. Methods/design The proposed trial is a multi-centre randomised study in pregnant women who are suspected on clinical grounds of having an IUGR child at a gestational age between 36+0 and 41+0 weeks. After informed consent women will be randomly allocated to either induction of labour or expectant management with maternal and fetal monitoring. Randomisation will be web-based. The primary outcome measure will be a composite neonatal morbidity and mortality. Secondary outcomes will be severe maternal morbidity, maternal quality of life and costs. Moreover, we aim to assess neurodevelopmental and neurobehavioral outcome at two years as assessed by a postal enquiry (Child Behavioral Check List-CBCL and Ages and Stages Questionnaire-ASQ. Analysis will be by intention to treat. Quality of life analysis and a preference study will also be performed in the same study population. Health technology assessment with an economic analysis is part of this so called Digitat trial (Disproportionate Intrauterine Growth Intervention Trial At Term. The study aims to include 325 patients per arm. Discussion This trial will provide evidence for which strategy is superior in terms of neonatal and maternal morbidity and mortality, costs and maternal quality of life aspects. This will be the first randomised trial for IUGR at term. Trial registration Dutch Trial Register and ISRCTN

Survivorship care plans: are randomized controlled trials assessing outcomes that are relevant to stakeholders?

Science.gov (United States)

Birken, Sarah A; Urquhart, Robin; Munoz-Plaza, Corrine; Zizzi, Alexandra R; Haines, Emily; Stover, Angela; Mayer, Deborah K; Hahn, Erin E

2018-03-23

The purpose of this study was to compare outcomes assessed in extant randomized controlled trials (RCTs) to outcomes that stakeholders expect from survivorship care plans (SCPs). To facilitate the transition from active treatment to follow-up care for the 15.5 million US cancer survivors, many organizations require SCP use. However, results of several RCTs of SCPs' effectiveness have been null, possibly because they have evaluated outcomes on which SCPs should be expected to have limited influence. Stakeholders (e.g., survivors, oncologists) may expect outcomes that differ from RCTs' outcomes. We identified RCTs' outcomes using a PubMed literature review. We identified outcomes that stakeholders expect from SCPs using semistructured interviews with stakeholders in three healthcare systems in the USA and Canada. Finally, we mapped RCTs' outcomes onto stakeholder-identified outcomes. RCT outcomes did not fully address outcomes that stakeholders expected from SCPs, and RCTs assessed outcomes that stakeholders did not expect from SCPs. RCTs often assessed outcomes only from survivors' perspectives. RCTs of SCPs' effectiveness have not assessed outcomes that stakeholders expect. To better understand SCPs' effectiveness, future RCTs should assess outcomes of SCP use that are relevant from the perspective of multiple stakeholders. SCPs' effectiveness may be optimized when used with an eye toward outcomes that stakeholders expect from SCPs. For survivors, this means using SCPs as a map to guide them with respect to what kind of follow-up care they should seek, when they should seek it, and from whom they should seek it.

Mixed-meal tolerance test versus glucagon stimulation test for the assessment of beta-cell function in therapeutic trials in type 1 diabetes.

Science.gov (United States)

Greenbaum, Carla J; Mandrup-Poulsen, Thomas; McGee, Paula Friedenberg; Battelino, Tadej; Haastert, Burkhard; Ludvigsson, Johnny; Pozzilli, Paolo; Lachin, John M; Kolb, Hubert

2008-10-01

Beta-cell function in type 1 diabetes clinical trials is commonly measured by C-peptide response to a secretagogue in either a mixed-meal tolerance test (MMTT) or a glucagon stimulation test (GST). The Type 1 Diabetes TrialNet Research Group and the European C-peptide Trial (ECPT) Study Group conducted parallel randomized studies to compare the sensitivity, reproducibility, and tolerability of these procedures. In randomized sequences, 148 TrialNet subjects completed 549 tests with up to 2 MMTT and 2 GST tests on separate days, and 118 ECPT subjects completed 348 tests (up to 3 each) with either two MMTTs or two GSTs. Among individuals with up to 4 years' duration of type 1 diabetes, >85% had measurable stimulated C-peptide values. The MMTT stimulus produced significantly higher concentrations of C-peptide than the GST. Whereas both tests were highly reproducible, the MMTT was significantly more so (R(2) = 0.96 for peak C-peptide response). Overall, the majority of subjects preferred the MMTT, and there were few adverse events. Some older subjects preferred the shorter duration of the GST. Nausea was reported in the majority of GST studies, particularly in the young age-group. The MMTT is preferred for the assessment of beta-cell function in therapeutic trials in type 1 diabetes.

Size characterization of airborne SiO2 nanoparticles with on-line and off-line measurement techniques: an interlaboratory comparison study

Science.gov (United States)

Motzkus, C.; Macé, T.; Gaie-Levrel, F.; Ducourtieux, S.; Delvallee, A.; Dirscherl, K.; Hodoroaba, V.-D.; Popov, I.; Popov, O.; Kuselman, I.; Takahata, K.; Ehara, K.; Ausset, P.; Maillé, M.; Michielsen, N.; Bondiguel, S.; Gensdarmes, F.; Morawska, L.; Johnson, G. R.; Faghihi, E. M.; Kim, C. S.; Kim, Y. H.; Chu, M. C.; Guardado, J. A.; Salas, A.; Capannelli, G.; Costa, C.; Bostrom, T.; Jämting, Å. K.; Lawn, M. A.; Adlem, L.; Vaslin-Reimann, S.

2013-10-01

Results of an interlaboratory comparison on size characterization of SiO2 airborne nanoparticles using on-line and off-line measurement techniques are discussed. This study was performed in the framework of Technical Working Area (TWA) 34—"Properties of Nanoparticle Populations" of the Versailles Project on Advanced Materials and Standards (VAMAS) in the project no. 3 "Techniques for characterizing size distribution of airborne nanoparticles". Two types of nano-aerosols, consisting of (1) one population of nanoparticles with a mean diameter between 30.3 and 39.0 nm and (2) two populations of non-agglomerated nanoparticles with mean diameters between, respectively, 36.2-46.6 nm and 80.2-89.8 nm, were generated for characterization measurements. Scanning mobility particle size spectrometers (SMPS) were used for on-line measurements of size distributions of the produced nano-aerosols. Transmission electron microscopy, scanning electron microscopy, and atomic force microscopy were used as off-line measurement techniques for nanoparticles characterization. Samples were deposited on appropriate supports such as grids, filters, and mica plates by electrostatic precipitation and a filtration technique using SMPS controlled generation upstream. The results of the main size distribution parameters (mean and mode diameters), obtained from several laboratories, were compared based on metrological approaches including metrological traceability, calibration, and evaluation of the measurement uncertainty. Internationally harmonized measurement procedures for airborne SiO2 nanoparticles characterization are proposed.

Size characterization of airborne SiO2 nanoparticles with on-line and off-line measurement techniques: an interlaboratory comparison study

International Nuclear Information System (INIS)

Motzkus, C.; Macé, T.; Gaie-Levrel, F.; Ducourtieux, S.; Delvallee, A.; Dirscherl, K.; Hodoroaba, V.-D.; Popov, I.; Popov, O.; Kuselman, I.; Takahata, K.; Ehara, K.; Ausset, P.; Maillé, M.; Michielsen, N.; Bondiguel, S.; Gensdarmes, F.; Morawska, L.; Johnson, G. R.; Faghihi, E. M.

2013-01-01

Results of an interlaboratory comparison on size characterization of SiO 2 airborne nanoparticles using on-line and off-line measurement techniques are discussed. This study was performed in the framework of Technical Working Area (TWA) 34—“Properties of Nanoparticle Populations” of the Versailles Project on Advanced Materials and Standards (VAMAS) in the project no. 3 “Techniques for characterizing size distribution of airborne nanoparticles”. Two types of nano-aerosols, consisting of (1) one population of nanoparticles with a mean diameter between 30.3 and 39.0 nm and (2) two populations of non-agglomerated nanoparticles with mean diameters between, respectively, 36.2–46.6 nm and 80.2–89.8 nm, were generated for characterization measurements. Scanning mobility particle size spectrometers (SMPS) were used for on-line measurements of size distributions of the produced nano-aerosols. Transmission electron microscopy, scanning electron microscopy, and atomic force microscopy were used as off-line measurement techniques for nanoparticles characterization. Samples were deposited on appropriate supports such as grids, filters, and mica plates by electrostatic precipitation and a filtration technique using SMPS controlled generation upstream. The results of the main size distribution parameters (mean and mode diameters), obtained from several laboratories, were compared based on metrological approaches including metrological traceability, calibration, and evaluation of the measurement uncertainty. Internationally harmonized measurement procedures for airborne SiO 2 nanoparticles characterization are proposed

Clinical Trials of Blood Pressure Lowering and Antihypertensive Medication: is Cognitive Measurement State-Of-The-Art?

Science.gov (United States)

Elias, Merrill F; Torres, Rachael V; Davey, Adam

2018-02-22

Randomized controlled trials of blood pressure (BP) lowering and antihypertensive medication use on cognitive outcomes have often been disappointing, reporting mixed findings and small effect sizes. We evaluate the extent to which cognitive assessment protocols used in these trials approach state-of-the-art. Overall, we find that a primary focus on cognition and the systematic selection of cognitive outcomes across trials take a backseat to other trial goals. Twelve trials investigating change in cognitive functioning were examined and none met criteria for state-of-the-art assessment, including use of at least 4 tests indexing 2 cognitive domains. Four trials investigating incident dementia were also examined. Each trial used state-of-the-art diagnostic criteria to assess dementia, although follow-up periods were relatively short, with only 2 trials lasting for at least 3 years. Weaknesses in each trial may act to obscure or weaken the positive effects of BP lowering on cognitive functioning. Improving trial designs in terms of cognitive outcomes selected and length of follow-up periods employed could lead to more promising findings. We offer logical steps to achieve state-of-the-art assessment protocols, with examples, in hopes of improving future trials.

Randomised clinical trial

DEFF Research Database (Denmark)

Reimer, C; Lødrup, A; Smith, G

2016-01-01

of an alginate (Gaviscon Advance, Reckitt Benckiser, Slough, UK) on reflux symptoms in patients with persistent symptoms despite once daily PPI. MethodsThis was a multicentre, randomised, placebo-controlled, 7-day double-blind trial preceded by a 7-day run-in period. Reflux symptoms were assessed using...

Prospective registration, bias risk and outcome-reporting bias in randomised clinical trials of traditional Chinese medicine

DEFF Research Database (Denmark)

Liu, Jian-Ping; Han, Mei; Li, Xin-Xue

2013-01-01

Clinical trials on Traditional Chinese Medicine (TCM) should be registered in a publicly accessible international trial register and report on all outcomes. We systematically assessed and evaluated TCM trials in registries with their subsequent publications.......Clinical trials on Traditional Chinese Medicine (TCM) should be registered in a publicly accessible international trial register and report on all outcomes. We systematically assessed and evaluated TCM trials in registries with their subsequent publications....

Comprehensive safety assessment of a human inactivated diploid enterovirus 71 vaccine based on a phase III clinical trial.

Science.gov (United States)

Zhang, Wei; Kong, Yujia; Jiang, Zhiwei; Li, Chanjuan; Wang, Ling; Xia, Jielai

2016-04-02

Human enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease (HFMD). In a previous phase III trial in children, a human diploid cell-based inactivated EV71 vaccine elicited EV71 specific immune responses and protection against EV71 associated HFMD. This study aimed to assess the factors influencing the severity of adverse events observed in this previous trial. This was a randomized, double-blinded, placebo-controlled, phase III clinical trial of a human diploid vaccine carried out in 12,000 children in Guangxi Zhuang Autonomous Region, China (ClinicalTrials.gov: NCT01569581). Solicited events were recorded for 7 days and unsolicited events were reported for 28 days after each injection. Age trend analysis of adverse reaction was conducted in each treatment group. Multiple logistic regression models were built to identify factors influencing the severity of adverse reactions. Fewer solicited adverse reactions were observed in older participants within the first 7 days after vaccination (P < 0.0001), except local pain and pruritus. More severe adverse reactions were observed after the initial injection than after the booster injection. Serious cold or respiratory tract infections (RTI) were observed more often in children aged 6-36 months than in older children. Only the severity of local swelling was associated with body mass index. Children with throat discomfort before injection had a higher risk of serious cold or RTI. These results indicated that the human diploid cell-based vaccine achieved a satisfactory safety profile.

A Pilot Randomized Controlled Trial of a Holistic Needs Assessment Questionnaire in a Supportive and Palliative Care Service.

Science.gov (United States)

Ahmed, Nisar; Hughes, Philippa; Winslow, Michelle; Bath, Peter A; Collins, Karen; Noble, Bill

2015-11-01

At present, there is no widely used systematic evidence-based holistic approach to assessment of patients' supportive and palliative care needs. To determine whether the use of a holistic needs assessment questionnaire, Sheffield Profile for Assessment and Referral for Care (SPARC), will lead to improved health care outcomes for patients referred to a palliative care service. This was an open, pragmatic, randomized controlled trial. Patients (n = 182) referred to the palliative care service were randomized to receive SPARC at baseline (n = 87) or after a period of two weeks (waiting-list control n = 95). Primary outcome measure is the difference in score between Measure Yourself Concerns and Wellbeing (MYCAW) patient-nominated Concern 1 on the patient self-scoring visual analogue scale at baseline and the two-week follow-up. Secondary outcomes include difference in scores in the MYCAW, EuroQoL (EQ-5D), and Patient Enablement Instrument (PEI) scores at Weeks 2, 4, and 6. There was a significant association between change in MYCAW score and whether the patients were in the intervention or control group (χ(2)trend = 5.51; degrees of freedom = 1; P = 0.019). A higher proportion of patients in the control group had an improvement in MYCAW score from baseline to Week 2: control (34 of 70 [48.6%]) vs. intervention (19 of 66 [28.8%]). There were no significant differences (no detectable effect) between the control and intervention groups in the scores for EQ-5D and Patient Enablement Instrument at 2-, 4-, or 6-week follow-up. This trial result identifies a potential negative effect of SPARC in specialist palliative care services, raising questions that standardized holistic needs assessment questionnaires may be counterproductive if not integrated with a clinical assessment that informs the care plan. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Assessing Clinical Research Capacity in Vietnam: A Framework for Strengthening Capability for Clinical Trials in Developing Countries.

Science.gov (United States)

Kagan, Jonathan; Giang, Dao Duc; Iademarco, Michael F; Phung, Van Tt; Lau, Chuen-Yen; Quang, Nguyen Ngo

2016-01-01

Although improving health systems promises important benefits, most developing nations lack the resources to support nationally driven clinical research. Strengthened clinical research capacity can advance national health goals by supporting greater autonomy in aligning research with national priorities. From March through June 2010, we assessed six elements of clinical research capacity in Vietnam: research agenda; clinical investigators and biostatisticians; donors and sponsors; community involvement; scientific, ethical, safety, and quality oversight; and clinical research institutions. Assessments were drawn from interviews with investigators, Ministry of Health staff members, nongovernment organizations, and U.S. Mission staff members, and document review. Observations and recommendations were shared with collaborators. Reassessment in 2015 found growth in the number of clinical trials, improved regulation in human subjects protection and community engagement, and modest advances in research agenda setting. Training and investment in institutions remain challenging. A framework for assessing clinical research capacity can affirm strengths and weaknesses and guide the coordination of capacity-building efforts.

Development, Validation, and Interlaboratory Evaluation of a Quantitative Multiplexing Method To Assess Levels of Ten Endogenous Allergens in Soybean Seed and Its Application to Field Trials Spanning Three Growing Seasons.

Science.gov (United States)

Hill, Ryan C; Oman, Trent J; Wang, Xiujuan; Shan, Guomin; Schafer, Barry; Herman, Rod A; Tobias, Rowel; Shippar, Jeff; Malayappan, Bhaskar; Sheng, Li; Xu, Austin; Bradshaw, Jason

2017-07-12

As part of the regulatory approval process in Europe, comparison of endogenous soybean allergen levels between genetically engineered (GE) and non-GE plants has been requested. A quantitative multiplex analytical method using tandem mass spectrometry was developed and validated to measure 10 potential soybean allergens from soybean seed. The analytical method was implemented at six laboratories to demonstrate the robustness of the method and further applied to three soybean field studies across multiple growing seasons (including 21 non-GE soybean varieties) to assess the natural variation of allergen levels. The results show environmental factors contribute more than genetic factors to the large variation in allergen abundance (2- to 50-fold between environmental replicates) as well as a large contribution of Gly m 5 and Gly m 6 to the total allergen profile, calling into question the scientific rational for measurement of endogenous allergen levels between GE and non-GE varieties in the safety assessment.

Acupuncture and asthma: a review of controlled trials

NARCIS (Netherlands)

Kleijnen, J.; ter Riet, G.; Knipschild, P.

1991-01-01

BACKGROUND: Published controlled trials of acupuncture in asthma have often contained a small number of subjects and the results are contradictory. Controlled trials have been reviewed to determine whether clearer conclusions could be obtained by assessing as many studies as possible according to

Update on TROG trials

International Nuclear Information System (INIS)

Joseph, D.

2001-01-01

Full text: Validation of treatment methodologies can only be achieved in the context of unambiguous, efficiently managed, randomised and controlled clinical trials. Since 1991, the Trans-Tasman Radiation Oncology Group (TROG) has coordinated over 29 protocols in radiation oncology, including several key randomised controlled trials. The impetus behind TROG is the establishment of an evidence base for particular approaches to radiotherapy and its adjunct use with alternative and complementary treatment methods. As the level of technology incorporated into radiotherapy continues to increase, as the need for improved accuracy in dose assessment increases and as the requirements of realistic quality assurance (QA) for clinical trials becomes more demanding it is imperative that all professionals involved in radiotherapy, including physicists, become actively involved in the QA of trials. This is particularly important for large scale multi-centre trials which intend to prove the benefits of particular treatment approaches on a national or international stage rather then in the context of a single clinic. This talk will: 1. Examine the outcomes of TROG trials to date in terms of the information obtained. 2. Briefly consider current and impending TROG trials and their requirements in terms of clinical and physics input. 3. Examine the results of international clinical trials in terms of the influence they have had on radiotherapy practice and health outcomes, and the advantages they have obtained by consistent co-operation between clinical and technological staff. 4. Consider the benefits of multi-centre clinical trials and the QA controls that are necessary to ensure accuracy of resulting recommendations. Copyright (2001) Australasian College of Physical Scientists and Engineers in Medicine

Research design considerations for single-dose analgesic clinical trials in acute pain

DEFF Research Database (Denmark)

Cooper, Stephen A; Desjardins, Paul J; Turk, Dennis C

2016-01-01

This article summarizes the results of a meeting convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) on key considerations and best practices governing the design of acute pain clinical trials. We discuss the role of early phase clinical trials......, including pharmacokinetic-pharmacodynamic (PK-PD) trials, and the value of including both placebo and active standards of comparison in acute pain trials. This article focuses on single-dose and short-duration trials with emphasis on the perioperative and study design factors that influence assay...... sensitivity. Recommendations are presented on assessment measures, study designs, and operational factors. Although most of the methodological advances have come from studies of postoperative pain after dental impaction, bunionectomy, and other surgeries, the design considerations discussed are applicable...

A Very Early Rehabilitation Trial after stroke (AVERT): a Phase III, multicentre, randomised controlled trial.

Science.gov (United States)

Langhorne, Peter; Wu, Olivia; Rodgers, Helen; Ashburn, Ann; Bernhardt, Julie

2017-09-01

Mobilising patients early after stroke [early mobilisation (EM)] is thought to contribute to the beneficial effects of stroke unit care but it is poorly defined and lacks direct evidence of benefit. We assessed the effectiveness of frequent higher dose very early mobilisation (VEM) after stroke. We conducted a parallel-group, single-blind, prospective randomised controlled trial with blinded end-point assessment using a web-based computer-generated stratified randomisation. The trial took place in 56 acute stroke units in five countries. We included adult patients with a first or recurrent stroke who met physiological inclusion criteria. Patients received either usual stroke unit care (UC) or UC plus VEM commencing within 24 hours of stroke. The primary outcome was good recovery [modified Rankin scale (mRS) score of 0-2] 3 months after stroke. Secondary outcomes at 3 months were the mRS, time to achieve walking 50 m, serious adverse events, quality of life (QoL) and costs at 12 months. Tertiary outcomes included a dose-response analysis. Patients, outcome assessors and investigators involved in the trial were blinded to treatment allocation. We recruited 2104 (UK, n  = 610; Australasia, n  = 1494) patients: 1054 allocated to VEM and 1050 to UC. Intervention protocol targets were achieved. Compared with UC, VEM patients mobilised 4.8 hours [95% confidence interval (CI) 4.1 to 5.7 hours; p  pattern of an improved odds of efficacy and safety outcomes in association with increased daily frequency of out-of-bed sessions but a reduced odds with an increased amount of mobilisation (minutes per day). UC clinicians started mobilisation earlier each year altering the context of the trial. Other potential confounding factors included staff patient interaction. Patients in the VEM group were mobilised earlier and with a higher dose of therapy than those in the UC group, which was already early. This VEM protocol was associated with reduced odds of favourable

A Systematic Review of Ebola Treatment Trials to Assess the Extent to Which They Adhere to Ethical Guidelines.

Directory of Open Access Journals (Sweden)

Thomas Richardson

pre-trial evidence base for its effectiveness against Ebola is speculative.Some limited and appropriate deviation from standard research expectations in disaster situations is increasingly accepted. However, this is not an excuse for poor ethics oversight and international regulations are in place which should not be ignored. New guidelines are needed that better define the boundaries between using medicines for compassionate use and conducting a clinical trial. Greater support should be offered for local research ethics committees in affected areas so that they can provide robust ethical review. Further systematic reviews should be carried out in epidemics of any novel infectious diseases to assess if comparable findings arise.

The RAPID-CTCA trial (Rapid Assessment of Potential Ischaemic Heart Disease with CTCA) - a multicentre parallel-group randomised trial to compare early computerised tomography coronary angiography versus standard care in patients presenting with suspected or confirmed acute coronary syndrome: study protocol for a randomised controlled trial.

Science.gov (United States)

Gray, Alasdair J; Roobottom, Carl; Smith, Jason E; Goodacre, Steve; Oatey, Katherine; O'Brien, Rachel; Storey, Robert F; Na, Lumine; Lewis, Steff C; Thokala, Praveen; Newby, David E

2016-12-07

Emergency department attendances with chest pain requiring assessment for acute coronary syndrome (ACS) are a major global health issue. Standard assessment includes history, examination, electrocardiogram (ECG) and serial troponin testing. Computerised tomography coronary angiography (CTCA) enables additional anatomical assessment of patients for coronary artery disease (CAD) but has only been studied in very low-risk patients. This trial aims to investigate the effect of early CTCA upon interventions, event rates and health care costs in patients with suspected/confirmed ACS who are at intermediate risk. Participants will be recruited in about 35 tertiary and district general hospitals in the UK. Patients ≥18 years old with symptoms with suspected/confirmed ACS with at least one of the following will be included: (1) ECG abnormalities, e.g. ST-segment depression >0.5 mm; (2) history of ischaemic heart disease; (3) troponin elevation above the 99 th centile of the normal reference range or increase in high-sensitivity troponin meeting European Society of Cardiology criteria for 'rule-in' of myocardial infarction (MI). The early use of ≥64-slice CTCA as part of routine assessment will be compared to standard care. The primary endpoint will be 1-year all-cause death or recurrent type 1 or type 4b MI at 1 year, measured as the time to such event. A number of secondary clinical, process and safety endpoints will be collected and analysed. Cost effectiveness will be estimated in terms of the lifetime incremental cost per quality-adjusted life year gained. We plan to recruit 2424 (2500 with ~3% drop-out) evaluable patients (1212 per arm) to have 90% power to detect a 20% versus 15% difference in 1-year death or recurrent type 1 MI or type 4b MI, two-sided p Acute Coronary Events score, previous CAD and baseline troponin level. The results will be expressed as a hazard ratio with the corresponding 95% confidence intervals and p value. The Rapid Assessment of

VISTA-Rehab: a resource for stroke rehabilitation trials.

Science.gov (United States)

Ali, Myzoon; Ashburn, Ann; Bowen, Audrey; Brodie, Eric; Corr, Susan; Drummond, Avril; Edmans, Judi; Gladman, John; Kalra, Lalit; Langhorne, Peter; Lees, Kennedy R; Lincoln, Nadina; Logan, Pip; Mead, Gillian; Patchick, Emma; Pollock, Alex; Pomeroy, Val; Sackley, Catherine; Sunnerhagen, Katherina S; van Vliet, Paulette; Walker, Marion; Brady, Marian

2010-12-01

Stroke rehabilitation is a complex intervention. Many factors influence the interaction between the patient and the elements of the intervention. Rehabilitation interventions are aimed at altering different domains of patient outcome including body functions, activity and participation. As a consequence, randomised clinical trials in this area are difficult to design. We developed an archive of stroke rehabilitation trials (VISTA-Rehab) to act as a resource to help trialists model and design future rehabilitation studies. We developed specific eligibility criteria for the entry of stroke rehabilitation trials into the archive. We established a Steering Committee to oversee projects and publications and commenced the recruitment of rehabilitation trials into this resource. As of August 2009, VISTA-Rehab contains data from 23 stroke rehabilitation trials (>3400 patients). Demographic data, including age [median=73, interquartile range (63,79)], gender (male=53%) and initial dependency [median baseline Barthel index score=6, interquartile range (9,19)], are available for all patients. Outcome measures include the modified Rankin Scale, Barthel Index, Rivermead Motor Assessment, Fugl-Meyer Assessment, General Health Questionnaire and Nottingham Extended Activities of Daily Living Scale. VISTA-Rehab expands the Virtual International Stroke Trials Archive to include rehabilitation trials. Anonymised data can be used to examine questions specific to stroke rehabilitation and to generate novel hypotheses. © 2010 The Authors. International Journal of Stroke © 2010 World Stroke Organization.

Requirements Elicitation in a Telemedicine Pain-treatment Trial

NARCIS (Netherlands)

Widya, I.A.; Bults, Richard G.A.; van Beijnum, Bernhard J.F.; Sandsjö, L.; Schaake, L.; Huis in 't Veld, M.H.A.; Jones, Valerie M.; Hermens, Hermanus J.; Ryan, K.; Robinson, W.

2009-01-01

This paper presents the early phase requirements elicitation for a work-related neck-shoulder pain teletreatment trial and the assessment of those requirements in respect of their importance to the trial and the feasibility of the needed software adaptations of the telemedicine system within the

The Hawthorne Effect: a randomised, controlled trial

Directory of Open Access Journals (Sweden)

van Haselen Robbert

2007-07-01

Full Text Available Abstract Background The 'Hawthorne Effect' may be an important factor affecting the generalisability of clinical research to routine practice, but has been little studied. Hawthorne Effects have been reported in previous clinical trials in dementia but to our knowledge, no attempt has been made to quantify them. Our aim was to compare minimal follow-up to intensive follow-up in participants in a placebo controlled trial of Ginkgo biloba for treating mild-moderate dementia. Methods Participants in a dementia trial were randomised to intensive follow-up (with comprehensive assessment visits at baseline and two, four and six months post randomisation or minimal follow-up (with an abbreviated assessment at baseline and a full assessment at six months. Our primary outcomes were cognitive functioning (ADAS-Cog and participant and carer-rated quality of life (QOL-AD. Results We recruited 176 participants, mainly through general practices. The main analysis was based on Intention to treat (ITT, with available data. In the ANCOVA model with baseline score as a co-variate, follow-up group had a significant effect on outcome at six months on the ADAS-Cog score (n = 140; mean difference = -2.018; 95%CI -3.914, -0.121; p = 0.037 favouring the intensive follow-up group, and on participant-rated quality of life score (n = 142; mean difference = -1.382; 95%CI -2.642, -0.122; p = 0.032 favouring minimal follow-up group. There was no significant difference on carer quality of life. Conclusion We found that more intensive follow-up of individuals in a placebo-controlled clinical trial of Ginkgo biloba for treating mild-moderate dementia resulted in a better outcome than minimal follow-up, as measured by their cognitive functioning. Trial registration Current controlled trials: ISRCTN45577048

Do Published Data in Trials Assessing Cancer Drugs Reflect the Real Picture of Efficacy and Safety?

Science.gov (United States)

Lv, Jia-Wei; Chen, Yu-Pei; Zhou, Guan-Qun; Liu, Xu; Guo, Ying; Mao, Yan-Ping; Ma, Jun; Sun, Ying

2017-11-01

Background: The reporting quality of publications is of vital importance to ensure accurate evidence dissemination. This study aimed to compare the consistency of results reporting between the ClinicalTrials.gov results database and the respective matching publications. Methods: We identified 323 phase III/IV cancer drug trials with a randomized controlled design and searched PubMed for publications in a 50% random sample (n=160). Data were extracted independently from ClinicalTrials.gov and publications. A scoring system was applied to determine characteristics associated with reporting quality. Results: Of 117 reviewed trials with publications, result reporting was significantly more complete in ClinicalTrials.gov for efficacy measurement (92.3% vs 90.6%), serious adverse events (SAEs; 100% vs 43.6%), and other adverse events (OAEs; 100% vs 62.4%). For trials with both posted and published results for design information (n=117), efficacy measurements (n=98), SAEs (n=51), and OAEs (n=73), discrepancies were found in 16 (13.7%), 38 (38.8%), 26 (51.0%), and 54 (74.0%) trials, respectively. Overreporting of treatment effects (7 trials) and alteration of primary end points favoring statistically significant outcomes (11 trials) were the major discrepancies in efficacy reporting; incomplete (66 trials) and underreporting (20 trials) of SAEs were the predominant issues in benefit/risk reporting. Median quality score was 21 (range, 14-28). Trials that had parallel assignment, were phase IV, had primary funding by industry, were completed after 2009, and had earlier results posted possessed better reporting quality. Conclusions: Although most trials showed reasonable completeness and consistency, some discrepancies are prevalent and persistent, jeopardizing evidence-based decision-making. Our findings highlight the need to consult results systematically from both ClinicalTrials.gov and publications. Copyright © 2017 by the National Comprehensive Cancer Network.

Assessment of data quality in an international multi-centre randomised trial of coronary artery surgery

Directory of Open Access Journals (Sweden)

Bochenek Andrzej

2011-09-01

Full Text Available Abstract Background ART is a multi-centre randomised trial of cardiac surgery which provided a unique opportunity to evaluate the data from a large number of centres from a variety of countries. We attempted to assess data quality, including recruitment rates, timeliness and completeness of the data obtained from the centres in different socio-economic strata. Methods The analysis was based on the 2-page CRF completed at the 6 week follow-up. CRF pages were categorised into "clean" (no edit query and "dirty" (any incomplete, inconsistent or illegible data. The timelines were assessed on the basis of the time interval from the visit and receipt of complete CRF. Data quality was defined as the number of data queries (in percent and time delay (in days between visit and receipt of correct data. Analyses were stratified according to the World Bank definitions into: "Developing" countries (Poland, Brazil and India and "Developed" (Italy, UK, Austria and Australia. Results There were 18 centres in the "Developed" and 10 centres in the "Developing" countries. The rate of enrolment did not differ significantly by economic level ("Developing":4.1 persons/month, "Developed":3.7 persons/month. The time interval for the receipt of data was longer for "Developing" countries (median:37 days compared to "Developed" ones (median:11 days (p Conclusions In this study we showed that data quality was comparable between centres from "Developed" and "Developing" countries. Data was received in a less timely fashion from Developing countries and appropriate systems should be instigated to minimize any delays. Close attention should be paid to the training of centres and to the central management of data quality. Trial registration ISRCTN46552265

Robustness assessments are needed to reduce bias in meta-analyses that include zero-event randomized trials

DEFF Research Database (Denmark)

Keus, F; Wetterslev, J; Gluud, C

2009-01-01

of statistical method on inference. RESULTS: In seven meta-analyses of seven outcomes from 15 trials, there were zero-event trials in 0 to 71.4% of the trials. We found inconsistency in significance in one of seven outcomes (14%; 95% confidence limit 0.4%-57.9%). There was also considerable variability......OBJECTIVES: Meta-analysis of randomized trials with binary data can use a variety of statistical methods. Zero-event trials may create analytic problems. We explored how different methods may impact inferences from meta-analyses containing zero-event trials. METHODS: Five levels of statistical...... methods are identified for meta-analysis with zero-event trials, leading to numerous data analyses. We used the binary outcomes from our Cochrane review of randomized trials of laparoscopic vs. small-incision cholecystectomy for patients with symptomatic cholecystolithiasis to illustrate the influence...

OARSI Clinical Trials Recommendations

DEFF Research Database (Denmark)

Katz, J N; Losina, E; Lohmander, L S

2015-01-01

To highlight methodological challenges in the design and conduct of randomized trials of surgical interventions and to propose strategies for addressing these challenges. This paper focuses on three broad areas: enrollment; intervention; and assessment including implications for analysis. For eac...

Feasibility of a multicentre, randomised controlled trial of laparoscopic versus open colorectal surgery in the acute setting: the LaCeS feasibility trial protocol.

Science.gov (United States)

Harji, Deena; Marshall, Helen; Gordon, Katie; Crow, Hannah; Hiley, Victoria; Burke, Dermot; Griffiths, Ben; Moriarty, Catherine; Twiddy, Maureen; O'Dwyer, John L; Verjee, Azmina; Brown, Julia; Sagar, Peter

2018-02-22

Acute colorectal surgery forms a significant proportion of emergency admissions within the National Health Service. There is limited evidence to suggest minimally invasive surgery may be associated with improved clinical outcomes in this cohort of patients. Consequently, there is a need to assess the clinical effectiveness and cost-effectiveness of laparoscopic surgery in the acute colorectal setting. However,emergency colorectal surgical trials have previously been difficult to conduct due to issues surrounding recruitment and equipoise. The LaCeS (randomised controlled trial of Laparoscopic versus open Colorectal Surgery in the acute setting) feasibility trial will determine the feasibility of conducting a definitive, phase III trial of laparoscopic versus open acute colorectal resection. The LaCeS feasibility trial is a prospective, multicentre, single-blinded, parallel group, pragmatic randomised controlled feasibility trial. Patients will be randomised on a 1:1 basis to receive eitherlaparoscopic or open surgery. The trial aims to recruit at least 66 patients from five acute general surgical units across the UK. Patients over the age of 18 with a diagnosis of acute colorectal pathology requiring resection on clinical and radiological/endoscopic investigations, with a National Confidential Enquiry into Patient Outcome and Death classification of urgent will be considered eligible for participation. The primary outcome is recruitment. Secondary outcomes include assessing the safety profile of laparoscopic surgery using intraoperative and postoperative complication rates, conversion rates and patient-safety indicators as surrogate markers. Clinical and patient-reported outcomes will also be reported. The trial will contain an embedded qualitative study to assess clinician and patient acceptability of trial processes. The LaCeS feasibility trial is approved by the Yorkshire and The Humber, Bradford Leeds Research Ethics Committee (REC reference: 15/ YH/0542). The

Mixed-Meal Tolerance Test Versus Glucagon Stimulation Test for the Assessment of β-Cell Function in Therapeutic Trials in Type 1 Diabetes

Science.gov (United States)

Greenbaum, Carla J.; Mandrup-Poulsen, Thomas; McGee, Paula Friedenberg; Battelino, Tadej; Haastert, Burkhard; Ludvigsson, Johnny; Pozzilli, Paolo; Lachin, John M.; Kolb, Hubert

2008-01-01

OBJECTIVE—β-Cell function in type 1 diabetes clinical trials is commonly measured by C-peptide response to a secretagogue in either a mixed-meal tolerance test (MMTT) or a glucagon stimulation test (GST). The Type 1 Diabetes TrialNet Research Group and the European C-peptide Trial (ECPT) Study Group conducted parallel randomized studies to compare the sensitivity, reproducibility, and tolerability of these procedures. RESEARCH DESIGN AND METHODS—In randomized sequences, 148 TrialNet subjects completed 549 tests with up to 2 MMTT and 2 GST tests on separate days, and 118 ECPT subjects completed 348 tests (up to 3 each) with either two MMTTs or two GSTs. RESULTS—Among individuals with up to 4 years’ duration of type 1 diabetes, >85% had measurable stimulated C-peptide values. The MMTT stimulus produced significantly higher concentrations of C-peptide than the GST. Whereas both tests were highly reproducible, the MMTT was significantly more so (R2 = 0.96 for peak C-peptide response). Overall, the majority of subjects preferred the MMTT, and there were few adverse events. Some older subjects preferred the shorter duration of the GST. Nausea was reported in the majority of GST studies, particularly in the young age-group. CONCLUSIONS—The MMTT is preferred for the assessment of β-cell function in therapeutic trials in type 1 diabetes. PMID:18628574

Extremity dosimetry trial: Devonport royal dockyard

International Nuclear Information System (INIS)

Kenyon, R.; Collison, R.

2008-01-01

This trial was undertaken to assess extremity dosemeters, which were made available to Devonport Royal Dockyard and determine the most suitable to the site. The trial included operational and laboratory-based exposures. Operational exposures were within a submarine reactor compartment and a waste storage area. Laboratory exposures were undertaken using 241 Am, 137 Cs and 60 Co sources to compare and contrast the dosemeters energy response. In addition, the low dose response and the response if placed in the incorrect orientation were also assessed. Ten passive and two active dosemeters were tested, with three highlighted as the most technically suitable, DSTL Harshaw DXT-RAD, HPA Harshaw EXT-RAD and the AMEC Panasonic UD-807A. The most technically suitable dosemeter was the DSTL Harshaw DXT-RAD, due to good responses within all aspects of the trial and the user's preference for the ring type design. The John Caunt ED2 electronic dosemeter 2 (ED2) also performed well, but suffered radio frequency interference. (authors)

Clinical Trials in Dentistry: A Cross-sectional Analysis of World Health Organization-International Clinical Trial Registry Platform.

Science.gov (United States)

Sivaramakrishnan, Gowri; Sridharan, Kannan

2016-06-01

Clinical trials are the back bone for evidence-based practice (EBP) and recently EBP has been considered the best source of treatment strategies available. Clinical trial registries serve as databases of clinical trials. As regards to dentistry in specific data on the number of clinical trials and their quality is lacking. Hence, the present study was envisaged. Clinical trials registered in WHO-ICTRP (http://apps.who.int/trialsearch/AdvSearch.aspx) in dental specialties were considered. The details assessed from the collected trials include: Type of sponsors; Health condition; Recruitment status; Study design; randomization, method of randomization and allocation concealment; Single or multi-centric; Retrospective or prospective registration; and Publication status in case of completed studies. A total of 197 trials were identified. Maximum trials were from United States (n = 30) and United Kingdom (n = 38). Seventy six trials were registered in Clinical Trials.gov, 54 from International Standards of Reporting Clinical Trials, 13 each from Australia and New Zealand Trial Register and Iranian Registry of Clinical Trials, 10 from German Clinical Trial Registry, eight each from Brazilian Clinical Trial Registry and Nederland's Trial Register, seven from Japan Clinical Trial Registry, six from Clinical Trial Registry of India and two from Hong Kong Clinical Trial Registry. A total of 78.7% studies were investigator-initiated and 64% were completed while 3% were terminated. Nearly four-fifths of the registered trials (81.7%) were interventional studies of which randomized were the large majority (94.4%) with 63.2% being open label, 20.4% using single blinding technique and 16.4% were doubled blinded. The number, methodology and the characteristics of clinical trials in dentistry have been noted to be poor especially in terms of being conducted multi-centrically, employing blinding and the method for randomization and allocation concealment. More emphasis has to be

Results of the Interlaboratory Exercise CNS/CIEMAT-05 among Environmental Radioactivity Laboratories (Vegetable Ash); Evaluacion de la Intercomparacion CSN/CIEMAT-2005 entre Laboratorios Nacionales Radiactividad Ambiental (Ceniza Vegetal)

Energy Technology Data Exchange (ETDEWEB)

Romero Gonzalez, M. L.; Barrera Izquierdo, M.; Valino Garcia, F.

2006-07-01

The document describes the outcome of the CSN/CIEMAT-05 interlaboratory test comparison among environmental radioactivity laboratories. The exercise was organised according to the ISO-43 and the IUPAC {sup I}nternational harmonised protocol for the proficiency testing of analytical chemistry laboratories{sup .} The exercise has been designed to evaluate the capability of national laboratories to determine environmental levels of radionuclides in vegetable ash samples. The sample has been prepared by the Environmental Radiation Laboratory, from the University of Barcelona, and it contains the following radionuclides: Sr-90, Pu-238, Am-241, Th-230, Pb-210, U-238, Ra-226, K-40, Ra-228, TI-208, Cs- 137 and Co-60. Reference values have been established TROUGH the kind collaboration of three international laboratories of recognized experience: IAEA MEL and IRSN-Orsay. The results of the exercise were computed for 35 participating laboratories and their analytical performance was assessed using the z-score approach. Robust statistics of the participant's results was applied to obtain the median and standard deviation, to achieve a more complete and objetiva study of the laboratories' performance. Some difficulties encountered to dissolve the test sample caused a lower response of analyses involving radiochemical separation, thus some laboratories couldn't apply their routine methods and no conclusions on PU-238, Am-241 and Th-230 performances have been obtained. The exercise has revealed an homogeneous behaviour of laboratories, being statistical parameters from the results close to the reference values. The study has shown that participant laboratories perform radioactive determinations in vegetable ash samples with satisfactory quality levels. (Author) 6 refs.

Commentary: considerations for using the 'Trials within Cohorts' design in a clinical trial of an investigational medicinal product.

Science.gov (United States)

Bibby, Anna C; Torgerson, David J; Leach, Samantha; Lewis-White, Helen; Maskell, Nick A

2018-01-08

The 'trials within cohorts' (TwiC) design is a pragmatic approach to randomised trials in which trial participants are randomly selected from an existing cohort. The design has multiple potential benefits, including the option of conducting multiple trials within the same cohort. To date, the TwiC design methodology been used in numerous clinical settings but has never been applied to a clinical trial of an investigational medicinal product (CTIMP). We have recently secured the necessary approvals to undertake the first CTIMP using the TwiC design. In this paper, we describe some of the considerations and modifications required to ensure such a trial is compliant with Good Clinical Practice and international clinical trials regulations. We advocate using a two-stage consent process and using the consent stages to explicitly differentiate between trial participants and cohort participants who are providing control data. This distinction ensured compliance but had consequences with respect to costings, recruitment and the trial assessment schedule. We have demonstrated that it is possible to secure ethical and regulatory approval for a CTIMP TwiC. By including certain considerations at the trial design stage, we believe this pragmatic and efficient methodology could be utilised in other CTIMPs in future.

Solid oxide fuel cell field trial evaluation

Energy Technology Data Exchange (ETDEWEB)

Wilcox, C.P.; Winstanley, R.; Nietsch, T.; Smith, C.; Knight, R.; Seymore, C.

2000-07-01

This report focuses on issues relating to a field trial of a solid oxide fuel cell (SOFC). Aspects examined include markets for SOFC systems, the choice of systems for demonstration in year 2002, the assessment of industrial interest, and evaluation and ranking of candidate systems. The identification and evaluation of interest in field trials, the estimation of the capital and running costs of a field trial, and identification of the benefits to the UK and barriers to implementation of SOFC systems are discussed. (UK)

Observer variability in a phase II trial. Assessing consistency in RECIST application

International Nuclear Information System (INIS)

Skougaard, Kristin; Nielsen, Dorte; Vittrup Jensen, Benny; Dusgaard McCullagh, Mark James; Hjorth Johannesen, Helle; Westergren Hendel, Helle

2012-01-01

Objective: To assess the consistency of Response Evaluation Criteria in Solid Tumours (RECIST) application in a phase II trial. Material and methods: Patients with metastatic non-resectable colorectal cancer treated with a combination of an antibody and a chemotherapeutic drug, were included. Computed tomography (CT) scans (thorax, abdomen and pelvis) were performed at baseline and after every fourth treatment cycle. RECIST was intended for response evaluation. The scans were consecutively read by a heterogeneous group of radiologists as a part of daily work and hereafter retrospectively reviewed by a dedicated experienced radiologist. Agreement on best overall response (BOR) between readers and reviewer was quantified using κ-coefficients and the discrepancy rate was correlated with the number of different readers per patient using a χ 2 -test. Results: One hundred patients with 396 CT scans were included. Discrepancies between the readers and the reviewer were found in 47 patients. The majority of discrepancies concerned the application of RECIST. With the review, BOR changed in 17 patients, although, only in six patients the change was potentially treatment altering. Overall, the κ-coefficient of agreement between readers and reviewer was 0.71 (good). However, in the subgroup of responding patients the κ-coefficient was 0.21 (fair). The number of patients with discrepancies was significantly higher with three or more different readers per patient than with less (p =0.0003). Conclusion: RECIST was not consistently applied and the majority of the reader discrepancies were RECIST related. Post review, 17 patients changed BOR; six patients in a potentially treatment altering manner. Additionally, we found that the part of patients with discrepancies increased significantly with more than three different readers per patient. The findings support a peer-review approach where a few dedicated radiologists perform double blinded readings of all the on-going cancer

An analysis of registered clinical trials in otolaryngology from 2007 to 2010: ClinicalTrials.gov.

Science.gov (United States)

Witsell, David L; Schulz, Kristine A; Lee, Walter T; Chiswell, Karen

2013-11-01

To describe the conditions studied, interventions used, study characteristics, and funding sources of otolaryngology clinical trials from the ClinicalTrials.gov database; compare this otolaryngology cohort of interventional studies to clinical visits in a health care system; and assess agreement between clinical trials and clinical activity. Database analysis. Trial registration data downloaded from ClinicalTrials.gov and administrative data from the Duke University Medical Center from October 1, 2007 to September 27, 2010. Data extraction from ClinicalTrials.gov was done using MeSH and non-MeSH disease condition terms. Studies were subcategorized to create the following groupings for descriptive analysis: ear, nose, allergy, voice, sleep, head and neck cancer, thyroid, and throat. Duke Health System visits were queried by using selected ICD-9 codes for otolaryngology and non-otolaryngology providers. Visits were grouped similarly to ClinicalTrials.gov for further analysis. Chi-square tests were used to explore differences between groups. A total of 1115 of 40,970 registered interventional trials were assigned to otolaryngology. Head and neck cancer trials predominated. Study models most frequently incorporated parallel design (54.6%), 2 study groups (46.6%), and randomization (69.1%). Phase 2 or 3 studies constituted 46.4% of the cohort. Comparison of the ClinicalTrials.gov database with administrative health system visit data by disease condition showed discordance between national research activity and clinical visit volume for patients with otolaryngology complaints. Analysis of otolaryngology-related clinical research as listed in ClinicalTrials.gov can inform patients, physicians, and policy makers about research focus areas. The relative burden of otolaryngology-associated conditions in our tertiary health system exceeds research activity within the field.

Ezetimibe for the treatment of nonalcoholic steatohepatitis: assessment by novel magnetic resonance imaging and magnetic resonance elastography in a randomized trial (MOZART trial).

Science.gov (United States)

Loomba, Rohit; Sirlin, Claude B; Ang, Brandon; Bettencourt, Ricki; Jain, Rashmi; Salotti, Joanie; Soaft, Linda; Hooker, Jonathan; Kono, Yuko; Bhatt, Archana; Hernandez, Laura; Nguyen, Phirum; Noureddin, Mazen; Haufe, William; Hooker, Catherine; Yin, Meng; Ehman, Richard; Lin, Grace Y; Valasek, Mark A; Brenner, David A; Richards, Lisa

2015-04-01

Ezetimibe inhibits intestinal cholesterol absorption and lowers low-density lipoprotein cholesterol. Uncontrolled studies have suggested that it reduces liver fat as estimated by ultrasound in nonalcoholic steatohepatitis (NASH). Therefore, we aimed to examine the efficacy of ezetimibe versus placebo in reducing liver fat by the magnetic resonance imaging-derived proton density-fat fraction (MRI-PDFF) and liver histology in patients with biopsy-proven NASH. In this randomized, double-blind, placebo-controlled trial, 50 patients with biopsy-proven NASH were randomized to either ezetimibe 10 mg orally daily or placebo for 24 weeks. The primary outcome was a change in liver fat as measured by MRI-PDFF in colocalized regions of interest within each of the nine liver segments. Novel assessment by two-dimensional and three-dimensional magnetic resonance elastography was also performed. Ezetimibe was not significantly better than placebo at reducing liver fat as measured by MRI-PDFF (mean difference between the ezetimibe and placebo arms -1.3%, P = 0.4). Compared to baseline, however, end-of-treatment MRI-PDFF was significantly lower in the ezetimibe arm (15%-11.6%, P < 0.016) but not in the placebo arm (18.5%-16.4%, P = 0.15). There were no significant differences in histologic response rates, serum alanine aminotransferase and aspartate aminotransferase levels, or longitudinal changes in two-dimensional and three-dimensional magnetic resonance elastography-derived liver stiffness between the ezetimibe and placebo arms. Compared to histologic nonresponders (25/35), histologic responders (10/35) had a significantly greater reduction in MRI-PDFF (-4.35 ± 4.9% versus -0.30 ± 4.1%, P < 0.019). Ezetimibe did not significantly reduce liver fat in NASH. This trial demonstrates the application of colocalization of MRI-PDFF-derived fat maps and magnetic resonance elastography-derived stiffness maps of the liver before and after treatment to noninvasively assess treatment

A trial assessing N-3 as treatment for injury-induced cachexia (ATLANTIC trial: does a moderate dose fish oil intervention improve outcomes in older adults recovering from hip fracture?

Directory of Open Access Journals (Sweden)

Cleland Leslie

2010-10-01

Full Text Available Abstract Background Proximal femoral fractures are associated with increased morbidity and mortality. Pre-existing malnutrition and weight loss amongst this patient group is of primary concern, with conventional nutrition support being largely ineffective. The inflammatory response post proximal femoral fracture surgery and the subsequent risk of cachexia may explain the inability of conventional high energy high protein management to produce an anabolic response amongst these patients. Omega-3 fatty acids derived from fish oils have been extensively studied for their anti-inflammatory benefits. Due to their anti-inflammatory properties, the benefit of fish oil combined with individualized nutrition support amongst proximal femoral fracture patients post surgery is an attractive potential therapeutic strategy. The aim of the ATLANTIC trial is to assess the potential benefits of an anti-inflammatory dose of fish oil within the context of a 12 week individualised nutrition program, commencing seven days post proximal femoral fracture surgery. Methods/Design This randomized controlled, double blinded trial, will recruit 150 community dwelling elderly patients aged ≥65 years, within seven days of surgery for proximal femoral fracture. Participants will be randomly allocated to receive either a 12 week individualized nutrition support program complemented with 20 ml/day anti-inflammatory dose fish oil (~3.6 g eicosapentaenoic acid, ~2.4 g docosahexanoic acid; intervention, or, a 12 week individualized nutrition support program complemented with 20 ml/day low dose fish oil (~0.36 g eicosapentaenoic acid, ~0.24 g docosahexanoic acid; control. Discussion The ATLANTIC trial is the first of its kind to provide fish oil combined with individualized nutrition therapy as an intervention to address the inflammatory response experienced post proximal femoral fracture surgery amongst elderly patients. The final outcomes of this trial will assist clinicians in

SPME as a tool in WEA - CONCAWE Contribution to OSPAR Demonstration Project 2005 - 2006

NARCIS (Netherlands)

Leslie, H.A.

2006-01-01

This document represents a compilation of various data and deliverables from the study programme. An executive summary is followed by the presentation of data generated in an interlaboratory study of effluents assessed using both EGOM-LLE and biomimetic SPME methods.

Five year results of an international proficiency testing programme for measurement of antifungal drug concentrations

NARCIS (Netherlands)

Lempers, V.J.C.; Alffenaar, J.W.C.; Touw, D.J.; Burger, D.M.; Uges, D.R.A.; Aarnoutse, R.E.; Brüggemann, R.J.M.

2014-01-01

OBJECTIVES: Since 2007 the Dutch Association for Quality Assessment in Therapeutic Drug Monitoring (KKGT) has organized an international interlaboratory proficiency testing (PT) programme for measurement of antifungal drugs in plasma. We describe the 5 year results of the laboratories' performance.

Assessing sample representativeness in randomized controlled trials: application to the National Institute of Drug Abuse Clinical Trials Network.

Science.gov (United States)

Susukida, Ryoko; Crum, Rosa M; Stuart, Elizabeth A; Ebnesajjad, Cyrus; Mojtabai, Ramin

2016-07-01

To compare the characteristics of individuals participating in randomized controlled trials (RCTs) of treatments of substance use disorder (SUD) with individuals receiving treatment in usual care settings, and to provide a summary quantitative measure of differences between characteristics of these two groups of individuals using propensity score methods. Design Analyses using data from RCT samples from the National Institute of Drug Abuse Clinical Trials Network (CTN) and target populations of patients drawn from the Treatment Episodes Data Set-Admissions (TEDS-A). Settings Multiple clinical trial sites and nation-wide usual SUD treatment settings in the United States. A total of 3592 individuals from 10 CTN samples and 1 602 226 individuals selected from TEDS-A between 2001 and 2009. Measurements The propensity scores for enrolling in the RCTs were computed based on the following nine observable characteristics: sex, race/ethnicity, age, education, employment status, marital status, admission to treatment through criminal justice, intravenous drug use and the number of prior treatments. Findings The proportion of those with ≥ 12 years of education and the proportion of those who had full-time jobs were significantly higher among RCT samples than among target populations (in seven and nine trials, respectively, at P difference in the mean propensity scores between the RCTs and the target population was 1.54 standard deviations and was statistically significant at P different from individuals receiving treatment in usual care settings. Notably, RCT participants tend to have more years of education and a greater likelihood of full-time work compared with people receiving care in usual care settings. © 2016 Society for the Study of Addiction.

Comparison of serum copper determination by colorimetric and atomic absorption spectrometric methods in seven different laboratories. The S.F.B.C. (Société Française de Biologie Clinique) Trace Element Group.

Science.gov (United States)

Arnaud, J; Chappuis, P; Zawislak, R; Houot, O; Jaudon, M C; Bienvenu, F; Bureau, F

1993-02-01

An interlaboratory collaborative trial was conducted on the determination of serum copper using two different methods, based on colorimetry (test combination Copper, Boehringer Mannheim, Mannheim, Germany) and flame atomic absorption spectrometry (FAAS). The general performance of the colorimetric method was below that of FAAS, except for sensitivity and linear range, as assessed by detection limit (0.44 versus 1.32 mumol/L) and upper limit of linearity (150 versus 50 mumol/L). The range of the between-run CVs and the recovery of standard additions were, respectively, 2.3-11.9% and 92-127% for the colorimetric method and 1.1-6.0% and 93-101% for the FAAS method. Interferences were minimal with both methods. The two techniques correlated satisfactorily (the correlation coefficients ranged from 0.945-0.970 among laboratories) but the colorimetric assay exhibited slightly higher results than the FAAS method. Each method was transferable among laboratories.

Marketing and clinical trials: a case study.

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Francis, David; Roberts, Ian; Elbourne, Diana R; Shakur, Haleema; Knight, Rosemary C; Garcia, Jo; Snowdon, Claire; Entwistle, Vikki A; McDonald, Alison M; Grant, Adrian M; Campbell, Marion K

2007-11-20

Publicly funded clinical trials require a substantial commitment of time and money. To ensure that sufficient numbers of patients are recruited it is essential that they address important questions in a rigorous manner and are managed well, adopting effective marketing strategies. Using methods of analysis drawn from management studies, this paper presents a structured assessment framework or reference model, derived from a case analysis of the MRC's CRASH trial, of 12 factors that may affect the success of the marketing and sales activities associated with clinical trials. The case study demonstrates that trials need various categories of people to buy in - hence, to be successful, trialists must embrace marketing strategies to some extent. The performance of future clinical trials could be enhanced if trialists routinely considered these factors.

Clinical Neuropathology practice news 1-2014: Pyrosequencing meets clinical and analytical performance criteria for routine testing of MGMT promoter methylation status in glioblastoma

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Preusser, Matthias; Berghoff, Anna S.; Manzl, Claudia; Filipits, Martin; Weinhäusel, Andreas; Pulverer, Walter; Dieckmann, Karin; Widhalm, Georg; Wöhrer, Adelheid; Knosp, Engelbert; Marosi, Christine; Hainfellner, Johannes A.

2014-01-01

Testing of the MGMT promoter methylation status in glioblastoma is relevant for clinical decision making and research applications. Two recent and independent phase III therapy trials confirmed a prognostic and predictive value of the MGMT promoter methylation status in elderly glioblastoma patients. Several methods for MGMT promoter methylation testing have been proposed, but seem to be of limited test reliability. Therefore, and also due to feasibility reasons, translation of MGMT methylation testing into routine use has been protracted so far. Pyrosequencing after prior DNA bisulfite modification has emerged as a reliable, accurate, fast and easy-to-use method for MGMT promoter methylation testing in tumor tissues (including formalin-fixed and paraffin-embedded samples). We performed an intra- and inter-laboratory ring trial which demonstrates a high analytical performance of this technique. Thus, pyrosequencing-based assessment of MGMT promoter methylation status in glioblastoma meets the criteria of high analytical test performance and can be recommended for clinical application, provided that strict quality control is performed. Our article summarizes clinical indications, practical instructions and open issues for MGMT promoter methylation testing in glioblastoma using pyrosequencing. PMID:24359605

Standards for Clinical Trials in Male and Female Sexual Dysfunction: I. Phase I to Phase IV Clinical Trial Design.

Science.gov (United States)

Fisher, William A; Gruenwald, Ilan; Jannini, Emmanuele A; Lev-Sagie, Ahinoam; Lowenstein, Lior; Pyke, Robert E; Reisman, Yakov; Revicki, Dennis A; Rubio-Aurioles, Eusebio

2016-12-01

This series of articles outlines standards for clinical trials of treatments for male and female sexual dysfunctions, with a focus on research design and patient-reported outcome assessment. These articles consist of revision, updating, and integration of articles on standards for clinical trials in male and female sexual dysfunction from the 2010 International Consultation on Sexual Medicine developed by the authors as part of the 2015 International Consultation on Sexual Medicine. We are guided in this effort by several principles. In contrast to previous versions of these guidelines, we merge discussion of standards for clinical trials in male and female sexual dysfunction in an integrated approach that emphasizes the common foundational practices that underlie clinical trials in the two settings. We present a common expected standard for clinical trial design in male and female sexual dysfunction, a common rationale for the design of phase I to IV clinical trials, and common considerations for selection of study population and study duration in male and female sexual dysfunction. We present a focused discussion of fundamental principles in patient- (and partner-) reported outcome assessment and complete this series of articles with specific discussions of selected aspects of clinical trials that are unique to male and to female sexual dysfunction. Our consideration of standards for clinical trials in male and female sexual dysfunction attempts to embody sensitivity to existing and new regulatory guidance and to address implications of the evolution of the diagnosis of sexual dysfunction that have been brought forward in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. The first article in this series focuses on phase I to phase IV clinical trial design considerations. Subsequent articles in this series focus on the measurement of patient-reported outcomes, unique aspects of clinical trial design for men, and unique aspects of clinical

Non-sedation versus sedation with a daily wake-up trial in critically ill patients receiving mechanical ventilation (NONSEDA Trial)

DEFF Research Database (Denmark)

Toft, Palle; Olsen, Hanne Tanghus; Jørgensen, Helene Korvenius

2014-01-01

comparing sedation with no sedation, a priori powered to have all-cause mortality as primary outcome.The objective is to assess the benefits and harms of non-sedation versus sedation with a daily wake-up trial in critically ill patients. METHODS: The non-sedation (NONSEDA) trial is an investigator......-sedation supplemented with pain management during mechanical ventilation.Control intervention is sedation with a daily wake-up trial.The primary outcome will be all cause mortality at 90 days after randomization. Secondary outcomes will be: days until death throughout the total observation period; coma- and delirium...... in mortality with a type I error risk of 5% and a type II error risk of 20% (power at 80%). DISCUSSION: The trial investigates potential benefits of non-sedation. This might have large impact on the future treatment of mechanically ventilated critically ill patients.Trial register: ClinicalTrials.gov NCT...

Understanding and retention of trial-related information among participants in a clinical trial after completing the informed consent process.

Science.gov (United States)

Mexas, Fernanda; Efron, Anne; Luiz, Ronir Raggio; Cailleaux-Cezar, Michelle; Chaisson, Richard E; Conde, Marcus B

2014-02-01

for assessing the level of understanding of trial-related information during the informed consent (IC) process in developing countries are lacking. To assess the understanding and retention of trial-related information presented in the IC process by administering an informed consent assessment instrument (ICAI) to participants in a clinical trial for a new tuberculosis (TB) regimen being conducted in Rio de Janeiro (Brazil). Methods The format of the ICAI was based on the language and structure of the United States National Cancer Institute's IC comprehension checklist. The ICAI was designed to assess points of the RioMAR study IC process that addressed the principles of research ethics requested by Brazilian Regulatory Authority: autonomy, beneficence, non-maleficence, and justice. Briefly, (1) Is the respondent participating in a clinical trial? (2) Are two different treatments being evaluated? (3) Is the treatment arm chosen by chance? (4) Is an HIV test required? (5) Are liver function tests required? (6) Can participants leave the study at any time? (7) Are the risks and benefits of taking part in the study clear? (8) May pregnant women participate in the study? (9) Can one of the study drugs reduce the effectiveness of contraceptives? (10) Are patients paid to participate in the study? The ICAI was applied at two time points: immediately after enrollment in the clinical trial and 2 months later. A total of 61 patients who enrolled in the RioMAR study participated in this study. The percentage of correct answers to all questions was 82% at the time of the first ICAI; 31 participants (51%) did not recall that an HIV test was required (question 4) and 43 (70%) did not know that they could leave the study (question 6). Other individual questions were answered correctly by at least 76% of participants. There was no association between incorrect answers and age, gender, monthly family income, neighborhood, or level of education (p > 0.07). When the responses to the

Trial 1 versus Trial 2 of the Test of Memory Malingering: Evaluating accuracy without a "gold standard".

Science.gov (United States)

Mossman, Douglas; Wygant, Dustin B; Gervais, Roger O; Hart, Kathleen J

2018-01-01

This study examines the accuracy of the Test of Memory Malingering (TOMM), a frequently administered measure for evaluating effort during neurocognitive testing. In the last few years, several authors have suggested that the initial recognition trial of the TOMM (Trial 1) might be a more useful index for detecting feigned or exaggerated impairment than Trial 2, which is the source for inference recommended by the original instruction manual (Tombaugh, 1996). We used latent class modeling (LCM) implemented in a Bayesian framework to evaluate archival Trial 1 and Trial 2 data collected from 1,198 adults who had undergone outpatient forensic evaluations. All subjects were tested with 2 other performance validity tests (the Word Memory Test and the Computerized Assessment of Response Bias), and for 70% of the subjects, data from the California Verbal Learning Test-Second Edition Forced Choice trial were also available. Our results suggest that not even a perfect score on Trial 1 or Trial 2 justifies saying that an evaluee is definitely responding genuinely, although such scores imply a lower-than-base-rate probability of feigning. If one uses a Trial 2 cut-off higher than the manual's recommendation, Trial 2 does better than Trial 1 at identifying individuals who are almost certainly feigning while maintaining a negligible false positive rate. Using scores from both trials, one can identify a group of definitely feigning and very likely feigning subjects who comprise about 2 thirds of all feigners; only 1% of the members of this group would not be feigning. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Pediatric Clinical Trials Conducted in South Korea from 2006 to 2015: An Analysis of the South Korean Clinical Research Information Service, US ClinicalTrials.gov and European Clinical Trials Registries.

Science.gov (United States)

Choi, Sheung-Nyoung; Lee, Ji-Hyun; Song, In-Kyung; Kim, Eun-Hee; Kim, Jin-Tae; Kim, Hee-Soo

2017-12-01

The status of pediatric clinical trials performed in South Korea in the last decade, including clinical trials of drugs with unapproved indications for children, has not been previously examined. The aim was to provide information regarding the current state of pediatric clinical trials and create a basis for future trials performed in South Korea by reviewing three databases of clinical trials registrations. We searched for pediatric clinical studies (participants South Korea between 2006 and 2015 registered on the Clinical Research Information Service (CRIS), ClinicalTrials.gov, and the European Clinical Trials Registry (EuCTR). Additionally, we reviewed whether unapproved indications were involved in each trial by comparing the trials with a list of authorized trials provided by the Ministry of Food and Drug Safety (MFDS). The primary and secondary outcomes were to determine the change in number of pediatric clinical trials with unapproved indications over time and to assess the status of unauthorized pediatric clinical trials from the MFDS and the publication of articles after these clinical trials, respectively. We identified 342 clinical studies registered in the CRIS (n = 81), ClinicalTrials.gov (n = 225), and EuCTR (n = 36), of which 306 were reviewed after excluding duplicate registrations. Among them, 181 studies were interventional trials dealing with drugs and biological agents, of which 129 (71.3%) involved unapproved drugs. Of these 129 trials, 107 (82.9%) were authorized by the MFDS. Pediatric clinical trials in South Korea aiming to establish the safety and efficacy of drugs in children are increasing; however, non-MFDS-authorized studies remain an issue.

The DEMO trial: a randomized, parallel-group, observer-blinded clinical trial of strength versus aerobic versus relaxation training for patients with mild to moderate depression

DEFF Research Database (Denmark)

Krogh, Jesper; Saltin, Bengt; Gluud, Christian

2009-01-01

OBJECTIVE: To assess the benefit and harm of exercise training in adults with clinical depression. METHOD: The DEMO trial is a randomized pragmatic trial for patients with unipolar depression conducted from January 2005 through July 2007. Patients were referred from general practitioners or psych......: Our findings do not support a biologically mediated effect of exercise on symptom severity in depressed patients, but they do support a beneficial effect of strength training on work capacity. TRIAL REGISTRATION: (ClinicalTrials.gov) Identifier: NCT00103415.......OBJECTIVE: To assess the benefit and harm of exercise training in adults with clinical depression. METHOD: The DEMO trial is a randomized pragmatic trial for patients with unipolar depression conducted from January 2005 through July 2007. Patients were referred from general practitioners...... or psychiatrists and were eligible if they fulfilled the International Classification of Diseases, Tenth Revision, criteria for unipolar depression and were aged between 18 and 55 years. Patients (N = 165) were allocated to supervised strength, aerobic, or relaxation training during a 4-month period. The primary...

Decision aids for people considering taking part in clinical trials.

Science.gov (United States)

Gillies, Katie; Cotton, Seonaidh C; Brehaut, Jamie C; Politi, Mary C; Skea, Zoe

2015-11-27

Several interventions have been developed to promote informed consent for participants in clinical trials. However, many of these interventions focus on the content and structure of information (e.g. enhanced information or changes to the presentation format) rather than the process of decision making. Patient decision aids support a decision making process about medical options. Decision aids support the decision process by providing information about available options and their associated outcomes, alongside information that enables patients to consider what value they place on particular outcomes, and provide structured guidance on steps of decision making. They have been shown to be effective for treatment and screening decisions but evidence on their effectiveness in the context of informed consent for clinical trials has not been synthesised. To assess the effectiveness of decision aids for clinical trial informed consent compared to no intervention, standard information (i.e. usual practice) or an alternative intervention on the decision making process. We searched the following databases and to March 2015: Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library; MEDLINE (OvidSP) (from 1950); EMBASE (OvidSP) (from 1980); PsycINFO (OvidSP) (from 1806); ASSIA (ProQuest) (from 1987); WHO International Clinical Trials Registry Platform (ICTRP) (http://apps.who.int/trialsearch/); ClinicalTrials.gov; ISRCTN Register (http://www.controlled-trials.com/isrctn/). We also searched reference lists of included studies and relevant reviews. We contacted study authors and other experts. There were no language restrictions. We included randomised and quasi-randomised controlled trials comparing decision aids in the informed consent process for clinical trials alone, or in conjunction with standard information (such as written or verbal) or alongside alternative interventions (e.g. paper-based versus web-based decision aids). Included trials involved

Evaluation bias in objective response rate and disease control rate between blinded independent central review and local assessment: a study-level pooled analysis of phase III randomized control trials in the past seven years.

Science.gov (United States)

Zhang, Jianrong; Zhang, Yiyin; Tang, Shiyan; Liang, Hengrui; Chen, Difei; Jiang, Long; He, Qihua; Huang, Yu; Wang, Xinyu; Deng, Kexin; Jiang, Shuhan; Zhou, Jiaqing; Xu, Jiaxuan; Chen, Xuanzuo; Liang, Wenhua; He, Jianxing

2017-12-01

In previous studies, complete-case implementation of blind independent central review has been considered unnecessary based on no sign of systematic bias between central and local assessments. In order to further evaluate its value, this study investigated evaluation status between both assessments in phase III trials of anti-cancer drugs for non-hematologic solid tumors. Eligible trials were searched in PubMed with the date of Jan 1, 2010 to Jun 30, 2017. We compared objective response rate (ORR) and disease control rate (DCR) between central and local assessments by study-level pooled analysis and correlation analysis. In pooled analysis, direct comparison was measured by the odds ratio (OR) of central-assessed response status to local-assessed response status; to investigate evaluation bias between central and local assessments, the above calculated OR between experimental (exp-) and control (con-) arms were compared, measured by the ratio of OR. A total of 28 included trials involving 17,466 patients were included (28 with ORR, 16 with DCR). Pooled analysis showed central assessment reported lower ORR and DCR than local assessment, especially in trials with open-label design, central-assessed primary endpoint, and positive primary endpoint outcome, respectively. However, this finding could be found in both experimental [exp-ORR: OR=0.81 (95% CI: 0.76-0.87), Pevaluation bias between two assessments was indicated through further analysis [ORR: ratio of OR=1.02 (0.97-1.07), P=0.42, I 2 =0%; DCR: ratio of OR=0.98 (0.93-1.03), P=0.37, I 2 =0%], regardless of mask (open/blind), sample size, tumor type, primary endpoint (central-assessed/local-assessed), and primary endpoint outcome (positive/negative). Correlation analysis demonstrated a high-degree concordance between central and local assessments (exp-ORR, con-ORR, exp-DCR, con-DCR: r>0.90, P<0.01). Blind independent central review remained irreplaceable to monitor local assessment, but its complete

An interlaboratory comparison of ITS2-PCR for the identification of yeasts, using the ABI Prism 310 and CEQ8000 capillary electrophoresis systems

Directory of Open Access Journals (Sweden)

Verschraegen Gerda

2005-03-01

Full Text Available Abstract Background Currently, most laboratories identify yeasts routinely on the basis of morphology and biochemical reactivity. This approach has quite often limited discriminatory power and may require long incubation periods. Due to the increase of fungal infections and due to specific antifungal resistence patterns for different species, accurate and rapid identification has become more important. Several molecular techniques have been described for fast and reliable identification of yeast isolates, but interlaboratory exchangeability of identification schemes of molecular techniques has hardly been studied. Here, we compared amplified ITS2 fragment length determination by an ABI Prism 310 (Applied Biosystems, Foster City, Ca. capillary electrophoresis system with that obtained by a CEQ8000 (Beckman Coulter, Fullerton, Ca. capillary electrophoresis system. Results Although ITS2 size estimations on both systems differed and separate libraries had to be constructed for each system, both approaches had the same discriminatory power with regard to the 44 reference strains, identical identifications were obtained for 39/ 40 clinical isolates in both laboratories and strains from 51 samples were correctly identified using CEQ8000, when compared to phenotypic identification. Conclusion Identification of yeasts with ITS2-PCR followed by fragment analysis can be carried out on different capillary electrophoresis systems with comparable discriminatory power.

Assessing the effectiveness and cost-effectiveness of audit and feedback on physician’s prescribing indicators: study protocol of a randomized controlled trial with economic evaluation

Science.gov (United States)

2012-01-01

Background Physician prescribing is the most frequent medical intervention with a highest impact on healthcare costs and outcomes. Therefore improving and promoting rational drug use is a great interest. We aimed to assess the effectiveness and cost-effectiveness of two forms of conducting prescribing audit and feedback interventions and a printed educational material intervention in improving physician prescribing. Method/design A four-arm randomized trial with economic evaluation will be conducted in Tehran. Three interventions (routine feedback, revised feedback, and printed educational material) and a no intervention control arm will be compared. Physicians working in outpatient practices are randomly allocated to one of the four arms using stratified randomized sampling. The interventions are developed based on a review of literature, physician interviews, current experiences in Iran and with theoretical insights from the Theory of Planned Behavior. Effects of the interventions on improving antibiotics and corticosteroids prescribing will be assessed in regression analyses. Cost data will be assessed from a health care provider’s perspective and incremental cost-effectiveness ratios will be calculated. Discussion This study will determine the effectiveness and cost-effectiveness of three interventions and allow us to determine the most effective interventions in improving prescribing pattern. If the interventions are cost-effective, they will likely be applied nationwide. Trial registration Iranian Registry of Clinical Trials Registration Number: IRCT201106086740N1Pharmaceutical Sciences Research Center of TUMS Ethics Committee Registration Number: 90-02-27-07 PMID:23351564