Feedback in Clinical Education, Part I: Characteristics of Feedback Provided by Approved Clinical Instructors

Science.gov (United States)

Nottingham, Sara; Henning, Jolene

2014-01-01

Context Providing students with feedback is an important component of athletic training clinical education; however, little information is known about the feedback that Approved Clinical Instructors (ACIs; now known as preceptors) currently provide to athletic training students (ATSs). Objective To characterize the feedback provided by ACIs to ATSs during clinical education experiences. Design Qualitative study. Setting One National Collegiate Athletic Association Division I athletic training facility and 1 outpatient rehabilitation clinic that were clinical sites for 1 entry-level master's degree program accredited by the Commission on Accreditation of Athletic Training Education. Patients or Other Participants A total of 4 ACIs with various experience levels and 4 second-year ATSs. Data Collection and Analysis Extensive field observations were audio recorded, transcribed, and integrated with field notes for analysis. The constant comparative approach of open, axial, and selective coding was used to inductively analyze data and develop codes and categories. Member checking, triangulation, and peer debriefing were used to promote trustworthiness of the study. Results The ACIs gave 88 feedback statements in 45 hours and 10 minutes of observation. Characteristics of feedback categories included purpose, timing, specificity, content, form, and privacy. Conclusions Feedback that ACIs provided included several components that made each feedback exchange unique. The ACIs in our study provided feedback that is supported by the literature, suggesting that ACIs are using current recommendations for providing feedback. Feedback needs to be investigated across multiple athletic training education programs to gain more understanding of certain areas of feedback, including frequency, privacy, and form. PMID:24143902

Risk of Clinically Relevant Pharmacokinetic-based Drug-drug Interactions with Drugs Approved by the U.S. Food and Drug Administration Between 2013 and 2016.

Science.gov (United States)

Yu, Jingjing; Zhou, Zhu; Tay-Sontheimer, Jessica; Levy, Rene H; Ragueneau-Majlessi, Isabelle

2018-03-23

A total of 103 drugs (including 14 combination drugs) were approved by the U.S. Food and Drug Administration from 2013 to 2016. Pharmacokinetic-based drug interaction profiles were analyzed using the University of Washington Drug Interaction Database and the clinical relevance of these observations was characterized based on information from New Drug Application reviews. CYP3A was identified as a major contributor to clinical drug-drug interactions (DDIs), involved in approximately 2/3 of all interactions. Transporters (alone or with enzymes) were found to participate in about half of all interactions, although most of these were weak-to-moderate interactions. When considered as victims, eight new molecular entities (NMEs; cobimetinib, ibrutnib, isavuconazole, ivabradine, naloxegol, paritaprevir, simeprevir, and venetoclax) were identified as sensitive substrates of CYP3A, two NMEs (pirfenidone and tasimelteon) were sensitive substrates of CYP1A2, one NME (dasabuvir) was a sensitive substrate of CYP2C8, one NME (eliglustat) was a sensitive substrate of CYP2D6, and one NME (grazoprevir) was a sensitive substrate of OATP1B1/3 (with changes in exposure greater than 5-fold when co-administered with a strong inhibitor). Interestingly, approximately 75% of identified CYP3A substrates were also substrates of P-gp. As perpetrators, most clinical DDIs involved weak-to-moderate inhibition or induction, with only two drugs (Viekira Pak and idelalisib) showing strong inhibition of CYP3A, and one NME (lumacaftor) considered as a strong CYP3A inducer. Among drugs with large changes in exposure (≥ 5-fold), whether as victim or perpetrator, the most represented therapeutic classes were antivirals and oncology drugs, suggesting a significant risk of clinical DDIs in these patient populations. The American Society for Pharmacology and Experimental Therapeutics.

Gaps, tensions, and conflicts in the FDA approval process: implications for clinical practice.

Science.gov (United States)

Deyo, Richard A

2004-01-01

Despite many successes, drug approval at the Food and Drug Administration (FDA) is subject to gaps, internal tensions, and conflicts of interest. Recalls of drugs and devices and studies demonstrating advantages of older drugs over newer ones highlight the importance of these limitations. The FDA does not compare competing drugs and rarely requires tests of clinical efficacy for new devices. It does not review advertisements before use, assess cost-effectiveness, or regulate surgery (except for devices). Many believe postmarketing surveillance of drugs and devices is inadequate. A source of tension within the agency is pressure for speedy approvals. This may have resulted in "burn-out" among medical officers and has prompted criticism that safety is ignored. Others argue, however, that the agency is unnecessarily slow and bureaucratic. Recent reports identify conflicts of interest (stock ownership, consulting fees, research grants) among some members of the FDA's advisory committees. FDA review serves a critical function, but physicians should be aware that new drugs may not be as effective as old ones; that new drugs are likely to have undiscovered side effects at the time of marketing; that direct-to-consumer ads are sometimes misleading; that new devices generally have less rigorous evidence of efficacy than new drugs; and that value for money is not considered in approval.

Radiological Medical Device Innovation: Approvals via the Premarket Approval Pathway From 2000 to 2015.

Science.gov (United States)

Ghobadi, Comeron W; Hayman, Emily L; Finkle, Joshua H; Walter, Jessica R; Xu, Shuai

2017-01-01

The aim of this study was to critically assess the clinical evidence leading to radiologic medical device approvals via the premarket approval pathway from 2000 to 2015. This study used the publically available FDA premarket database for radiologic device approvals over the past 15 years (September 1, 2000, to August 31, 2015). Approval characteristics were collected for each device, and statistical analysis was performed on the data for each pivotal trial. Additionally, methodological quality of the pivotal trial was determined using the Quality Assessment of Diagnostic Accuracy Studies tool. Twenty-three class III radiologic device approvals were identified, with breast imaging accounting for 16 (70%) and computer-aided detection software accounting for 9 (39%) approvals. The median premarket approval time was 475 days (range, 180-1,116). Twenty-one devices were approved on the basis of multireader, multicenter studies, one on the basis of a randomized controlled trial, and one on the basis of a preclinical technical equivalence trial. The median number of patients per pivotal trial was 201 (range, 25-3,946). Twenty-six of the 34 pivotal trials (76%) had at least one methodologic bias. Breast imaging devices had a greater number of patients per pivotal trial (P = .009) and more prospective studies. With regard to all modalities, increased time to device approval correlated with weaker trial quality (r = 0.600, P assessing diagnostic technologies. Given that radiologic devices play a key role in modern medicine, further efforts should be made to increase transparency of clinical data leading to approval. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

21 CFR 314.610 - Approval based on evidence of effectiveness from studies in animals.

Science.gov (United States)

2010-04-01

... based on evidence of effectiveness from studies in animals. (a) FDA may grant marketing approval for a... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Approval based on evidence of effectiveness from... the effectiveness of these products only when: (1) There is a reasonably well-understood...

Monitoring additive manufacturing based products in clinical trials

NARCIS (Netherlands)

Marinakis, Yorgos; Harms, Rainer; Walsh, Steven Thomas

2017-01-01

Under U.S. federal regulation 31 CFR §312, medical interventions must report on a series of clinical trials phases before being submitted for approval for release to the U.S. market. Clinical trials are now being performed on medical interventions that were constructed through additive

Autosomal dominant polycystic kidney disease: recent advances in clinical management [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Zhiguo Mao

2016-08-01

Full Text Available The first clinical descriptions of autosomal dominant polycystic kidney disease (ADPKD go back at least 500 years to the late 16th century. Advances in understanding disease presentation and pathophysiology have mirrored the progress of clinical medicine in anatomy, pathology, physiology, cell biology, and genetics. The identification of PKD1 and PKD2, the major genes mutated in ADPKD, has stimulated major advances, which in turn have led to the first approved drug for this disorder and a fresh reassessment of patient management in the 21st century. In this commentary, we consider how clinical management is likely to change in the coming decade.

An approved personal dosimetry service based on an electronic dosimeter

International Nuclear Information System (INIS)

Marshall, T.O.; Bartlett, D.T.; Burgess, P.H.; Campbell, J.I.; Hill, C.E.; Pook, E.A.; Sandford, D.J.

1991-01-01

At the Second Conference on Radiation Protection and Dosimetry a paper was presented which, in part, announced the development of an electronic dosimeter to be undertaken in the UK by the National Radiological Protection Board (NRPB) and Siemens Plessey Controls Ltd. This dosimeter was to be of a standard suitable for use as the basis of an approved personal dosimetry service for photon and beta radiations. The project has progressed extremely well and dosimeters and readers are about to become commercially available. The system and the specification of the dosimeter are presented. The NRPB is in the process of applying for approval by the Health and Safety Executive (HSE) to operate as personal monitoring service based on this dosimeter. As part of the approval procedure the dosimeter is being type tested and is also undergoing an HSE performance test and wearer trials. The tests and the wearer trials are described and a summary of the results to date presented. The way in which the service will be organized and operated is described and a comparison is made between the running of the service and others based on passive dosimeters at NRPB

Regulatory approval and a first-in-human phase I clinical trial of a monoclonal antibody produced in transgenic tobacco plants.

Science.gov (United States)

Ma, Julian K-C; Drossard, Jürgen; Lewis, David; Altmann, Friedrich; Boyle, Julia; Christou, Paul; Cole, Tom; Dale, Philip; van Dolleweerd, Craig J; Isitt, Valerie; Katinger, Dietmar; Lobedan, Martin; Mertens, Hubert; Paul, Mathew J; Rademacher, Thomas; Sack, Markus; Hundleby, Penelope A C; Stiegler, Gabriela; Stoger, Eva; Twyman, Richard M; Vcelar, Brigitta; Fischer, Rainer

2015-10-01

Although plant biotechnology has been widely investigated for the production of clinical-grade monoclonal antibodies, no antibody products derived from transgenic plants have yet been approved by pharmaceutical regulators for clinical testing. In the Pharma-Planta project, the HIV-neutralizing human monoclonal antibody 2G12 was expressed in transgenic tobacco (Nicotiana tabacum). The scientific, technical and regulatory demands of good manufacturing practice (GMP) were addressed by comprehensive molecular characterization of the transgene locus, confirmation of genetic and phenotypic stability over several generations of transgenic plants, and by establishing standard operating procedures for the creation of a master seed bank, plant cultivation, harvest, initial processing, downstream processing and purification. The project developed specifications for the plant-derived antibody (P2G12) as an active pharmaceutical ingredient (API) based on (i) the guidelines for the manufacture of monoclonal antibodies in cell culture systems; (ii) the draft European Medicines Agency Points to Consider document on quality requirements for APIs produced in transgenic plants; and (iii) de novo guidelines developed with European national regulators. From the resulting process, a GMP manufacturing authorization was issued by the competent authority in Germany for transgenic plant-derived monoclonal antibodies for use in a phase I clinical evaluation. Following preclinical evaluation and ethical approval, a clinical trial application was accepted by the UK national pharmaceutical regulator. A first-in-human, double-blind, placebo-controlled, randomized, dose-escalation phase I safety study of a single vaginal administration of P2G12 was carried out in healthy female subjects. The successful completion of the clinical trial marks a significant milestone in the commercial development of plant-derived pharmaceutical proteins. © 2015 Society for Experimental Biology, Association of

The big picture on nanomedicine: the state of investigational and approved nanomedicine products.

Science.gov (United States)

Etheridge, Michael L; Campbell, Stephen A; Erdman, Arthur G; Haynes, Christy L; Wolf, Susan M; McCullough, Jeffrey

2013-01-01

Developments in nanomedicine are expected to provide solutions to many of modern medicine's unsolved problems, so it is no surprise that the literature contains many articles discussing the subject. However, existing reviews tend to focus on specific sectors of nanomedicine or to take a very forward-looking stance and fail to provide a complete perspective on the current landscape. This article provides a more comprehensive and contemporary inventory of nanomedicine products. A keyword search of literature, clinical trial registries, and the Web yielded 247 nanomedicine products that are approved or in various stages of clinical study. Specific information on each was gathered, so the overall field could be described based on various dimensions, including FDA classification, approval status, nanoscale size, treated condition, nanostructure, and others. In addition to documenting the many nanomedicine products already in use in humans, this study identifies several interesting trends forecasting the future of nanomedicine. In this one of a kind review, the state of nanomedicine commercialization is discussed, concentrating only on nanomedicine-based developments and products that are either in clinical trials or have already been approved for use. Copyright © 2013 Elsevier Inc. All rights reserved.

Approval procedures for clinical trials in the field of radiation oncology; Genehmigungsverfahren klinischer Studien im Bereich der Radioonkologie

Energy Technology Data Exchange (ETDEWEB)

Simon, Monique; Buettner, Daniel [Deutsches Konsortium fuer Translationale Krebsforschung (DKTK), Dresden (Germany); Deutsches Krebsforschungszentrum (DKFZ), Heidelberg (Germany); Medizinische Fakultaet und Universitaetsklinikum Carl Gustav Carus, Technische Universitaet Dresden, Klinik fuer Strahlentherapie und Radioonkologie und OncoRay - Nationales Zentrum fuer Strahlenforschung in der Onkologie, Dresden (Germany); Habeck, Matthias; Habeck, Uta; Brix, Gunnar [Bundesamt fuer Strahlenschutz (BfS), Fachbereich Strahlenschutz und Gesundheit, Neuherberg (Germany); Krause, Mechthild; Baumann, Michael [Deutsches Konsortium fuer Translationale Krebsforschung (DKTK), Dresden (Germany); Deutsches Krebsforschungszentrum (DKFZ), Heidelberg (Germany); Medizinische Fakultaet und Universitaetsklinikum Carl Gustav Carus, Technische Universitaet Dresden, Klinik fuer Strahlentherapie und Radioonkologie und OncoRay - Nationales Zentrum fuer Strahlenforschung in der Onkologie, Dresden (Germany); Helmholtz-Zentrum Dresden - Rossendorf, Institut fuer Radioonkologie und OncoRay - Nationales Zentrum fuer Strahlenforschung in der Onkologie, Dresden (Germany); Willich, Normann [Universitaetsklinikum Muenster, Klinik fuer Strahlentherapie - Radioonkologie, Muenster (Germany); Wenz, Frederik [Universitaetsmedizin Mannheim, Medizinische Fakultaet Mannheim, Universitaet Heidelberg, Klinik fuer Strahlentherapie und Radioonkologie, Mannheim (Germany); Schmidberger, Heinz [Universitaetsmedizin Mainz, Klinik fuer Radioonkologie und Strahlentherapie, Mainz (Germany); Debus, Juergen [Universitaetsklinikum Heidelberg, Klinik fuer Radioonkologie und Strahlentherapie, Heidelberg (Germany); Noelling, Torsten

2015-12-15

Application of ionizing radiation for the purpose of medical research in Germany needs to be approved by the national authority for radiation protection (Bundesamt fuer Strahlenschutz, BfS). For studies in the field of radiation oncology, differentiation between use of radiation for ''medical care (Heilkunde)'' versus ''medical research'' frequently leads to contradictions. The aim of this article is to provide principle investigators, individuals, and institutions involved in the process, as well as institutional review or ethics committees, with the necessary information for this assessment. Information on the legal frame and the approval procedures are also provided. A workshop was co-organized by the German Society for Radiation Oncology (DEGRO), the Working Party for Radiation Oncology (ARO) of the German Cancer Society (DKG), the German Society for Medical Physics (DGMP), and the German Cancer Consortium (DKTK) in October 2013. This paper summarizes the results of the workshop and the follow-up discussions between the organizers and the BfS. Differentiating between ''Heilkunde'' which does not need to be approved by the BfS and ''medical research'' is whether the specific application of radiation (beam quality, dose, schedule, target volume, etc.) is a clinically established and recognized procedure. This must be answered by the qualified physician(s) (''fachkundiger Arzt'' according to German radiation protection law) in charge of the study and the treatments of the patients within the study, taking into consideration of the best available evidence from clinical studies, guidelines and consensus papers. Among the important parameters for assessment are indication, total dose, and fractionation. Radiation treatments applied outside clinical trials do not require approval by the BfS, even if they are applied within a randomized or nonrandomized clinical trial

77 FR 60085 - Approval and Promulgation of Air Quality Implementation Plans; West Virginia; The 2002 Base Year...

Science.gov (United States)

2012-10-02

... Promulgation of Air Quality Implementation Plans; West Virginia; The 2002 Base Year Inventory for the... proposing to approve the fine particulate matter (PM 2.5 ) 2002 base year emissions inventory portion of the... Quality Standard (NAAQS) SIP. EPA is proposing to approve the 2002 base year PM 2.5 emissions inventory...

Feedback in Clinical Education, Part II: Approved Clinical Instructor and Student Perceptions of and Influences on Feedback

Science.gov (United States)

Nottingham, Sara; Henning, Jolene

2014-01-01

Context: Approved Clinical Instructors (ACIs; now known as preceptors) are expected to provide feedback to athletic training students (ATSs) during clinical education experiences. Researchers in other fields have found that clinical instructors and students often have different perceptions of actual and ideal feedback and that several factors may influence the feedback exchanges between instructors and students. However, understanding of these issues in athletic training education is minimal. Objective: To investigate the current characteristics and perceptions of and the influences on feedback exchanges between ATSs and ACIs. Design: Qualitative study. Setting: One entry-level master's degree program accredited by the Commission on Accreditation of Athletic Training Education. Patients or Other Participants: Four ACIs and 4 second-year ATSs. Data Collection and Analysis: Individual, semistructured interviews were conducted with participants and integrated with field notes and observations for analysis. We used the constant comparative approach to inductively analyze data and develop codes and categories. Member checking, triangulation, and peer debriefing were used to promote trustworthiness of the study. Results: Participants described that feedback plays an important role in clinical education and has several purposes related to improving performance. The ACIs and ATSs also discussed several preferred characteristics of feedback. Participants identified 4 main influences on their feedback exchanges, including the ACI, the ATS, personalities, and the learning environment. Conclusions: The ACIs and ATSs had similar perceptions of ideal feedback in addition to the actual feedback that was provided during their clinical education experiences. Most of the preferences for feedback were aligned with recommendations in the literature, suggesting that existing research findings are applicable to athletic training clinical education. Several factors influenced the

77 FR 60094 - Approval and Promulgation of Air Quality Implementation Plans; West Virginia; The 2002 Base Year...

Science.gov (United States)

2012-10-02

... Promulgation of Air Quality Implementation Plans; West Virginia; The 2002 Base Year Inventory for the... proposing to approve the fine particulate matter (PM 2.5 ) 2002 base year emissions inventory portion of the... Standard (NAAQS) SIP. EPA is proposing to approve the 2002 base year PM 2.5 emissions inventory for the...

77 FR 60087 - Approval and Promulgation of Air Quality Implementation Plans; West Virginia; The 2002 Base Year...

Science.gov (United States)

2012-10-02

... Promulgation of Air Quality Implementation Plans; West Virginia; The 2002 Base Year Inventory for the... proposing to approve the fine particulate matter (PM 2.5 ) 2002 base year emissions inventory portion of the... National Ambient Air Quality Standard (NAAQS) SIP. EPA is proposing to approve the 2002 base year PM 2.5...

Fate of clinical research studies after ethical approval--follow-up of study protocols until publication.

Directory of Open Access Journals (Sweden)

Anette Blümle

Full Text Available Many clinical studies are ultimately not fully published in peer-reviewed journals. Underreporting of clinical research is wasteful and can result in biased estimates of treatment effect or harm, leading to recommendations that are inappropriate or even dangerous.We assembled a cohort of clinical studies approved 2000-2002 by the Research Ethics Committee of the University of Freiburg, Germany. Published full articles were searched in electronic databases and investigators contacted. Data on study characteristics were extracted from protocols and corresponding publications. We characterized the cohort, quantified its publication outcome and compared protocols and publications for selected aspects.Of 917 approved studies, 807 were started and 110 were not, either locally or as a whole. Of the started studies, 576 (71% were completed according to protocol, 128 (16% discontinued and 42 (5% are still ongoing; for 61 (8% there was no information about their course. We identified 782 full publications corresponding to 419 of the 807 initiated studies; the publication proportion was 52% (95% CI: 0.48-0.55. Study design was not significantly associated with subsequent publication. Multicentre status, international collaboration, large sample size and commercial or non-commercial funding were positively associated with subsequent publication. Commercial funding was mentioned in 203 (48% protocols and in 205 (49% of the publications. In most published studies (339; 81% this information corresponded between protocol and publication. Most studies were published in English (367; 88%; some in German (25; 6% or both languages (27; 6%. The local investigators were listed as (co-authors in the publications corresponding to 259 (62% studies.Half of the clinical research conducted at a large German university medical centre remains unpublished; future research is built on an incomplete database. Research resources are likely wasted as neither health care

Premature Discontinuation of Prospective Clinical Studies Approved by a Research Ethics Committee - A Comparison of Randomised and Non-Randomised Studies.

Directory of Open Access Journals (Sweden)

Anette Blümle

Full Text Available Premature discontinuation of clinical studies affects about 25% of randomised controlled trials (RCTs which raises concerns about waste of scarce resources for research. The risk of discontinuation of non-randomised prospective studies (NPSs is yet unclear.To compare the proportion of discontinued studies between NPSs and RCTs that received ethical approval.We systematically surveyed prospective longitudinal clinical studies that were approved by a single REC in Freiburg, Germany between 2000 and 2002. We collected study characteristics, identified subsequent publications, and surveyed investigators to elucidate whether a study was discontinued and, if so, why.Of 917 approved studies, 547 were prospective longitudinal studies (306 RCTs and 241 NPSs. NPSs were on average smaller than RCTs, more frequently single centre and pilot studies, and less frequently funded by industry. NPSs were less frequently discontinued than RCTs: 32/221 (14% versus 78/288 (27%, p<0.001, missing data excluded. Poor recruitment was the most frequent reason for discontinuation in both NPSs (36% and RCTs (37%.Compared to RCTs, NPSs were at lower risk for discontinuation. Measures to reliably predict, sustain, and stimulate recruitment could prevent discontinuation of many RCTs but also of some NPSs.

Clinical translation of autologous cell-based tissue engineering techniques as Class III therapeutics in China: Taking cartilage tissue engineering as an example

Directory of Open Access Journals (Sweden)

Wei Zhang

2014-04-01

Full Text Available Autologous cell-based tissue engineering (TE techniques have been clinically approved for approximately 4 years in China, since the first cartilage TE technique was approved for clinical use by the Zhejiang Health Bureau. TE techniques offer a promising alternative to traditional transplantation surgery, and are different from those for transplanted tissues (biologics or pharmaceutical, the clinical translational procedures are unique and multitasked, and the requirements may differ from those of the target tissues. Thus, the translational procedure is still unfamiliar to most researchers and needs further improvement. This perspectives paper describes the key guidelines and regulations involved in the current translational process, and shares our translational experiences in cartilage TE to provide an example of autologous cell-based TE translation in China. Finally, we discuss the scientific and social challenges and provide some suggestions for future improvements.

Clinical trial registration, reporting, publication and FDAAA compliance: a cross-sectional analysis and ranking of new drugs approved by the FDA in 2012

Science.gov (United States)

Miller, Jennifer E; Korn, David; Ross, Joseph S

2015-01-01

Objective To evaluate clinical trial registration, reporting and publication rates for new drugs by: (1) legal requirements and (2) the ethical standard that all human subjects research should be publicly accessible to contribute to generalisable knowledge. Design Cross-sectional analysis of all clinical trials submitted to the Food and Drug Administration (FDA) for drugs approved in 2012, sponsored by large biopharmaceutical companies. Data sources Information from Drugs@FDA, ClinicalTrials.gov, MEDLINE-indexed journals and drug company communications. Main outcome measures Clinical trial registration and results reporting in ClinicalTrials.gov, publication in the medical literature, and compliance with the 2007 FDA Amendments Acts (FDAAA), analysed on the drug level. Results The FDA approved 15 drugs sponsored by 10 large companies in 2012. We identified 318 relevant trials involving 99 599 research participants. Per drug, a median of 57% (IQR 32–83%) of trials were registered, 20% (IQR 12–28%) reported results in ClinicalTrials.gov, 56% (IQR 41–83%) were published, and 65% (IQR 41–83%) were either published or reported results. Almost half of all reviewed drugs had at least one undisclosed phase II or III trial. Per drug, a median of 17% (IQR 8–20%) of trials supporting FDA approvals were subject to FDAAA mandated public disclosure; of these, a median of 67% (IQR 0–100%) were FDAAA-compliant. 68% of research participants (67 629 of 99 599) participated in FDAAA-subject trials, with 51% (33 405 of 67 629) enrolled in non-compliant trials. Transparency varied widely among companies. Conclusions Trial disclosures for new drugs remain below legal and ethics standards, with wide variation in practices among drugs and their sponsors. Best practices are emerging. 2 of our 10 reviewed companies disclosed all trials and complied with legal disclosure requirements for their 2012 approved drugs. Ranking new drugs on transparency criteria may improve

Patient-Centered Drug Approval: The Role of Patient Advocacy in the Drug Approval Process.

Science.gov (United States)

Mattingly, T Joseph; Simoni-Wastila, Linda

2017-10-01

Recent approval of eteplirsen for Duchenne muscular dystrophy (DMD), a rare disease with few treatment alternatives, has reignited the debate over the U.S. drug approval process. The evolution of legal and regulatory restrictions to the marketing and sale of pharmaceuticals has spanned more than a century, and throughout this history, patient advocacy has played a significant role. Scientific evidence from clinical trials serves as the foundation for drug approval, but the patient voice has become increasingly influential. Although the gold standard for establishing safety and efficacy through randomized controlled trials has been in place for more than 50 years, it poses several limitations for rare disorders where patient recruitment for traditional clinical trials is a major barrier. Organized efforts by patient advocacy groups to help patients with rare diseases access investigational therapy have had a legislative and regulatory effect. After approval by the FDA, patient access to therapy may still be limited by cost. A managed care organization (MCO) with the fiduciary responsibility of managing the health of a population must weigh coverage decisions for costly therapies with questionable effectiveness against alternatives within the constraint of a finite budget. Even when the FDA deems a drug safe and effective, an MCO may determine that the drug should only be made available at a tier level where out-of-pocket costs are still too high for many patients. This limitation of availability may be due to cost, other treatment alternatives, or outcomes from existing clinical evidence. However, if the MCO makes a costly new treatment for a rare disease readily available, it may temporarily satisfy a small contingency at the cost of all of its members. This article examines the risks and benefits of patient-centered drug approval and the potential economic effect of patient-centered drug approval on population health. There is no funding to disclose. Mattingly

Emerging concepts in dendrimer-based nanomedicine: from design principles to clinical applications.

Science.gov (United States)

Kannan, R M; Nance, E; Kannan, S; Tomalia, D A

2014-12-01

Dendrimers are discrete nanostructures/nanoparticles with 'onion skin-like' branched layers. Beginning with a core, these nanostructures grow in concentric layers to produce stepwise increases in size that are similar to the dimensions of many in vivo globular proteins. These branched tree-like concentric layers are referred to as 'generations'. The outer generation of each dendrimer presents a precise number of functional groups that may act as a monodispersed platform for engineering favourable nanoparticle-drug and nanoparticle-tissue interactions. These features have attracted significant attention in medicine as nanocarriers for traditional small drugs, proteins, DNA/RNA and in some instances as intrinsically active nanoscale drugs. Dendrimer-based drugs, as well as diagnostic and imaging agents, are emerging as promising candidates for many nanomedicine applications. First, we will provide a brief survey of recent nanomedicines that are either approved or in the clinical approval process. This will be followed by an introduction to a new 'nanoperiodic' concept which proposes nanoparticle structure control and the engineering of 'critical nanoscale design parameters' (CNDPs) as a strategy for optimizing pharmocokinetics, pharmocodynamics and site-specific targeting of disease. This paradigm has led to the emergence of CNDP-directed nanoperiodic property patterns relating nanoparticle behaviour to critical in vivo clinical translation issues such as cellular uptake, transport, elimination, biodistribution, accumulation and nanotoxicology. With a focus on dendrimers, these CNDP-directed nanoperiodic patterns are used as a strategy for designing and optimizing nanoparticles for a variety of drug delivery and imaging applications, including a recent dendrimer-based theranostic nanodevice for imaging and treating cancer. Several emerging preclinical dendrimer-based nanotherapy concepts related to inflammation, neuro-inflammatory disorders, oncology and infectious

Role Strain in Collegiate Athletic Training Approved Clinical Instructors

Science.gov (United States)

Henning, Jolene M; Weidner, Thomas G

2008-01-01

Context: Certified athletic trainers who serve as Approved Clinical Instructors (ACIs) in the collegiate setting are balancing various roles (eg, patient care and related administrative tasks, clinical education). Whether this balancing act is associated with role strain in athletic trainers has not been examined. Objective: To examine the degree of, and contributing factors (eg, socialization experiences, professional and employment demographics, job congruency) to, role strain in collegiate ACIs. Design: Cross-sectional survey design. Setting: Geographically stratified random sample of ACIs affiliated with accredited athletic training education programs at National Collegiate Athletic Association (NCAA) Division I, II, and III institutions. Patients or Other Participants: 118 collegiate ACIs (47 head athletic trainers, 45 assistant athletic trainers, 26 graduate assistant athletic trainers). Main Outcome Measure(s): The Athletic Training ACI Role Strain Inventory, which measures total degree of role strain, 7 subscales of role strain, socialization experiences, professional and employment characteristics, and congruency in job responsibilities. Results: A total of 49% (n  =  58) of the participants experienced a moderate to high degree of role strain. Role Overload was the highest contributing subscale to total role strain. No differences were noted between total role strain and role occupant groups, NCAA division, or sex. Graduate assistant athletic trainers experienced a greater degree of role incompetence than head athletic trainers did (P  =  .001). Division II ACIs reported a greater degree of inter-role conflict than those in Division I (P  =  .02). Female ACIs reported a greater degree of role incompetence than male ACIs (P  =  .01). Those ACIs who stated that the ACI training provided by their institution did not adequately prepare them for the role as an ACI experienced greater role strain (P < .001). Conclusions: The ACIs in the

Linaclotide: first global approval.

Science.gov (United States)

McWilliams, Vanessa; Whiteside, Glenn; McKeage, Kate

2012-11-12

Linaclotide is a once-daily, orally administered, first-in-class agonist of guanylate cyclase-C that is minimally absorbed. It is being developed to treat gastrointestinal disorders by Ironwood Pharmaceuticals and its partners, Forest Laboratories (North America), Almirall (Europe) and Astellas Pharma (Asia-Pacific). Linaclotide has received its first global approval in the US for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) and chronic idiopathic constipation (CIC), and a marketing submission has been filed in the EU for IBS-C. This article summarizes the milestones in the development of linaclotide leading to this first approval for IBS-C and CIC. This profile has been extracted and modified from the Adis R&D Insight drug pipeline database. Adis R&D Insight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch.

Longitudinal evaluation of a World Wide Web-based antimicrobial stewardship program: assessing factors associated with approval patterns and trends over time.

Science.gov (United States)

Venugopal, Vidya; Lehmann, Christoph U; Diener-West, Marie; Agwu, Allison L

2014-02-01

The Johns Hopkins Children's Medical and Surgery Center developed a Web-based Antimicrobial Stewardship Program (ASP) in 2005. The present study aimed to assess longitudinal antimicrobial request and approval patterns for this ASP. We analyzed a total of 16,229 antimicrobial requests for 3,542 patients between June 1, 2005, and June 30, 2009. Antimicrobial approval was the outcome of interest. We assessed gaming by studying trends in automatically approved requests. Nonparametric tests for trend were performed to detect changes in approval patterns. Multiple logistic regression was used to identify factors associated with approval. The vast majority (91.3%) of antimicrobial requests were approved, with an increase of 6.1% over time (P Web-based ASP allows management of a large number of antimicrobial requests, without apparent gaming. Observed differences in approval patterns based on patient, requestor, and antimicrobial factors may inform the development of ASPs and evaluation of provider education and training. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Heterogeneity of Clinical Trials for Antihypertensive Drugs in Japan: Exploratory Analysis of Confirmatory Phase III Trials Used for Marketing Approval.

Science.gov (United States)

Kaneko, Reina; Sano, Kota; Ono, Shunsuke

2018-07-01

The results of pivotal trials, which provide a rationale for marketing approval decisions for new drugs, are considered for various comparative purposes in postmarketing analyses. Using meta-regression analysis of 91 randomized controlled trials of 61 approved antihypertensive drugs in Japan, we show that mean baseline blood pressure (BP) of each arm was associated with predetermined entry criteria (EC), age, and trial start year (TSY). BP changes following treatment were associated with EC, subject characteristics (e.g., age, complications, baseline BP), study design (e.g., concomitant drug use), and TSY. Effect sizes were generally larger in trials for the first and second drugs in the same class than in trials for follow-on drugs. Results of pivotal trials may vary depending on many factors, suggesting possible challenges associated with the comparison of these results indirectly. Due to the heterogeneity in pivotal trials, caution should be exercised when comparing approved drugs and conducting meta-analyses retrospectively. © 2017, The American Society for Clinical Pharmacology and Therapeutics.

Pharmacotherapy of alcoholism - an update on approved and off-label medications.

Science.gov (United States)

Soyka, Michael; Müller, Christian A

2017-08-01

Only a few medications are available for the treatment of alcohol use disorders (AUDs). Areas covered: This paper discusses approved AUD medications, including the opioid antagonists naltrexone and nalmefene (the latter is licensed for reduction of alcohol consumption only), the putative glutamate receptor antagonist acamprosate and the aldehyde dehydrogenase inhibitor disulfiram. It also covers off-label medications of interest, including topiramate, gabapentin, ondansetron, varenicline, baclofen, sodium oxybate and antidepressants. Clinical implications, benefits and risks of treatment are discussed. Expert opinion: Acamprosate, naltrexone, nalmefene and disulfiram are the only approved 'alcohol-specific' drugs. Acamprosate and naltrexone have been evaluated in numerous clinical trials and represent evidence-based treatments in AUDs. Nalmefene use, however, is controversial. Supervised disulfiram is a second-line treatment approach. Compounds developed and licensed for different neuropsychiatric disorders are potential alternatives. Encouraging results have been reported for topiramate, gabapentin and also varenicline, which might be useful in patients with comorbid nicotine dependence. The GABA (γ-aminobutyric acid)-B receptor agonist baclofen has shown mixed results; it is currently licensed for the treatment of AUDs in France only. Gabapentin may be close to approval in the USA. Further studies of these novel treatment approaches in AUDs are needed.

Far-Infrared Based Pedestrian Detection for Driver-Assistance Systems Based on Candidate Filters, Gradient-Based Feature and Multi-Frame Approval Matching.

Science.gov (United States)

Wang, Guohua; Liu, Qiong

2015-12-21

Far-infrared pedestrian detection approaches for advanced driver-assistance systems based on high-dimensional features fail to simultaneously achieve robust and real-time detection. We propose a robust and real-time pedestrian detection system characterized by novel candidate filters, novel pedestrian features and multi-frame approval matching in a coarse-to-fine fashion. Firstly, we design two filters based on the pedestrians' head and the road to select the candidates after applying a pedestrian segmentation algorithm to reduce false alarms. Secondly, we propose a novel feature encapsulating both the relationship of oriented gradient distribution and the code of oriented gradient to deal with the enormous variance in pedestrians' size and appearance. Thirdly, we introduce a multi-frame approval matching approach utilizing the spatiotemporal continuity of pedestrians to increase the detection rate. Large-scale experiments indicate that the system works in real time and the accuracy has improved about 9% compared with approaches based on high-dimensional features only.

Far-Infrared Based Pedestrian Detection for Driver-Assistance Systems Based on Candidate Filters, Gradient-Based Feature and Multi-Frame Approval Matching

Directory of Open Access Journals (Sweden)

Guohua Wang

2015-12-01

Full Text Available Far-infrared pedestrian detection approaches for advanced driver-assistance systems based on high-dimensional features fail to simultaneously achieve robust and real-time detection. We propose a robust and real-time pedestrian detection system characterized by novel candidate filters, novel pedestrian features and multi-frame approval matching in a coarse-to-fine fashion. Firstly, we design two filters based on the pedestrians’ head and the road to select the candidates after applying a pedestrian segmentation algorithm to reduce false alarms. Secondly, we propose a novel feature encapsulating both the relationship of oriented gradient distribution and the code of oriented gradient to deal with the enormous variance in pedestrians’ size and appearance. Thirdly, we introduce a multi-frame approval matching approach utilizing the spatiotemporal continuity of pedestrians to increase the detection rate. Large-scale experiments indicate that the system works in real time and the accuracy has improved about 9% compared with approaches based on high-dimensional features only.

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

77 FR 24399 - Approval and Promulgation of Implementation Plans; Georgia; Atlanta; Ozone 2002 Base Year...

Science.gov (United States)

2012-04-24

... Promulgation of Implementation Plans; Georgia; Atlanta; Ozone 2002 Base Year Emissions Inventory AGENCY... approve the ozone 2002 base year emissions inventory, portion of the state implementation plan (SIP... technology (RACT), contingency measures, a 2002 base- year emissions inventory and other planning SIP...

30 CFR 14.10 - Post-approval product audit.

Science.gov (United States)

2010-07-01

..., AND APPROVAL OF MINING PRODUCTS REQUIREMENTS FOR THE APPROVAL OF FLAME-RESISTANT CONVEYOR BELTS General Provisions § 14.10 Post-approval product audit. (a) Approved conveyor belts will be subject to... based. MSHA will select an approved conveyor belt to be audited; the selected belt will be...

Targeting NK cells for anti-cancer immunotherapy: clinical and pre-clinical approaches

Directory of Open Access Journals (Sweden)

Sebastian eCarotta

2016-04-01

Full Text Available The recent success of checkpoint blockade has highlighted the potential of immunotherapy approaches for cancer treatment. While the majority of approved immunotherapy drugs target T cell subsets, it is appreciated that other components of the immune system have important roles in tumor immune-surveillance as well and thus represent promising additional targets for immunotherapy. Natural killer cells are the body’s first line of defense against infected or transformed cells as they kill target cells in an antigen-independent manner. Although several studies have clearly demonstrated the active role of NK cells in cancer-immune surveillance, only few clinically approved therapies currently exist that harness their potential. Our increased understanding of NK cell biology over the past few years has renewed the interest in NK cell based anti-cancer therapies, which has lead to a steady increase of NK cell based clinical and pre-clinical trials. Here, the role of NK cells in cancer immunesurveillance is summarized and several novel approaches to enhance NK cell cytotoxicity against cancer are discussed.

Integration of technology-based outcome measures in clinical trials of Parkinson and other neurodegenerative diseases.

Science.gov (United States)

Artusi, Carlo Alberto; Mishra, Murli; Latimer, Patricia; Vizcarra, Joaquin A; Lopiano, Leonardo; Maetzler, Walter; Merola, Aristide; Espay, Alberto J

2018-01-01

We sought to review the landscape of past, present, and future use of technology-based outcome measures (TOMs) in clinical trials of neurodegenerative disorders. We systematically reviewed PubMed and ClinicalTrials.gov for published and ongoing clinical trials in neurodegenerative disorders employing TOMs. In addition, medical directors of selected pharmaceutical companies were surveyed on their companies' ongoing efforts and future plans to integrate TOMs in clinical trials as primary, secondary, or exploratory endpoints. We identified 164 published clinical trials indexed in PubMed that used TOMs as outcome measures in Parkinson disease (n = 132) or other neurodegenerative disorders (n = 32). The ClinicalTrials.gov search yielded 42 clinical trials using TOMs, representing 2.7% of ongoing trials. Sensor-based technology accounted for over 75% of TOMs applied. Gait and physical activity were the most common targeted domains. Within the next 5 years, 83% of surveyed pharmaceutical companies engaged in neurodegenerative disorders plan to deploy TOMs in clinical trials. Although promising, TOMs are underutilized in clinical trials of neurodegenerative disorders. Validating relevant endpoints, standardizing measures and procedures, establishing a single platform for integration of data and algorithms from different devices, and facilitating regulatory approvals should advance TOMs integration into clinical trials. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nanotechnology-based drug delivery systems for Alzheimer's disease management: Technical, industrial, and clinical challenges.

Science.gov (United States)

Wen, Ming Ming; El-Salamouni, Noha S; El-Refaie, Wessam M; Hazzah, Heba A; Ali, Mai M; Tosi, Giovanni; Farid, Ragwa M; Blanco-Prieto, Maria J; Billa, Nashiru; Hanafy, Amira S

2017-01-10

Alzheimer's disease (AD) is a neurodegenerative disease with high prevalence in the rapidly growing elderly population in the developing world. The currently FDA approved drugs for the management of symptomatology of AD are marketed mainly as conventional oral medications. Due to their gastrointestinal side effects and lack of brain targeting, these drugs and dosage regiments hinder patient compliance and lead to treatment discontinuation. Nanotechnology-based drug delivery systems (NTDDS) administered by different routes can be considered as promising tools to improve patient compliance and achieve better therapeutic outcomes. Despite extensive research, literature screening revealed that clinical activities involving NTDDS application in research for AD are lagging compared to NTDDS for other diseases such as cancers. The industrial perspectives, processability, and cost/benefit ratio of using NTDDS for AD treatment are usually overlooked. Moreover, active and passive immunization against AD are by far the mostly studied alternative AD therapies because conventional oral drug therapy is not yielding satisfactorily results. NTDDS of approved drugs appear promising to transform this research from 'paper to clinic' and raise hope for AD sufferers and their caretakers. This review summarizes the recent studies conducted on NTDDS for AD treatment, with a primary focus on the industrial perspectives and processability. Additionally, it highlights the ongoing clinical trials for AD management. Copyright © 2016 Elsevier B.V. All rights reserved.

77 FR 26441 - Approval and Promulgation of Implementation Plans; North Carolina; Charlotte; Ozone 2002 Base...

Science.gov (United States)

2012-05-04

... Promulgation of Implementation Plans; North Carolina; Charlotte; Ozone 2002 Base Year Emissions Inventory... final action to approve the ozone 2002 base year emissions inventory portion of the state implementation... Air Act (CAA or Act). EPA will take action on the South Carolina submission for the ozone 2002 base...

The Evolution of Approval Services.

Science.gov (United States)

Warzala, Martin

1994-01-01

Describes major developments in book approval plans used by academic libraries for acquisition and for information dissemination and document distribution services based on approval-like concepts. Topics addressed include publishers; marketing; the impact of library automation; value-added services; the economic climate; the influence of…

Methodological challenges for the evaluation of clinical effectiveness in the context of accelerated regulatory approval: an overview.

Science.gov (United States)

Woolacott, Nerys; Corbett, Mark; Jones-Diette, Julie; Hodgson, Robert

2017-10-01

Regulatory authorities are approving innovative therapies with limited evidence. Although this level of data is sufficient for the regulator to establish an acceptable risk-benefit balance, it is problematic for downstream health technology assessment, where assessment of cost-effectiveness requires reliable estimates of effectiveness relative to existing clinical practice. Some key issues associated with a limited evidence base include using data, from nonrandomized studies, from small single-arm trials, or from single-center trials; and using surrogate end points. We examined these methodological challenges through a pragmatic review of the available literature. Methods to adjust nonrandomized studies for confounding are imperfect. The relative treatment effect generated from single-arm trials is uncertain and may be optimistic. Single-center trial results may not be generalizable. Surrogate end points, on average, overestimate treatment effects. Current methods for analyzing such data are limited, and effectiveness claims based on these suboptimal forms of evidence are likely to be subject to significant uncertainty. Assessments of cost-effectiveness, based on the modeling of such data, are likely to be subject to considerable uncertainty. This uncertainty must not be underestimated by decision makers: methods for its quantification are required and schemes to protect payers from the cost of uncertainty should be implemented. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Structure-based discovery of clinically approved drugs as Zika virus NS2B-NS3 protease inhibitors that potently inhibit Zika virus infection in vitro and in vivo.

Science.gov (United States)

Yuan, Shuofeng; Chan, Jasper Fuk-Woo; den-Haan, Helena; Chik, Kenn Ka-Heng; Zhang, Anna Jinxia; Chan, Chris Chung-Sing; Poon, Vincent Kwok-Man; Yip, Cyril Chik-Yan; Mak, Winger Wing-Nga; Zhu, Zheng; Zou, Zijiao; Tee, Kah-Meng; Cai, Jian-Piao; Chan, Kwok-Hung; de la Peña, Jorge; Pérez-Sánchez, Horacio; Cerón-Carrasco, José Pedro; Yuen, Kwok-Yung

2017-09-01

Zika virus (ZIKV) infection may be associated with severe complications in fetuses and adults, but treatment options are limited. We performed an in silico structure-based screening of a large chemical library to identify potential ZIKV NS2B-NS3 protease inhibitors. Clinically approved drugs belonging to different drug classes were selected among the 100 primary hit compounds with the highest predicted binding affinities to ZIKV NS2B-NS3-protease for validation studies. ZIKV NS2B-NS3 protease inhibitory activity was validated in most of the selected drugs and in vitro anti-ZIKV activity was identified in two of them (novobiocin and lopinavir-ritonavir). Molecular docking and molecular dynamics simulations predicted that novobiocin bound to ZIKV NS2B-NS3-protease with high stability. Dexamethasone-immunosuppressed mice with disseminated ZIKV infection and novobiocin treatment had significantly (P < 0.05) higher survival rate (100% vs 0%), lower mean blood and tissue viral loads, and less severe histopathological changes than untreated controls. This structure-based drug discovery platform should facilitate the identification of additional enzyme inhibitors of ZIKV. Copyright © 2017 Elsevier B.V. All rights reserved.

77 FR 24440 - Approval and Promulgation of Implementation Plans; Georgia; Atlanta; Ozone 2002 Base Year...

Science.gov (United States)

2012-04-24

... ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 52 [EPA-R04-OAR-2010-0021(b); FRL-9661-9] Approval and Promulgation of Implementation Plans; Georgia; Atlanta; Ozone 2002 Base Year Emissions Inventory AGENCY... 2002 base year emissions inventory portion of the state implementation plan (SIP) revision submitted by...

Comparison of treatment effect sizes from pivotal and postapproval trials of novel therapeutics approved by the FDA based on surrogate markers of disease: a meta-epidemiological study.

Science.gov (United States)

Wallach, Joshua D; Ciani, Oriana; Pease, Alison M; Gonsalves, Gregg S; Krumholz, Harlan M; Taylor, Rod S; Ross, Joseph S

2018-03-21

The U.S. Food and Drug Administration (FDA) often approves new drugs based on trials that use surrogate markers for endpoints, which involve certain trade-offs and may risk making erroneous inferences about the medical product's actual clinical effect. This study aims to compare the treatment effects among pivotal trials supporting FDA approval of novel therapeutics based on surrogate markers of disease with those observed among postapproval trials for the same indication. We searched Drugs@FDA and PubMed to identify published randomized superiority design pivotal trials for all novel drugs initially approved by the FDA between 2005 and 2012 based on surrogate markers as primary endpoints and published postapproval trials using the same surrogate markers or patient-relevant outcomes as endpoints. Summary ratio of odds ratios (RORs) and difference between standardized mean differences (dSMDs) were used to quantify the average difference in treatment effects between pivotal and matched postapproval trials. Between 2005 and 2012, the FDA approved 88 novel drugs for 90 indications based on one or multiple pivotal trials using surrogate markers of disease. Of these, 27 novel drugs for 27 indications were approved based on pivotal trials using surrogate markers as primary endpoints that could be matched to at least one postapproval trial, for a total of 43 matches. For nine (75.0%) of the 12 matches using the same non-continuous surrogate markers as trial endpoints, pivotal trials had larger treatment effects than postapproval trials. On average, treatment effects were 50% higher (more beneficial) in the pivotal than the postapproval trials (ROR 1.5; 95% confidence interval CI 1.01-2.23). For 17 (54.8%) of the 31 matches using the same continuous surrogate markers as trial endpoints, pivotal trials had larger treatment effects than the postapproval trials. On average, there was no difference in treatment effects between pivotal and postapproval trials (dSMDs 0.01; 95

75 FR 80061 - Abbott Laboratories, Inc.; Withdrawal of Approval of a New Drug Application for MERIDIA

Science.gov (United States)

2010-12-21

... withdrawing approval of a new drug application (NDA) for MERIDIA (sibutramine hydrochloride (HCl)) oral... requested that Abbott voluntarily withdraw MERIDIA (sibutramine HCl) oral capsules from the market, based on FDA's recent analysis of clinical trial data from the Sibutramine Cardiovascular Outcomes Trial (SCOUT...

Characteristics of efficacy evidence supporting approval of supplemental indications for prescription drugs in United States, 2005-14: systematic review.

Science.gov (United States)

Wang, Bo; Kesselheim, Aaron S

2015-09-23

To characterize the types of comparators and endpoints used in efficacy trials for approvals of supplemental indications, compared with the data supporting these drugs' originally approved indications. Systematic review. Publicly accessible data on supplemental indications approved by the US Food and Drug Administration from 2005 to 2014. Types of comparators (active, placebo, historical, none) and endpoints (clinical outcomes, clinical scales, surrogate) in the efficacy trials for these drugs' supplemental and original indication approvals. The cohort included 295 supplemental indications. Thirty per cent (41/136) of supplemental approvals for new indications were supported by efficacy trials with active comparators, compared with 51% (47/93) of modified use approvals and 11% (7/65) of approvals expanding the patient population (Pindications, 30% (28/93) of modified indication approvals, and 22% (14/65) of expanded population approvals (P=0.29). Orphan drugs had supplemental approvals for 40 non-orphan indications, which were supported by similar proportions of trials using active comparators (28% (11/40) for non-orphan supplemental indications versus 24% (10/42) for original orphan indications; P=0.70) and clinical outcome endpoints (25% (10/40) versus 31% (13/42); P=0.55). Wide variations were seen in the evidence supporting approval of supplemental indications, with the fewest active comparators and clinical outcome endpoints used in trials leading to supplemental approvals that expanded the patient population. © Wang et al 2015.

77 FR 42686 - Approval and Promulgation of Air Quality Implementation Plans; Maryland; the 2002 Base Year...

Science.gov (United States)

2012-07-20

... Promulgation of Air Quality Implementation Plans; Maryland; the 2002 Base Year Inventory AGENCY: Environmental... matter (PM 2.5 ) 2002 base year emissions inventory portion of the Maryland State Implementation Plan... National Ambient Air Quality Standard (NAAQS) SIP. EPA is proposing to approve the 2002 base year PM 2.5...

Variation in standards of research compensation and child assent practices: a comparison of 69 institutional review board-approved informed permission and assent forms for 3 multicenter pediatric clinical trials.

Science.gov (United States)

Kimberly, Michael B; Hoehn, K Sarah; Feudtner, Chris; Nelson, Robert M; Schreiner, Mark

2006-05-01

To systematically compare standards for compensation and child participant assent in informed permission, assent, and consent forms (IP-A-CFs) approved by 55 local institutional review boards (IRBs) reviewing 3 standardized multicenter research protocols. Sixty-nine principal investigators participating in any of 3 national, multicenter clinical trials submitted standardized research protocols for their trials to their local IRBs for approval. Copies of the subsequently IRB-approved IP-A-CFs were then forwarded to an academic clinical research organization. This collection of IRB-approved forms allowed for a quasiexperimental retrospective evaluation of the variation in informed permission, assent, and consent standards operationalized by the local IRBs. Standards for compensation and child participant assent varied substantially across 69 IRB-approved IP-A-CFs. Among the 48 IP-A-CFs offering compensation, monetary compensation was offered by 33 as reimbursement for travel, parking, or food expenses, whereas monetary or material compensation was offered by 22 for subject inconvenience and by 13 for subject time. Compensation ranged widely within and across studies (study 1, $180-1425; study 2, $0-500; and study 3, $0-100). Regarding child participant assent, among the 57 IP-A-CFs that included a form of assent documentation, 33 included a line for assent on the informed permission or consent form, whereas 35 included a separate form written in simplified language. Of the IP-A-CFs that stipulated the documentation of assent, 31 specified > or =1 age ranges for obtaining assent. Informed permission or consent forms were addressed either to parents or child participants. In response to identical clinical trial protocols, local IRBs generate IP-A-CFs that vary considerably regarding compensation and child participant assent.

Danish clinical databases: An overview

DEFF Research Database (Denmark)

Green, Anders

2011-01-01

Clinical databases contain data related to diagnostic procedures, treatments and outcomes. In 2001, a scheme was introduced for the approval, supervision and support to clinical databases in Denmark.......Clinical databases contain data related to diagnostic procedures, treatments and outcomes. In 2001, a scheme was introduced for the approval, supervision and support to clinical databases in Denmark....

Virotherapy: cancer gene therapy at last? [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Alan E. Bilsland

2016-08-01

Full Text Available For decades, effective cancer gene therapy has been a tantalising prospect; for a therapeutic modality potentially able to elicit highly effective and selective responses, definitive efficacy outcomes have often seemed out of reach. However, steady progress in vector development and accumulated experience from previous clinical studies has finally led the field to its first licensed therapy. Following a pivotal phase III trial, Imlygic (talimogene laherparepvec/T-Vec received US approval as a treatment for cutaneous and subcutaneous melanoma in October 2015, followed several weeks later by its European authorisation. These represent the first approvals for an oncolytic virotherapy. Imlygic is an advanced-generation herpesvirus-based vector optimised for oncolytic and immunomodulatory activities. Many other oncolytic agents currently remain in development, providing hope that current success will be followed by other diverse vectors that may ultimately come to constitute a new class of clinical anti-cancer agents. In this review, we discuss some of the key oncolytic viral agents developed in the adenovirus and herpesvirus classes, and the prospects for further enhancing their efficacy by combining them with novel immunotherapeutic approaches.

Newborn Congenital Cytomegalovirus Screening Based on Clinical Manifestations and Evaluation of DNA-based Assays for In Vitro Diagnostics.

Science.gov (United States)

Fujii, Tomoyuki; Oka, Akira; Morioka, Ichiro; Moriuchi, Hiroyuki; Koyano, Shin; Yamada, Hideto; Saito, Shigeru; Sameshima, Hiroshi; Nagamatsu, Takeshi; Tsuchida, Shinya; Inoue, Naoki

2017-10-01

To establish a strategy for congenital cytomegalovirus (cCMV) screening and to establish confirmatory assays approved as in vitro diagnostics by the regulatory authorities, we evaluated the clinical risks and performance of diagnostic assays developed by commercial companies, since cCMV infection has significant clinical consequences. Newborns with clinical manifestations considered to be consequences of cCMV infection (n = 575) were screened for the presence of cytomegalovirus (CMV) DNA in urine specimens collected onto filter paper placed in their diapers using the polymerase chain reaction-based assay reported previously. Liquid urine specimens were obtained from all of 20 CMV-positive newborns and 107 of the CMV-negative newborns identified in the screening. We used these 127 specimens, as well as 12 from cCMV cases identified in a previous study and 41 from healthy newborns, to compare the performance of 2 commercial assays and 1 in-house assay. The risk-based screening allowed the identification of cCMV cases at least 10-fold more efficiently than our previous universal screening, although there appears to be a limit to the identification of asymptomatically infected newborns. Although CMV-specific IgM during pregnancy was found frequently in mothers of cCMV newborns, CMV-IgM alone is not an effective diagnostic marker. The urine-filter-based assay and the 3 diagnostic assays yielded identical results. Although risk-based and universal newborn screening strategies for cCMV infection each have their respective advantages and disadvantages, urine-filter-based assay followed by confirmatory in vitro diagnostics assays is able to identify cCMV cases efficiently.

Nose-to-brain drug delivery: An update on clinical challenges and progress towards approval of anti-Alzheimer drugs.

Science.gov (United States)

Agrawal, Mukta; Saraf, Swarnlata; Saraf, Shailendra; Antimisiaris, Sophia G; Chougule, Mahavir Bhupal; Shoyele, Sunday A; Alexander, Amit

2018-05-23

According to the Alzheimer Association Report (2017), Alzheimer's disease (AD) is the 6th primary cause of death in the USA, which affects nearly 5.5 million people. In the year 2017 itself, the cost of AD treatment in the USA has been reported to rise to $259 billion. This statistic shows the severity of the disease in the USA which is very much similar across the globe. On the other hand, the treatment remains limited to a few conventional oral medications (approved by FDA). These are mainly acting superficially from mild to the moderate AD. The therapeutic efficacy of the drug is not only affected by its reduced concentration in the brain owing to the existence of blood-brain-barrier (BBB) but also due to its low brain permeability. In this context, the intranasal (IN) route of drug administration has emerged as an alternative route over the systemic (oral and parenteral) drug delivery to the brain. The delivery of the drug via an IN route offers various advantages over systemic drug delivery system, as it directly delivers the drug into the brain via olfactory route. Presence of drug in the olfactory bulb, in turn, increases the drug bioavailability in the brain and reduces the drug degradation as well as wastage of the drug through` systemic clearance. However, there is also some limitation associated with IN like poor drug permeation through the nasal mucosa and mucociliary clearance. The delivery system various through novel strategies (nano drug carrier system, colloidal carriers, mucoadhesive devices, controlled delivery system, pro-drug, etc.) are adapted to overcome the above-stated limitations. Although, after all, such successful research claims, very few of the nose-to-brain drug delivery of anti-AD drugs have gained market approval due to lack of sufficient clinical evidence. Onzetra Xsail® is one such marketed preparations approved for IN delivery used for the treatment of a brain disorder; migraine. In the field of patents also, no work is found

Eight-year follow-up data from the U.S. clinical trial for Sientra's FDA-approved round and shaped implants with high-strength cohesive silicone gel.

Science.gov (United States)

Stevens, W Grant; Harrington, Jennifer; Alizadeh, Kaveh; Broadway, David; Zeidler, Kamakshi; Godinez, Tess B

2015-05-01

On March 9, 2012, the Food and Drug Administration (FDA) approved Sientra's premarket approval application for its portfolio of silicone gel breast implants based on their review of Sientra's 3-year study data from the largest pivotal silicone gel breast implant study to date. This included the first approval of shaped breast implants in the United States. The authors provide an update to the 8-year safety and effectiveness of the Sientra High-Strength silicone gel breast implants. The Sientra Core study is an ongoing 10 year open-label, prospective, multi-center clinical study, which includes 1788 patients implanted with 3506 Sientra implants across four indications (Primary Augmentation, Revision Augmentation, Primary Reconstruction, and Revision Reconstruction). For the safety analysis, the incidence of post-operative complications, including all breast implant-related adverse effects (eg, infection, asymmetry), was estimated based on Kaplan-Meier risk rates. The effectiveness analyses include surgeon and patient satisfaction and changes in bra/cup size. Through 8 years, the overall risk of rupture was 4.6%, the risk of capsular contracture was 11.8% (rates were lower when using True Texture™), and the risk of reoperation was 28.3%. Out of the 580 reoperations in 456 patients, over half of all reoperations were due to cosmetic reasons (n = 299). The most common reasons for reoperation were capsular contracture (19.0%), style and/or size change (18.4%), and asymmetry (8.8%). Patient satisfaction remains high through 8 years, with 87% indicating that their breast implants make them feel more feminine than prior to enrollment. Safety data from the FDA Core study continues to support a comprehensive safety and effectiveness profile of Sientra's portfolio of round and shaped implants through 8 years. 3 Therapeutic. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

Analysis of time to regulatory and ethical approval of SATVI TB ...

African Journals Online (AJOL)

Background. Tuberculosis (TB) vaccine trials in South Africa must be approved by the Medicines Control Council (MCC) and by a human research ethics committee (HREC). Delays in regulatory and ethical approval may affect operational and budget planning and clinical development of the product. Aim. Our aim was to ...

Insight into the cellular fate and toxicity of aluminium adjuvants used in clinically approved human vaccinations.

Science.gov (United States)

Mold, Matthew; Shardlow, Emma; Exley, Christopher

2016-08-12

Aluminium adjuvants remain the most widely used and effective adjuvants in vaccination and immunotherapy. Herein, the particle size distribution (PSD) of aluminium oxyhydroxide and aluminium hydroxyphosphate adjuvants was elucidated in attempt to correlate these properties with the biological responses observed post vaccination. Heightened solubility and potentially the generation of Al(3+) in the lysosomal environment were positively correlated with an increase in cell mortality in vitro, potentially generating a greater inflammatory response at the site of simulated injection. The cellular uptake of aluminium based adjuvants (ABAs) used in clinically approved vaccinations are compared to a commonly used experimental ABA, in an in vitro THP-1 cell model. Using lumogallion as a direct-fluorescent molecular probe for aluminium, complemented with transmission electron microscopy provides further insight into the morphology of internalised particulates, driven by the physicochemical variations of the ABAs investigated. We demonstrate that not all aluminium adjuvants are equal neither in terms of their physical properties nor their biological reactivity and potential toxicities both at the injection site and beyond. High loading of aluminium oxyhydroxide in the cytoplasm of THP-1 cells without immediate cytotoxicity might predispose this form of aluminium adjuvant to its subsequent transport throughout the body including access to the brain.

The approval process for biosimilar erythropoiesis-stimulating agents.

Science.gov (United States)

Wish, Jay B

2014-09-05

A biosimilar drug or follow-on biologic drug is defined by the Public Health Service Act as a product that is "highly similar to the reference product notwithstanding minor differences in clinically active components and there are no clinically meaningful differences between the biologic product and the reference product in terms of the safety, purity and potency of the product." The advantage of biosimilar drugs is that they are significantly less expensive than the reference products, allowing for increased accessibility and cost savings. Recognizing these advantages, the US Congress passed the Biologics Price Competition and Innovation Act in 2009 as part of health care reform. The Biologics Price Competition and Innovation Act allows sponsors of biosimilar agents to seek approval by showing structural and functional similarity to the reference agent, with the extent of required clinical studies to be determined on the basis of the degree of biosimilarity with the reference product. The goal is to bring biosimilar agents to the market more efficiently while still protecting the safety of the public. The European Union has had such a process in place for a number of years. Two biosimilar epoetin agents have been approved in the European Union since 2007, and their companies are conducting trials to seek approval in the United States, because Amgen's patent protection for epoetin alfa expires in 2014. Trials completed for European Union approval of both agents showed similar efficacy and safety to the reference epoetin alfa. As with all biologics, immunogenicity concerns may persist because of the fragility of the manufacturing process and the worldwide experience with pure red cell aplasia as a result of epoetin therapy. The uptake of biosimilar epoetins after approval in the United States will depend on the balance of cost advantage against safety concerns. Competition in the marketplace will likely decrease the cost of the reference agent as well. Copyright �

Clinical outcomes in clinical trials of anti-HIV treatment

DEFF Research Database (Denmark)

Reekie, J; Mocroft, A; J, Neaton

2007-01-01

Since the introduction of combination antiretroviral therapy, there has been a decrease in both AIDS-defining illnesses and deaths. This decrease meant that performing clinical trials with clinical outcomes in HIV infection became more time consuming and hence costly. Improved understanding...... and knowledge of HIV led to short-term trials using surrogate outcomes such as viral load and CD4 count. This established a faster drug approval process that complimented the rapid need to evaluate and provide access to drugs based on short-term trials. However, no treatment has yet been found that eradicates...... the infection, so when treatment is started it is currently a lifelong commitment. Is it reasonable then that guidelines are based almost completely on short-term randomized trials and observational studies of surrogate markers, or is there still a need for trials with clinical outcomes?...

Biosimilars approval process.

Science.gov (United States)

Zuñiga, Leyre; Calvo, Begoña

2010-04-01

For similar biological medicinal products, the so-called biosimilars, clinical trials are required rather than just the bioequivalence studies required to support the registration of a generic small molecule drug product. The EU Directive 2001/83/EC, as amended, stated that where a biological medicinal product which is similar to a reference biological product, does not meet the conditions in the definition of generic medicinal products the results of appropriate pre-clinical tests or clinical trials relating to these conditions must be provided. The challenge is to determine the exact nature of the non-clinical and clinical programme required to gain regulatory approval. The applicant is encouraged to provide a detailed description of the strategy used to demonstrate the biosimilar and the reference product have similar profiles in terms of quality, safety and efficacy. The extent to which comparability can be proven will have quite an impact on how many non-clinical and clinical studies the biosimilar applicant will be required to conduct. The dossier submitted by the applicant to the EMEA should cover all aspects of the comparability assessment and must include data on possible unwanted immune reactions to the therapeutic protein. Post-marketing pharmacovigilance plans are also expected to be included in the biosimilar dossier. Copyright 2009 Elsevier Inc. All rights reserved.

77 FR 24723 - AstraZeneca Pharmaceuticals LP; Withdrawal of Approval of a New Drug Application for IRESSA

Science.gov (United States)

2012-04-25

.... IRESSA is indicated as monotherapy after failure of both platinum-based and docetaxel chemotherapies for the continued treatment of patients with locally advanced or metastatic non-small cell lung cancer who... a condition of approval under subpart H failed to verify and confirm clinical benefit. In a letter...

Evidence-based clinical practice

DEFF Research Database (Denmark)

Gluud, Christian

2002-01-01

, and single clinics. Accordingly, there is an urgent need to improve this situation. Guidelines for Good Clinical (Research) Practice, conduct of more trials as multicentre trials, The Consort Statement, and The Cochrane Collaboration may all help in the application of the best research evidence in clinical......Evidence-based medicine combines the patient's preferences with clinical experience and the best research evidence. Randomized clinical trials are considered the most valid research design for evaluating health-care interventions. However, empirical research shows that intervention effects may...... practice. By investments in education, applied research, and The Cochrane Collaboration, evidence-based medicine may form a stronger basis for clinical practice....

Marketing Approval of Ethical Kampo Medicines.

Science.gov (United States)

Hakamatsuka, Takashi

2017-01-01

Kampo medicine is an original traditional medicine in Japan. Currently, 148 ethical Kampo formulations (Kampo prescription drugs) are registered in the National Health Insurance Price List. Kampo medicines can be prescribed under the national insurance system, which shows that they are part of conventional medicine in Japan. Japan has a unified drug approval system that does not distinguish between Western and Kampo medicines, and both are subject to the same regulations. The application for the market approval of ethical Kampo medicines is based on the general notification for drugs, i.e., "Handling of Ethical Combination Drugs" in "Precautions Necessary When Applying for Drug Marketing Approval" (Yakushokushinsa Notification No. 1121-12 of November 21, 2014). Furthermore, applications for the market approval of ethical Kampo medicines should follow the Kampo-specific notification of "Handling of Ethical Kampo Medicines" (Yakushin Notification No. 804 of June 25, 1980). Data from comparative studies with standard decoctions must be submitted with approval applications according to Yakushin 2 Notification No. 120 of May 31, 1985. The safety, efficacy, and quality of Kampo medicines are comprehensively assured by the Japanese Pharmacopoeia, Good Manufacturing Practice, Good Agricultural and Collection Practices, marketing approval certificate, approval standard, and pharmacovigilance. I believe that the basic framework for the market approval of ethical Kampo medicines has been established as described above. The key factors for the practical application of superior manufacturing technology and research achievements and the promotion of drug development are the specific guidelines for the approval of drugs of herbal origin.

77 FR 75933 - Approval and Promulgation of Air Quality Implementation Plans; West Virginia; The 2002 Base Year...

Science.gov (United States)

2012-12-26

... email. The www.regulations.gov Web site is an ``anonymous access'' system, which means EPA will not know... Promulgation of Air Quality Implementation Plans; West Virginia; The 2002 Base Year Emissions Inventory for the...: Proposed rule. SUMMARY: EPA is proposing to approve the 2002 base year emissions inventory portion of the...

48 CFR 52.222-16 - Approval of Wage Rates.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Approval of Wage Rates. 52....222-16 Approval of Wage Rates. As prescribed in 22.407(b), insert the following clause: Approval of Wage Rates (FEB 1988) All straight time wage rates, and overtime rates based thereon, for laborers and...

The cancer precision medicine knowledge base for structured clinical-grade mutations and interpretations

Science.gov (United States)

Huang, Linda; Fernandes, Helen; Zia, Hamid; Tavassoli, Peyman; Rennert, Hanna; Pisapia, David; Imielinski, Marcin; Sboner, Andrea; Rubin, Mark A; Kluk, Michael

2017-01-01

Objective: This paper describes the Precision Medicine Knowledge Base (PMKB; https://pmkb.weill.cornell.edu), an interactive online application for collaborative editing, maintenance, and sharing of structured clinical-grade cancer mutation interpretations. Materials and Methods: PMKB was built using the Ruby on Rails Web application framework. Leveraging existing standards such as the Human Genome Variation Society variant description format, we implemented a data model that links variants to tumor-specific and tissue-specific interpretations. Key features of PMKB include support for all major variant types, standardized authentication, distinct user roles including high-level approvers, and detailed activity history. A REpresentational State Transfer (REST) application-programming interface (API) was implemented to query the PMKB programmatically. Results: At the time of writing, PMKB contains 457 variant descriptions with 281 clinical-grade interpretations. The EGFR, BRAF, KRAS, and KIT genes are associated with the largest numbers of interpretable variants. PMKB’s interpretations have been used in over 1500 AmpliSeq tests and 750 whole-exome sequencing tests. The interpretations are accessed either directly via the Web interface or programmatically via the existing API. Discussion: An accurate and up-to-date knowledge base of genomic alterations of clinical significance is critical to the success of precision medicine programs. The open-access, programmatically accessible PMKB represents an important attempt at creating such a resource in the field of oncology. Conclusion: The PMKB was designed to help collect and maintain clinical-grade mutation interpretations and facilitate reporting for clinical cancer genomic testing. The PMKB was also designed to enable the creation of clinical cancer genomics automated reporting pipelines via an API. PMID:27789569

Zohydro approval by food and drug administration: controversial or frightening?

Science.gov (United States)

Manchikanti, Laxmaiah; Atluri, Sairam; Candido, Kenneth D; Boswell, Mark V; Simopoulos, Thomas T; Grider, Jay S; Falco, Frank J E; Hirsch, Joshua A

2014-01-01

consequences, despite numerous regulations enforced by multiple organizations. The approval of Zohydro and its defense from the FDA were based on a misunderstanding of the prevalence of chronic severe disabling pain. Based on inaccurate data from the Institute of Medicine, in part caused by conflicts of interest, 100 million persons have been described to suffer from severe pain - the correct number is 22.6 million. This manuscript analyzes 3 important principles of drug approval and utilization based on safety, efficacy, and medical necessity. Based on the limited literature that the authors were able to review including that which was submitted to the FDA by the manufacturers, it appears the safety, efficacy, and medical necessity were not demonstrated. In fact, the study submitted to the FDA showed a 50% pain improvement in only 48% of the patients in the treatment group and 21% of the patients in the placebo group at 85 day follow-up. This is a statistically significant result but its clinical relevance is unknown. The FDA approval decision occurring against the backdrop of the advisory panel recommendation is concerning and may result in serious consequences in the future.

Unwarranted claims of drug efficacy in pharmaceutical sales visits: are drugs approved on the basis of surrogate outcomes promoted appropriately?

Science.gov (United States)

Habibi, Roojin; Lexchin, Joel; Mintzes, Barbara; Holbrook, Anne

2017-11-01

This study compares physicians' recall of the claims of benefits on cardiovascular disease and diabetes made by pharmaceutical sales representatives for drugs approved on the basis of a surrogate outcome, i.e., an off-label claim, compared with those approved on the basis of a serious morbidity or mortality (clinical) outcome. Physicians in primary care practices in Montreal, Vancouver, Sacramento and Toulouse, who saw sales representatives as part of their usual practice and served a non-referral population, were contacted in blocks of 25 from a randomized list of all physicians practising in the relevant metropolitan area. We compared how frequently physicians reported that sales reps made claims of serious morbidity or mortality (clinically meaningful) benefits for drugs approved on the basis of surrogate outcomes vs. drugs approved on the basis of clinical outcomes. There were 448 promotions for 58 unique brand name cardiovascular and diabetes drugs. Claims of clinically meaningful benefit were reported in 156 (45%) of the 347 promotions for surrogate outcome drugs, constituting unwarranted efficacy claims, i.e., off-label promotion. Claims of clinical benefit were reported in 72 of the 101 promotions (71%) for drugs approved on the basis of clinical outcomes, adjusted OR = 0.3 (95% CI 0.2, 0.6), P sales visit promotions for drugs approved only on the basis of surrogate outcomes extended beyond the regulator-approved efficacy information for the product in almost half of promotions. Unapproved claims of drug efficacy constitute a form of off-label promotion and merit greater attention from regulators. © 2017 The British Pharmacological Society.

A Comprehensive Review of US FDA-Approved Immune Checkpoint Inhibitors in Urothelial Carcinoma

Directory of Open Access Journals (Sweden)

Fu-Shun Hsu

2017-01-01

Full Text Available Few effective treatment options are available for patients with advanced or metastatic urothelial carcinoma (UC after unsuccessful first-line platinum-based chemotherapy. To date, immune checkpoint inhibitors are novel therapeutic agents for UC treatment. From May 2016 to May 2017, five anti-PD-1/PD-L1 monoclonal antibodies received accelerated or regular approval from the US Food and Drug Administration (FDA for the treatment of patients with locally advanced or metastatic UC. The present comprehensive review presents the background information of these five US FDA-approved anticancer agents to provide a basic but concise understanding of these agents for advanced studies. We summarize their immune checkpoint mechanisms, clinical efficacy, recommended usage protocols, adverse events, and the limitations of the PD-L1 biomarker assays.

Nurse-Managed Clinics: A Blueprint for Success Using the Covey Framework.

Science.gov (United States)

Starck, Patricia L.; And Others

1995-01-01

Describes the process from inception to successful operation of a university-based, nurse-managed clinic, based on Covey's seven habits of highly effective people. Includes information on the planning process, financing, political strategies for gaining approval, and ongoing development of services. (JOW)

Establishment approval in international trade of animal products

NARCIS (Netherlands)

Rau, M.L.; Ge, L.; Valeeva, N.I.; Wagenberg, van C.P.A.

2012-01-01

This report provides an overview of different approaches of establishment approval as well as its implementation and organisation in international agrifood trade. The focus is on animal products as establishment approval is particularly used for exporting these products. Based on trade data, 8

FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer.

Science.gov (United States)

Beaver, Julia A; Amiri-Kordestani, Laleh; Charlab, Rosane; Chen, Wei; Palmby, Todd; Tilley, Amy; Zirkelbach, Jeanne Fourie; Yu, Jingyu; Liu, Qi; Zhao, Liang; Crich, Joyce; Chen, Xiao Hong; Hughes, Minerva; Bloomquist, Erik; Tang, Shenghui; Sridhara, Rajeshwari; Kluetz, Paul G; Kim, Geoffrey; Ibrahim, Amna; Pazdur, Richard; Cortazar, Patricia

2015-11-01

On February 3, 2015, the FDA granted accelerated approval to palbociclib (IBRANCE, Pfizer Inc.), an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), for use in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. The approval is based on a randomized, multicenter, open-label phase I/II trial (PALOMA-1) in 165 patients randomized to palbociclib (125 mg orally daily for 21 consecutive days, followed by 7 days off treatment) plus letrozole (2.5 mg orally daily) or letrozole alone. The phase II portion of the trial was divided into two cohorts: cohort 1 enrolled 66 biomarker-unselected patients and cohort 2 enrolled 99 biomarker-positive patients. The major efficacy outcome measure was investigator-assessed progression-free survival (PFS). A large magnitude of improvement in PFS was observed in patients receiving palbociclib plus letrozole compared with patients receiving letrozole alone (HR, 0.488; 95% confidence interval, 0.319-0.748). Multiple sensitivity analyses were supportive of clinical benefit. The most common adverse reaction in patients receiving palbociclib plus letrozole was neutropenia. This article summarizes the FDA thought process and data supporting accelerated approval based on PALOMA-1 that may be contingent upon verification and description of clinical benefit in the ongoing and fully accrued confirmatory trial PALOMA-2. ©2015 American Association for Cancer Research.

A SOA-Based Platform to Support Clinical Data Sharing

Directory of Open Access Journals (Sweden)

R. Gazzarata

2017-01-01

Full Text Available The eSource Data Interchange Group, part of the Clinical Data Interchange Standards Consortium, proposed five scenarios to guide stakeholders in the development of solutions for the capture of eSource data. The fifth scenario was subdivided into four tiers to adapt the functionality of electronic health records to support clinical research. In order to develop a system belonging to the “Interoperable” Tier, the authors decided to adopt the service-oriented architecture paradigm to support technical interoperability, Health Level Seven Version 3 messages combined with LOINC (Logical Observation Identifiers Names and Codes vocabulary to ensure semantic interoperability, and Healthcare Services Specification Project standards to provide process interoperability. The developed architecture enhances the integration between patient-care practice and medical research, allowing clinical data sharing between two hospital information systems and four clinical data management systems/clinical registries. The core is formed by a set of standardized cloud services connected through standardized interfaces, involving client applications. The system was approved by a medical staff, since it reduces the workload for the management of clinical trials. Although this architecture can realize the “Interoperable” Tier, the current solution actually covers the “Connected” Tier, due to local hospital policy restrictions.

Trends in global approvals of biotech crops (1992-2014).

Science.gov (United States)

Aldemita, Rhodora R; Reaño, Ian Mari E; Solis, Renando O; Hautea, Randy A

2015-01-01

With the increasing number of genetically modified (GM) events, traits, and crops that are developed to benefit the global population, approval of these technologies for food, feed, cultivation and import in each country may vary depending on needs, demand and trade interest. ISAAA established a GMO Approval Database to document global approvals of biotech crops. GM event name, crops, traits, developer, year of approval for cultivation, food/feed, import, and relevant dossiers were sourced from credible government regulatory websites and biosafety clearinghouses. This paper investigates the trends in GM approvals for food, feed and cultivation based on the number of approving countries, GM crops, events, and traits in the last 23 y (1992-2014), rationale for approval, factors influencing approvals, and their implications in GM crop adoption. Results show that in 2014, there was an accumulative increase in the number of countries granting approvals at 29 (79% developing countries) for commercial cultivation and 31 (70% developing countries) for food and 19 (80% developing developing) for feed; 2012 had the highest number of approving countries and cultivation approvals; 2011 had the highest number of country approvals for feed, and 2014 for food approvals. Herbicide tolerance trait had the highest events approved, followed by insect tolerance traits. Approvals for food product quality increased in the second decade. Maize had the highest number of events approved (single and stacked traits), and stacked traits product gradually increased which is already 30% of the total trait approvals. These results may indicate understanding and acceptance of countries to enhance regulatory capability to be able to benefit from GM crop commercialization. Hence, the paper provided information on the trends on the growth of the GM crop industry in the last 23 y which may be vital in predicting future GM crops and traits.

Project W-314 phase I environmental permits and approvals plan

International Nuclear Information System (INIS)

TOLLEFSON, K.S.

1999-01-01

This document describes the range of environmental actions, including required permits and other agency approvals, for Project W-314 activities in the Hanford Site's Tank Waste Remediation System. This document outlines alternative approaches to satisfying applicable environmental standards, and describes selected strategies for acquiring permits and other approvals needed for waste feed delivery to proceed. This document also includes estimated costs and schedule to obtain the required permits and approvals based on the selected strategy. It also provides estimated costs for environmental support during design and construction based on the preliminary project schedule provided

Zika antiviral chemotherapy: identification of drugs and promising starting points for drug discovery from an FDA-approved library [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Bruno S. Pascoalino

2016-10-01

Full Text Available Background The recent epidemics of Zika virus (ZIKV implicated it as the cause of serious and potentially lethal congenital conditions such microcephaly and other central nervous system defects, as well as the development of the Guillain-Barré syndrome in otherwise healthy patients. Recent findings showed that anti-Dengue antibodies are capable of amplifying ZIKV infection by a mechanism similar to antibody-dependent enhancement, increasing the severity of the disease. This scenario becomes potentially catastrophic when the global burden of Dengue and the advent of the newly approved anti-Dengue vaccines in the near future are taken into account. Thus, antiviral chemotherapy should be pursued as a priority strategy to control the spread of the virus and prevent the complications associated with Zika. Methods Here we describe a fast and reliable cell-based, high-content screening assay for discovery of anti-ZIKV compounds. This methodology has been used to screen the National Institute of Health Clinical Collection compound library, a small collection of FDA-approved drugs. Results and conclusion From 725 FDA-approved compounds triaged, 29 (4% were found to have anti-Zika virus activity, of which 22 had confirmed (76% of confirmation by dose-response curves. Five candidates presented selective activity against ZIKV infection and replication in a human cell line. These hits have abroad spectrum of chemotypes and therapeutic uses, offering valuable opportunities for selection of leads for antiviral drug discovery.

Alcohol addiction - the safety of available approved treatment options.

Science.gov (United States)

Antonelli, Mariangela; Ferrulli, Anna; Sestito, Luisa; Vassallo, Gabriele A; Tarli, Claudia; Mosoni, Carolina; Rando, Maria M; Mirijello, Antonio; Gasbarrini, Antonio; Addolorato, Giovanni

2018-02-01

Alcohol Use Disorders (AUD) is a leading cause of mortality and morbidity worldwide. At present disulfiram, naltrexone and acamprosate are approved for the treatment of AUD in U.S. and Europe. Nalmefene is approved in Europe and sodium oxybate is approved in Italy and Austria only. Baclofen received a 'temporary recommendation for use' in France. Areas covered: The safety of the above mentioned medications on liver, digestive system, kidney function, nervous system, pregnancy and lactation and their possible side effects are described and discussed. Expert opinion: Mechanism of action and metabolism of these drugs as well as patients' clinical characteristics can affect the safety of treatment. All approved medications are valid tools for the treatment of AUD in patients without advanced liver disease. For some drugs, attention should be paid to patients with renal failure and medications may be used with caution, adjusting the dosage according to kidney function. In patients with AUD and advanced liver disease, at present only baclofen has been formally tested in randomized controlled trials showing its safety in this population.

Automation of CT-based haemorrhagic stroke assessment for improved clinical outcomes: study protocol and design.

Science.gov (United States)

Chinda, Betty; Medvedev, George; Siu, William; Ester, Martin; Arab, Ali; Gu, Tao; Moreno, Sylvain; D'Arcy, Ryan C N; Song, Xiaowei

2018-04-19

Haemorrhagic stroke is of significant healthcare concern due to its association with high mortality and lasting impact on the survivors' quality of life. Treatment decisions and clinical outcomes depend strongly on the size, spread and location of the haematoma. Non-contrast CT (NCCT) is the primary neuroimaging modality for haematoma assessment in haemorrhagic stroke diagnosis. Current procedures do not allow convenient NCCT-based haemorrhage volume calculation in clinical settings, while research-based approaches are yet to be tested for clinical utility; there is a demonstrated need for developing effective solutions. The project under review investigates the development of an automatic NCCT-based haematoma computation tool in support of accurate quantification of haematoma volumes. Several existing research methods for haematoma volume estimation are studied. Selected methods are tested using NCCT images of patients diagnosed with acute haemorrhagic stroke. For inter-rater and intrarater reliability evaluation, different raters will analyse haemorrhage volumes independently. The efficiency with respect to time of haematoma volume assessments will be examined to compare with the results from routine clinical evaluations and planimetry assessment that are known to be more accurate. The project will target the development of an enhanced solution by adapting existing methods and integrating machine learning algorithms. NCCT-based information of brain haemorrhage (eg, size, volume, location) and other relevant information (eg, age, sex, risk factor, comorbidities) will be used in relation to clinical outcomes with future project development. Validity and reliability of the solution will be examined for potential clinical utility. The project including procedures for deidentification of NCCT data has been ethically approved. The study involves secondary use of existing data and does not require new consent of participation. The team consists of clinical neuroimaging

Patient recruitment into a multicenter randomized clinical trial for kidney disease: report of the focal segmental glomerulosclerosis clinical trial (FSGS CT).

Science.gov (United States)

Ferris, Maria; Norwood, Victoria; Radeva, Milena; Gassman, Jennifer J; Al-Uzri, Amira; Askenazi, David; Matoo, Tej; Pinsk, Maury; Sharma, Amita; Smoyer, William; Stults, Jenna; Vyas, Shefali; Weiss, Robert; Gipson, Debbie; Kaskel, Frederick; Friedman, Aaron; Moxey-Mims, Marva; Trachtman, Howard

2013-02-01

We describe the experience of the focal segmental glomerulosclerosis clinical trial (FSGS CT) in the identification and recruitment of participants into the study. This National Institutes of Health funded study, a multicenter, open-label, randomized comparison of cyclosporine versus oral dexamethasone pulses plus mycophenolate mofetil, experienced difficulty and delays meeting enrollment goals. These problems occurred despite the support of patient advocacy groups and aggressive recruitment strategies. Multiple barriers were identified including: (1) inaccurate estimates of the number of potential incident FSGS patients at participating centers; (2) delays in securing one of the test agents; (3) prolonged time between IRB approval and execution of a subcontract (mean 7.5 ± 0.8 months); (4) prolonged time between IRB approval and enrollment of the first patient at participating sites (mean 19.6 ± 1.4 months); and (5) reorganization of clinical coordinating core infrastructure to align resources with enrollment. A Web-based anonymous survey of site investigators revealed site-related barriers to patient recruitment. The value of a variety of recruitment tools was of marginal utility in facilitating patient enrollment. We conclude that improvements in the logistics of study approval and regulatory start-up and testing of promising novel agents are important factors in promoting enrollment into randomized clinical trials in nephrology. © 2013 Wiley Periodicals, Inc.

A simple versatile solution for collecting multidimensional clinical data based on the CakePHP web application framework.

Science.gov (United States)

Biermann, Martin

2014-04-01

Clinical trials aiming for regulatory approval of a therapeutic agent must be conducted according to Good Clinical Practice (GCP). Clinical Data Management Systems (CDMS) are specialized software solutions geared toward GCP-trials. They are however less suited for data management in small non-GCP research projects. For use in researcher-initiated non-GCP studies, we developed a client-server database application based on the public domain CakePHP framework. The underlying MySQL database uses a simple data model based on only five data tables. The graphical user interface can be run in any web browser inside the hospital network. Data are validated upon entry. Data contained in external database systems can be imported interactively. Data are automatically anonymized on import, and the key lists identifying the subjects being logged to a restricted part of the database. Data analysis is performed by separate statistics and analysis software connecting to the database via a generic Open Database Connectivity (ODBC) interface. Since its first pilot implementation in 2011, the solution has been applied to seven different clinical research projects covering different clinical problems in different organ systems such as cancer of the thyroid and the prostate glands. This paper shows how the adoption of a generic web application framework is a feasible, flexible, low-cost, and user-friendly way of managing multidimensional research data in researcher-initiated non-GCP clinical projects. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

REVIEW OF NRC APPROVED DIGITAL CONTROL SYSTEMS ANALYSIS

International Nuclear Information System (INIS)

Markman, D.W.

1999-01-01

Preliminary design concepts for the proposed Subsurface Repository at Yucca Mountain indicate extensive reliance on modern, computer-based, digital control technologies. The purpose of this analysis is to investigate the degree to which the U. S. Nuclear Regulatory Commission (NRC) has accepted and approved the use of digital control technology for safety-related applications within the nuclear power industry. This analysis reviews cases of existing digitally-based control systems that have been approved by the NRC. These cases can serve as precedence for using similar types of digitally-based control technologies within the Subsurface Repository. While it is anticipated that the Yucca Mountain Project (YMP) will not contain control systems as complex as those required for a nuclear power plant, the review of these existing NRC approved applications will provide the YMP with valuable insight into the NRCs review process and design expectations for safety-related digital control systems. According to the YMP Compliance Program Guidance, portions of various NUREGS, Regulatory Guidelines, and nuclear IEEE standards the nuclear power plant safety related concept would be applied to some of the designs on a case-by-case basis. This analysis will consider key design methods, capabilities, successes, and important limitations or problems of selected control systems that have been approved for use in the Nuclear Power industry. An additional purpose of this analysis is to provide background information in support of further development of design criteria for the YMP. The scope and primary objectives of this analysis are to: (1) Identify and research the extent and precedence of digital control and remotely operated systems approved by the NRC for the nuclear power industry. Help provide a basis for using and relying on digital technologies for nuclear related safety critical applications. (2) Identify the basic control architecture and methods of key digital control

Evidence-based clinical practice

DEFF Research Database (Denmark)

Garattini, Silvio; Jakobsen, Janus C; Wetterslev, Jørn

2016-01-01

was considered through literature searches combined with personal files. Treatments should generally not be chosen based only on evidence from observational studies or single randomised clinical trials. Systematic reviews with meta-analysis of all identifiable randomised clinical trials with Grading...

Regulation of Clinical Trials with Advanced Therapy Medicinal Products in Germany.

Science.gov (United States)

Renner, Matthias; Anliker, Brigitte; Sanzenbacher, Ralf; Schuele, Silke

2015-01-01

In the European Union, clinical trials for Advanced Therapy Medicinal Products are regulated at the national level, in contrast to the situation for a Marketing Authorisation Application, in which a centralised procedure is foreseen for these medicinal products. Although based on a common understanding regarding the regulatory requirement to be fulfilled before conduct of a clinical trial with an Advanced Therapy Investigational Medicinal Product, the procedures and partly the scientific requirements for approval of a clinical trial application differ between the European Union Member States. This chapter will thus give an overview about the path to be followed for a clinical trial application and the subsequent approval process for an Advanced Therapy Investigational Medicinal Product in Germany and will describe the role of the stakeholders that are involved. In addition, important aspects of manufacturing, quality control and non-clinical testing of Advanced Therapy Medicinal Products in the clinical development phase are discussed. Finally, current and future approaches for harmonisation of clinical trial authorisation between European Union Member States are summarised.

38 CFR 17.65 - Approvals and provisional approvals of community residential care facilities.

Science.gov (United States)

2010-07-01

... approvals of community residential care facilities. 17.65 Section 17.65 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS MEDICAL Community Residential Care § 17.65 Approvals and provisional approvals of community residential care facilities. (a) An approval of a facility meeting all of...

Oligonucleotide-based pharmaceuticals: Non-clinical and clinical safety signals and non-clinical testing strategies.

Science.gov (United States)

Mustonen, Enni-Kaisa; Palomäki, Tiina; Pasanen, Markku

2017-11-01

Antisense oligonucleotides, short interfering RNAs (siRNAs) and aptamers are oligonucleotide-based pharmaceuticals with a promising role in targeted therapies. Currently, five oligonucleotide-based pharmaceuticals have achieved marketing authorization in Europe or USA and many more are undergoing clinical testing. However, several safety concerns have been raised in non-clinical and clinical studies. Oligonucleotides share properties with both chemical and biological pharmaceuticals and therefore they pose challenges also from the regulatory point of view. We have analyzed the safety data of oligonucleotides and evaluated the applicability of current non-clinical toxicological guidelines for assessing the safety of oligonucleotide-based pharmaceuticals. Oligonucleotide-based pharmaceuticals display a similar toxicological profile, exerting adverse effects on liver and kidney, evoking hematological alterations, as well as causing immunostimulation and prolonging the coagulation time. It is possible to extrapolate some of these effects from non-clinical studies to humans. However, evaluation strategies for genotoxicity testing of "non-natural" oligonucleotides should be revised. Additionally, the selective use of surrogates and prediction of clinical endpoints for non-clinically observed immunostimulation is complicated by its multiple potential manifestations, demanding improvements in the testing strategies. Utilizing more relevant and mechanistic-based approaches and taking better account of species differences, could possibly improve the prediction of relevant immunological/proinflammatory effects in humans. Copyright © 2017 Elsevier Inc. All rights reserved.

From selection hits to clinical leads: progress in aptamer discovery

Directory of Open Access Journals (Sweden)

Keith E Maier

2016-01-01

Full Text Available Aptamers were discovered more than 25 years ago, yet only one has been approved by the US Food and Drug Administration to date. With some noteworthy advances in their chemical design and the enzymes we use to make them, aptamers and aptamer-based therapeutics have seen a resurgence in interest. New aptamer drugs are being approved for clinical evaluation, and it is certain that we will see increasingly more aptamers and aptamer-like drugs in the future. In this review, we will discuss the production of aptamers with an emphasis on the advances and modifications that enabled early aptamers to succeed in clinical trials as well as those that are likely to be important for future generations of these drugs.

Regulatory approval of cancer risk-reducing (chemopreventive) drugs: moving what we have learned into the clinic.

Science.gov (United States)

Meyskens, Frank L; Curt, Gregory A; Brenner, Dean E; Gordon, Gary; Herberman, Ronald B; Finn, Olivera; Kelloff, Gary J; Khleif, Samir N; Sigman, Caroline C; Szabo, Eva

2011-03-01

This article endeavors to clarify the current requirements and status of regulatory approval for chemoprevention (risk reduction) drugs and discusses possible improvements to the regulatory pathway for chemoprevention. Covering a wide range of topics in as much depth as space allows, this report is written in a style to facilitate the understanding of nonscientists and to serve as a framework for informing the directions of experts engaged more deeply with this issue. Key topics we cover here are as follows: a history of definitive cancer chemoprevention trials and their influence on the evolution of regulatory assessments; a brief review of the long-standing success of pharmacologic risk reduction of cardiovascular diseases and its relevance to approval for cancer risk reduction drugs; the use and limitations of biomarkers for developing and the approval of cancer risk reduction drugs; the identification of individuals at a high(er) risk for cancer and who are appropriate candidates for risk reduction drugs; business models that should incentivize pharmaceutical industry investment in cancer risk reduction; a summary of scientific and institutional barriers to development of cancer risk reduction drugs; and a summary of major recommendations that should help facilitate the pathway to regulatory approval for pharmacologic cancer risk reduction drugs.

Pharmaceutical R&D performance by firm size: approval success rates and economic returns.

Science.gov (United States)

DiMasi, Joseph A

2014-01-01

The R&D productivity of pharmaceutical firms has become an increasingly significant concern of industry, regulators, and policymakers. To address an important aspect of R&D performance, public and private data sources were used to estimate clinical phase transition and clinical approval probabilities for the pipelines of the 50 largest pharmaceutical firms (by sales) by 3 firms size groups (top 10 firms, top 11-20 firms, and top 21-50 firms). For self-originated compounds, the clinical approval success rates were 14.3%, 16.4%, and 18.4% for top 10 firms, top 11-20 firms, and top 21-50 firms, respectively. The results showing higher success rates for smaller firms were largely driven by outcomes for the small-molecule drugs. Adjustments for the relatively small differences in therapeutic class distributions across the firm size groups showed that the success rate for small-molecule self-originated drugs was 6% below average for top 10 firms and 17% above average for top 21-50 firms. Although success rates for small firms were higher, this advantage was offset to some degree by lower returns on approved drugs, suggesting different strategic objectives with regard to risk and reward by firm size.

Clinical trials for stem cell transplantation: when are they needed?

Science.gov (United States)

Van Pham, Phuc

2016-04-27

In recent years, both stem cell research and the clinical application of these promising cells have increased rapidly. About 1000 clinical trials using stem cells have to date been performed globally. More importantly, more than 10 stem cell-based products have been approved in some countries. With the rapid growth of stem cell applications, some countries have used clinical trials as a tool to diminish the rate of clinical stem cell applications. However, the point at which stem cell clinical trials are essential remains unclear. This commentary discusses when stem cell clinical trials are essential for stem cell transplantation therapies.

Cleveland Clinic Next Generation Neuroimaging

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Lowe, Mark

2009-09-30

This was an award to purchase equipment for state-of-the-art MRI radiofrequency coils. There was no personnel effort or construction as a part of this project. This report details the final status of the approved budget items for this project. All approved budget items were successfully delivered and installed. The equipment provided to Cleveland Clinic under this project will allow Cleveland Clinic researchers to build imaging equipment with improved capability to investigate brain disorders.

Trends in global approvals of biotech crops (1992–2014)

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Aldemita, Rhodora R; Reaño, Ian Mari E; Solis, Renando O; Hautea, Randy A

2015-01-01

ABSTRACT With the increasing number of genetically modified (GM) events, traits, and crops that are developed to benefit the global population, approval of these technologies for food, feed, cultivation and import in each country may vary depending on needs, demand and trade interest. ISAAA established a GMO Approval Database to document global approvals of biotech crops. GM event name, crops, traits, developer, year of approval for cultivation, food/feed, import, and relevant dossiers were sourced from credible government regulatory websites and biosafety clearinghouses. This paper investigates the trends in GM approvals for food, feed and cultivation based on the number of approving countries, GM crops, events, and traits in the last 23 y (1992–2014), rationale for approval, factors influencing approvals, and their implications in GM crop adoption. Results show that in 2014, there was an accumulative increase in the number of countries granting approvals at 29 (79% developing countries) for commercial cultivation and 31 (70% developing countries) for food and 19 (80% developing developing) for feed; 2012 had the highest number of approving countries and cultivation approvals; 2011 had the highest number of country approvals for feed, and 2014 for food approvals. Herbicide tolerance trait had the highest events approved, followed by insect tolerance traits. Approvals for food product quality increased in the second decade. Maize had the highest number of events approved (single and stacked traits), and stacked traits product gradually increased which is already 30% of the total trait approvals. These results may indicate understanding and acceptance of countries to enhance regulatory capability to be able to benefit from GM crop commercialization. Hence, the paper provided information on the trends on the growth of the GM crop industry in the last 23 y which may be vital in predicting future GM crops and traits. PMID:26039675

19 CFR 115.41 - Certificate of approval for containers approved after manufacture.

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2010-04-01

... after manufacture. 115.41 Section 115.41 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT... PURSUANT TO INTERNATIONAL CUSTOMS CONVENTIONS Procedures for Approval of Containers After Manufacture § 115.41 Certificate of approval for containers approved after manufacture. The Certifying Authority shall...

The limits of evidence in drug approval and availability: a case study of cilostazol and naftidrofuryl for the treatment of intermittent claudication.

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Hong, Haeyeon; Mackey, William C

2014-08-01

Despite numerous efforts to develop effective medications for the treatment of intermittent claudication (IC) over the past 4 decades, a gold standard medical management option has yet to be defined. Although not life-threatening, IC interferes with mobility and activities of daily living, significantly impairing quality of life and potentially causing depression. Cilostazol, the leading pharmacologic agent for IC in the United States, was approved by the US Food and Drug Administration (FDA) in 1999 based on controversial data. Meanwhile, naftidrofuryl, the first-line pharmacologic agent for IC in the United Kingdom and Europe, has never been approved by the FDA and therefore is not available in the United States. The clinical data for cilostazol and naftidrofuryl are plagued by flaws related to lack of protocol standardization, objective endpoints, and strict eligibility criteria in study subjects, making identification of a true treatment effect impossible. Furthermore, no prospective randomized trial comparing the efficacy of cilostazol and naftidrofuryl has been conducted, because the manufacturers of these agents have much to lose and little to gain from such a study. This article provides an overview of the pharmacology of cilostazol and naftidrofuryl, and the clinical studies leading to their approval and clinical acceptance. It further explores the possible sources of bias in analyzing these clinical trials, some of which have been brought to light by the National Institute for Health and Clinical Excellence (NICE) of the United Kingdom in its technology appraisal guidance. It also speculates the ways in which economic incentives may affect drug-marketing decisions. A literature review of pharmacology and clinical trials for cilostazol and naftidrofuryl was performed in PubMed. The majority of included clinical trials were initially identified through the most recent Cochrane review articles as well as the FDA's approval packet for cilostazol. The

Clinical advantages of 3.0 T MRI over 1.5 T

International Nuclear Information System (INIS)

Willinek, Winfried A.; Schild, Hans H.

2008-01-01

Since approval by the FDA in 2000, human MR imaging (MRI) at 3.0 T has been increasingly used in clinical practice. In spite of the potential technical challenges, a number of clinical advantages of 3.0 T MRI over 1.5 T have been identified in the recent years. This article reviews the benefits and the current knowledge of 3.0 T whole-body MRI from an evidence-based perspective and summarizes its clinical applications

Clinical advantages of 3.0 T MRI over 1.5 T

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Willinek, Winfried A. [Department of Radiology, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn (Germany)], E-mail: winfried.willinek@ukb.uni-bonn.de; Schild, Hans H. [Department of Radiology, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn (Germany)

2008-01-15

Since approval by the FDA in 2000, human MR imaging (MRI) at 3.0 T has been increasingly used in clinical practice. In spite of the potential technical challenges, a number of clinical advantages of 3.0 T MRI over 1.5 T have been identified in the recent years. This article reviews the benefits and the current knowledge of 3.0 T whole-body MRI from an evidence-based perspective and summarizes its clinical applications.

U.S. FDA Approval Summary: Nivolumab for Treatment of Unresectable or Metastatic Melanoma Following Progression on Ipilimumab.

Science.gov (United States)

Hazarika, Maitreyee; Chuk, Meredith K; Theoret, Marc R; Mushti, Sirisha; He, Kun; Weis, Shawna L; Putman, Alexander H; Helms, Whitney S; Cao, Xianhua; Li, Hongshan; Zhao, Hong; Zhao, Liang; Welch, Joel; Graham, Laurie; Libeg, Meredith; Sridhara, Rajeshwari; Keegan, Patricia; Pazdur, Richard

2017-07-15

On December 22, 2014, the FDA granted accelerated approval to nivolumab (OPDIVO; Bristol-Myers Squibb) for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on a clinically meaningful, durable objective response rate (ORR) in a non-comparative analysis of 120 patients who received 3 mg/kg of nivolumab intravenously every 2 weeks with at least 6-month follow-up in an ongoing, randomized, open-label, active-controlled clinical trial. The ORR as assessed by a blinded independent review committee per RECIST v1.1 was 31.7% (95% confidence interval, 23.5-40.8). Ongoing responses were observed in 87% of responding patients, ranging from 2.6+ to 10+ months. In 13 patients, the response duration was 6 months or longer. The risks of nivolumab, including clinically significant immune-mediated adverse reactions (imARs), were assessed in 268 patients who received at least one dose of nivolumab. The FDA review considered whether the ORR and durations of responses were reasonably likely to predict clinical benefit, the adequacy of the safety database, and systematic approaches to the identification, description, and patient management for imARs in product labeling. Clin Cancer Res; 23(14); 3484-8. ©2017 AACR . ©2017 American Association for Cancer Research.

78 FR 49274 - Agency Information Collection Activities: Submission to OMB for Review and Approval; Public...

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2013-08-13

... Collection Request Title: Black Lung Clinics Program Performance Measures OMB No. 0915-0292--Extension...) conducts an annual data collection of user information for the Black Lung Clinic Program, which has been ongoing with OMB approval since 2004. The purpose of the Black Lung Clinic Program is to improve the...

Cognitive Properties of Approval Voting : an Experimental Approach

Directory of Open Access Journals (Sweden)

Krzysztof Przybyszewski

2011-01-01

Full Text Available The paper summarizes two series of experiments demonstrating the cognitive properties of approval voting. The former series is devoted to mental processes induced in decision makers who use the method of approval voting. Based on cognitive effort, the use of choice strategies is presented in this paper. The observations of respondents show that most of them use relatively effortless strategy of eliminating alternatives and attributes. Few respondents use more sophisticated methods. The other series of experiments analyses the number of alternatives chosen in approval voting. It appears that the average number is not constant, even for similar votes but it depends on the subject of voting. The number of chosen alternatives and the subjective significance of the scope of voting are negatively or positively correlated in the case of special votes. The analyzed experiments show that the cognitive properties of approval voting have a diverse structure. (original abstract

A Tool for Predicting Regulatory Approval After Phase II Testing of New Oncology Compounds.

Science.gov (United States)

DiMasi, J A; Hermann, J C; Twyman, K; Kondru, R K; Stergiopoulos, S; Getz, K A; Rackoff, W

2015-11-01

We developed an algorithm (ANDI) for predicting regulatory marketing approval for new cancer drugs after phase II testing has been conducted, with the objective of providing a tool to improve drug portfolio decision-making. We examined 98 oncology drugs from the top 50 pharmaceutical companies (2006 sales) that first entered clinical development from 1999 to 2007, had been taken to at least phase II development, and had a known final outcome (research abandonment or regulatory marketing approval). Data on safety, efficacy, operational, market, and company characteristics were obtained from public sources. Logistic regression and machine-learning methods were used to provide an unbiased approach to assess overall predictability and to identify the most important individual predictors. We found that a simple four-factor model (activity, number of patients in the pivotal phase II trial, phase II duration, and a prevalence-related measure) had high sensitivity and specificity for predicting regulatory marketing approval. © 2015 American Society for Clinical Pharmacology and Therapeutics.

77 FR 31359 - Medicare and Medicaid Programs; Announcement of the Re-Approval of the Joint Commission as an...

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2012-05-25

... Organization Under the Clinical Laboratory Improvement Amendments of 1988 AGENCY: Centers for Medicare... Commission for re-approval as an accreditation organization for clinical laboratories under the Clinical... On October 31, 1988, the Congress enacted the Clinical Laboratory Improvement Amendments of 1988...

Redfield Energy Approval

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This September 19, 2016 letter from EPA approves the petition from Poet Biorefining-Lake Crystal, regarding non-This October 27, 2016 letter from EPA approves the petition from Redfield Energy, LLC, regarding non-grandfathered ethanol produced

Moving oncolytic viruses into the clinic: clinical-grade production, purification, and characterization of diverse oncolytic viruses

Directory of Open Access Journals (Sweden)

Guy Ungerechts

2016-01-01

Full Text Available Oncolytic viruses (OVs are unique anticancer agents based on their pleotropic modes of action, which include, besides viral tumor cell lysis, activation of antitumor immunity. A panel of diverse viruses, often genetically engineered, has advanced to clinical investigation, including phase 3 studies. This diversity of virotherapeutics not only offers interesting opportunities for the implementation of different therapeutic regimens but also poses challenges for clinical translation. Thus, manufacturing processes and regulatory approval paths need to be established for each OV individually. This review provides an overview of clinical-grade manufacturing procedures for OVs using six virus families as examples, and key challenges are discussed individually. For example, different virus features with respect to particle size, presence/absence of an envelope, and host species imply specific requirements for measures to ensure sterility, for handling, and for determination of appropriate animal models for toxicity testing, respectively. On the other hand, optimization of serum-free culture conditions, increasing virus yields, development of scalable purification strategies, and formulations guaranteeing long-term stability are challenges common to several if not all OVs. In light of the recent marketing approval of the first OV in the Western world, strategies for further upscaling OV manufacturing and optimizing product characterization will receive increasing attention.

Moving oncolytic viruses into the clinic: clinical-grade production, purification, and characterization of diverse oncolytic viruses.

Science.gov (United States)

Ungerechts, Guy; Bossow, Sascha; Leuchs, Barbara; Holm, Per S; Rommelaere, Jean; Coffey, Matt; Coffin, Rob; Bell, John; Nettelbeck, Dirk M

2016-01-01

Oncolytic viruses (OVs) are unique anticancer agents based on their pleotropic modes of action, which include, besides viral tumor cell lysis, activation of antitumor immunity. A panel of diverse viruses, often genetically engineered, has advanced to clinical investigation, including phase 3 studies. This diversity of virotherapeutics not only offers interesting opportunities for the implementation of different therapeutic regimens but also poses challenges for clinical translation. Thus, manufacturing processes and regulatory approval paths need to be established for each OV individually. This review provides an overview of clinical-grade manufacturing procedures for OVs using six virus families as examples, and key challenges are discussed individually. For example, different virus features with respect to particle size, presence/absence of an envelope, and host species imply specific requirements for measures to ensure sterility, for handling, and for determination of appropriate animal models for toxicity testing, respectively. On the other hand, optimization of serum-free culture conditions, increasing virus yields, development of scalable purification strategies, and formulations guaranteeing long-term stability are challenges common to several if not all OVs. In light of the recent marketing approval of the first OV in the Western world, strategies for further upscaling OV manufacturing and optimizing product characterization will receive increasing attention.

Innovating by developing new uses of already-approved drugs: trends in the marketing approval of supplemental indications.

Science.gov (United States)

DiMasi, Joseph A

2013-06-01

Much of the literature on trends and factors affecting biopharmaceutical innovation has focused overwhelmingly on the development and approval of never-before approved drugs and biologics. Little attention has been paid to new uses for already-approved compounds, which can be an important form of innovation. This paper aimed to determine and analyze recent trends in the number and type of new or modified US indication approvals for drugs and biologics. We also examine regulatory approval-phase times for new-use efficacy supplements and compare them to approval-phase times for original-use approvals over the same period. We developed a data set of efficacy supplements approved by the US Food and Drug Administration (FDA) from 1998 to 2011 that includes information on the type, approval-phase time (time from submission to the FDA of an application for marketing approval to approval of the application), and FDA therapeutic-significance rating for the approved application, which we obtained from an FDA Web site. This data set was merged with a Tufts Center for the Study of Drug Development (CSDD) data set of US new drug and biologics approvals. We developed descriptive statistics on trends in the number and type of new-use efficacy supplements, on US regulatory approval-phase times for the supplements, and on original new drug and biologics approvals over the study period and for the time from original- to new-use approval. The total number of new-use efficacy-supplement approvals did not exhibit a marked trend, but the number of new pediatric-indication approvals increased substantially. Approval-phase times for new-use supplements varied by therapeutic class and FDA therapeutic-significance rating. Mean approval-phase times were highest for central nervous system compounds (13.8 months) and lowest for antineoplastics (8.9 months). The mean time from original to supplement approval was substantially longer for new pediatric indications than for other new uses. Mean

59th Medical Wing Clinical Research Division Clinical Investigations Program Pathology Poster

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2017-04-28

59 MDW/SGVU SUBJECT: Professional Presentation Approval 1. Your paper, entitled 59th Medical Wing Clinical Research Division Clinical Investigations...Program Pathology Poster presented at/published to For hanging in a hallway of the 591h Medical Wing Clinical Research Division, Bldg 4430 in...Graduate Health Sciences Education student and your department has told you they cannot fund your publication, the 59th Clinical Research Division may

Industry funded clinical trials: bias and quality.

Science.gov (United States)

Del Parigi, Angelo

2012-01-01

The quality of the clinical data supporting the development and ultimately the approval for medical use of new drugs is often challenged. Many share the perception that the business goals of the pharmaceutical industry overrule the best scientific efforts to accrue critical knowledge on a new molecule, in order to inform investment of resources, regulatory approvals and appropriate use by patients. Despite this common belief, few scientists have attempted to assess objectively the quality of industry funded (IF) clinical trials by measuring it and comparing it with non-industry funded (NIF) clinical trials in a data-driven fashion. Overall, the average quality of IF clinical research has been reported to be higher than the quality of NIF clinical research.

MRD Testing in Multiple Myeloma: From a Surrogate Marker of Clinical Outcomes to an Every-Day Clinical Tool.

Science.gov (United States)

Landgren, Ola

2018-01-01

Minimal residual disease (MRD) testing in multiple myeloma is here to stay. Studies show that MRD negativity is consistently associated with longer progression-free survival (PFS). It is just a matter of time until MRD negativity will become a regulatory endpoint for drug approval. Until that can happen, more analysis will be required to define the exact details of MRD in the regulatory setting. For example, for randomized studies there is need to define the amount of improvement in MRD negativity between the experimental arm and the control arm at a given time-point for a drug to obtain regulatory accelerated approval. Such efforts are underway. For the multiple myeloma field as a whole, important tasks for the (near) coming future are as follows: (1) to conduct or finalize the expanded analysis to define the exact details of MRD in the regulatory setting, (2) to develop new and better MRD assays-both more sensitive MRD assays for bone marrow aspirates and nonbone marrow aspirate-based assays (eg, blood-based and imaging-based MRD assays), and (3) to design novel clinical studies to formally assess the effect of MRD negativity in clinical decision making. The aim with this issue of the Journal is to provide a deep and comprehensive summary of the latest MRD knowledge in the field, and to outline future directions. Copyright © 2018 Elsevier Inc. All rights reserved.

Nationwide Risk-Based PCB Remediation Waste Disposal Approvals under Title 40 of the Code of Federal Regulations (CFR) Section 761.61(c)

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This page contains information about Nationwide Risk-Based Polychlorinated Biphenyls (PCBs) Remediation Waste Disposal Approvals under Title 40 of the Code of Federal Regulations (CFR) Section 761.61(c)

Companion diagnostics: a regulatory perspective from the last 5 years of molecular companion diagnostic approvals.

Science.gov (United States)

Roscoe, Donna M; Hu, Yun-Fu; Philip, Reena

2015-01-01

Companion diagnostics are essential for the safe and effective use of the corresponding therapeutic products. The US FDA has approved a number of companion diagnostics used to select cancer patients for treatment with contemporaneously approved novel therapeutics. The processes of co-development and co-approval of a therapeutic product and its companion diagnostic have been a learning experience that continues to evolve. Using several companion diagnostics as examples, this article describes the challenges associated with the scientific, clinical and regulatory hurdles faced by FDA and industry alike. Taken together, this discussion is intended to assist manufacturers toward a successful companion diagnostics development plan.

30 CFR 18.95 - Approval of machines constructed of components approved, accepted or certified under Bureau of...

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2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Approval of machines constructed of components... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Field Approval of Electrically Operated Mining Equipment § 18.95 Approval of machines constructed of components approved...

Routine clinical heart examinations using SQUID magnetocardiography at University of Tsukuba Hospital

Science.gov (United States)

Inaba, T.; Nakazawa, Y.; Yoshida, K.; Kato, Y.; Hattori, A.; Kimura, T.; Hoshi, T.; Ishizu, T.; Seo, Y.; Sato, A.; Sekiguchi, Y.; Nogami, A.; Watanabe, S.; Horigome, H.; Kawakami, Y.; Aonuma, K.

2017-11-01

A 64-channel Nb-based DC-SQUID magnetocardiography (MCG) system was installed at the University of Tsukuba Hospital (UTH) in March 2007 after obtaining Japanese pharmaceutical approval and insurance reimbursement approval. In the period between 2008 and 2016, the total number of patients was 10 085. The heart diseases diagnosed in fetuses as well as adults are mainly atrial arrhythmia, abnormal repolarization, ventricular arrhythmia, and fetal arrhythmia. In most cases of insufficient diagnostic accuracy with electrocardiography, SQUID MCG precisely revealed these heart diseases as an abnormal electrical current distribution. Based on success in routine examinations, SQUID MCG is now an indispensable clinical instrument with diagnostic software tuned up during routine use at UTH.

Clinical and Outcome Research in oncology The need for integration

Directory of Open Access Journals (Sweden)

Apolone Giovanni

2003-04-01

Full Text Available Abstract Cancer is one of the main healthcare problems in Europe. Although significant progress has recently been made, long-term survival is still disappointing for most common solid tumours. The explosion of information has strengthened the need to create and sustain coordinated interaction between technology, biology, clinical research, clinical practice and health policy. A simple process based on automatic and passive translation from bench to clinical research and eventually to the bed side is usually assumed but cannot be taken for granted. A critical role might be played by Outcome Research (OR, defined as the discipline that describes, interprets, and predicts the impact of various influences, especially interventions, on final endpoints (from survival to satisfaction with care that matter to decision makers (from patients to society at large, with special emphasis on the use of patient-reported outcomes (PRO. Recently, under pressure from several parts of society, the FDA, recognizing the need for faster drug approval, has modified existing regulations and created new rules to allow anti-cancer drugs to be approved more quickly and, in certain but quite common circumstances, single arm trials and surrogate endpoints to be used as measures of clinical benefit. In this context, the faster approval process may lead to drugs being marketed without there being a complete picture of how effective or safe they are. The FDA move to speed up drug approval, together with the use of not fully validated surrogate endpoints, give OR the unique opportunity to help understand the value of drugs that have received accelerated approval. Despite this opportunity, OR has yet to demonstrate its role in this specific setting and provide proof of the validity, reliability and added value of its primary endpoint measures when evaluated in a broader context. The implementation of lines of OR in the development and evaluation of anti-cancer drugs hinges upon

4 pitfalls to clinical integration.

Science.gov (United States)

Redding, John

2012-11-01

Four common mistakes can easily thwart clinical integration: Assuming that EHR adoption is the cornerstone of successful integration; Delaying the development of ambulatory services that support clinical integration; Believing that knowledge of clinical integration initiatives will passively diffuse through the ranks; Attaching too much weight to Federal Trade Commission/Department of Justice approval of a clinical integration model.

Drugs Approved for Breast Cancer

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... Ask about Your Treatment Research Drugs Approved for Breast Cancer This page lists cancer drugs approved by the ... are not listed here. Drugs Approved to Prevent Breast Cancer Evista (Raloxifene Hydrochloride) Raloxifene Hydrochloride Tamoxifen Citrate Drugs ...

Neratinib: First Global Approval.

Science.gov (United States)

Deeks, Emma D

2017-10-01

Neratinib (Nerlynx™) is an oral, irreversible inhibitor of the human epidermal growth factor receptors HER1 (EGFR), HER2 and HER4. The drug originally arose from research by Wyeth (now Pfizer) and is now being developed by Puma Biotechnology primarily for the treatment of HER2-positive (HER+) breast cancer. Neratinib is approved in the USA for the extended adjuvant treatment of patients with HER2+ early-stage breast cancer who have been previously treated with a trastuzumab-based adjuvant regimen, and is in the preregistration phase for this indication in the EU. Neratinib, as monotherapy and/or combination therapy, is also in phase 3 development for metastatic breast cancer and in phase 1/2 development for advanced breast cancer and other solid tumours, including non-small cell lung cancer, colorectal cancer and glioblastoma. This article summarizes the milestones in the development of neratinib leading to this first approval for breast cancer.

A drug's life: the pathway to drug approval.

Science.gov (United States)

Keng, Michael K; Wenzell, Candice M; Sekeres, Mikkael A

2013-10-01

In the United States, drugs and medical devices are regulated by the US Food and Drug Administration (FDA). A drug must undergo rigorous testing prior to marketing to and medical use by the general public. The FDA grants marketing approval for drug products based on a comprehensive review of safety and efficacy data. This review article explains the history behind the establishment of the FDA and examines the historical legislation and approval processes for drugs, specifically in the fields of medical oncology and hematology. The agents imatinib (Gleevec, Novartis) and decitabine (Dacogen, Eisai) are used to illustrate both the current FDA regulatory process-specifically the orphan drug designation and accelerated approval process-and why decitabine failed to gain an indication for acute myeloid leukemia. The purpose and construct of the Oncologic Drugs Advisory Committee are also discussed, along with examples of 2 renal cell cancer drugs-axitinib (Inlyta, Pfizer) and tivozanib-that used progression-free survival as an endpoint. Regulatory approval of oncology drugs is the cornerstone of the development of new treatment agents and modalities, which lead to improvements in the standard of cancer care. The future landscape of drug development and regulatory approval will be influenced by the new breakthrough therapy designation, and choice of drug will be guided by genomic insights.

Clinical librarians as facilitators of nurses' evidence-based practice.

Science.gov (United States)

Määttä, Sylvia; Wallmyr, Gudrun

2010-12-01

The aim of this study was to explore nurses' and ward-based clinical librarians' reflections on ward-based clinical librarians as facilitators for nurses' use of evidences-based practice. Nurses' use of evidence-based practice is reported to be weak. Studies have suggested that clinical librarians may promote evidence-based practice. To date, little is known about clinical librarians participating nurses in the wards. A descriptive, qualitative design was adopted for the study. In 2007, 16 nurses who had been attended by a clinical librarian in the wards were interviewed in focus groups. Two clinical librarians were interviewed by individual interviews. In the analysis, a content analysis was used. Three themes were generated from the interviews with nurses: 'The grip of everyday work', 'To articulate clinical nursing issues' and 'The clinical librarians at a catalyst'. The nurses experienced the grip of everyday work as a hindrance and had difficulties to articulate and formulate relevant nursing issues. In such a state, the nurses found the clinical librarian presence in the ward as enhancing the awareness of and the use of evidence-based practice. Three themes emerged from the analysis with the librarians. They felt as outsiders, had new knowledge and acquired a new role as ward-based clinical librarians. Facilitation is needed if nurses' evidence-based practice is going to increase. The combined use of nurses and clinical librarians' knowledge and skills can be optimised. To achieve this, nurses' skills in consuming and implementing evidence ought to be strengthened. The fusion of the information and knowledge management skill of the ward-based clinical librarian and the clinical expertise of the nurses can be of value. With such a collaborative model, nurse and ward-based clinical librarian might join forces to increase the use of evidence-based practice. © 2010 Blackwell Publishing Ltd.

Drugs Approved for Thyroid Cancer

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... Ask about Your Treatment Research Drugs Approved for Thyroid Cancer This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Thyroid Cancer Cabozantinib-S-Malate Caprelsa (Vandetanib) Cometriq (Cabozantinib-S-Malate) Doxorubicin ...

FDA Approval: Ibrutinib for Patients with Previously Treated Mantle Cell Lymphoma and Previously Treated Chronic Lymphocytic Leukemia.

Science.gov (United States)

de Claro, R Angelo; McGinn, Karen M; Verdun, Nicole; Lee, Shwu-Luan; Chiu, Haw-Jyh; Saber, Haleh; Brower, Margaret E; Chang, C J George; Pfuma, Elimika; Habtemariam, Bahru; Bullock, Julie; Wang, Yun; Nie, Lei; Chen, Xiao-Hong; Lu, Donghao Robert; Al-Hakim, Ali; Kane, Robert C; Kaminskas, Edvardas; Justice, Robert; Farrell, Ann T; Pazdur, Richard

2015-08-15

On November 13, 2013, the FDA granted accelerated approval to ibrutinib (IMBRUVICA capsules; Pharmacyclics, Inc.) for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. On February 12, 2014, the FDA granted accelerated approval for the treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy. Ibrutinib is a first-in-class Bruton's tyrosine kinase (BTK) inhibitor that received all four expedited programs of the FDA: Fast-Track designation, Breakthrough Therapy designation, Priority Review, and Accelerated Approval. Both approvals were based on overall response rate (ORR) and duration of response (DOR) in single-arm clinical trials in patients with prior treatment. In MCL (N = 111), the complete and partial response rates were 17.1% and 48.6%, respectively, for an ORR of 65.8% [95% confidence interval (CI), 56.2%-74.5%]. The median DOR was 17.5 months (95% CI, 15.8-not reached). In CLL (N = 48), the ORR was 58.3% (95% CI, 43.2%-72.4%), and the DOR ranged from 5.6 to 24.2 months. The most common adverse reactions (≥ 30% in either trial) were thrombocytopenia, diarrhea, neutropenia, bruising, upper respiratory tract infection, anemia, fatigue, musculoskeletal pain, peripheral edema, and nausea. ©2015 American Association for Cancer Research.

Mineralized Collagen: Rationale, Current Status, and Clinical Applications

Directory of Open Access Journals (Sweden)

Zhi-Ye Qiu

2015-07-01

Full Text Available This paper presents a review of the rationale for the in vitro mineralization process, preparation methods, and clinical applications of mineralized collagen. The rationale for natural mineralized collagen and the related mineralization process has been investigated for decades. Based on the understanding of natural mineralized collagen and its formation process, many attempts have been made to prepare biomimetic materials that resemble natural mineralized collagen in both composition and structure. To date, a number of bone substitute materials have been developed based on the principles of mineralized collagen, and some of them have been commercialized and approved by regulatory agencies. The clinical outcomes of mineralized collagen are of significance to advance the evaluation and improvement of related medical device products. Some representative clinical cases have been reported, and there are more clinical applications and long-term follow-ups that currently being performed by many research groups.

High-end clinical domain information systems for effective healthcare delivery.

Science.gov (United States)

Mangalampalli, Ashish; Rama, Chakravarthy; Muthiyalian, Raja; Jain, Ajeet K

2007-01-01

The Electronic Health Record (EHR) provides doctors with a quick, reliable, secure, real-time and user-friendly source of all relevant patient data. The latest information system technologies, such as Clinical Data Warehouses (CDW), Clinical Decision-Support (CDS) systems and data-mining techniques (Online Analytical Processing (OLAP) and Online Transactional Processing (OLTP)), are used to maintain and utilise patient data intelligently, based on the users' requirements. Moreover, clinical trial reports for new drug approvals are now being submitted electronically for faster and easier processing. Also, information systems are used in educating patients about the latest developments in medical science through the internet and specially configured kiosks in hospitals and clinics.

A clinical pilot study of a modular video-CT augmentation system for image-guided skull base surgery

Science.gov (United States)

Liu, Wen P.; Mirota, Daniel J.; Uneri, Ali; Otake, Yoshito; Hager, Gregory; Reh, Douglas D.; Ishii, Masaru; Gallia, Gary L.; Siewerdsen, Jeffrey H.

2012-02-01

Augmentation of endoscopic video with preoperative or intraoperative image data [e.g., planning data and/or anatomical segmentations defined in computed tomography (CT) and magnetic resonance (MR)], can improve navigation, spatial orientation, confidence, and tissue resection in skull base surgery, especially with respect to critical neurovascular structures that may be difficult to visualize in the video scene. This paper presents the engineering and evaluation of a video augmentation system for endoscopic skull base surgery translated to use in a clinical study. Extension of previous research yielded a practical system with a modular design that can be applied to other endoscopic surgeries, including orthopedic, abdominal, and thoracic procedures. A clinical pilot study is underway to assess feasibility and benefit to surgical performance by overlaying CT or MR planning data in realtime, high-definition endoscopic video. Preoperative planning included segmentation of the carotid arteries, optic nerves, and surgical target volume (e.g., tumor). An automated camera calibration process was developed that demonstrates mean re-projection accuracy (0.7+/-0.3) pixels and mean target registration error of (2.3+/-1.5) mm. An IRB-approved clinical study involving fifteen patients undergoing skull base tumor surgery is underway in which each surgery includes the experimental video-CT system deployed in parallel to the standard-of-care (unaugmented) video display. Questionnaires distributed to one neurosurgeon and two otolaryngologists are used to assess primary outcome measures regarding the benefit to surgical confidence in localizing critical structures and targets by means of video overlay during surgical approach, resection, and reconstruction.

Biosimilars 101: considerations for U.S. oncologists in clinical practice

International Nuclear Information System (INIS)

Camacho, Luis H; Frost, Craig P; Abella, Esteban; Morrow, Phuong K; Whittaker, Sadie

2014-01-01

Biosimilars of biologics used for cancer treatment and supportive care are expected to enter the U.S. market soon. Biosimilars will be highly similar to their reference products, but unlike generic drugs, not identical. Differences between a biosimilar and its reference product may arise because of the complexity of biologics, and differences in the cell lines and processes used during manufacturing. Biosimilars will be approved in the United States through a regulatory pathway based on comparative analytical and clinical studies for their characterization and demonstration of no clinically meaningful differences from their reference products. Unlike generics, initial approval may not include interchangeability, as additional evidence may be required before a biosimilar could be approved as interchangeable with its reference product; interchangeable designation could allow pharmacy-level substitution without prescriber intervention. In some cases, the U.S. Food and Drug Administration (FDA) may extrapolate an indication that has not been formally investigated for the biosimilar but that is approved for the reference product. Robust safety monitoring of all biologics is important to track and accurately attribute adverse events, particularly because their inherent complexity and manufacturing differences make them susceptible to structural changes that can affect safety (e.g., immunogenicity). Accuracy of postapproval safety reports will partly depend on the biosimilar naming approach. Potential cost savings should be evaluated in the context of differences in manufacturers' patient-assistance programs, copayments, and institutional costs. A manufacturer's ability to ensure reliable supply of high-quality biosimilars should also be considered. Broad understanding of these issues is critical for oncologists preparing for their use in clinical practice

Tissue engineered constructs: perspectives on clinical translation.

Science.gov (United States)

Lu, Lichun; Arbit, Harvey M; Herrick, James L; Segovis, Suzanne Glass; Maran, Avudaiappan; Yaszemski, Michael J

2015-03-01

In this article, a "bedside to bench and back" approach for developing tissue engineered medical products (TEMPs) for clinical applications is reviewed. The driving force behind this approach is unmet clinical needs. Preclinical research, both in vitro and in vivo using small and large animal models, will help find solutions to key research questions. In clinical research, ethical issues regarding the use of cells and tissues, their sources, donor consent, as well as clinical trials are important considerations. Regulatory issues, at both institutional and government levels, must be addressed prior to the translation of TEMPs to clinical practice. TEMPs are regulated as drugs, biologics, devices, or combination products by the U.S. Food and Drug Administration (FDA). Depending on the mode of regulation, applications for TEMP introduction must be filed with the FDA to demonstrate safety and effectiveness in premarket clinical studies, followed by 510(k) premarket clearance or premarket approval (for medical devices), biologics license application approval (for biologics), or new drug application approval (for drugs). A case study on nerve cuffs is presented to illustrate the regulatory process. Finally, perspectives on commercialization such as finding a company partner and funding issues, as well as physician culture change, are presented.

Concept-Based Learning in Clinical Experiences: Bringing Theory to Clinical Education for Deep Learning.

Science.gov (United States)

Nielsen, Ann

2016-07-01

Concept-based learning is used increasingly in nursing education to support the organization, transfer, and retention of knowledge. Concept-based learning activities (CBLAs) have been used in clinical education to explore key aspects of the patient situation and principles of nursing care, without responsibility for total patient care. The nature of best practices in teaching and the resultant learning are not well understood. The purpose of this multiple-case study research was to explore and describe concept-based learning in the context of clinical education in inpatient settings. Four clinical groups (each a case) were observed while they used CBLAs in the clinical setting. Major findings include that concept-based learning fosters deep learning, connection of theory with practice, and clinical judgment. Strategies used to support learning, major teaching-learning foci, and preconditions for concept-based teaching and learning will be described. Concept-based learning is promising to support integration of theory with practice and clinical judgment through application experiences with patients. [J Nurs Educ. 2016;55(7):365-371.]. Copyright 2016, SLACK Incorporated.

Research ethics board approval for an international thromboprophylaxis trial.

Science.gov (United States)

Lutz, Kristina; Wilton, Kelly; Zytaruk, Nicole; Julien, Lisa; Hall, Richard; Harvey, Johanne; Skrobik, Yoanna; Vlahakis, Nicholas; Meade, Laurie; Matte, Andrea; Meade, Maureen; Burns, Karen; Albert, Martin; Cash, Bronwyn Barlow; Vallance, Shirley; Klinger, James; Heels-Ansdell, Diane; Cook, Deborah

2012-06-01

Research ethics board (REB) review of scientific protocols is essential, ensuring participants' dignity, safety, and rights. The objectives of this study were to examine the time from submission to approval, to analyze predictors of approval time, and to describe the scope of conditions from REBs evaluating an international thromboprophylaxis trial. We generated survey items through literature review and investigators' discussions, creating 4 domains: respondent and institutional demographics, the REB application process, and alternate consent models. We conducted a document analysis that involved duplicate assessment of themes from REB critique of the protocol and informed consent forms (ICF). Approval was granted from 65 REB institutions, requiring 58 unique applications. We analyzed 44 (75.9%) of 58 documents and surveys. Survey respondents completing the applications had 8 (5-12) years of experience; 77% completed 4 or more REB applications in previous 5 years. Critical care personnel were represented on 54% of REBs. The time to approval was a median (interquartile range) of 75 (42, 150) days, taking longer for sites with national research consortium membership (89.1 vs 31.0 days, P = .03). Document analysis of the application process and ICF yielded 5 themes: methodology, data management, consent procedures, cataloguing, and miscellaneous. Protocol-specific themes focused on trial implementation, external critiques, and budget. The only theme specific to the ICF was risks and benefits. The most frequent comments on the protocol and ICF were about methodology and miscellaneous issues; ICF comments also addressed study risks and benefits. More studies on methods to enhance efficiency and consistency of the REB approval processes for clinical trials are needed while still maintaining high ethical standards. Copyright © 2012 Elsevier Inc. All rights reserved.

Biomedicines?Moving Biologic Agents into Approved Treatment Options

OpenAIRE

Cornetta, Kenneth

2013-01-01

The development of biologic agents for therapeutic purposes, or biomedicines, has seen an active area of research both at the bench and in clinical trials. There is mounting evidence that biologic products can provide effective therapy for diseases that have been unresponsive to traditional pharmacologic approaches. Monoclonal antibody therapy for cancer and rheumatologic diseases has become a well accepted part of disease treatment plans. Gene therapy products have been approved in China and...

Five-year follow-up data from the U.S. clinical trial for Sientra's U.S. Food and Drug Administration-approved Silimed® brand round and shaped implants with high-strength silicone gel.

Science.gov (United States)

Stevens, W Grant; Harrington, Jennifer; Alizadeh, Kaveh; Berger, Lewis; Broadway, David; Hester, T Roderick; Kress, Donald; dʼIncelli, Rosalyn; Kuhne, JoAnn; Beckstrand, Maggi

2012-11-01

In March of 2012, the U.S. Food and Drug Administration approved Sientra's application for premarket approval for its Silimed brand silicone gel implants, based on data from the largest silicone gel breast implant study to date. This was the first approval for shaped silicone gel breast implants. This article presents the results of Sientra's study through 5 years. Sientra's study is an ongoing, 10-year, open-label, prospective, multicenter clinical study designed to assess the safety and effectiveness of Sientra's implants in patients undergoing augmentation and reconstruction. A total of 1788 subjects were implanted with 3506 implants, including 1116 primary augmentation, 363 revision-augmentation, 225 primary reconstruction, and 84 revision-reconstruction subjects. Physical evaluations and complications were recorded at each visit. Effectiveness was measured by postimplantation bra cup size and assessment of subject satisfaction and quality of life. Of the 1788 subjects, 571 underwent magnetic resonance imaging to assess silent rupture. Safety endpoints were analyzed using the Kaplan-Meier method. Across all cohorts, the risk of rupture was 1.8 percent (95 percent CI, 1.2 to 2.6 percent), the risk of capsular contracture (Baker grade III/IV) was 9.0 percent (95 percent CI, 7.6 to 10.6 percent), and the risk of reoperation was 23.8 percent (95 percent CI, 21.8 to 26.0 percent). Over 99 percent of surgeons reported satisfaction with the postoperative results, and subject satisfaction remained high 5 years after implantation. The 5-year results of Sientra's study continue to provide a comprehensive safety and effectiveness profile of Sientra's portfolio of Silimed brand shaped and round implants. Therapeutic, IV.

[Ethic review on clinical experiments of medical devices in medical institutions].

Science.gov (United States)

Shuai, Wanjun; Chao, Yong; Wang, Ning; Xu, Shining

2011-07-01

Clinical experiments are always used to evaluate the safety and validity of medical devices. The experiments have two types of clinical trying and testing. Ethic review must be done by the ethics committee of the medical department with the qualification of clinical research, and the approval must be made before the experiments. In order to ensure the safety and validity of clinical experiments of medical devices in medical institutions, the contents, process and approval criterions of the ethic review were analyzed and discussed.

CLARA: an integrated clinical research administration system

Science.gov (United States)

Bian, Jiang; Xie, Mengjun; Hogan, William; Hutchins, Laura; Topaloglu, Umit; Lane, Cheryl; Holland, Jennifer; Wells, Thomas

2014-01-01

Administration of human subject research is complex, involving not only the institutional review board but also many other regulatory and compliance entities within a research enterprise. Its efficiency has a direct and substantial impact on the conduct and management of clinical research. In this paper, we report on the Clinical Research Administration (CLARA) platform developed at the University of Arkansas for Medical Sciences. CLARA is a comprehensive web-based system that can streamline research administrative tasks such as submissions, reviews, and approval processes for both investigators and different review committees on a single integrated platform. CLARA not only helps investigators to meet regulatory requirements but also provides tools for managing other clinical research activities including budgeting, contracting, and participant schedule planning. PMID:24778201

Analysis of lomustine drug content in FDA-approved and compounded lomustine capsules.

Science.gov (United States)

KuKanich, Butch; Warner, Matt; Hahn, Kevin

2017-02-01

OBJECTIVE To determine the lomustine content (potency) in compounded and FDA-approved lomustine capsules. DESIGN Evaluation study. SAMPLE 2 formulations of lomustine capsules (low dose [7 to 11 mg] and high dose [40 to 48 mg]; 5 capsules/dose/source) from 3 compounders and from 1 manufacturer of FDA-approved capsules. PROCEDURES Lomustine content was measured by use of a validated high-pressure liquid chromatography method. An a priori acceptable range of 90% to 110% of the stated lomustine content was selected on the basis of US Pharmacopeia guidelines. RESULTS The measured amount of lomustine in all compounded capsules was less than the stated content (range, 59% to 95%) and was frequently outside the acceptable range (failure rate, 2/5 to 5/5). Coefficients of variation for lomustine content ranged from 4.1% to 16.7% for compounded low-dose capsules and from 1.1% to 10.8% for compounded high-dose capsules. The measured amount of lomustine in all FDA-approved capsules was slightly above the stated content (range, 104% to 110%) and consistently within the acceptable range. Coefficients of variation for lomustine content were 0.5% for low-dose and 2.3% for high-dose FDA-approved capsules. CONCLUSIONS AND CLINICAL RELEVANCE Compounded lomustine frequently did not contain the stated content of active drug and had a wider range of lomustine content variability than did the FDA-approved product. The sample size was small, and larger studies are needed to confirm these findings; however, we recommend that compounded veterinary formulations of lomustine not be used when appropriate doses can be achieved with FDA-approved capsules or combinations of FDA-approved capsules.

42 CFR 482.82 - Condition of participation: Data submission, clinical experience, and outcome requirements for re...

Science.gov (United States)

2010-10-01

..., clinical experience, and outcome requirements for re-approval of transplant centers. 482.82 Section 482.82... Hospitals Transplant Center Data Submission, Clinical Experience, and Outcome Requirements § 482.82 Condition of participation: Data submission, clinical experience, and outcome requirements for re-approval...

Korean Clinic Based Outcome Measure Studies

OpenAIRE

Jongbae Park

2003-01-01

Background: Evidence based medicine has become main tools for medical practice. However, conducting a highly ranked in the evidence hierarchy pyramid is not easy or feasible at all times and places. There remains a room for descriptive clinical outcome measure studies with admitting the limit of the intepretation. Aims: Presents three Korean clinic based outcome measure studies with a view to encouraging Korean clinicians to conduct similar studies. Methods: Three studies are presented...

Effect of clinically approved HDAC inhibitors on Plasmodium, Leishmania and Schistosoma parasite growth.

Science.gov (United States)

Chua, Ming Jang; Arnold, Megan S J; Xu, Weijun; Lancelot, Julien; Lamotte, Suzanne; Späth, Gerald F; Prina, Eric; Pierce, Raymond J; Fairlie, David P; Skinner-Adams, Tina S; Andrews, Katherine T

2017-04-01

Malaria, schistosomiasis and leishmaniases are among the most prevalent tropical parasitic diseases and each requires new innovative treatments. Targeting essential parasite pathways, such as those that regulate gene expression and cell cycle progression, is a key strategy for discovering new drug leads. In this study, four clinically approved anti-cancer drugs (Vorinostat, Belinostat, Panobinostat and Romidepsin) that target histone/lysine deacetylase enzymes were examined for in vitro activity against Plasmodium knowlesi, Schistosoma mansoni, Leishmania amazonensis and L. donovani parasites and two for in vivo activity in a mouse malaria model. All four compounds were potent inhibitors of P. knowlesi malaria parasites (IC 50 9-370 nM), with belinostat, panobinostat and vorinostat having 8-45 fold selectivity for the parasite over human neonatal foreskin fibroblast (NFF) or human embryonic kidney (HEK 293) cells, while romidepsin was not selective. Each of the HDAC inhibitor drugs caused hyperacetylation of P. knowlesi histone H4. None of the drugs was active against Leishmania amastigote or promastigote parasites (IC 50  > 20 μM) or S. mansoni schistosomula (IC 50  > 10 μM), however romidepsin inhibited S. mansoni adult worm parings and egg production (IC 50 ∼10 μM). Modest in vivo activity was observed in P. berghei infected mice dosed orally with vorinostat or panobinostat (25 mg/kg twice daily for four days), with a significant reduction in parasitemia observed on days 4-7 and 4-10 after infection (P < 0.05), respectively. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effect of clinically approved HDAC inhibitors on Plasmodium, Leishmania and Schistosoma parasite growth

Directory of Open Access Journals (Sweden)

Ming Jang Chua

2017-04-01

Full Text Available Malaria, schistosomiasis and leishmaniases are among the most prevalent tropical parasitic diseases and each requires new innovative treatments. Targeting essential parasite pathways, such as those that regulate gene expression and cell cycle progression, is a key strategy for discovering new drug leads. In this study, four clinically approved anti-cancer drugs (Vorinostat, Belinostat, Panobinostat and Romidepsin that target histone/lysine deacetylase enzymes were examined for in vitro activity against Plasmodium knowlesi, Schistosoma mansoni, Leishmania amazonensis and L. donovani parasites and two for in vivo activity in a mouse malaria model. All four compounds were potent inhibitors of P. knowlesi malaria parasites (IC50 9–370 nM, with belinostat, panobinostat and vorinostat having 8–45 fold selectivity for the parasite over human neonatal foreskin fibroblast (NFF or human embryonic kidney (HEK 293 cells, while romidepsin was not selective. Each of the HDAC inhibitor drugs caused hyperacetylation of P. knowlesi histone H4. None of the drugs was active against Leishmania amastigote or promastigote parasites (IC50 > 20 μM or S. mansoni schistosomula (IC50 > 10 μM, however romidepsin inhibited S. mansoni adult worm parings and egg production (IC50 ∼10 μM. Modest in vivo activity was observed in P. berghei infected mice dosed orally with vorinostat or panobinostat (25 mg/kg twice daily for four days, with a significant reduction in parasitemia observed on days 4–7 and 4–10 after infection (P < 0.05, respectively.

Clinical intuition versus statistics: different modes of tacit knowledge in clinical epidemiology and evidence-based medicine.

Science.gov (United States)

Braude, Hillel D

2009-01-01

Despite its phenomenal success since its inception in the early nineteen-nineties, the evidence-based medicine movement has not succeeded in shaking off an epistemological critique derived from the experiential or tacit dimensions of clinical reasoning about particular individuals. This critique claims that the evidence-based medicine model does not take account of tacit knowing as developed by the philosopher Michael Polanyi. However, the epistemology of evidence-based medicine is premised on the elimination of the tacit dimension from clinical judgment. This is demonstrated through analyzing the dichotomy between clinical and statistical intuition in evidence-based medicine's epistemology of clinical reasoning. I argue that clinical epidemiology presents a more nuanced epistemological model for the application of statistical epidemiology to the clinical context. Polanyi's theory of tacit knowing is compatible with the model of clinical reasoning associated with clinical epidemiology, but not evidence-based medicine.

Defending submission-year analyses of new drug approvals.

Science.gov (United States)

Carpenter, Daniel P

2003-01-01

In response to the critique of Mary Olsen, Daniel Carpenter, on behalf of his co-authors, addresses the issue of analysis based on the year a new drug is submitted for Food and Drug Administration (FDA) approval, not the year it is approved. Both substantive knowledge of the FDA drug review process and sound social science theory favor submission-year averaging. The history and bureaucratic mechanics of the Center for Drug Evaluation and Review (CDER) conform to the author's assumption. The statistical theory of optimal experimentation also points to the beginning of review as a locus for effects upon decisions.

Assessment of hospital pharmacists' clinical knowledge and ...

African Journals Online (AJOL)

reproduction in any medium, provided the original work is properly credited. ... drug use, which improves the quality of life. ... balance of clinical knowledge, practical skills, ... Ethical approval ... plans, clinical decision making, and finding the.

Comparison of the new Japanese legislation for expedited approval of regenerative medicine products with the existing systems in the USA and European Union.

Science.gov (United States)

Jokura, Yoji; Yano, Kazuo; Yamato, Masayuki

2018-02-01

Legislation for expedited-approval pathways and programmes for drugs, biologics or medical devices has been enacted for rapid commercialization of innovative products in the United States of America (USA) and the European Union (EU). However, less innovative products are increasingly benefitting from these expedited-approval pathways, and obligations to collect and report post-marketing data on approved products are being bypassed frequently. The Japanese government recently enacted legislation for a new conditional and time-limited approval pathway dedicated to regenerative medicine products. The current study examines this new legislation and compares it with existing US and EU regulatory frameworks, with a particular focus on how it addresses the limitations of existing systems. Regulations, guidance documents and approval information were gathered from the websites of the respective authorities in the USA, the EU and Japan, and the systems were categorized through qualitative analysis. The pathways and programmes from each region were categorized into four groups, based on the requirement of pre- or post-marketing clinical data. Expedited-approval pathways in the USA and the EU provide similar qualification criteria, such as severity of target disease; however, such criteria are not specified for the new pathway in Japan. Only the Japanese pathway stipulates a time limitation on exceptional approval, requiring post-marketing study for conditional and time-limited products. Continuous improvement is necessary to solve previously addressed issues within the expedited-approval pathways and programmes and to ensure that innovative medical products are rigourously screened, but also readily available to patients in need. The time limitation of conditional approval could be a potential solution to some of these problems. Copyright © 2017 The Authors. Tissue Engineering Regenerative Medicine published by John Wiley & Sons, Ltd. Copyright © 2017 The Authors. Tissue

Radiation requirements for uranium project approvals

International Nuclear Information System (INIS)

Hondros, J.

2014-01-01

Uranium mining projects in Australia must receive approval under both state and national laws based on a wide ranging impact assessment of the project. The process may take a number of years and involves multiple levels and parts of government and public consultation and scrutiny. The impact assessment is broad and usually covers; environmental, social, health, public safety and economic aspects. Information provided in the approvals documentation needs to be presented in a credible and understandable manner for all audiences. This means making complex information simpler, while making sure that it maintains its technical integrity. Poorly communicated information, which is overly complex, overly simplified or incomplete, can result in significant delays to the project approval which can potentially impact on project timelines. For uranium projects, along with other projects involving radioactive materials, such as minerals sands and rare earths, radiation and its impacts usually draw a disproportionate amount of both government and public scrutiny compared to other potential impacts and risks. It is therefore of key importance that radiation assessments are properly performed and results clearly presented and communicated with sufficient detail for stakeholders to make informed decisions. It is also important to ensure that the radiation risk is presented in perspective with other risks of the project. This presentation outlines a structure for a radiation impact assessment based on experience from a number of projects in Australia. The structure aims to be clear and simple and ensure the right balance between scientific fact, digestible information and demonstrable competence. (author)

Miracle drug: Brazil approves never-tested cancer medicine.

Science.gov (United States)

Kuchenbecker, Ricardo S; Mota, Daniel M

2017-07-01

Background Brazil recently approved synthetic phosphoetanolamine, a popularly dubbed 'cancer pill', a substance that has been shown to kill cancer cells in lab animal models but was not yet formally accessed in humans, and thus despite the existence of any evidence of its efficacy and safety. Methods The authors describe the recent decision of Brazil to aprove phosphoetanolamine in the context of growing 'judicialization' to promote access to medicines and thus reinforcing a growing sense of legal uncertainty. Results The approval of phosphoetanolamine despite the existence of any evidence of its efficacy and safety represents to the authors one of the saddest and surrealistic episodes in Brazil's recent public health history. Brazil's current economic crisis is fueling the 'judicialization' to promote access to medicines and thus reinforcing a growing sense of legal uncertainty in the context of rising economic constrains and a progressive failing state. The authors state that the Phosphoetanolamine's approval bill violates current legal prohibition of commercialisation of drugs without the Brazilian national drug regulatory agency's approval and thus may represent a potential menace to Brazil's pharmacogovernance and the country's governance to health technology assessment at the Brazilian national health systems. Conclusion Phosphoetanolamine's approval illustrates that the combination of flawed decision making, economic crisis and political interference may threaten weak governance mechanisms for drug regulation and health technology assessment and thus representing an extra burden in the sustainability of universal access-based national health systems.

Clinical track faculty: merits and issues.

Science.gov (United States)

Lee, Won-Hee; Kim, Cho Ja; Roh, Young Sook; Shin, Hyunsook; Kim, Mi Ja

2007-01-01

Clinical track faculty (CTF) has been in operation for more than two decades in the United States, and 12 of the top 20 schools of nursing with the highest National Institutes of Health funding in the United States have CTF in place. Yet, only limited articles have been published regarding the merits and issues related to its operation. This article examines the advantages/merits of establishing CTF in schools of nursing, discusses the qualification criteria and types of appointment for CTF, and analyzes issues related to operating CTF in Korea. A questionnaire survey and two workshops were conducted involving faculty from a college of nursing and clinical nurse managers from university-affiliated medical centers and community agencies. Most of the respondents indicated that establishing CTF was advantageous. Merits included the following: increasing reality-based clinical education and training; decreasing the reality shock of students; increasing student satisfaction; and linking education, practice, and research more effectively. Major issues were as follows: getting the approval of medical centers/universities; developing an agreement on CTF operation between the college of nursing and clinical agencies; clarifying types and criteria of appointment and promotion; and developing a statement on role and compensation policies. Most issues are similar to what U.S. schools of nursing have faced, except for the first one. In conclusion, establishing CTF in Korea appears to be highly desirable. Merits outweigh issues/concerns, and Korean nursing schools may look for an opportune time for obtaining the approval of medical centers/universities. Nursing schools in other countries that face a similar challenge of providing clinical teaching with high research performance may consider instituting CTF.

[Discussion on developing a data management plan and its key factors in clinical study based on electronic data capture system].

Science.gov (United States)

Li, Qing-na; Huang, Xiu-ling; Gao, Rui; Lu, Fang

2012-08-01

Data management has significant impact on the quality control of clinical studies. Every clinical study should have a data management plan to provide overall work instructions and ensure that all of these tasks are completed according to the Good Clinical Data Management Practice (GCDMP). Meanwhile, the data management plan (DMP) is an auditable document requested by regulatory inspectors and must be written in a manner that is realistic and of high quality. The significance of DMP, the minimum standards and the best practices provided by GCDMP, the main contents of DMP based on electronic data capture (EDC) and some key factors of DMP influencing the quality of clinical study were elaborated in this paper. Specifically, DMP generally consists of 15 parts, namely, the approval page, the protocol summary, role and training, timelines, database design, creation, maintenance and security, data entry, data validation, quality control and quality assurance, the management of external data, serious adverse event data reconciliation, coding, database lock, data management reports, the communication plan and the abbreviated terms. Among them, the following three parts are regarded as the key factors: designing a standardized database of the clinical study, entering data in time and cleansing data efficiently. In the last part of this article, the authors also analyzed the problems in clinical research of traditional Chinese medicine using the EDC system and put forward some suggestions for improvement.

A planning support system to optimize approval of private housing development projects

Science.gov (United States)

Hussnain, M. Q.; Wakil, K.; Waheed, A.; Tahir, A.

2016-06-01

Out of 182 million population of Pakistan, 38% reside in urban areas having an average growth rate of 1.6%, raising the urban housing demand significantly. Poor state response to fulfil the housing needs has resulted in a mushroom growth of private housing schemes (PHS) over the years. Consequently, only in five major cities of Punjab, there are 383 legal and 150 illegal private housing development projects against 120 public sector housing schemes. A major factor behind the cancerous growth of unapproved PHS is the prolonged and delayed approval process in concerned approval authorities requiring 13 months on average. Currently, manual and paper-based approaches are used for vetting and for granting the permission which is highly subjective and non-transparent. This study aims to design a flexible planning support system (PSS) to optimize the vetting process of PHS projects under any development authority in Pakistan by reducing time and cost required for site and documents investigations. Relying on the review of regulatory documents and interviews with professional planners and land developers, this study describes the structure of a PSS developed using open- source geo-spatial tools such as OpenGeo Suite, PHP, and PostgreSQL. It highlights the development of a Knowledge Module (based on regulatory documents) containing equations related to scheme type, size (area), location, access road, components of layout plan, planning standards and other related approval checks. Furthermore, it presents the architecture of the database module and system data requirements categorized as base datasets (built-in part of PSS) and input datasets (related to the housing project under approval). It is practically demonstrated that developing a customized PSS to optimize PHS approval process in Pakistan is achievable with geospatial technology. With the provision of such a system, the approval process for private housing schemes not only becomes quicker and user-friendly but also

Approving cancer treatments based on endpoints other than overall survival: an analysis of historical data using the PACE Continuous Innovation Indicators™ (CII).

Science.gov (United States)

Brooks, Neon; Campone, Mario; Paddock, Silvia; Shortenhaus, Scott; Grainger, David; Zummo, Jacqueline; Thomas, Samuel; Li, Rose

2017-01-01

There is an active debate about the role that endpoints other than overall survival (OS) should play in the drug approval process. Yet the term 'surrogate endpoint' implies that OS is the only critical metric for regulatory approval of cancer treatments. We systematically analyzed the relationship between U.S. Food and Drug Administration (FDA) approval and publication of OS evidence to understand better the risks and benefits of delaying approval until OS evidence is available. Using the PACE Continuous Innovation Indicators (CII) platform, we analyzed the effects of cancer type, treatment goal, and year of approval on the lag time between FDA approval and publication of first significant OS finding for 53 treatments approved between 1952 and 2016 for 10 cancer types (n = 71 approved indications). Greater than 59% of treatments were approved before significant OS data for the approved indication were published. Of the drugs in the sample, 31% had lags between approval and first published OS evidence of 4 years or longer. The average number of years between approval and first OS evidence varied by cancer type and did not reliably predict the eventual amount of OS evidence accumulated. Striking the right balance between early access and minimizing risk is a central challenge for regulators worldwide. We illustrate that endpoints other than OS have long helped to provide timely access to new medicines, including many current standards of care. We found that many critical drugs are approved many years before OS data are published, and that OS may not be the most appropriate endpoint in some treatment contexts. Our examination of approved treatments without significant OS data suggests contexts where OS may not be the most relevant endpoint and highlights the importance of using a wide variety of fit-for-purpose evidence types in the approval process.

Current concepts in clinical research: web-based, automated, arthroscopic surgery prospective database registry.

Science.gov (United States)

Lubowitz, James H; Smith, Patrick A

2012-03-01

In 2011, postsurgical patient outcome data may be compiled in a research registry, allowing comparative-effectiveness research and cost-effectiveness analysis by use of Health Insurance Portability and Accountability Act-compliant, institutional review board-approved, Food and Drug Administration-approved, remote, Web-based data collection systems. Computerized automation minimizes cost and minimizes surgeon time demand. A research registry can be a powerful tool to observe and understand variations in treatment and outcomes, to examine factors that influence prognosis and quality of life, to describe care patterns, to assess effectiveness, to monitor safety, and to change provider practice through feedback of data. Registry of validated, prospective outcome data is required for arthroscopic and related researchers and the public to advocate with governments and health payers. The goal is to develop evidence-based data to determine the best methods for treating patients. Copyright © 2012 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Case studies on clinical evaluation of biosimilar monoclonal antibody: scientific considerations for regulatory approval.

Science.gov (United States)

Kudrin, Alex; Knezevic, Ivana; Joung, Jeewon; Kang, Hye-Na

2015-01-01

The objective of this paper is to provide considerations based on comprehensive case studies important for regulatory evaluation of monoclonal antibodies as similar biotherapeutic products (SBPs) with a special emphasis on clinical aspects. Scientific principles from WHO Guidelines on SBPs were used as a basis for the exercise. Working groups consisted of regulators, manufacturers and academia. The following topics were discussed by the working groups: clinical criteria for biosimilarity, extrapolation approach and the overall regulatory decision making process. In order to determine typical pitfalls in the design of a SBP clinical programme and evaluate the gap of knowledge, amongst different industry and regulatory stakeholders on the appraisal of the data arising from SBP clinical studies, we have presented two fictional but realistic clinical case studies. The first case consists of the fictional development programme for an infliximab SBP candidate. The second case describes clinical studies proposed for a fictional rituximab SBP candidate. In the first scenario a highly similar quality profile has been taken forward into clinical studies whereas there was an important residual difference in functional attributes for the rituximab SBP candidate. These case studies were presented at the WHO implementation workshop for the WHO guidelines on evaluation of similar biotherapeutic products held in Seoul, Republic of Korea, in May 2014. The goal was to illustrate the interpretation of the clinical data arising from studies with SBP candidates and elicit knowledge gaps in clinical assessment. This paper reflects the outcome of the exercise and discussions held in Seoul and offers an analysis of the case studies as a learning opportunity on clinical development and evaluation of SBPs. Copyright © 2014 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Electronic Approval of Invoices (AEF)

CERN Document Server

2004-01-01

With a view to the simplification of administrative procedures, AS and FI Departments have completed the second phase of the new procedure for the electronic approval of invoices via the EDH application. The aim of this new procedure is to rationalise the invoice approval process, notably by eliminating paper copies from the approval circuit. This will simplify the processing of invoices and facilitate their timely settlement, while at the same time maintaining a high level of security. Phase II includes handling the electronic approval process of invoices whose amounts do not correspond exactly to those of the associated orders. In such cases, budgetary approval is required for the entire invoiced amount. Further information can be obtained at : http://ais.cern.ch/projs/AEF/help/F_help.htm Phase II of the procedure will be introduced gradually with effect from April 2004. Finance Department, Accounts Payable Section Tel: 72295 Organisation and Procedures Tel: 75885 Information Technologies Department,...

78 FR 28503 - Approval and Promulgation of Air Quality Implementation Plans; Indiana; Lake and Porter Counties...

Science.gov (United States)

2013-05-15

...: FRL-9812-4] Approval and Promulgation of Air Quality Implementation Plans; Indiana; Lake and Porter...). ACTION: Direct final rule. SUMMARY: EPA is approving Indiana's request to revise the Lake and Porter... approving new MOVES2010a-based budgets for the Lake and Porter County, Indiana 1997 8-hour ozone maintenance...

40 CFR 80.585 - What is the process for approval of a test method for determining the sulfur content of diesel or...

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 16 2010-07-01 2010-07-01 false What is the process for approval of a... voluntary consensus-based standards bodies. For such a method to be approved, the following information must... approved: Any test method approved by a voluntary consensus-based standards body, such as the American...

Accurate cloud-based smart IMT measurement, its validation and stroke risk stratification in carotid ultrasound: A web-based point-of-care tool for multicenter clinical trial.

Science.gov (United States)

Saba, Luca; Banchhor, Sumit K; Suri, Harman S; Londhe, Narendra D; Araki, Tadashi; Ikeda, Nobutaka; Viskovic, Klaudija; Shafique, Shoaib; Laird, John R; Gupta, Ajay; Nicolaides, Andrew; Suri, Jasjit S

2016-08-01

This study presents AtheroCloud™ - a novel cloud-based smart carotid intima-media thickness (cIMT) measurement tool using B-mode ultrasound for stroke/cardiovascular risk assessment and its stratification. This is an anytime-anywhere clinical tool for routine screening and multi-center clinical trials. In this pilot study, the physician can upload ultrasound scans in one of the following formats (DICOM, JPEG, BMP, PNG, GIF or TIFF) directly into the proprietary cloud of AtheroPoint from the local server of the physician's office. They can then run the intelligent and automated AtheroCloud™ cIMT measurements in point-of-care settings in less than five seconds per image, while saving the vascular reports in the cloud. We statistically benchmark AtheroCloud™ cIMT readings against sonographer (a registered vascular technologist) readings and manual measurements derived from the tracings of the radiologist. One hundred patients (75 M/25 F, mean age: 68±11 years), IRB approved, Toho University, Japan, consisted of Left/Right common carotid artery (CCA) artery (200 ultrasound scans), (Toshiba, Tokyo, Japan) were collected using a 7.5MHz transducer. The measured cIMTs for L/R carotid were as follows (in mm): (i) AtheroCloud™ (0.87±0.20, 0.77±0.20); (ii) sonographer (0.97±0.26, 0.89±0.29) and (iii) manual (0.90±0.20, 0.79±0.20), respectively. The coefficient of correlation (CC) between sonographer and manual for L/R cIMT was 0.74 (Preliability and accuracy of the results. The proposed AtheroCloud™ system is completely reliable, automated, fast (3-5 seconds depending upon the image size having an internet speed of 180Mbps), accurate, and an intelligent, web-based clinical tool for multi-center clinical trials and routine telemedicine clinical care. Copyright © 2016 Elsevier Ltd. All rights reserved.

Non-clinical influences on clinical decision-making: a major challenge to evidence-based practice.

Science.gov (United States)

Hajjaj, F M; Salek, M S; Basra, M K A; Finlay, A Y

2010-05-01

This article reviews an aspect of daily clinical practice which is of critical importance in virtually every clinical consultation, but which is seldom formally considered. Non-clinical influences on clinical decision-making profoundly affect medical decisions. These influences include patient-related factors such as socioeconomic status, quality of life and patient's expectations and wishes, physician-related factors such as personal characteristics and interaction with their professional community, and features of clinical practice such as private versus public practice as well as local management policies. This review brings together the different strands of knowledge concerning non-clinical influences on clinical decision-making. This aspect of decision-making may be the biggest obstacle to the reality of practising evidence-based medicine. It needs to be understood in order to develop clinical strategies that will facilitate the practice of evidence-based medicine.

40 CFR 145.31 - Approval process.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Approval process. 145.31 Section 145.31 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE UIC PROGRAM REQUIREMENTS Program Approval, Revision and Withdrawal § 145.31 Approval process. (a...

40 CFR 52.2122 - Approval status.

Science.gov (United States)

2010-07-01

... sources covered by CTGs issued by the previous January. (b) EPA disapproved South Carolina's generic...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) South Carolina § 52.2122 Approval status. (a) With the exceptions set forth in this subpart, the Administrator approves South Carolina's plans for...

Polypharmacology of Approved Anticancer Drugs.

Science.gov (United States)

Amelio, Ivano; Lisitsa, Andrey; Knight, Richard A; Melino, Gerry; Antonov, Alexey V

2017-01-01

The major drug discovery efforts in oncology have been concentrated on the development of selective molecules that are supposed to act specifically on one anticancer mechanism by modulating a single or several closely related drug targets. However, a bird's eye view on data from multiple available bioassays implies that most approved anticancer agents do, in fact, target many more proteins with different functions. Here we will review and systematize currently available information on the targets of several anticancer drugs along with revision of their potential mechanisms of action. Polypharmacology of the current antineoplastic agents suggests that drug clinical efficacy in oncology can be achieved only via modulation of multiple cellular mechanisms. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

75 FR 48302 - Notice of Request for Extension of Approval of an Information Collection; Credit Account Approval...

Science.gov (United States)

2010-08-10

....gov ). FOR FURTHER INFORMATION CONTACT: For information on credit account approval for reimbursable..., at (301) 851-2908. SUPPLEMENTARY INFORMATION: Title: Credit Account Approval for Reimbursable... Inspection Service [Docket No. APHIS-2010-0071] Notice of Request for Extension of Approval of an Information...

78 FR 54617 - Notice of Request for Extension of Approval of an Information Collection; Credit Account Approval...

Science.gov (United States)

2013-09-05

...] Notice of Request for Extension of Approval of an Information Collection; Credit Account Approval for... (202) 799-7039 before coming. FOR FURTHER INFORMATION CONTACT: For information on credit account... Coordinator, at (301) 851-2908. SUPPLEMENTARY INFORMATION: Title: Credit Account Approval for Reimbursable...

Evidence-based clinical practice, [corrected] evidence-based medicine and the Cochrane collaboration.

Science.gov (United States)

Gambrill, E

1999-03-01

Encouraging professionals in training and later to consider practice-related research findings when making important clinical decisions is an on-going concern. Evidenced-Based Medicine (EBM) and the Cochrane Collaboration (CC) provide a source of tools and ideas for doing so, as well as a roster of colleagues who share this interest. Evidenced-based medicine involves integrating clinical expertise with the best available external evidence from systematic research as well as considering the values and expectations of patients/clients. Advantage can be taken of educational formats developed in EBM, such as problem-based learning and critical-appraisal workshops in which participants learn how to ask key answerable questions related to important clinical practice questions (e.g., regarding effectiveness, accuracy of assessment measures, prediction, prevention, and quality of clinical practice guidelines) and to access and critically appraise related research. The Cochrane Collaboration is a world-wide network of centers that prepare, maintain, and disseminate high-quality systematic reviews on the efficacy of healthcare. These databases allow access to evidence related to clinical practice decisions. Forging reciprocal working relationships with those involved in EBM reciprocal and the CC should contribute to the pursuit of shared goals such as basing clinical decisions on the best-available evidence and involving clients as informed consumers.

40 CFR 52.1772 - Approval status.

Science.gov (United States)

2010-07-01

...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) North Carolina § 52.1772 Approval status. (a) With the exceptions set forth in this subpart, the Administrator approves North Carolina's plans for... CTGs issued by the previous January. (b) New Source review permits issued pursuant to section 173 of...

Employment-based reinforcement of adherence to an FDA approved extended release formulation of naltrexone in opioid-dependent adults: a randomized controlled trial.

Science.gov (United States)

DeFulio, Anthony; Everly, Jeffrey J; Leoutsakos, Jeannie-Marie S; Umbricht, Annie; Fingerhood, Michael; Bigelow, George E; Silverman, Kenneth

2012-01-01

Naltrexone provides excellent opioid blockade, but its clinical utility is limited because opioid-dependent patients typically refuse it. An injectable suspension of naltrexone for extended release (XR-NTX) was recently approved by the FDA for treatment of opioid dependence. XR-NTX treatment may require concurrent behavioral intervention to maximize adherence and effectiveness, thus we sought to evaluate employment-based reinforcement as a method of improving adherence to XR-NTX in opiate dependent adults. Opioid-dependent adults (n=38) were detoxified and inducted onto oral naltrexone, then randomly assigned to contingency or prescription conditions. Participants received up to six doses of XR-NTX at four-week intervals. All participants could earn vouchers for attendance and performance at a therapeutic workplace. Contingency participants were required to accept XR-NTX injections to access the workplace and earn vouchers. Prescription participants could earn vouchers independent of their acceptance of XR-NTX injections. Contingency participants accepted significantly more naltrexone injections than prescription participants (87% versus 52%, p=.002), and were more likely to accept all injections (74% versus 26%, p=.004). Participants in the two conditions provided similar percentages of samples negative for opiates (72% versus 65%) and for cocaine (58% versus 54%). Opiate positivity was significantly more likely when samples were also cocaine positive, independent of naltrexone blockade (p=.002). Long-term adherence to XR-NTX in unemployed opiate dependent adults is low under usual care conditions. Employment-based reinforcement can maintain adherence to XR-NTX. Ongoing cocaine use appears to interfere with the clinical effectiveness of XR-NTX on opiate use. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Annotating Evidence Based Clinical Guidelines : A Lightweight Ontology

NARCIS (Netherlands)

Hoekstra, R.; de Waard, A.; Vdovjak, R.; Paschke, A.; Burger, A.; Romano, P.; Marshall, M.S.; Splendiani, A.

2012-01-01

This paper describes a lightweight ontology for representing annotations of declarative evidence based clinical guidelines. We present the motivation and requirements for this representation, based on an analysis of several guidelines. The ontology provides the means to connect clinical questions

9 CFR 147.52 - Approved tests.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Approved tests. 147.52 Section 147.52 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Approved Tests § 147.52 Approved tests. (a) The procedures for the bacteriological examination of poultry...

A common feature pharmacophore for FDA-approved drugs inhibiting the Ebola virus.

Science.gov (United States)

Ekins, Sean; Freundlich, Joel S; Coffee, Megan

2014-01-01

We are currently faced with a global infectious disease crisis which has been anticipated for decades. While many promising biotherapeutics are being tested, the search for a small molecule has yet to deliver an approved drug or therapeutic for the Ebola or similar filoviruses that cause haemorrhagic fever. Two recent high throughput screens published in 2013 did however identify several hits that progressed to animal studies that are FDA approved drugs used for other indications. The current computational analysis uses these molecules from two different structural classes to construct a common features pharmacophore. This ligand-based pharmacophore implicates a possible common target or mechanism that could be further explored. A recent structure based design project yielded nine co-crystal structures of pyrrolidinone inhibitors bound to the viral protein 35 (VP35). When receptor-ligand pharmacophores based on the analogs of these molecules and the protein structures were constructed, the molecular features partially overlapped with the common features of solely ligand-based pharmacophore models based on FDA approved drugs. These previously identified FDA approved drugs with activity against Ebola were therefore docked into this protein. The antimalarials chloroquine and amodiaquine docked favorably in VP35. We propose that these drugs identified to date as inhibitors of the Ebola virus may be targeting VP35. These computational models may provide preliminary insights into the molecular features that are responsible for their activity against Ebola virus in vitro and in vivo and we propose that this hypothesis could be readily tested.

Medical simulation-based education improves medicos' clinical skills.

Science.gov (United States)

Wang, Zhaoming; Liu, Qiaoyu; Wang, Hai

2013-03-01

Clinical skill is an essential part of clinical medicine and plays quite an important role in bridging medicos and physicians. Due to the realities in China, traditional medical education is facing many challenges. There are few opportunities for students to practice their clinical skills and their dexterities are generally at a low level. Medical simulation-based education is a new teaching modality and helps to improve medicos' clinical skills to a large degree. Medical simulation-based education has many significant advantages and will be further developed and applied.

7 CFR 1710.406 - Loan approval.

Science.gov (United States)

2010-01-01

... 7 Agriculture 11 2010-01-01 2010-01-01 false Loan approval. 1710.406 Section 1710.406 Agriculture... GENERAL AND PRE-LOAN POLICIES AND PROCEDURES COMMON TO ELECTRIC LOANS AND GUARANTEES Application Requirements and Procedures for Loans § 1710.406 Loan approval. (a) A loan is approved when the Administrator...

40 CFR 123.61 - Approval process.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 21 2010-07-01 2010-07-01 false Approval process. 123.61 Section 123... REQUIREMENTS Program Approval, Revision, and Withdrawal § 123.61 Approval process. (a) After determining that a...; and (6) Briefly outline the fundamental aspects of the State's proposed program, and the process for...

EXAMPLE OF A RISK-BASED DISPOSAL APPROVAL: SOLIDIFICATION OF HANFORD SITE TRANSURANIC (TRU) WASTE

International Nuclear Information System (INIS)

PRIGNANO AL

2007-01-01

The Hanford Site requested, and the U.S. Environmental Protection Agency (EPA) Region 10 approved, a Toxic Substances Control Act of 1976 (TSCA) risk-based disposal approval (RBDA) for solidifying approximately four cubic meters of waste from a specific area of one of the K East Basin: the North Loadout Pit (NLOP). The NLOP waste is a highly radioactive sludge that contained polychlorinated biphenyls (PCBs) regulated under TSCA. The prescribed disposal method for liquid PCB waste under TSCA regulations is either thermal treatment or decontamination. Due to the radioactive nature of the waste, however, neither thermal treatment nor decontamination was a viable option. As a result, the proposed treatment consisted of solidifying the material to comply with waste acceptance criteria at the Waste Isolation Pilot Plant (WPP) in Carlsbad, New Mexico, or possibly the Environmental Restoration Disposal Facility at the Hanford Site, depending on the resulting transuranic (TRU) content of the stabilized waste. The RBDA evaluated environmental risks associated with potential airborne PCBs. In addition, the RBDA made use of waste management controls already in place at the treatment unit. The treatment unit, the T Plant Complex, is a Resource Conservation and Recovery Act of 1976 (RCRA)-permitted facility used for storing and treating radioactive waste. The EPA found that the proposed activities did not pose an unreasonable risk to human health or the environment. Treatment took place from October 26,2005 to June 9,2006, and 332 208-liter (55-gallon) containers of solidified waste were produced. All treated drums assayed to date are TRU and will be disposed at WIPP

Introducing a performance-based objective clinical examination into ...

African Journals Online (AJOL)

Purpose: To describe how a formative Objective Structured Clinical Examination was applied to fourth year pharmacy students at a university in Northern Cyprus. Methods: A blueprint-guided performance-based objective clinical examination was implemented. Group-prepared case scenarios based on course objectives ...

Clinical Subtypes of Dementia with Lewy Bodies Based on the Initial Clinical Presentation.

Science.gov (United States)

Morenas-Rodríguez, Estrella; Sala, Isabel; Subirana, Andrea; Pascual-Goñi, Elba; Sánchez-Saudinós, MaBelén; Alcolea, Daniel; Illán-Gala, Ignacio; Carmona-Iragui, María; Ribosa-Nogué, Roser; Camacho, Valle; Blesa, Rafael; Fortea, Juan; Lleó, Alberto

2018-06-04

Dementia with Lewy bodies (DLB) is a heterogeneous disease in which clinical presentation, symptoms, and evolution widely varies between patients. To investigate the existence of clinical subtypes in DLB based on the initial clinical presentation. 81 patients with a clinical diagnosis of probable DLB were consecutively included. All patients underwent a neurological evaluation including a structured questionnaire about neuropsychiatric symptoms and sleep, an assessment of motor impairment (Unified Parkinson Disease Rating Scale subscale III), and a formal neuropsychological evaluation. Onset of core symptoms (hallucinations, parkinsonism, and fluctuations) and dementia were systematically reviewed from medical records. We applied a K-means clustering method based on the initial clinical presentation. Cluster analysis yielded three different groups. Patients in cluster I (cognitive-predominant, n = 46) presented more frequently with cognitive symptoms (95.7%, n = 44, p presented more frequently with psychotic symptoms (77.3%, n = 17), and had a shorter duration until the onset of hallucinations (p clinical DLB can be defined when considering the differential initial presentations. The proposed subtypes have distinct clinical profiles and progression patterns.

A data grid for imaging-based clinical trials

Science.gov (United States)

Zhou, Zheng; Chao, Sander S.; Lee, Jasper; Liu, Brent; Documet, Jorge; Huang, H. K.

2007-03-01

Clinical trials play a crucial role in testing new drugs or devices in modern medicine. Medical imaging has also become an important tool in clinical trials because images provide a unique and fast diagnosis with visual observation and quantitative assessment. A typical imaging-based clinical trial consists of: 1) A well-defined rigorous clinical trial protocol, 2) a radiology core that has a quality control mechanism, a biostatistics component, and a server for storing and distributing data and analysis results; and 3) many field sites that generate and send image studies to the radiology core. As the number of clinical trials increases, it becomes a challenge for a radiology core servicing multiple trials to have a server robust enough to administrate and quickly distribute information to participating radiologists/clinicians worldwide. The Data Grid can satisfy the aforementioned requirements of imaging based clinical trials. In this paper, we present a Data Grid architecture for imaging-based clinical trials. A Data Grid prototype has been implemented in the Image Processing and Informatics (IPI) Laboratory at the University of Southern California to test and evaluate performance in storing trial images and analysis results for a clinical trial. The implementation methodology and evaluation protocol of the Data Grid are presented.

MO-A-BRC-00: TG167: Clinical Recommendations for Innovative Brachytherapy Devices and Applicators

Energy Technology Data Exchange (ETDEWEB)

NONE

2016-06-15

Although a multicenter, Phase III, prospective, randomized trial is the gold standard for evidence-based medicine, it is rarely used to evaluate innovative radiotherapy devices because of many practical and ethical reasons. It is usually sufficient to compare the dose distributions and dose rates for determining equivalence of the innovative device to an existing one. Thus, quantitative evaluation of the dosimetric characteristics of an innovative brachytherapy device or application is a critical part in which physicists are actively involved. The physicist’s role, along with physician colleagues, in this process is highlighted for innovative products or applications and includes evaluation of 1) dosimetric considerations for clinical implementation (including calibrations, dose calculations, and radiobiological aspects) to comply with existing societal dosimetric prerequisites for sources in routine clinical use, 2) risks and benefits from regulatory and safety perspectives, and 3) resource assessment and preparedness. Further, calibration methods should be traceable to a primary standards dosimetry laboratory such as NIST in the U.S. or to other primary standards dosimetry laboratory located elsewhere. Clinical users should follow standards as approved by their country’s regulatory agencies that approved such a brachytherapy device. Integration of this system into the medical source calibration infrastructure of secondary standard dosimetry laboratories such as the ADCLs is encouraged before a source is introduced into widespread routine clinical use. The AAPM and GEC-ESTRO have developed guidelines for the safe and consistent application of brachytherapy using innovative brachytherapy devices and applications. The current report covers regulatory approvals, calibration, dose calculations, radiobiological issues, and overall safety concerns that should be addressed during the commissioning stage preceding clinical use. These guidelines are based on review of

MO-A-BRC-00: TG167: Clinical Recommendations for Innovative Brachytherapy Devices and Applicators

International Nuclear Information System (INIS)

2016-01-01

Although a multicenter, Phase III, prospective, randomized trial is the gold standard for evidence-based medicine, it is rarely used to evaluate innovative radiotherapy devices because of many practical and ethical reasons. It is usually sufficient to compare the dose distributions and dose rates for determining equivalence of the innovative device to an existing one. Thus, quantitative evaluation of the dosimetric characteristics of an innovative brachytherapy device or application is a critical part in which physicists are actively involved. The physicist’s role, along with physician colleagues, in this process is highlighted for innovative products or applications and includes evaluation of 1) dosimetric considerations for clinical implementation (including calibrations, dose calculations, and radiobiological aspects) to comply with existing societal dosimetric prerequisites for sources in routine clinical use, 2) risks and benefits from regulatory and safety perspectives, and 3) resource assessment and preparedness. Further, calibration methods should be traceable to a primary standards dosimetry laboratory such as NIST in the U.S. or to other primary standards dosimetry laboratory located elsewhere. Clinical users should follow standards as approved by their country’s regulatory agencies that approved such a brachytherapy device. Integration of this system into the medical source calibration infrastructure of secondary standard dosimetry laboratories such as the ADCLs is encouraged before a source is introduced into widespread routine clinical use. The AAPM and GEC-ESTRO have developed guidelines for the safe and consistent application of brachytherapy using innovative brachytherapy devices and applications. The current report covers regulatory approvals, calibration, dose calculations, radiobiological issues, and overall safety concerns that should be addressed during the commissioning stage preceding clinical use. These guidelines are based on review of

[Modeling a clinical process for differentiated thyroid cancer health care in Hospital Base Valdivia, Chile].

Science.gov (United States)

Ávila-Schwerter, C; Torres-Andrade, M C; Méndez, C A; Márquez-Manzano, M

2016-01-01

To design a clinical process model in the management of differentiated thyroid cancer in order to improve accessibility to this treatment. Based on modified Participatory Action Research, a model design process was conducted using a literature review and meetings with organisations committed to the redesigning process, and to agree an improved and feasible process. The process map was constructed by participatory action including, characterisation of the value chain, fault detection in the flow of the process, relevant documents and process for proposing modifications and approvals necessary for this purpose. Links were established between the main process and the support and strategic processes. The participatory model helped to cut the waiting times for diagnosis and treatment of this disease from 12 to 4 months. For each unit to be able to fully visualise the map of the process and understand their contribution as a set of integrated contributions and not fragmented, helps in the comprehensive management of patients and operation processes based on the hierarchical and dominant organisational model in Chilean hospitals. To analyse and remodel clinical processes by participatory action helps to limit failures in the fluidity of care of the patients, by presenting each participating unit with a general view of the process, the problems, and the possible solutions. Furthermore, this approach helps to clarify the process in order to make it more efficient, to harmonise relationships, and to improve coordination in order to optimise patient care. Copyright © 2015 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.

40 CFR 52.1323 - Approval status.

Science.gov (United States)

2010-07-01

... on January 16, 1979 (44 FR 3274) are met. (b) The Administrator approves Rule 10 CSR 10-2.290 as.... (c) The Administrator approves Rule 10 CSR 10-2.230 as identified under § 52.1320, paragraph (c)(70... SIP would be the emission limits stated in the rule. (d) The Administrator approves Rule 10 CSR 10-5...

Pre-clinical and Clinical Development of Low Dose Methamphetamine for the Treatment of Traumatic Brain Injury

Science.gov (United States)

2014-12-01

Aim 3: Secure FDA approval of a phase I/II clinical trial plan and obtain an amended IND in preparation for initiating human clinical testing in TBI...Neurology 6:193–201. Raineri M, Gonzalez B, Goitia B, Garcia-Rill E, Krasnova IN, Cadet JL, Urbano FJ, Bisagno V. 2012. Modafinil abrogates

30 CFR 14.7 - Approval marking and distribution records.

Science.gov (United States)

2010-07-01

..., EVALUATION, AND APPROVAL OF MINING PRODUCTS REQUIREMENTS FOR THE APPROVAL OF FLAME-RESISTANT CONVEYOR BELTS General Provisions § 14.7 Approval marking and distribution records. (a) An approved conveyor belt must be marketed only under the name specified in the approval. (b) Approved conveyor belt must be legibly and...

76 FR 59134 - Medicare and Medicaid Programs; Approval of the Joint Commission's Continued Deeming Authority...

Science.gov (United States)

2011-09-23

... address the requirement that physician assistants, nurse practitioners, or clinical nurse specialists.... SUMMARY: This notice announces our decision to approve the Joint Commission for continued recognition as a... complaints against accredited facilities. ++ Survey review and decision-making process for accreditation. A...

78 FR 13067 - Agency Information Collection Activities: Proposed Collection; Comment Request; Foreign Clinical...

Science.gov (United States)

2013-02-26

... conducted under an IND as support for an IND or application for marketing approval for a drug or biological... and approval by an independent ethics committee (IEC). Under Sec. 312.120(a), FDA accepts as support for an IND or application for marketing approval a well-designed and well-conducted foreign clinical...

Excipients and their role in approved injectable products: current usage and future directions.

Science.gov (United States)

Nema, Sandeep; Brendel, Ronald J

2011-01-01

This review article is a current survey of excipients used in approved injectable products. Information provided includes concentration ranges, function, frequency of use, and role in dosage form. This article is an update of a paper published more than a decade ago (reference 11). Since then many new products have been approved. Safety concerning excipients has evolved as the scientific community continues to learn about their usage. New excipients are being used in early phases of clinical trials to support novel therapeutic entities like RNAi, aptamers, anti-sense, fusion proteins, monoclonal antibodies, and variant scaffolds. Because these excipients are not inert, various pharmacopoeias are responding with monographs or informational chapters addressing excipient functionality. The final sections of this article discuss new excipients, serving specific needs that traditional excipients are unable to provide and for which safety studies are necessary to support a novel excipient for marketing applications. Excipients are added to parenteral dosage forms to serve a variety of functions including stabilization and as vehicles. This review article is a survey of excipients used in approved injectable products. Information provided includes excipient concentrations, functional roles, and frequency of use. This article is an update of an article originally published over a decade ago. Since then new products have been approved and safety concerns have evolved as the scientific community has learned about the usage of excipients. In addition, new excipients are being used in early phases of clinical trials to support novel therapeutic entities such as RNAi, aptamers, anti-sense, fusion proteins, monoclonal antibodies, and variant scaffolds. Because these excipients are not inert, various pharmacopoeias are responding with monographs or informational chapters addressing excipient functionality. The final sections of this article discuss new excipients, serving

Drugs Approved for Kidney (Renal Cell) Cancer

Science.gov (United States)

... Your Treatment Research Drugs Approved for Kidney (Renal Cell) Cancer This page lists cancer drugs approved by the ... not listed here. Drugs Approved for Kidney (Renal Cell) Cancer Afinitor (Everolimus) Aldesleukin Avastin (Bevacizumab) Axitinib Bevacizumab Cabometyx ( ...

Competency-Based Assessment for Clinical Supervisors: Design-Based Research on a Web-Delivered Program

Science.gov (United States)

Williams, Lauren Therese; Grealish, Laurie; Jamieson, Maggie

2015-01-01

Background Clinicians need to be supported by universities to use credible and defensible assessment practices during student placements. Web-based delivery of clinical education in student assessment offers professional development regardless of the geographical location of placement sites. Objective This paper explores the potential for a video-based constructivist Web-based program to support site supervisors in their assessments of student dietitians during clinical placements. Methods This project was undertaken as design-based research in two stages. Stage 1 describes the research consultation, development of the prototype, and formative feedback. In Stage 2, the program was pilot-tested and evaluated by a purposeful sample of nine clinical supervisors. Data generated as a result of user participation during the pilot test is reported. Users’ experiences with the program were also explored via interviews (six in a focus group and three individually). The interviews were transcribed verbatim and thematic analysis conducted from a pedagogical perspective using van Manen’s highlighting approach. Results This research succeeded in developing a Web-based program, “Feed our Future”, that increased supervisors’ confidence with their competency-based assessments of students on clinical placements. Three pedagogical themes emerged: constructivist design supports transformative Web-based learning; videos make abstract concepts tangible; and accessibility, usability, and pedagogy are interdependent. Conclusions Web-based programs, such as Feed our Future, offer a viable means for universities to support clinical supervisors in their assessment practices during clinical placements. A design-based research approach offers a practical process for such Web-based tool development, highlighting pedagogical barriers for planning purposes. PMID:25803172

Evidence-based health care: its place within clinical governance.

Science.gov (United States)

McSherry, R; Haddock, J

This article explores the principles of evidence-based practice and its role in achieving quality improvements within the clinical governance framework advocated by the recent White Papers 'The New NHS: Modern, Dependable' (Department of Health (DoH), 1997) and 'A First Class Service: Quality in the New NHS' (DoH, 1998a). Within these White Papers there is an emphasis on improving quality of care, treatment and services through employing the principles of clinical governance. A major feature of clinical governance is guaranteeing quality to the public and the NHS, and ensuring that clinical, managerial and educational practice is based on scientific evidence. This article also examines what evidence-based practice is and what processes are required to promote effective healthcare interventions. The authors also look at how clinical governance relates to other methods/systems involved in clinical effectiveness. Finally, the importance for nurses and other healthcare professionals of familiarizing themselves with the development of critical appraisal skills, and their implications for developing evidence-based practice, is emphasized.

Blockchain protocols in clinical trials: Transparency and traceability of consent [version 5; referees: 1 approved, 2 approved with reservations, 2 not approved

Directory of Open Access Journals (Sweden)

Mehdi Benchoufi

2018-02-01

Full Text Available Clinical trial consent for protocols and their revisions should be transparent for patients and traceable for stakeholders. Our goal is to implement a process allowing for collection of patients’ informed consent, which is bound to protocol revisions, storing and tracking the consent in a secure, unfalsifiable and publicly verifiable way, and enabling the sharing of this information in real time. For that, we build a consent workflow using a trending technology called Blockchain. This is a distributed technology that brings a built-in layer of transparency and traceability. From a more general and prospective point of view, we believe Blockchain technology brings a paradigmatical shift to the entire clinical research field. We designed a Proof-of-Concept protocol consisting of time-stamping each step of the patient’s consent collection using Blockchain, thus archiving and historicising the consent through cryptographic validation in a securely unfalsifiable and transparent way. For each protocol revision, consent was sought again.  We obtained a single document, in an open format, that accounted for the whole consent collection process: a time-stamped consent status regarding each version of the protocol. This document cannot be corrupted and can be checked on any dedicated public website. It should be considered a robust proof of data. However, in a live clinical trial, the authentication system should be strengthened to remove the need for third parties, here trial stakeholders, and give participative control to the peer users. In the future, the complex data flow of a clinical trial could be tracked by using Blockchain, which core functionality, named Smart Contract, could help prevent clinical trial events not occurring in the correct chronological order, for example including patients before they consented or analysing case report form data before freezing the database. Globally, Blockchain could help with reliability, security

Blockchain protocols in clinical trials: Transparency and traceability of consent [version 4; referees: 1 approved, 2 approved with reservations, 2 not approved

Directory of Open Access Journals (Sweden)

Mehdi Benchoufi

2017-12-01

Full Text Available Clinical trial consent for protocols and their revisions should be transparent for patients and traceable for stakeholders. Our goal is to implement a process allowing for collection of patients’ informed consent, which is bound to protocol revisions, storing and tracking the consent in a secure, unfalsifiable and publicly verifiable way, and enabling the sharing of this information in real time. For that, we build a consent workflow using a trending technology called Blockchain. This is a distributed technology that brings a built-in layer of transparency and traceability. From a more general and prospective point of view, we believe Blockchain technology brings a paradigmatical shift to the entire clinical research field. We designed a Proof-of-Concept protocol consisting of time-stamping each step of the patient’s consent collection using Blockchain, thus archiving and historicising the consent through cryptographic validation in a securely unfalsifiable and transparent way. For each protocol revision, consent was sought again.  We obtained a single document, in an open format, that accounted for the whole consent collection process: a time-stamped consent status regarding each version of the protocol. This document cannot be corrupted and can be checked on any dedicated public website. It should be considered a robust proof of data. However, in a live clinical trial, the authentication system should be strengthened to remove the need for third parties, here trial stakeholders, and give participative control to the peer users. In the future, the complex data flow of a clinical trial could be tracked by using Blockchain, which core functionality, named Smart Contract, could help prevent clinical trial events not occurring in the correct chronological order, for example including patients before they consented or analysing case report form data before freezing the database. Globally, Blockchain could help with reliability, security

Automatic learning-based beam angle selection for thoracic IMRT

International Nuclear Information System (INIS)

Amit, Guy; Marshall, Andrea; Purdie, Thomas G.; Jaffray, David A.; Levinshtein, Alex; Hope, Andrew J.; Lindsay, Patricia; Pekar, Vladimir

2015-01-01

Purpose: The treatment of thoracic cancer using external beam radiation requires an optimal selection of the radiation beam directions to ensure effective coverage of the target volume and to avoid unnecessary treatment of normal healthy tissues. Intensity modulated radiation therapy (IMRT) planning is a lengthy process, which requires the planner to iterate between choosing beam angles, specifying dose–volume objectives and executing IMRT optimization. In thorax treatment planning, where there are no class solutions for beam placement, beam angle selection is performed manually, based on the planner’s clinical experience. The purpose of this work is to propose and study a computationally efficient framework that utilizes machine learning to automatically select treatment beam angles. Such a framework may be helpful for reducing the overall planning workload. Methods: The authors introduce an automated beam selection method, based on learning the relationships between beam angles and anatomical features. Using a large set of clinically approved IMRT plans, a random forest regression algorithm is trained to map a multitude of anatomical features into an individual beam score. An optimization scheme is then built to select and adjust the beam angles, considering the learned interbeam dependencies. The validity and quality of the automatically selected beams evaluated using the manually selected beams from the corresponding clinical plans as the ground truth. Results: The analysis included 149 clinically approved thoracic IMRT plans. For a randomly selected test subset of 27 plans, IMRT plans were generated using automatically selected beams and compared to the clinical plans. The comparison of the predicted and the clinical beam angles demonstrated a good average correspondence between the two (angular distance 16.8° ± 10°, correlation 0.75 ± 0.2). The dose distributions of the semiautomatic and clinical plans were equivalent in terms of primary target volume

40 CFR 52.2352 - Change to approved plan.

Science.gov (United States)

2010-07-01

... Utah's approved State Implementation Plan (SIP). This rule language pertains to State Sales Tax... 40 Protection of Environment 4 2010-07-01 2010-07-01 false Change to approved plan. 52.2352... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Utah § 52.2352 Change to approved...

Approved and Experimental Small-Molecule Oncology Kinase Inhibitor Drugs: A Mid-2016 Overview.

Science.gov (United States)

Fischer, Peter M

2017-03-01

Kinase inhibitor research is a comparatively recent branch of medicinal chemistry and pharmacology and the first small-molecule kinase inhibitor, imatinib, was approved for clinical use only 15 years ago. Since then, 33 more kinase inhibitor drugs have received regulatory approval for the treatment of a variety of cancers and the volume of reports on the discovery and development of kinase inhibitors has increased to an extent where it is now difficult-even for those working in the field-easily to keep an overview of the compounds that are being developed, as currently there are 231 such compounds, targeting 38 different protein and lipid kinases (not counting isoforms), in clinical use or under clinical investigation. The purpose of this review is thus to provide an overview of the biomedical rationales for the kinases being targeted on the one hand, and the design principles, as well as chemical, pharmacological, pharmaceutical, and toxicological kinase inhibitor properties, on the other hand. Two issues that are especially important in kinase inhibitor research, target selectivity and drug resistance, as well as the underlying structural concepts, are discussed in general terms and in the context of relevant kinases and their inhibitors. © 2016 Wiley Periodicals, Inc.

Nurses' Clinical Decision Making on Adopting a Wound Clinical Decision Support System.

Science.gov (United States)

Khong, Peck Chui Betty; Hoi, Shu Yin; Holroyd, Eleanor; Wang, Wenru

2015-07-01

Healthcare information technology systems are considered the ideal tool to inculcate evidence-based nursing practices. The wound clinical decision support system was built locally to support nurses to manage pressure ulcer wounds in their daily practice. However, its adoption rate is not optimal. The study's objective was to discover the concepts that informed the RNs' decisions to adopt the wound clinical decision support system as an evidence-based technology in their nursing practice. This was an exploratory, descriptive, and qualitative design using face-to-face interviews, individual interviews, and active participatory observation. A purposive, theoretical sample of 14 RNs was recruited from one of the largest public tertiary hospitals in Singapore after obtaining ethics approval. After consenting, the nurses were interviewed and observed separately. Recruitment stopped when data saturation was reached. All transcribed interview data underwent a concurrent thematic analysis, whereas observational data were content analyzed independently and subsequently triangulated with the interview data. Eight emerging themes were identified, namely, use of the wound clinical decision support system, beliefs in the wound clinical decision support system, influences of the workplace culture, extent of the benefits, professional control over nursing practices, use of knowledge, gut feelings, and emotions (fear, doubt, and frustration). These themes represented the nurses' mental outlook as they made decisions on adopting the wound clinical decision support system in light of the complexities of their roles and workloads. This research has provided insight on the nurses' thoughts regarding their decision to interact with the computer environment in a Singapore context. It captured the nurses' complex thoughts when deciding whether to adopt or reject information technology as they practice in a clinical setting.

Systematic Review: FDA-Approved Prescription Medications for Adults With Constipation

Science.gov (United States)

Lacy, Brian E.

2006-01-01

Constipation is a common, often chronic, gastrointestinal disorder that can negatively impact the lives of those it affects and can be difficult to treat satisfactorily. The objective of this systematic review is to identify and analyze the available published literature on US Food and Drug Administration–approved prescription therapies for adults with constipation (episodic and chronic) and to assess their place in therapy, based on the methodologic strength and results of identified clinical trials. Ovid MEDLINE, PubMed, and EMBASE databases were used to search the published literature. Studies were included if they were randomized and prospective, conducted in adults (age ≥18), published as full-length manuscripts in English, and compared the test agent with placebo or a comparator(s). Studies were excluded if they involved patients with constipation attributed to secondary causes. Because fully published manuscripts from phase III efficacy trials involving the recently approved medication lubiprostone were not available, a manual search was performed of abstracts from the two annual major gastroenterology meetings (American College of Gastroenterology and Digestive Disease Week) from the past 4 years. Data on study design; number, age, and sex of patients; duration of treatment period; primary efficacy variable; secondary efficacy variables; adverse events; and discontinuations because of adverse events were abstracted from eligible articles. Eligible studies were assessed using well-established recommendations and a preformatted standardized form. A scoring system, with scores ranging from 1 to 15, was used to individually and separately assess the methodologic quality of the studies. Results of this analysis indicate a general lack of methodologically high-quality clinical trials supporting the use of lactulose and PEG 3350 to treat patients with chronic constipation, but data support their use in acute, episodic constipation. Conversely, high

Approval plans issues and innovations

CERN Document Server

Katz, Linda S

2013-01-01

How can you, as an acquisition librarians, keep current on the output of hundreds of publishers? The answer, of course, is that you cannot. For over 30 years, approval plans have been used by librarians to acquire current titles, save staff time, and build core collections. Even today, these reasons seem appropriate, as libraries try to maintain up-to-date collections and control personnel and operating budgets. However, as shown in Approval Plans: Issues and Innovations, the use of approval plans is not so simple and straightforward; their use is subject to complex procedures and policies--an

[A web-based integrated clinical database for laryngeal cancer].

Science.gov (United States)

E, Qimin; Liu, Jialin; Li, Yong; Liang, Chuanyu

2014-08-01

To establish an integrated database for laryngeal cancer, and to provide an information platform for laryngeal cancer in clinical and fundamental researches. This database also meet the needs of clinical and scientific use. Under the guidance of clinical expert, we have constructed a web-based integrated clinical database for laryngeal carcinoma on the basis of clinical data standards, Apache+PHP+MySQL technology, laryngeal cancer specialist characteristics and tumor genetic information. A Web-based integrated clinical database for laryngeal carcinoma had been developed. This database had a user-friendly interface and the data could be entered and queried conveniently. In addition, this system utilized the clinical data standards and exchanged information with existing electronic medical records system to avoid the Information Silo. Furthermore, the forms of database was integrated with laryngeal cancer specialist characteristics and tumor genetic information. The Web-based integrated clinical database for laryngeal carcinoma has comprehensive specialist information, strong expandability, high feasibility of technique and conforms to the clinical characteristics of laryngeal cancer specialties. Using the clinical data standards and structured handling clinical data, the database can be able to meet the needs of scientific research better and facilitate information exchange, and the information collected and input about the tumor sufferers are very informative. In addition, the user can utilize the Internet to realize the convenient, swift visit and manipulation on the database.

Medicare covers the majority of FDA-approved devices and Part B drugs, but restrictions and discrepancies remain.

Science.gov (United States)

Chambers, James D; May, Katherine E; Neumann, Peter J

2013-06-01

The Food and Drug Administration (FDA) and Medicare use different standards to determine, first, whether a new drug or medical device can be marketed to the public and, second, if the federal health insurance program will pay for use of the drug or device. This discrepancy creates hurdles and uncertainty for drug and device manufacturers. We analyzed discrepancies between FDA approval and Medicare national coverage determinations for sixty-nine devices and Part B drugs approved during 1999-2011. We found that Medicare covered FDA-approved drugs or devices 80 percent of the time. However, Medicare often added conditions beyond FDA approval, particularly for devices and most often restricting coverage to patients with the most severe disease. In some instances, Medicare was less restrictive than the FDA. Our findings highlight the importance for drug and device makers of anticipating Medicare's needs when conducting clinical studies to support their products. Our findings also provide important insights for the FDA's and Medicare's pilot parallel review program.

48 CFR 750.7105 - Approving authorities.

Science.gov (United States)

2010-10-01

... CONTRACT MANAGEMENT EXTRAORDINARY CONTRACTUAL ACTIONS Extraordinary Contractual Actions To Protect Foreign Policy Interests of the United States 750.7105 Approving authorities. All authority to approve actions...

Blockchain protocols in clinical trials: Transparency and traceability of consent [version 3; referees: 1 approved, 2 approved with reservations, 1 not approved

Directory of Open Access Journals (Sweden)

Mehdi Benchoufi

2017-07-01

Full Text Available Clinical trial consent for protocols and their revisions should be transparent for patients and traceable for stakeholders. Our goal is to implement a process allowing the collection of patients’ informed consent, which is bound to protocol revisions, storing and tracking the consent in a secure, unfalsifiable and publicly verifiable way, and enabling the sharing of this information in real time. For that, we will built a consent workflow using a rising technology called Blockchain. This is a distributed technology that brings a built-in layer of transparency and traceability. From a more general and prospective point of view, we believe Blockchain technology brings a paradigmatical shift to the entire clinical research field. We designed a Proof-of-Concept protocol consisting of time-stamping each step of the patient’s consent collection using Blockchain; thus archiving and historicising the consent through cryptographic validation in a securely unfalsifiable and transparent way. For each revision of the protocol, consent was sought again. We obtained a single document, in a standard open format, that accounted for the whole consent collection process: timestamped consent status with regards to each version of the protocol. This document cannot be corrupted, and can be checked on any dedicated public website. It should be considered as a robust proof of data. However, in a live clinical trial, the authentication system should be strengthened in order to remove the need for third parties, here the trial stakeholders, and give participative control to the peer-to-peer users. In the future, we think that the complex data flow of a clinical trial can be tracked using Blockchain, that a blockchain core functionality, named Smart Contract, could help prevent clinical trial events not to happen in the right chronological order: for example including patients before they consented or analysing case report forms data before freezing the database

Vedolizumab: first global approval.

Science.gov (United States)

Poole, Raewyn M

2014-07-01

Vedolizumab [Entyvio(®) (US, Europe)], a humanized monoclonal antibody α4β7 integrin receptor antagonist, has been developed by Millennium Pharmaceuticals (d/b/a Takeda Pharmaceuticals International) for the treatment of ulcerative colitis and Crohn's disease. Vedolizumab has received its first global approval for the treatment of ulcerative colitis and Crohn's disease in the US, for use in adult patients with moderate-to-severe disease who have had an inadequate response, loss of response or intolerance to one or more standard therapies (corticosteroids, immunomodulators or tumour necrosis factor-α inhibitor) or demonstrated dependence on corticosteroids. Vedolizumab has since been approved for ulcerative colitis and Crohn's disease in the EU, Norway, Iceland and Liechtenstein. This article summarizes the milestones in the development of vedolizumab leading to its first approval for the treatment of ulcerative colitis and Crohn's disease.

Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial

DEFF Research Database (Denmark)

Comi, G; Martinelli, V; Rodegher, M

2009-01-01

BACKGROUND: Glatiramer acetate, approved for the treatment of relapsing-remitting multiple sclerosis, reduces relapses and disease activity and burden monitored by MRI. We assessed the efficacy of early treatment with glatiramer acetate in delaying onset of clinically definite multiple sclerosis....... treatment with glatiramer acetate is efficacious in delaying conversion to clinically definite multiple sclerosis in patients presenting with clinically isolated syndrome and brain lesions detected by MRI. FUNDING: Teva Pharmaceutical Industries, Israel.......BACKGROUND: Glatiramer acetate, approved for the treatment of relapsing-remitting multiple sclerosis, reduces relapses and disease activity and burden monitored by MRI. We assessed the efficacy of early treatment with glatiramer acetate in delaying onset of clinically definite multiple sclerosis...

Regulatory issues with multiplicity in drug approval: Principles and controversies in a changing landscape.

Science.gov (United States)

Benda, Norbert; Brandt, Andreas

2018-01-01

Recently, new draft guidelines on multiplicity issues in clinical trials have been issued by European Medicine Agency (EMA) and Food and Drug Administration (FDA), respectively. Multiplicity is an issue in clinical trials, if the probability of a false-positive decision is increased by insufficiently accounting for testing multiple hypotheses. We outline the regulatory principles related to multiplicity issues in confirmatory clinical trials intended to support a marketing authorization application in the EU, describe the reasons for an increasing complexity regarding multiple hypotheses testing and discuss the specific multiplicity issues emerging within the regulatory context and being relevant for drug approval.

Recent advances in (therapeutic protein drug development [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

H.A. Daniel Lagassé

2017-02-01

Full Text Available Therapeutic protein drugs are an important class of medicines serving patients most in need of novel therapies. Recently approved recombinant protein therapeutics have been developed to treat a wide variety of clinical indications, including cancers, autoimmunity/inflammation, exposure to infectious agents, and genetic disorders. The latest advances in protein-engineering technologies have allowed drug developers and manufacturers to fine-tune and exploit desirable functional characteristics of proteins of interest while maintaining (and in some cases enhancing product safety or efficacy or both. In this review, we highlight the emerging trends and approaches in protein drug development by using examples of therapeutic proteins approved by the U.S. Food and Drug Administration over the previous five years (2011–2016, namely January 1, 2011, through August 31, 2016.

19 CFR 115.55 - Termination of approval.

Science.gov (United States)

2010-04-01

... vehicle by a major repair or alteration of any of the essential features required in § 115.51. Repairs by... TREASURY CARGO CONTAINER AND ROAD VEHICLE CERTIFICATION PURSUANT TO INTERNATIONAL CUSTOMS CONVENTIONS Procedures for Approval of Individual Road Vehicles § 115.55 Termination of approval. Approval of a road...

20 CFR 617.22 - Approval of training.

Science.gov (United States)

2010-04-01

.... Perkins Vocational and Applied Technology Education Act, and employers). (i) This means that training is...) Conditions for approval. Training shall be approved for an adversely affected worker if the State agency...) available for an adversely affected worker. (i) This means that for the worker for whom approval of training...

Failure to report and provide commentary on research ethics board approval and informed consent in medical journals.

Science.gov (United States)

Finlay, K A; Fernandez, C V

2008-10-01

The Declaration of Helsinki prohibits the publication of articles that do not meet defined ethical standards for reporting of research ethics board (REB) approval and informed consent. Despite this prohibition and a call to highlight the deficiency for the reader, articles with potential ethical shortcomings continue to be published. To determine what proportion of articles in major medical journals lack statements confirming REB approval and informed consent, and whether accompanying commentary alerts readers to this deficiency. Retrospective, observational study. Online review of five major medical journals. All clinical research articles published online between 1 January 2005 and 31 December 2006 in the BMJ, Lancet, Annals of Internal Medicine, JAMA and the New England Journal of Medicine. Statement of REB approval and informed consent. Of 1780 articles reviewed, 1133 (63.7%) met inclusion criteria (manuscripts reporting human subjects, human tissue or identifiable personal data research), 36 (3.2%) articles lacked a statement of REB approval, 62 (5.5%) lacked disclosure of informed consent and 15 (1.3%) articles lacked both. Articles that did not state REB approval were associated with not stating informed consent (pjournals without editorial statements to alert the reader to this deficiency.

Evidence-based clinical guidelines for eating disorders : International comparison

NARCIS (Netherlands)

Hilbert, Anja; Hoek, Hans W.; Schmidt, Ricarda

2017-01-01

Purpose of review: The current systematic review sought to compare available evidence-based clinical treatment guidelines for all specific eating disorders. Recent findings: Nine evidence-based clinical treatment guidelines for eating disorders were located through a systematic search. The

30 CFR 75.1108 - Approved conveyor belts.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Approved conveyor belts. 75.1108 Section 75... Fire-Resistant Hydraulic Fluids on Underground Equipment § 75.1108 Approved conveyor belts. (a) Until December 31, 2009 conveyor belts placed in service in underground coal mines shall be: (1) Approved under...

45 CFR 1340.13 - Approval of applications.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Approval of applications. 1340.13 Section 1340.13... NEGLECT PREVENTION AND TREATMENT PROGRAM CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT Grants to States § 1340.13 Approval of applications. (a) The Commissioner shall approve an application for an award for...

[Evidence-based aspects of clinical mastitis treatment].

Science.gov (United States)

Mansion-de Vries, E M; Hoedemaker, M; Krömker, V

2015-01-01

Mastitis is one of the most common and expensive diseases in dairy cattle. The decision to treat clinical mastitis is usually made without any knowledge of the etiology, and can therefore only be evidence-based to a limited extent. Evidence-based medicine relies essentially on a combination of one's own clinical competence and scientific findings. In mastitis therapy, those insights depend mostly on pathogen-specific factors. Therefore, in evidence-based therapeutic decision making the pathogen identification should serve as a basis for the consideration of scientifically validated therapeutic concepts. The present paper considers evidence-based treatment of clinical mastitis based on a literature review. The authors conclude that an anti-inflammatory treatment using an NSAID should be conducted regardless of the pathogen. However, the choice of an antibiotic therapy depends on the mastitis causative pathogen, clinical symptoms and the animal itself. In principle, a local antibiotic treatment should be chosen for mild and moderate mastitis. It should be noted, that the benefit of an antibiotic therapy for coliform infections is questionable. With knowledge concerning the pathogen, it appears entirely reasonable to refrain from an antibiotic therapy. For severe (i.   e. feverish) mastitis, a parenteral antibiotic therapy should be selected. An extension of the antibiotic therapy beyond the manufacturer's information is only reasonable for streptococcal infections. It is important to make the decision on a prolonged antibiotic therapy only with the knowledge of the mastitis-causative pathogen. In terms of the therapy of a staphylococcus or streptococcus infection, a narrow-spectrum antibiotic from the penicillin family should be adopted when selecting the active agents.

Context based support for Clinical Reasoning

DEFF Research Database (Denmark)

Vilstrup Pedersen, Klaus

2004-01-01

In many areas of the medical domain, the decision process i.e. reasoning, involving health care professionals is distributed, cooperative and complex. Computer based decision support systems has usually been focusing on the outcome of the decision making and treated it as a single task....... In this paper a framework for a Clinical Reasoning Knowledge Warehouse (CRKW) is presented, intended to support the reasoning process, by providing the decision participants with an analysis platform that captures and enhances information and knowledge. The CRKW mixes theories and models from Artificial...... Intelligence, Knowledge Management Systems and Business Intelligence to make context sensitive, patient case specific analysis and knowledge management. The knowledge base consists of patient health records, reasoning process information and clinical guidelines. Patient specific information and knowledge...

Engineering adeno-associated viruses for clinical gene therapy.

Science.gov (United States)

Kotterman, Melissa A; Schaffer, David V

2014-07-01

Clinical gene therapy has been increasingly successful owing both to an enhanced molecular understanding of human disease and to progressively improving gene delivery technologies. Among these technologies, delivery vectors based on adeno-associated viruses (AAVs) have emerged as safe and effective and, in one recent case, have led to regulatory approval. Although shortcomings in viral vector properties will render extension of such successes to many other human diseases challenging, new approaches to engineer and improve AAV vectors and their genetic cargo are increasingly helping to overcome these barriers.

Preclinical pharmacokinetics, biodistribution, radiation dosimetry and acute toxicity studies required for regulatory approval of a Clinical Trial Application for a Phase I/II clinical trial of 111In-BzDTPA-pertuzumab

International Nuclear Information System (INIS)

Lam, Karen; Chan, Conrad; Done, Susan J.; Levine, Mark N.; Reilly, Raymond M.

2015-01-01

Introduction: 111 In-BzDTPA-pertuzumab is a novel imaging probe for detecting changes in HER2 expression in breast cancer (BC) caused by treatment with trastuzumab (Herceptin). Our aim was to evaluate the pharmacokinetics, normal tissue biodistribution, radiation dosimetry and acute toxicity of 111 In-BzDTPA-pertuzumab in non-tumor bearing mice in order to obtain regulatory approval to advance this agent to a first-in-humans Phase I/II clinical trial. Methods: Biodistribution and pharmacokinetic studies were performed in non-tumor bearing Balb/c mice injected i.v. with 111 In-BzDTPA-pertuzumab (2.5 MBq; 2 μg). The cumulative number of disintegrations per source organ derived from the biodistribution data was used to predict the radiation absorbed doses in humans using OLINDA/EXM software. Acute toxicity was studied at two weeks post-injection of 111 In-BzDTPA-pertuzumab (1.0 MBq, 20 μg) with comparison to control mice injected with unlabeled BzDTPA-pertuzumab (20 μg) or Sodium Chloride Injection USP. The dose of 111 In-BzDTPA-pertuzumab corresponded to 23-times the human radioactivity dose and 10-times the protein dose on a MBq/kg and mg/kg basis, respectively. Toxicity was assessed by monitoring body mass, complete blood cell count (CBC), hematocrit (Hct), hemoglobin (Hb), serum creatinine (SCr) and alanine aminotransferease (ALT) and by histopathological examination of tissues at necropsy. Results: 111 In-BzDTPA-pertuzumab exhibited a biphasic elimination from the blood with a distribution half-life (t 1/2 α) of 3.8 h and an elimination half-life (t 1/2 β) of 228.2 h. The radiopharmaceutical was distributed mainly in the blood, heart, lungs, liver, kidneys and spleen. The projected whole-body radiation absorbed dose in humans was 0.05 mSv/MBq corresponding to a total of 16.8 mSv for three separate administrations of 111 In-BzDTPA-pertuzumab (111 MBq) planned for the Phase I/II trial. There were slight changes in Hb and SCr levels associated with

27 CFR 5.55 - Certificates of label approval.

Science.gov (United States)

2010-04-01

..., DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF DISTILLED SPIRITS Requirements for Approval of... certificates of label approval and certificates of exemption from label approval, as well as appeal procedures...

46 CFR 188.10-3 - Approved container.

Science.gov (United States)

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Approved container. 188.10-3 Section 188.10-3 Shipping... PROVISIONS Definition of Terms Used in This Subchapter § 188.10-3 Approved container. This term means a container which is properly labeled, marked and approved by DOT for the commodity which it contains. [CGFR...

'Mind the gap' between the development of therapeutic innovations and the clinical practice in oncology: A proposal of the European Organisation for Research and Treatment of Cancer (EORTC) to optimise cancer clinical research.

Science.gov (United States)

Kempf, Emmanuelle; Bogaerts, Jan; Lacombe, Denis; Liu, Lifang

2017-11-01

In Europe, most of the cancer clinical research dedicated to therapeutic innovations aims primarily at regulatory approval. Once an anticancer drug enters the common market, each member state determines its real-world use based on its own criteria: pricing, reimbursement and clinical indications. Such an innovation-centred clinical research landscape might neglect patient-relevant issues in real-world setting, such as comparative effectiveness of distinct treatment options or long-term safety monitoring. The European Organisation for Research and Treatment of Cancer (EORTC) advocates reforming the current 'innovation-centred' system to a truly 'patient-centred' paradigm with systematically coordinated applied clinical research in conjunction with drug development, featuring the following strategy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical pharmacology review of escitalopram for the treatment of depression.

Science.gov (United States)

Pastoor, Devin; Gobburu, Joga

2014-01-01

Depression is a serious and debilitating psychiatric condition with serious societal health and economic implications. Escitalopram , the S-enantiomer of racemic citalopram, is an effective treatment for major depressive disorder. This review covers the clinical pharmacology of escitalopram, with emphasis on regulatory approval. Its pharmacokinetics, pharmacodynamics and clinical efficacy for major depressive disorder are evaluated, along with data regarding safety and tolerability. Drug development of escitalopram was heavily guided by prior approval of citalopram. Select safety and efficacy studies for escitalopram in combination with supportive evidence from the results of prior citalopram studies allowed for regulatory approval for acute and maintenance claims in both adults and adolescents, while minimizing burden on the sponsor. Escitalopram has been shown to have better efficacy and safety profile than other selective serotonin reuptake inhibitor and serotonin norepinephrine reuptake inhibitor drugs, including racemic citalopram. The first generic escitalopram was approved in 2012, along with Abbreviated New Drug Applications. The associated cost savings have helped reduce the burden of weighing the benefits of escitalopram over less-expensive alternatives.

A case-based assistant for clinical psychiatry expertise.

Science.gov (United States)

Bichindaritz, I

1994-01-01

Case-based reasoning is an artificial intelligence methodology for the processing of empirical knowledge. Recent case-based reasoning systems also use theoretic knowledge about the domain to constrain the case-based reasoning. The organization of the memory is the key issue in case-based reasoning. The case-based assistant presented here has two structures in memory: cases and concepts. These memory structures permit it to be as skilled in problem-solving tasks, such as diagnosis and treatment planning, as in interpretive tasks, such as clinical research. A prototype applied to clinical work about eating disorders in psychiatry, reasoning from the alimentary questionnaires of these patients, is presented as an example of the system abilities.

Building a web-based CAD server for clinical use, evaluation, and incremental learning. Implementation of analysis function based on execution result and clinical feedback

International Nuclear Information System (INIS)

Nomura, Yukihiro; Hayashi, Naoto; Masutani, Yoshitaka; Yoshikawa, Takeharu; Nemoto, Mitsutaka; Hanaoka, Shouhei; Maeda, Eriko; Ohtomo, Kuni; Miki, Soichiro

2010-01-01

Development of clinical image analysis software such as computer-assisted detection/diagnosis (CAD) involves a cycle of algorithm development, software implementation, clinical use, refinement of algorithm and software based on feedback. This cycle is expected to accelerate development of CAD software. We have been building a web-based CAD server that enables radiologists to use CAD software and to give feedback in clinical environment. The platform has been utilized in our hospital for 16 months, and more than 2,000 cases of feedback data have been accumulated. In this report, we introduce additional functions for performance evaluation based on executed results of CAD software and clinical feedback. (author)

Electronic Approval of Invoices (AEF)

CERN Multimedia

2003-01-01

With a view to the simplification of administrative procedures, AS and FI Divisions have drawn up a new procedure for the electronic approval of invoices via the EDH application. The aim of this new procedure is to rationalise the invoice approval process, notably by eliminating paper copies from the approval circuit. This will simplify the processing of invoices and facilitate their timely settlement, while at the same time maintaining a high level of security. This new procedure, in its current phase, will be gradually implemented from 1 November 2003 onwards. For clarification and further information, please see: http://ais.cern.ch/projs/AEF/help/help.htm . Finance Division, Accounts Payable Tel.: 7.22.95

First Approval of Improved Medical Device Conditional on Use-Result Survey in Japan　- Regulatory Review of Polymer-Free Drug-Coated BioFreedom Coronary Stent.

Science.gov (United States)

Konishi, Akihide; Ho, Mami; Shirai, Yuko; Shirato, Haruki

2018-05-25

A prospective randomized clinical trial showed that the BioFreedom stent (Biosensors International), which is a polymer-free and carrier-free drug-coated stent, was significantly superior to a bare-metal stent (BMS) in patients at high bleeding risk who were receiving a 1-month course of dual antiplatelet therapy (DAPT). However, the stent thrombosis rate (2.01% for BioFreedom vs. 2.20% for BMS) was 4-6-fold higher than that of approved drug-eluting stents based on real-world data in Japan. Furthermore, the frequency of stent thrombosis at more than 1 month with the BioFreedom stent was slightly higher than that at less than 1 month. This result suggested that it would not be acceptable to stop DAPT universally at 1 month. Thus, the target patients for the BioFreedom stent are unspecified patients at high bleeding risk needing to continue DAPT for as long as necessary in Japan. Therefore, based on the pre- and post-marketing balance of medical devices regulations, regulatory approval was given for unspecified patients conditionally upon real-world data collection of 2,000 patients with a Use-Results Survey, instead of conducting additional pre-marketing clinical trial(s). The Use-Results Survey System is part of a strategy to expedite patients' access to innovative medical devices and to accelerate the development of medical devices.

Survival benefit of glioblastoma patients after FDA approval of temozolomide concomitant with radiation and bevacizumab: A population-based study.

Science.gov (United States)

Zhu, Ping; Du, Xianglin L; Lu, Guangrong; Zhu, Jay-Jiguang

2017-07-04

Few population-based analyses have investigated survival change in glioblastoma multiforme (GBM) patients treated with concomitant radiotherapy-temozolomide (RT-TMZ) and adjuvant temozolomide (TMZ) and then bevacizumab (BEV) after Food and Drug Administration (FDA) approval, respectively. We aimed to explore the effects on survival with RT-TMZ, adjuvant TMZ and BEV in general GBM population based on the Surveillance, Epidemiology, and End Results (SEER) and Texas Cancer Registry (TCR) databases. A total of 28933 GBM patients from SEER (N = 24578) and TCR (N = 4355) between January 2000 and December 2013 were included. Patients were grouped into three calendar periods based on date of diagnosis: pre-RT-TMZ and pre-BEV (1/2000-2/2005, P1), post-RT-TMZ and pre-BEV (3/2005-4/2009, P2), and post-RT-TMZ and post-BEV (5/2009-12/2013, P3). The association between calendar period of diagnosis and survival was analyzed in SEER and TCR, separately, by the Kaplan-Meier method and Cox proportional hazards model. We found a significant increase in median overall survival (OS) across the three periods in both populations. In multivariate models, the risk of death was significantly reduced during P2 and further decreased in P3, which remained unchanged after stratification. Comparison and validation analysis were performed in the combined dataset, and consistent results were observed. We conclude that the OS of GBM patients in a "real-world" setting has been steadily improved from January 2000 to December 2013, which likely resulted from the administrations of TMZ concomitant with RT and adjuvant TMZ for newly diagnosed GBM and then BEV for recurrent GBM after respective FDA approval.

In-use vs. type-approval fuel consumption of current passenger cars in Europe

International Nuclear Information System (INIS)

Ntziachristos, L.; Mellios, G.; Tsokolis, D.; Keller, M.; Hausberger, S.; Ligterink, N.E.; Dilara, P.

2014-01-01

In-use fuel consumption data of 924 passenger cars (611 petrol, 313 diesel) were collected from various European sources and were evaluated in comparison to their corresponding type-approval values. The analysis indicated that the average in-use fuel consumption was higher than the type-approval one by 11% for petrol cars and 16% for diesel cars. Comparison of this dataset with the Travelcard database in the Netherlands showed that the deviation increased for late model years and in particular for cars with low type-approval values. The deviation was higher than 60% for vehicles registered in 2012 within the 90–100 gCO 2 /km bin. Unrealistic vehicle resistances used in type-approval were identified as one of the prime reasons of the difference. A simplified linear model developed in the study may be used to predict in-use fuel consumption based on data publicly available. The model utilizes the fuel consumption measured in type-approval, the mass, and the engine capacity to provide in-use fuel consumption. This may be either used to correct fuel consumption factors currently utilized by emission models (e.g. COPERT, HBEFA, VERSIT+, and others) or could be used independently to make projections on how fuel consumption may develop on the basis of changing future passenger cars characteristics. - Highlights: • In-use fuel consumption of petrol and diesel passenger cars is 11% and 16% higher than type-approval, respectively. • The relative difference between in-use and type-approval increases for late model and vehicles with low consumption. • Unrealistically low vehicle resistances are identified as a prime reason of low type-approval fuel consumption. • A model developed predicts in-use consumption on the basis of type-approval consumption, vehicle mass, and engine capacity

EVIDENCE-BASED MEDICINE – II. CLINICAL USE AND CRITICS

Directory of Open Access Journals (Sweden)

Angela Čuk

2004-01-01

Full Text Available Background. Evidence-based medicine employs systematic searching, evaluation and use of current research findings as the basis for clinical decision-making. However, there are some problems and uncertainties hindering introduction and spreading of the use of the method in clinical practice. Physicians often have no time for literature searching and for use of the method in practice. For certain questions in clinical practice there are no answers in medical literature. Most of the evidences in medical literature are only available in English. Introduction of the method is hampered also by the fact that clinical decision-making is complex and does not allow procedures prescribed in advance. Rigidity and universality of decisions resulting from the evidence may appear impersonal and may affect the relationship between the physician and the patient. Trends towards evidence based medicine are followed also by big multinational pharmaceutical corporations. They carry out large and expensive clinical trials using the results for promotional purposes. In this way, they get the competitive advantage and influence the objectivity of physicians’ clinical decision-making.Conclusions. With introduction of evidence based medicine into clinical practice physicians acquire new information and use a new form of continuing education by following new developments in their field. This way, new findings from medical literature get into clinical practice faster and more efficiently. In addition, physicians get more professional satisfaction and quality in clinical practice is higher.

Delays in clinical development of neurological drugs in Japan.

Science.gov (United States)

Ikeda, Masayuki

2017-06-28

The delays in the approval and development of neurological drugs between Japan and other countries have been a major issue for patients with neurological diseases. The objective of this study was to analyze factors contributing to the delay in the launching of neurological drugs in Japan. We analyzed data from Japan and the US for the approval of 42 neurological drugs, all of which were approved earlier in the US than in Japan, and examined the potential factors that may cause the delay of their launch. Introductions of the 42 drugs in Japan occurred at a median of 87 months after introductions in the US. The mean review time of new drug applications for the 20 drugs introduced in Japan in January 2011 or later (15 months) was significantly shorter than that for the other 22 drugs introduced in Japan in December 2010 or earlier (24 months). The lag in the Japan's review time behind the US could not explain the approval delays. In the 31 of the 42 drugs, the application data package included overseas data. The mean review time of these 31 drugs (17 months) was significantly shorter than that of the other 11 drugs without overseas data (26 months). The mean approval lag behind the US of the 31 drugs (78 months) was also significantly shorter than that of the other 11 drugs (134 months). These results show that several important reforms in the Japanese drug development and approval system (e.g., inclusion of global clinical trial data) have reduced the delays in the clinical development of neurological drugs.

The effect of motivational interviewing-based intervention using self-determination theory on promotion of physical activity among women in reproductive age: A randomized clinical trial

Science.gov (United States)

Mahmoodabad, Seyed Saeed Mazloomy; Tonekaboni, Nooshin Rouhani; Farmanbar, Rabiollah; Fallahzadeh, Hossein; Kamalikhah, Tahereh

2017-01-01

Background Physical activity (PA) prevents chronic diseases. Self-determination theory (SDT) provides a useful framework to understand the nature of motivational interviewing (MI). Objective This study aimed to determine the effect of MI-based intervention using SDT on the promotion of PA among women in reproductive age. Methods Seventy women in reproductive age were selected by clustering sampling method for this randomized controlled trial. The questionnaire included the variables of physical fitness test, SDT, and global physical activity questionnaire (GPAQ). The validity of the questionnaires was approved using content validity ratio (CVR) and index (CVI). The reliability and internal consistency of the questionnaires and measures was approved using test-retest method and Cronbach’s alpha test, respectively. The intervention group (n=35) received four MI sessions through theory and one standard education session about PA. The control group (n=35) received a standard education session about PA. Results Four months after the intervention, an increase in the mean scores of total PA (pamotivation (p<0.01, ES= −0.56) over time, compared to the control group. Conclusion MI-based intervention using SDT was effective on the promotion of PA. Trial registration The Trial was registered at the Iranian Registry of Clinical Trial (http://www.irct.ir) with the Irct ID: IRCT2015101924592N1. PMID:28713522

JAK inhibitors for the treatment of myeloproliferative neoplasms and other disorders [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

William Vainchenker

2018-01-01

Full Text Available JAK inhibitors have been developed following the discovery of the JAK2V617F in 2005 as the driver mutation of the majority of non-BCR-ABL1 myeloproliferative neoplasms (MPNs. Subsequently, the search for JAK2 inhibitors continued with the discovery that the other driver mutations (CALR and MPL also exhibited persistent JAK2 activation. Several type I ATP-competitive JAK inhibitors with different specificities were assessed in clinical trials and exhibited minimal hematologic toxicity. Interestingly, these JAK inhibitors display potent anti-inflammatory activity. Thus, JAK inhibitors targeting preferentially JAK1 and JAK3 have been developed to treat inflammation, autoimmune diseases, and graft-versus-host disease. Ten years after the beginning of clinical trials, only two drugs have been approved by the US Food and Drug Administration: one JAK2/JAK1 inhibitor (ruxolitinib in intermediate-2 and high-risk myelofibrosis and hydroxyurea-resistant or -intolerant polycythemia vera and one JAK1/JAK3 inhibitor (tofacitinib in methotrexate-resistant rheumatoid arthritis. The non-approved compounds exhibited many off-target effects leading to neurological and gastrointestinal toxicities, as seen in clinical trials for MPNs. Ruxolitinib is a well-tolerated drug with mostly anti-inflammatory properties. Despite a weak effect on the cause of the disease itself in MPNs, it improves the clinical state of patients and increases survival in myelofibrosis. This limited effect is related to the fact that ruxolitinib, like the other type I JAK2 inhibitors, inhibits equally mutated and wild-type JAK2 (JAK2WT and also the JAK2 oncogenic activation. Thus, other approaches need to be developed and could be based on either (1 the development of new inhibitors specifically targeting JAK2V617F or (2 the combination of the actual JAK2 inhibitors with other therapies, in particular with molecules targeting pathways downstream of JAK2 activation or the stability of JAK2

Towards a framework of success factors for clinical trials

DEFF Research Database (Denmark)

Buonansegna, Erika; Salomo, Søren; Maier, Anja

2012-01-01

Clinical trials in the pharmaceutical industry are the most critical part of the drug development process with respect to obtaining the market approval from the authorities. Clinical trials are highly expensive, time-consuming and often unsuccessful. While new product development (NPD) literature...

Automated Clinical Assessment from Smart home-based Behavior Data

Science.gov (United States)

Dawadi, Prafulla Nath; Cook, Diane Joyce; Schmitter-Edgecombe, Maureen

2016-01-01

Smart home technologies offer potential benefits for assisting clinicians by automating health monitoring and well-being assessment. In this paper, we examine the actual benefits of smart home-based analysis by monitoring daily behaviour in the home and predicting standard clinical assessment scores of the residents. To accomplish this goal, we propose a Clinical Assessment using Activity Behavior (CAAB) approach to model a smart home resident’s daily behavior and predict the corresponding standard clinical assessment scores. CAAB uses statistical features that describe characteristics of a resident’s daily activity performance to train machine learning algorithms that predict the clinical assessment scores. We evaluate the performance of CAAB utilizing smart home sensor data collected from 18 smart homes over two years using prediction and classification-based experiments. In the prediction-based experiments, we obtain a statistically significant correlation (r = 0.72) between CAAB-predicted and clinician-provided cognitive assessment scores and a statistically significant correlation (r = 0.45) between CAAB-predicted and clinician-provided mobility scores. Similarly, for the classification-based experiments, we find CAAB has a classification accuracy of 72% while classifying cognitive assessment scores and 76% while classifying mobility scores. These prediction and classification results suggest that it is feasible to predict standard clinical scores using smart home sensor data and learning-based data analysis. PMID:26292348

HyApproval - Handbook for the approval of hydrogen refuelling stations - First preliminary achievements

Energy Technology Data Exchange (ETDEWEB)

Wurster, R.; Vandendungen, G.; Guichard, J.; Molag, M.; Barron, J.; Reijalt, M.; Hill, H.J.; Landinger, H.

2007-05-15

The EU-funded project HyApproval [www.hyapproval.org] aims at developing a universal Handbook to facilitate the approval process of Hydrogen Refuelling Stations (HRS) in Europe. The main goal of the HyApproval partnership with 22 partners from Europe and one each from China, Japan and the USA is to provide a Handbook of technical and regulatory requirements to assist authorisation officials, companies and organisations in the safe implementation and operation of HRS. Achievements during the first 15 months: analyses of HRS technology concepts and of equipment and safety distances/ Intermediate Design Paper/ Regulations, Codes and Standards (RCS) review and comparison/ first Handbook draft and first review sessions with HySafe experts/ safety matrix/ identification of accident scenarios/ agreement on safety documentation/ critical review of reliability data from collections and risk studies/ risk assessment (RA) criteria definition and RA/ matrix of acceptability and awareness levels/ database of Fire Associations and First Responders/ calendar of hydrogen events/ general description of CGH{sub 2} interfaces. (au)

Biomedicines—Moving Biologic Agents into Approved Treatment Options

Directory of Open Access Journals (Sweden)

Kenneth Cornetta

2013-03-01

Full Text Available The development of biologic agents for therapeutic purposes, or biomedicines, has seen an active area of research both at the bench and in clinical trials. There is mounting evidence that biologic products can provide effective therapy for diseases that have been unresponsive to traditional pharmacologic approaches. Monoclonal antibody therapy for cancer and rheumatologic diseases has become a well accepted part of disease treatment plans. Gene therapy products have been approved in China and Europe. Bioengineering of new agents capitalizing on microRNA biology, nanoparticle technology, stem cell biology, and an increasing understanding of immunology predict a rich future for product development. [...

Revised guideline for the approval procedure of package designs in Germany

International Nuclear Information System (INIS)

Nitsche, F.; Roedel, R.

2004-01-01

The IAEA Regulations for the Safe Transport of Radioactive Material, TS-R-1 are applied in Germany through the implementation of the Dangerous Goods Transport Regulations for class 7 of the International Modal Organisations (ADR, RID, IMDG-Code, ICAO-TI). Based on this the approval procedures for packages designs applied in Germany are in compliance with the provisions of TS-R-1. The Guideline R 003 issued by the Ministry of Transport, Building and Housing (BMVBW) in 1991 is the basis for the package design approval procedures in Germany. This Guideline has been reviewed and revised to reflect latest developments in the regulations as well as in the regulatory practice. In particular it has been extended to the approval procedures of Type C packages, packages subject to transitional arrangements, special form and low dispersible radioactive material and provides more detailed information to the applicant about the requested documentation. Publication of this revised guideline has been delayed but it is expected to take place in October 2004. The paper gives an overview about the main parts and provisions of this revised Guideline R 003 with the focus on package design approval procedures

Patient-Reported Outcomes Labeling for Products Approved by the Office of Hematology and Oncology Products of the US Food and Drug Administration (2010-2014).

Science.gov (United States)

Gnanasakthy, Ari; DeMuro, Carla; Clark, Marci; Haydysch, Emily; Ma, Esprit; Bonthapally, Vijayveer

2016-06-01

To review the use of patient-reported outcome (PRO) data in medical product labeling granted by the US Food and Drug Administration (FDA) for new molecular entities and biologic license applications by the FDA Office of Hematology and Oncology Products (OHOP) between January 2010 and December 2014, to elucidate challenges faced by OHOP for approving PRO labeling, and to understand challenges faced by drug manufacturers to include PRO end points in oncology clinical trials. FDA Drug Approval Reports by Month were reviewed to obtain the number of new molecular entities and biologic license applications approved from 2010 to 2014. Drugs approved by the FDA OHOP during this period were selected for further review, focusing on brand and generic name; approval date; applicant; indication; PRO labeling describing treatment benefit, measures, end point status, and significant results; FDA reviewer feedback on PRO end points; and study design of registration trials. First in class, priority review, fast track, orphan drug, or accelerated approval status was retrieved for selected oncology drugs from 2011 to 2014. Descriptive analyses were performed by using Microsoft Excel 2010. Of 160 drugs approved by the FDA (2010-2014), 40 were approved by OHOP. Three (7.5%) of the 40 received PRO-related labeling (abiraterone acetate, ruxolitinib phosphate, and crizotinib). Compared with nononcology drugs (2011-2014), oncology drugs were more likely to be orphan and first in class. The majority of oncology drug reviews by FDA were fast track, priority, or accelerated. Although symptoms and functional decrements are common among patients with cancer, PRO labeling is rare in the United States, likely because of logistical hurdles and oncology study design. Recent developments within the FDA OHOP to capture PROs in oncology studies for the purpose of product labeling are encouraging. © 2016 by American Society of Clinical Oncology.

Recent advances in treatment of heart failure [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Takeshi Kitai

2015-12-01

Full Text Available With the total cases and economic burden of heart failure continuing to rise, there is an overwhelming need for novel therapies. Several drugs for heart failure have succeeded in preclinical and early-phase clinical trials, but most of them failed to show the real benefit in pivotal clinical trials. Meanwhile, the US Food and Drug Administration recently approved two promising new drugs to treat heart failure: ivabradine and sacubitril/valsartan. Furthermore, some of the newer agents in testing offer the potential for significant progress in addition to these drugs. Patiromer and zirconium cyclosilicate are attractive agents that are expected to prevent hyperkalemia during renin-angiotensin-aldosterone system inhibition, and serelaxin and urodilatin are promising drugs in the treatment of acute heart failure. Future clinical trials with more appropriate study designs, optimal clinical endpoints, and proper patient selection are mandatory to assess the true efficacy of these attractive compounds in clinical practice.

Designing an automated clinical decision support system to match clinical practice guidelines for opioid therapy for chronic pain

Directory of Open Access Journals (Sweden)

Clark Michael E

2010-04-01

Full Text Available Abstract Background Opioid prescribing for chronic pain is common and controversial, but recommended clinical practices are followed inconsistently in many clinical settings. Strategies for increasing adherence to clinical practice guideline recommendations are needed to increase effectiveness and reduce negative consequences of opioid prescribing in chronic pain patients. Methods Here we describe the process and outcomes of a project to operationalize the 2003 VA/DOD Clinical Practice Guideline for Opioid Therapy for Chronic Non-Cancer Pain into a computerized decision support system (DSS to encourage good opioid prescribing practices during primary care visits. We based the DSS on the existing ATHENA-DSS. We used an iterative process of design, testing, and revision of the DSS by a diverse team including guideline authors, medical informatics experts, clinical content experts, and end-users to convert the written clinical practice guideline into a computable algorithm to generate patient-specific recommendations for care based upon existing information in the electronic medical record (EMR, and a set of clinical tools. Results The iterative revision process identified numerous and varied problems with the initially designed system despite diverse expert participation in the design process. The process of operationalizing the guideline identified areas in which the guideline was vague, left decisions to clinical judgment, or required clarification of detail to insure safe clinical implementation. The revisions led to workable solutions to problems, defined the limits of the DSS and its utility in clinical practice, improved integration into clinical workflow, and improved the clarity and accuracy of system recommendations and tools. Conclusions Use of this iterative process led to development of a multifunctional DSS that met the approval of the clinical practice guideline authors, content experts, and clinicians involved in testing. The

Are the MDS-UPDRS-based composite scores clinically applicable?

Science.gov (United States)

Makkos, Attila; Kovács, Márton; Aschermann, Zsuzsanna; Harmat, Márk; Janszky, József; Karádi, Kázmér; Kovács, Norbert

2018-02-28

The International Parkinson and Movement Disorder Society-sponsored UPDRS (MDS-UPDRS) is a powerful clinical outcome measure. To evaluate the feasibility of various MDS-UPDRS-based composite scores and determine their minimal clinically important difference threshold values. Overall, 1,113 paired investigations of 452 patients were reviewed implementing three different techniques simultaneously. Based on the ordinal regression modeling, the MDS-UPDRS II+III, MDS-UPDRS I+II+III, and the total score of MDS-UPDRS are clinically applicable outcome measures. Any improvement greater than 4.9 points or any worsening more than 4.2 points on MDS-UPDRS II+III represent a minimal, yet clinically meaningful, change. In reference to MDS-UPDRS I+II+III, the smallest changes considered clinically relevant were 6.7 and 5.2 points for improvement and deterioration, respectively. The thresholds for the total score of MDS-UPDRS were 7.1 points for improvement and 6.3 points for worsening. Our findings support the application of various MDS-UPDRS-based composite scores. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

Analysis of the Education Program Approval Process: A Program Evaluation.

Science.gov (United States)

Fountaine, Charles A.; And Others

A study of the education program approval process involving the Veterans Administration (VA) and the State Approving Agencies (SAAs) had the following objectives: to describe the present education program approval process; to determine time and costs associated with the education program approval process; to describe the approval process at…

Clinical applications of PD-1-based therapy: a focus on pembrolizumab (MK-3475 in the management of melanoma and other tumor types

Directory of Open Access Journals (Sweden)

Gangadhar TC

2015-04-01

Full Text Available Tara C Gangadhar,1 April KS Salama2 1Division of Hematology/Oncology, Department of Medicine, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA; 2Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, NC, USA Abstract: Preclinical work has led to an increased understanding of the immunomodulatory mechanisms involved in the regulation of the antitumor response in a variety of tumor types. PD-1 (programmed death 1 appears to be a key checkpoint involved in immune suppression in the tumor microenvironment, even in diseases not previously thought to be sensitive to immune manipulation. More recently, the subsequent clinical development of PD-1-based therapy has resulted in a major breakthrough in the field of oncology. Pembrolizumab, a humanized highly selective IgG4 anti-PD-1 monoclonal antibody, was recently approved for the treatment of advanced melanoma based on promising early-phase clinical data. Encouraging results have also been seen in other malignancies, and PD-1-targeted therapies are likely to markedly change the treatment landscape. Future work will center on rationally designed combination strategies in order to potentiate the antitumor immune response and overcome mechanisms of resistance. Keywords: PD-1, cancer, pembrolizumab, nivolumab, immunotherapy, antitumor activity 

78 FR 57857 - Medicare and Medicaid Programs; Application from the Compliance Team for Initial CMS-Approval of...

Science.gov (United States)

2013-09-20

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Medicare & Medicaid Services [CMS-3287-PN] Medicare and Medicaid Programs; Application from the Compliance Team for Initial CMS-Approval of its Rural Health Clinic Accreditation Program AGENCY: Centers for Medicare and Medicaid Services, HHS. ACTION...

Clinical implications of recent studies using mTOR inhibitors to treat advanced hormone receptor-positive breast cancer

International Nuclear Information System (INIS)

Arena, Francis

2014-01-01

Breast cancer is a leading cause of cancer-related death worldwide. Approximately 75% of breast cancer is hormone receptor-positive (HR + ) and is managed with endocrine therapies. However, relapse or disease progression caused by primary or acquired endocrine resistance is frequent. Phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)-mediated signaling is one of the molecular mechanisms leading to endocrine resistance. mTOR inhibitors that target the PI3K/Akt/mTOR pathway are the first of the targeted therapies to be evaluated in clinical trials to overcome endocrine resistance. Although the clinical trial with temsirolimus, an mTOR inhibitor, did not show any benefit when compared with endocrine therapy alone, a Phase II clinical trial with sirolimus has been promising. Recently, everolimus was approved in combination with exemestane by the US Food and Drug Administration for treating postmenopausal women with advanced HR + breast cancer, based on the results of a Phase III trial. Therefore, everolimus represents the first and only targeted agent approved for combating endocrine resistance

Sacubitril/Valsartan: From Clinical Trials to Real-world Experience.

Science.gov (United States)

Joly, Joanna M; Desai, Akshay S

2018-04-23

Compared to enalapril, use of angiotensin-receptor blocker and neprilysin inhibitor sacubitril/valsartan to treat patients with heart failure and reduced ejection fraction (HFrEF) is associated with substantial reductions in both cardiovascular mortality and heart failure progression. The purpose of this review is to discuss the real-world experience of sacubitril/valsartan. In the years following the publication of the landmark PARADIGM-HF trial in 2014 and its subsequent FDA approval, a growing evidence base supports the safety and efficacy of sacubitril/valsartan in a broad spectrum of patients with HFrEF. Updated clinical practice guidelines have embraced the use of sacubitril/valsartan in preference to ACE inhibitors or ARBs in selected patients. In this review, we highlight the clinical trials that led to these key updates to clinical guidelines, offer practical strategies for patient selection and utilization in clinical practice, and identify important areas of uncertainty that require future research.

First approval procedure of the TL dosimetric service of the NPP in Slovenia

International Nuclear Information System (INIS)

Janzekovic, H.; Krizman, M.; Pucelj, B.; Stuhec, M.; Zdesar, U.

2001-01-01

The individual dosimetry of exposed workers in a NPP is one of the essential parts which demonstrates the radiation protection standards achieved in a facility. According to the current legislation the Ministry of Health of the Republic of Slovenia has the authority to grant approvals to personal dosimetric services which perform the dosimetric monitoring of workers in Slovenia. Due to the fact that the detailed approval procedure is not given in national regulations, the Ministry of Health in 2000 established a group of experts with the task to prepare technical and organising requirements for such approval. Based on international documents [1,2,3] the Approval procedure for the thermoluminescence dosimetric (TL) services was created. Following this procedure the assessment of the TL dosimetric service in the NPP was performed. The problems related to the technical and organising requirements with the emphasise on the QA/QC criteria of the TL dosimetric service will be discussed.(author)

78 FR 28275 - Office of Commercial Space Transportation; Safety Approval Performance Criteria

Science.gov (United States)

2013-05-14

... provide as a service, scenario based physiology training, which includes hypobaric chamber training. BST may offer its scenario based physiology altitude training as a service to a prospective launch and...: Notification of criteria used to evaluate the Black Sky Training, Inc. (BST) safety approval application...

Factors related to drug approvals: predictors of outcome?

Science.gov (United States)

Liberti, Lawrence; Breckenridge, Alasdair; Hoekman, Jarno; McAuslane, Neil; Stolk, Pieter; Leufkens, Hubert

2017-06-01

There is growing interest in characterising factors associated with positive regulatory outcomes for drug marketing authorisations. We assessed empirical studies published over the past 15 years seeking to identify predictive factors. Factors were classified to one of four 'factor clusters': evidentiary support; product or indication characteristics; company experience or strategy; social and regulatory factors. We observed a heterogeneous mix of technical factors (e.g., study designs, clinical evidence of efficacy) and less studied social factors (e.g., company-regulator interactions). We confirmed factors known to be of relevance to drug approval decisions (imperative) and a cohort of less understood (compensatory) social factors. Having robust supportive clinical evidence, addressing rare or serious illness, following scientific advice and prior company experience were associated with positive outcomes, which illustrated the multifactorial nature of regulatory decision making and factors need to be considered holistically while having varying, context-dependent importance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Methotrexate for the treatment of juvenile idiopathic arthritis: process to approval for JIA indication in Japan.

Science.gov (United States)

Mori, Masaaki; Naruto, Takuya; Imagawa, Tomoyuki; Murata, Takuji; Takei, Syuji; Tomiita, Minako; Itoh, Yasuhiko; Fujikawa, Satoshi; Yokota, Shumpei

2009-01-01

Methotrexate (MTX), the primary treatment for the articular-type juvenile idiopathic arthritis (JIA), is effective and brings about radiological improvement. Patient compliance is good, and it is recognized that its known side effects, namely, disruption of liver function and induction of pulmonary lesions, are unlikely to be severe at the low MTX doses that are administered. In Japan, MTX was granted approval in 1999 by the then Ministry of Health and Welfare specifically for treating rheumatoid arthritis in adult patients, allowing it be generally used in medical institutions for patients having National Health Insurance. However, in the pediatric field, its use outside the indications has so far been unavoidable, and has been left to the discretion of the physician. Finally, at the present conference, expansion of the indications of MTX for JIA was approved in Japan. It is noteworthy that this expansion of indications was achieved without requiring clinical trials on children sponsored by the pharmaceutical company: it was achieved rather by collecting necessary information through ongoing efforts (including collection and analysis of information about approval status in foreign countries, adequate evidence from the literature, implementation of a clinical use survey in Japan, etc.). It also merits attention that the maximum dose (10 mg/m2) was set on the basis of pharmacokinetic data from children, rather than relying on the dosing method and dose for adults.

Clinical use of gadobutrol for contrast-enhanced magnetic resonance imaging of neurological diseases

Directory of Open Access Journals (Sweden)

Cheng KT

2012-02-01

Full Text Available Kenneth T Cheng1, Hannah Y Cheng2, Kam Leung31Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA; 2Freelance Technical Writer, New Orleans, LA, USA; 3National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USAAbstract: Contrast-enhanced magnetic resonance imaging (CE-MRI is an important clinical tool for diagnosing neurological diseases. The appropriate use of a suitable MRI contrast agent or contrast pharmaceutical is essential for CE-MRI to produce desirable diagnostic images. Currently, there are seven contrast agents (CAs or pharmaceuticals approved for clinical imaging of the central nervous system (CNS in the US, Europe, or Japan. All of the clinically approved CAs are water-soluble gadolinium-based contrast agents (GBCAs which do not penetrate the CNS blood–brain barrier (BBB. These agents are used for imaging CNS areas without a BBB, or various pathologies, such as tumors and infection that break down the BBB and allow CAs to enter into the surrounding parenchyma. Clinically, GBCAs are most useful for detecting primary and secondary cerebral neoplastic lesions. Among these CNS GBCAs, gadobutrol (Gd-BT-DO3A, Gadovist™ is a neutral, nonionic, macrocyclic compound that showed promising results from clinical trials of CNS imaging. In comparison with other GBCAs, Gd-BT-DO3A has relatively high in vitro kinetic stability and r1 relaxivity. Gd-BT-DO3A has been recently approved by the US Food and Drug Administration (FDA in 2011 for CNS imaging. A review of available literature shows that Gd-BT-DO3A exhibits similar safety and clinical efficacy profiles to other GBCAs. Gd-BT-DO3A has the distinguishing feature that it is the only clinical agent commercially available in a formulation of 1.0 M concentration with a relatively higher in vitro T1 shortening per unit volume than other clinical GBCAs which are only

Double-Blinding and Bias in Medication and Cognitive-Behavioral Therapy Trials for Major Depressive Disorder [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Douglas Berger

2015-08-01

Full Text Available While double-blinding is a crucial aspect of study design in an interventional clinical trial of medication for a disorder with subjective endpoints such as major depressive disorder, psychotherapy clinical trials, particularly cognitive-behavioral therapy trials, cannot be double-blinded. This paper highlights the evidence-based medicine problem of double-blinding in the outcome research of a psychotherapy and opines that psychotherapy clinical trials should be called, “partially-controlled clinical data” because they are not double-blinded. The implications for practice are, 1. For practitioners to be clear with patients the level of rigor to which interventions have been studied, 2. For authors of psychotherapy outcome studies to be clear that the problem in the inability to blind a psychotherapy trial severely restricts the validity of any conclusions that can be drawn, and 3. To petition National Health Insurance plans to use caution in approving interventions studied without double-blinded confirmatory trials as they may lead patients to avoid other treatments shown to be effective in double-blinded trials.

49 CFR 1522.109 - TSA review and approval.

Science.gov (United States)

2010-10-01

... 49 Transportation 9 2010-10-01 2010-10-01 false TSA review and approval. 1522.109 Section 1522.109..., DEPARTMENT OF HOMELAND SECURITY SECURITY RULES FOR ALL MODES OF TRANSPORTATION TSA-APPROVED VALIDATION FIRMS AND VALIDATORS TSA-Approved Validation Firms and Validators for the Certified Cargo Screening Program...

49 CFR 1522.115 - Renewal of TSA approval.

Science.gov (United States)

2010-10-01

... 49 Transportation 9 2010-10-01 2010-10-01 false Renewal of TSA approval. 1522.115 Section 1522.115..., DEPARTMENT OF HOMELAND SECURITY SECURITY RULES FOR ALL MODES OF TRANSPORTATION TSA-APPROVED VALIDATION FIRMS AND VALIDATORS TSA-Approved Validation Firms and Validators for the Certified Cargo Screening Program...

29 CFR 1952.157 - Changes to approved plan.

Science.gov (United States)

2010-07-01

... (CONTINUED) APPROVED STATE PLANS FOR ENFORCEMENT OF STATE STANDARDS North Carolina § 1952.157 Changes to approved plan. (a) Legislation. (1) On March 29, 1994, the Assistant Secretary approved North Carolina's... section 17 of the Act as amended on November 5, 1990. (2) [Reserved] (b) The Voluntary Protection Program...

48 CFR 2922.103-4 - Approvals.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Approvals. 2922.103-4 Section 2922.103-4 Federal Acquisition Regulations System DEPARTMENT OF LABOR SOCIOECONOMIC PROGRAMS APPLICATION OF LABOR LAWS TO GOVERNMENT ACQUISITIONS Basic Labor Policies 2922.103-4 Approvals. The “agency...

38 CFR 21.7220 - Course approval.

Science.gov (United States)

2010-07-01

...) VOCATIONAL REHABILITATION AND EDUCATION All Volunteer Force Educational Assistance Program (Montgomery GI...; Pub. L. 98-525) (b) Course approval criteria. In administering benefits payable under 38 U.S.C...) Section 21.4265—Practical training approved as institutional training or on-job training; (10) Section 21...

Post-market clinical research conducted by medical device manufacturers: a cross-sectional survey.

Science.gov (United States)

Ross, Joseph S; Blount, Katrina L; Ritchie, Jessica D; Hodshon, Beth; Krumholz, Harlan M

2015-01-01

In the US, once a medical device is made available for use, several requirements have been established by the US Food and Drug Administration (FDA) to ensure ongoing post-market surveillance of device safety and effectiveness. Our objective was to determine how commonly medical device manufacturers initiate post-market clinical studies or augment FDA post-market surveillance requirements for higher-risk devices that are most often approved via the FDA's pre-market approval (PMA) pathway. We conducted a cross-sectional survey of 47 manufacturers with operations in California, Minnesota, and Massachusetts who market devices approved via the PMA pathway. Among 22 respondents (response rate =47%), nearly all self-reported conducting post-market clinical research studies, commonly between 1 and 5; only 1 respondent reported never conducting post-market clinical research studies. While manufacturers most often engaged in these studies to satisfy FDA requirements, other reasons were reported, including performance monitoring and surveillance and market acceptance initiatives. Risks of conducting and not conducting post-market clinical research studies were described through open-ended response to questions. Medical device manufacturers commonly initiate post-market clinical studies at the request of the FDA. Clinical data from these studies should be integrated into national post-market surveillance initiatives.

Progress Toward the Clinical Translation of Bioinspired Peptide and Protein Assemblies.

Science.gov (United States)

Hainline, Kelly M; Fries, Chelsea N; Collier, Joel H

2018-03-01

Supramolecular materials composed of proteins and peptides have been receiving considerable attention toward a range of diseases and conditions from vaccines to drug delivery. Owing to the relative newness of this class of materials, the bulk of work to date has been preclinical. However, examples of approved treatments particularly in vaccines, dentistry, and hemostasis demonstrate the translational potential of supramolecular polypeptides. Critical milestones in the clinical development of this class of materials and currently approved supramolecular polypeptide therapies are described in this study. Additional examples of not-yet-approved materials that are steadily advancing toward clinical use are also featured. Spherical assemblies such as virus-like particles, designed protein nanoparticles, and spherical peptide amphiphiles are highlighted, followed by fiber-forming systems such as fibrillizing peptides, fiber-forming peptide-amphiphiles, and filamentous bacteriophages. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

No longer "if," but "when": the coming abbreviated approval pathway for follow-on biologics.

Science.gov (United States)

Kelly, Jeremiah J; David, Michael

2009-01-01

Abbreviated approval of follow-on biologics involves answering complex scientific, legal, and policy questions. The Food and Drug Administration (FDA or the Agency) asserts that it lacks the statutory authority to approve follow-on versions of biologics licensed under Section 351 of the Public Health Service Act (PHSA). Despite persuasive arguments to the contrary the one hundred and tenth Congress entertained four legislative proposals to give FDA this authority, each markedly different. It is no longer a question of "if," but "when" FDA will receive authority to review and license abbreviated applications for follow-on biologics. Any legislation in the one hundred and eleventh Congress must determine: (1) if FDA should be granted authority to develop an abbreviated pathway through rulemaking or guidance; (2) if human clinical trials should be mandatory or discretionary; (3) the feasibility of interchangeability determinations in light of patient safety concerns; (4) the duration of marketing exclusivity for associated products; (5) which products are eligible for follow-on approval; and (6) the degree to which uniformity is achievable between the FD&C Act and the PHSA. This paper recommends the one hundred and eleventh Congress strike a balance between patient safety, incentives for product innovation, price competition, and the need for a flexible, transparent process that capitalizes on FDA's growing expertise with follow-on biologics approvals under Section 505(b)(2) of the FD&C Act.

33 CFR 115.70 - Advance approval of bridges.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Advance approval of bridges. 115... BRIDGES BRIDGE LOCATIONS AND CLEARANCES; ADMINISTRATIVE PROCEDURES § 115.70 Advance approval of bridges. (a) The General Bridge Act of 1946 requires the approval of the location and plans of bridges prior...

Quality assurance of approved out of programme psychiatry training and research over the past 5 years

Science.gov (United States)

Osman-Hicks, Victoria; Graham, Hannah; Leadbetter, Peter; Brittlebank, Andrew

2015-01-01

Aims and method This paper intends to analyse the number of applications, trainee demographic and approval rate of those applying for out of programme training (OOPT) or out of programme research (OOPR) between January 2008 and April 2013 using the committee’s anonymised database. We also describe the process of application and approval by the Quality Assurance Committee. Results There were 90 applications, including 10 resubmissions during the 64-month period. Most applicants (77%) were higher trainees; 53% of applicants were from the London deanery; 60% of applications were for research posts and higher degrees (OOPR). Overall, 64% were approved by the committee: 70% for OOPRs and 53% for OOPTs. Clinical implications This paper shows with transparency the breakdown of applications to the Quality Assurance Committee. Around two-thirds of applications to the committee are supported (64%). Relatively few psychiatry trainees (2.5%) have applied for an OOPT or an OOPR over the past 5 years. PMID:26191450

Lessons Learned from A System-Wide Evidence-Based Practice Program Implementation

Science.gov (United States)

2017-04-25

incorporating scientific evidence, clinical expertise and the patient’s values and preferences to provide quality healthcare . Despite growing...MEMORANDUM FOR ST DEPARTMENT OF THE AIR FORCE 59TH MEDICAL WING (AETC) JOINT BASE SAN ANTONIO - LACKLAND TEXAS ATTN: LT COL JACQUELINE KILLIAN...FROM: 59 MDW/SGVU SUBJECT: Professional Presentation Approval 14 FEB 2017 1. Your paper, entitled Lesson Learned From A System-Wide Evidence- Based

Progress in the Fight Against Multidrug-Resistant Bacteria? A Review of U.S. Food and Drug Administration-Approved Antibiotics, 2010-2015.

Science.gov (United States)

Deak, Dalia; Outterson, Kevin; Powers, John H; Kesselheim, Aaron S

2016-09-06

A weak antibiotic pipeline and the increase in drug-resistant pathogens have led to calls for more new antibiotics. Eight new antibiotics were approved by the U.S. Food and Drug Administration (FDA) between January 2010 and December 2015: ceftaroline, fidaxomicin, bedaquiline, dalbavancin, tedizolid, oritavancin, ceftolozane-tazobactam, and ceftazidime-avibactam. This study evaluates the development course and pivotal trials of these antibiotics for their innovativeness, development process, documented patient outcomes, and cost. Data sources were FDA approval packages and databases (January 2010 to December 2015); the Red Book (Truven Health Analytics); Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations (FDA); and supplementary information from company filings, press releases, and media reports. Four antibiotics were approved for acute bacterial skin and skin-structure infection. Seven had similar mechanisms of action to those of previously approved drugs. Six were initially developed by small to midsized companies, and 7 are currently marketed by 1 of 3 large companies. The drugs spent a median of 6.2 years in clinical trials (interquartile range [IQR], 5.4 to 8.8 years) and 8 months in FDA review (IQR, 7.5 to 8 months). The median number of patients enrolled in the pivotal trials was 666 (IQR, 553 to 739 patients; full range, 44 to 1005 patients), and median trial duration was 18 months (IQR, 15 to 22 months). Seven drugs were approved on the basis of pivotal trials evaluating noninferiority. One drug demonstrated superiority on an exploratory secondary end point, 2 showed decreased efficacy in patients with renal insufficiency, and 1 showed increased mortality compared with older drugs. Seven of the drugs are substantially more expensive than their trial comparators. Limitations are that future research may show benefit to patients, new drugs from older classes may show superior effectiveness in specific patient populations, and

How to design and write a clinical research protocol in Cosmetic Dermatology*

Science.gov (United States)

Bagatin, Ediléia; Miot, Helio A.

2013-01-01

Cosmetic Dermatology is a growing subspecialty. High-quality basic science studies have been published; however, few double-blind, randomized controlled clinical trials, which are the major instrument for evidence-based medicine, have been conducted in this area. Clinical research is essential for the discovery of new knowledge, improvement of scientific basis, resolution of challenges, and good clinical practice. Some basic principles for a successful researcher include interest, availability, persistence, and honesty. It is essential to learn how to write a protocol research and to know the international and national regulatory rules. A complete clinical trial protocol should include question, background, objectives, methodology (design, variable description, sample size, randomization, inclusion and exclusion criteria, intervention, efficacy and safety measures, and statistical analysis), consent form, clinical research form, and references. Institutional ethical review board approval and financial support disclosure are necessary. Publication of positive or negative results should be an authors' commitment. PMID:23539006

E-Approval Plans in Research Libraries

Science.gov (United States)

Pickett, Carmelita; Tabacaru, Simona; Harrell, Jeanne

2014-01-01

Research libraries have long invested in approval plan services, which offer an economical way to acquire scholarly and scientific publications. Traditional approval plans have evolved and now enable libraries to expand their e-book offerings to better serve researchers. Publishers offer a myriad of e-book purchasing options. These range from…

THERAPEUTIC ANTISENSE OLIGONUCLEOTIDES AGAINST CANCER: HURDLING TO THE CLINIC

Directory of Open Access Journals (Sweden)

Pedro Miguel Duarte Moreno

2014-10-01

Full Text Available Under clinical development since the early 90’s and with two successfully approved drugs (Fomivirsen and Mipomersen, oligonucleotide-based therapeutics have not yet delivered a clinical drug to the market in the cancer field. Whilst many pre-clinical data has been generated, a lack of understanding still exists on how to efficiently tackle all the different challenges presented for cancer targeting in a clinical setting. Namely, effective drug vectorization, careful choice of target gene or synergistic multi-gene targeting are surely decisive, while caution must be exerted to avoid potential toxic, often misleading off-target-effects. Here a brief overview will be given on the nucleic acid chemistry advances that established oligonucleotide technologies as a promising therapeutic alternative and ongoing cancer related clinical trials. Special attention will be given towards a perspective on the hurdles encountered specifically in the cancer field by this class of therapeutic oligonucleotides and a view on possible avenues for success is presented, with particular focus on the contribution from nanotechnology to the field.

Premarket Approvals (PMA)

Data.gov (United States)

U.S. Department of Health & Human Services — Premarket approval by FDA is the required process of scientific review to ensure the safety and effectiveness of all devices classified as Class III devices. An...

Clinical and Community-Based Education in U.S. Dental Schools.

Science.gov (United States)

Licari, Frank W; Evans, Caswell A

2017-08-01

This review of U.S. dental schools' clinical curricula suggests that the basic structure of clinical education has not changed significantly in the past 60 years, although important developments include the introduction of competency-based education and community-based clinical education. Most dental schools still have a two-year preclinical curriculum and a two-year clinical curriculum, and most schools still operate a large clinical facility where students receive the bulk of their clinical education and assessment for graduation. In those clinics, dental students are the main providers of patient treatment, with faculty serving in supervisory roles. In addition, a major portion of the entire dental curriculum continues to be dedicated to student education on the restoration of a single tooth or replacement of teeth. This article was written as part of the project "Advancing Dental Education in the 21 st Century."

77 FR 30327 - Approval of Information Collection Requirements; Comment Request

Science.gov (United States)

2012-05-22

... affirmative action programs based on functional or business units. A copy of this information collection... the request for Office of Management and Budget approval of the information collection request. FOR... regardless of race, sex, color, national origin, religion, or status as a qualified individual with a...

75 FR 28814 - FHA Lender Approval, Annual Renewal, Periodic Updates and Required Reports From FHA Approved Lenders

Science.gov (United States)

2010-05-24

... proposal. This information is required for: (1) FHA lender approval, (2) Annual renewal of each FHA lender... following information: Title of Proposal: FHA Lender Approval, Annual Renewal, Periodic Updates and Required... and HUD-92001-C. Description of the Need for the Information and Its Proposed Use: This information is...

Omalizumab for severe asthma: toward personalized treatment based on biomarker profile and clinical history

Directory of Open Access Journals (Sweden)

Tabatabaian F

2018-04-01

Full Text Available Farnaz Tabatabaian, Dennis K Ledford Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA Abstract: Asthma is a heterogeneous syndrome with numerous underlining molecular and inflammatory mechanisms contributing to the wide spectrum of clinical phenotypes. Multiple therapies targeting severe asthma with type 2 (T2 high inflammation are or soon will be available. T2 high inflammation is defined as inflammation associated with atopy or eosinophilia or an increase in cytokines associated with T-helper 2 lymphocytes. Omalizumab is a humanized anti-IgE monoclonal antibody and the first biologic therapy approved for moderate–severe allergic asthma. Despite the specificity of biologic therapies like omalizumab, clinical response is variable, with approximately 50% of treated patients achieving the primary outcome. A prior identification of the ideal candidate for therapy would improve patient outcomes and optimize the use of health care resources. As the number of biologic therapies for asthma increases, the goal is identification of biomarkers or clinical phenotypes likely to respond to a specific therapy. This review focuses on potential biomarkers and clinical history that may identify responders to omalizumab therapy for asthma. Keywords: severe persistent asthma, asthma phenotype and endotype, T2 high inflammation, omalizumab, asthma biomarkers, eosinophils, fractional exhaled nitric oxide, IgE

Heuristics in Managing Complex Clinical Decision Tasks in Experts' Decision Making.

Science.gov (United States)

Islam, Roosan; Weir, Charlene; Del Fiol, Guilherme

2014-09-01

Clinical decision support is a tool to help experts make optimal and efficient decisions. However, little is known about the high level of abstractions in the thinking process for the experts. The objective of the study is to understand how clinicians manage complexity while dealing with complex clinical decision tasks. After approval from the Institutional Review Board (IRB), three clinical experts were interviewed the transcripts from these interviews were analyzed. We found five broad categories of strategies by experts for managing complex clinical decision tasks: decision conflict, mental projection, decision trade-offs, managing uncertainty and generating rule of thumb. Complexity is created by decision conflicts, mental projection, limited options and treatment uncertainty. Experts cope with complexity in a variety of ways, including using efficient and fast decision strategies to simplify complex decision tasks, mentally simulating outcomes and focusing on only the most relevant information. Understanding complex decision making processes can help design allocation based on the complexity of task for clinical decision support design.

Three Drugs Approved for Urothelial Carcinoma by FDA.

Science.gov (United States)

2017-07-01

The FDA has approved one PD-1 checkpoint inhibitor, pembrolizumab, and two PD-L1 checkpoint inhibitors, avelumab and durvalumab, to treat metastatic urothelial carcinoma in patients whose disease continues to progress despite platinum-based chemotherapy. This brings the total number of checkpoint inhibitors for the disease to five, prompting questions about how best to use them. ©2017 American Association for Cancer Research.

Usefulness of problem-based learning in clinical nursing education ...

African Journals Online (AJOL)

Problem based learning (PBL) in clinical nursing is described as an effective learning strategy that can encourage students to become self-directed learners and to master clinical skills that can be transferable to service users. This study explores the usefulness of PBL in a nursing clinical setting from the nursing students' ...

The Alpha Stem Cell Clinic: a model for evaluating and delivering stem cell-based therapies.

Science.gov (United States)

Trounson, Alan; DeWitt, Natalie D; Feigal, Ellen G

2012-01-01

Cellular therapies require the careful preparation, expansion, characterization, and delivery of cells in a clinical environment. There are major challenges associated with the delivery of cell therapies and high costs that will limit the companies available to fully evaluate their merit in clinical trials, and will handicap their application at the present financial environment. Cells will be manufactured in good manufacturing practice or near-equivalent facilities with prerequisite safety practices in place, and cell delivery systems will be specialized and require well-trained medical and nursing staff, technicians or nurses trained to handle cells once delivered, patient counselors, as well as statisticians and database managers who will oversee the monitoring of patients in relatively long-term follow-up studies. The model proposed for Alpha Stem Cell Clinics will initially use the capacities and infrastructure that exist in the most advanced tertiary medical clinics for delivery of established bone marrow stem cell therapies. As the research evolves, they will incorporate improved procedures and cell preparations. This model enables commercialization of medical devices, reagents, and other products required for cell therapies. A carefully constructed cell therapy clinical infrastructure with the requisite scientific, technical, and medical expertise and operational efficiencies will have the capabilities to address three fundamental and critical functions: 1) fostering clinical trials; 2) evaluating and establishing safe and effective therapies, and 3) developing and maintaining the delivery of therapies approved by the Food and Drug Administration, or other regulatory agencies.

7 CFR 1710.105 - State regulatory approvals.

Science.gov (United States)

2010-01-01

... and Basic Policies § 1710.105 State regulatory approvals. (a) In States where a borrower is required... loans are approved by RUS: (1) Loans requiring an Environmental Impact Statement; (2) Loans to finance...

Factories Act 1961, Ionizing Radiations (Unsealed Radioactive Substances) Regulations 1968, Certificate of Approval No.1 (General)

International Nuclear Information System (INIS)

1969-01-01

Under the Ionising Radiations (Unsealed Radioactive Substances) Regulations No. 780 of 1968, the Chief Inspector of Factories has wide powers to ensure the protection of workers. By this Certificate he approved, for the purpose of measuring radiation doses, any radiation dosemeter, based on the phenomenon of radiation-induced thermoluminescence, supplied by an approved laboratory. (NEA) [fr

9 CFR 55.8 - Official CWD tests and approval of laboratories to conduct official CWD tests.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Official CWD tests and approval of laboratories to conduct official CWD tests. 55.8 Section 55.8 Animals and Animal Products ANIMAL AND PLANT... on live or dead animals, and will base the approval or disapproval of a test on the evaluation by...

Perspectives used for gaining approval of budgets.

Science.gov (United States)

Franks-Joiner, G L

1990-01-01

Nurse executives think about problems using a certain perspective which may influence decisions on budgetary matters. The nurse executives' perspective used in decision-making may influence which budget proposals are developed and approved. A study was performed to determine the perspective used by nurse executives in decision-making on supplementary budget item proposals and whether perspective use influenced approval. Findings showed that use of the system view or dual-domain perspective in a proposal may enhance nurse executives' changes of gaining approval.

78 FR 2315 - Projects Approved for Consumptive Uses of Water

Science.gov (United States)

2013-01-10

... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule..., receiving approval for the consumptive use of water pursuant to the Commission's approval by rule process...

78 FR 15402 - Projects Approved for Consumptive Uses of Water

Science.gov (United States)

2013-03-11

... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule..., receiving approval for the consumptive use of water pursuant to the Commission's approval by rule process...

78 FR 11947 - Projects Approved for Consumptive Uses of Water

Science.gov (United States)

2013-02-20

... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule..., receiving approval for the consumptive use of water pursuant to the Commission's approval by rule process...

78 FR 17281 - Projects Approved for Consumptive Uses of Water

Science.gov (United States)

2013-03-20

... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule..., receiving approval for the consumptive use of water pursuant to the Commission's approval by rule process...

77 FR 16317 - Projects Approved for Consumptive Uses of Water

Science.gov (United States)

2012-03-20

... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule..., receiving approval for the consumptive use of water pursuant to the Commission's approval by rule process...

77 FR 66909 - Projects Approved for Consumptive Uses of Water

Science.gov (United States)

2012-11-07

... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule... below, receiving approval for the consumptive use of water pursuant to the Commission's approval by rule...

77 FR 21143 - Projects Approved for Consumptive Uses of Water

Science.gov (United States)

2012-04-09

... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule..., receiving approval for the consumptive use of water pursuant to the Commission's approval by rule process...

77 FR 25010 - Projects Approved for Consumptive Uses of Water

Science.gov (United States)

2012-04-26

... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule... below, receiving approval for the consumptive use of water pursuant to the Commission's approval by rule...

77 FR 34455 - Projects Approved for Consumptive Uses of Water

Science.gov (United States)

2012-06-11

... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule..., receiving approval for the consumptive use of water pursuant to the Commission's approval by rule process...

77 FR 55891 - Projects Approved for Consumptive Uses of Water

Science.gov (United States)

2012-09-11

... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule..., receiving approval for the consumptive use of water pursuant to the Commission's approval by rule process...

77 FR 55892 - Projects Approved for Consumptive Uses of Water

Science.gov (United States)

2012-09-11

... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule..., receiving approval for the consumptive use of water pursuant to the Commission's approval by rule process...

77 FR 59239 - Projects Approved for Consumptive Uses of Water

Science.gov (United States)

2012-09-26

... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule..., receiving approval for the consumptive use of water pursuant to the Commission's approval by rule process...

Clinical TVA-based studies: a general review

Directory of Open Access Journals (Sweden)

Thomas eHabekost

2015-03-01

Full Text Available In combination with whole report and partial report tasks, the Theory of Visual Attention (TVA can be used to estimate individual differences in five basic attentional parameters: The visual processing speed, the storage capacity of visual short-term memory, the perceptual threshold, the efficiency of top-down selectivity, and the spatial bias of attentional weighting. TVA-based assessment has been used in about 30 studies to investigate attentional deficits in a range of neurological and psychiatric conditions: (a neglect and simultanagnosia, (b reading disturbances, (c aging and neurodegenerative diseases, and most recently (d neurodevelopmental disorders. The article introduces TVA based assessment, discusses its methodology and psychometric properties, and reviews the progress made in each of the four research fields. The empirical results demonstrate the general usefulness of TVA-based assessment for many types of clinical neuropsychological research. The method’s most important qualities are cognitive specificity and theoretical grounding, but it is also characterized by good reliability and sensitivity to minor deficits. The review concludes by pointing to promising new areas for clinical TVA-based research.

Uncertainty sources in radiopharmaceuticals clinical studies

International Nuclear Information System (INIS)

Degenhardt, Aemilie Louize; Oliveira, Silvia Maria Velasques de

2014-01-01

The radiopharmaceuticals should be approved for consumption by evaluating their quality, safety and efficacy. Clinical studies are designed to verify the pharmacodynamics, pharmacological and clinical effects in humans and are required for assuring safety and efficacy. The Bayesian analysis has been used for clinical studies effectiveness evaluation. This work aims to identify uncertainties associated with the process of production of the radionuclide and radiopharmaceutical labelling as well as the radiopharmaceutical administration and scintigraphy images acquisition and processing. For the development of clinical studies in the country, the metrological chain shall assure the traceability of the surveys performed in all phases. (author)

Delighted when Approved by Others, to Pieces when Rejected: Children's Social Anxiety Magnifies the Linkage between Self- and Other-Evaluations

Science.gov (United States)

Reijntjes, Albert; Thomaes, Sander; Boelen, Paul; van der Schoot, Menno; de Castro, Bram Orobio; Telch, Michael J.

2011-01-01

Background: Socially anxious children tend to attach great importance to others' evaluations of them. However, the extent to which they base their momentary feelings of self-worth (i.e., state self-esteem) on social (dis)approval is unclear. It is also unclear whether this exceedingly approval-based self-esteem is a common correlate of social…

Ciprofloxacin Use in Hospitalized Children: Approved or Off-label?

Science.gov (United States)

Faghihi, Toktam; Tekmehdash, Leila Yavari; Radfar, Mania; Gholami, Kheirollah

2017-01-01

Fluoroquinolones are not routinely used as the first-line antimicrobial therapy in pediatrics. The American Academy of Pediatrics (AAP) and the United States Food and Drug Administration (FDA) approved fluoroquinolones on certain indications in children. The aim of this study was to evaluate to what extent and how ciprofloxacin is used on approved indication or as off-label. Besides, dose adequacy and treatment duration were assessed. In a 10-month observational study, all children receiving systemic ciprofloxacin were assessed. We classified ciprofloxacin prescription to an AAP/FDA or off-label indication. The off-label prescriptions were further categorized to justified and unjustified therapy subgroups. The AAP/FDA category and the justified subgroup constituted the appropriate prescriptions. During the study period, 32 patients were prescribed ciprofloxacin. In general, 37% (12) of prescriptions determined to be appropriate. Of the appropriate prescriptions, 7 were AAP/FDA-approved indications. Children with Crohn's disease with abdominal abscess and children with infectious bloody diarrhea constituted the off-label; justified therapy subgroup. Unjustified prescriptions mainly occurred in the presence of a suitable alternative antibiotic for ciprofloxacin. Mean ± SD of ciprofloxacin dose (mg/kg/day) and duration (days) were 21.25 ± 6.35 and 13.56 ± 8.48, respectively. Of the appropriate prescriptions, 41% were underdosed. Underdosing was more encountered in patients with cystic fibrosis. Duration of treatment of the appropriate prescriptions was determined to be appropriate. The majority of children were receiving ciprofloxacin off-label and in an inappropriate manner. This issue emphasizes that antimicrobial stewardship program on ciprofloxacin use in pediatric hospitals should be implemented. Further studies evaluating clinical and microbiological outcomes of these programs in children are needed.

Augment clinical measurement using a constraint-based esophageal model

Science.gov (United States)

Kou, Wenjun; Acharya, Shashank; Kahrilas, Peter; Patankar, Neelesh; Pandolfino, John

2017-11-01

Quantifying the mechanical properties of the esophageal wall is crucial to understanding impairments of trans-esophageal flow characteristic of several esophageal diseases. However, these data are unavailable owing to technological limitations of current clinical diagnostic instruments that instead display esophageal luminal cross sectional area based on intraluminal impedance change. In this work, we developed an esophageal model to predict bolus flow and the wall property based on clinical measurements. The model used the constraint-based immersed-boundary method developed previously by our group. Specifically, we first approximate the time-dependent wall geometry based on impedance planimetry data on luminal cross sectional area. We then fed these along with pressure data into the model and computed wall tension based on simulated pressure and flow fields, and the material property based on the strain-stress relationship. As examples, we applied this model to augment FLIP (Functional Luminal Imaging Probe) measurements in three clinical cases: a normal subject, achalasia, and eosinophilic esophagitis (EoE). Our findings suggest that the wall stiffness was greatest in the EoE case, followed by the achalasia case, and then the normal. This is supported by NIH Grant R01 DK56033 and R01 DK079902.

Applying for ethical approval for research: the main issues.

Science.gov (United States)

Gelling, Leslie

2016-01-13

The need to obtain research ethical approval is common to all research involving human participants. This approval must be obtained before research participants can be approached and before data collection can begin. The process of ethical review is one way that research participants can be confident that possible risks have been considered, minimised and deemed acceptable. This article outlines some of the main issues researchers should consider when planning an application for research ethical approval by answering the following six questions: 'Do I need research ethical approval?', 'How many applications will I need to make?', 'Where should I apply for research ethical approval?', 'What do I need to include in my application?', 'What do research ethics committees look for?' and 'What other approvals might I need?' Answering these questions will enable researchers to navigate the ethical review process.

Poet Marion Approval

Science.gov (United States)

This update August 9, 2016 letter from EPA approves, with modifications, the petition from Poet Biorefining-North Manchester, LLC, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable

Poet Portland Approval

Science.gov (United States)

This update August 9, 2016 letter from EPA approves the petition, with modifications, from Poet Biorefining-Portland, LLC, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable fuel

Poet Alexandria Approval

Science.gov (United States)

This update August 9, 2016 letter from EPA approves, with modifications, the petition from Poet Biorefining-Alexandria, LLC, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable fuel

Poet Laddonia Approval

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This update Auugust 9, 2016 letter from EPA approves with modifications, the petition from Poet Biorefining Laddonia, Poet Laddonia Facility, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act f

Lack of proportionality. Seven specifications of public interest that override post-approval commercial interests on limited access to clinical data

Directory of Open Access Journals (Sweden)

Strech Daniel

2012-07-01

Full Text Available Abstract For the protection of commercial interests, licensing bodies such as the EMA and health technology assessment institutions such as NICE restrict full access to unpublished evidence. Their respective policies on data transparency, however, lack a systematic account of (1 what kinds of commercial interests remain relevant after market approval has been granted, (2 what the specific types of public interest are that may override these commercial interests post approval, and, most importantly, (3 what criteria guide the trade-off between public interest and legitimate measures for the protection of commercial interest. Comparing potential commercial interests with seven specifications of relevant public interest reveals the lack of proportionality inherent in the current practices of EMA and NICE.

A pilot test of the new Swiss regulatory procedure for categorizing clinical trials by risk: A randomized controlled trial.

Science.gov (United States)

Cevallos, Myriam; Züllig, Stephanie; Christen, Andri; Meier, Brigitte E; Goetz, Martin; Coslovsky, Michael; Trelle, Sven

2015-12-01

Several countries are working to adapt clinical trial regulations to align the approval process to the level of risk for trial participants. The optimal framework to categorize clinical trials according to risk remains unclear, however. Switzerland is the first European country to adopt a risk-based categorization procedure in January 2014. We assessed how accurately and consistently clinical trials are categorized using two different approaches: an approach using criteria set forth in the new law (concept) or an intuitive approach (ad hoc). This was a randomized controlled trial with a method-comparison study nested in each arm. We used clinical trial protocols from eight Swiss ethics committees approved between 2010 and 2011. Protocols were randomly assigned to be categorized in one of three risk categories using the concept or the ad hoc approach. Each protocol was independently categorized by the trial's sponsor, a group of experts and the approving ethics committee. The primary outcome was the difference in categorization agreement between the expert group and sponsors across arms. Linear weighted kappa was used to quantify agreements, with the difference between kappas being the primary effect measure. We included 142 of 231 protocols in the final analysis (concept=78; ad hoc=64). Raw agreement between the expert group and sponsors was 0.74 in the concept and 0.78 in the ad hoc arm. Chance-corrected agreement was higher in the ad hoc (kappa: 0.34 (95% confidence interval=0.10-0.58)) than in the concept arm (0.27 (0.06-0.50)), but the difference was not significant (p=0.67). The main limitation was the large number of protocols excluded from the analysis mostly because they did not fit with the clinical trial definition of the new law. A structured risk categorization approach was not better than an ad hoc approach. Laws introducing risk-based approaches should provide guidelines, examples and templates to ensure correct application. © The Author(s) 2015.

Anti-EGFR Therapy: Mechanism and Advances in Clinical Efficacy in Breast Cancer

Directory of Open Access Journals (Sweden)

John F. Flynn

2009-01-01

Full Text Available This review will focus on recent advances in the application of antiepidermal growth factor receptor (anti-EGFR for the treatment of breast cancer. The choice of EGFR, a member of the ErbB tyrosine kinase receptor family, stems from evidence pinpointing its role in various anti-EGFR therapies. Therefore, an increase in our understanding of EGFR mechanism and signaling might reveal novel targets amenable to intervention in the clinic. This knowledge base might also improve existing medical treatment options and identify research gaps in the design of new therapeutic agents. While the approved use of drugs like the dual kinase inhibitor Lapatinib represents significant advances in the clinical management of breast cancer, confirmatory studies must be considered to foster the use of anti-EGFR therapies including safety, pharmacokinetics, and clinical efficacy.

Teaching and Learning Science in Authoritative Classrooms: Teachers' Power and Students' Approval in Korean Elementary Classrooms

Science.gov (United States)

Lee, Jeong-A.; Kim, Chan-Jong

2017-09-01

This study aims to understand interactions in Korean elementary science classrooms, which are heavily influenced by Confucianism. Ethnographic observations of two elementary science teachers' classrooms in Korea are provided. Their classes are fairly traditional teaching, which mean teacher-centered interactions are dominant. To understand the power and approval in science classroom discourse, we have adopted Critical Discourse Analysis (CDA). Based on CDA, form and function analysis was adopted. After the form and function analysis, all episodes were analyzed in terms of social distance. The results showed that both teachers exercised their power while teaching. However, their classes were quite different in terms of getting approval by students. When a teacher got students' approval, he could conduct the science lesson more effectively. This study highlights the importance of getting approval by students in Korean science classrooms.

Poet Fostoria Approval

Science.gov (United States)

This August 9, 2016 letter from EPA approves, with modifications, the petition from Poet Biorefining-Fostoria, LLC, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable fuel (D-code 6)

Stratification of type 2 diabetes based on routine clinical markers

DEFF Research Database (Denmark)

Safai, Narges; Ali, Ashfaq; Rossing, Peter

2018-01-01

AIMS: We hypothesized that patients with dysregulated type 2 diabetes may be stratified based on routine clinical markers. METHODS: In this retrospective cohort study, diabetes related clinical measures including age at onset, diabetes duration, HbA1c, BMI, HOMA2-β, HOMA2-IR and GAD65...... autoantibodies, were used for sub-grouping patients by K-means clustering and for adjusting. Probability of diabetes complications (95% confidence interval), were calculated using logistic regression. RESULTS: Based on baseline data from patients with type 2 diabetes (n=2,290), the cluster analysis suggested up....... CONCLUSIONS: Patients with type 2 diabetes cluster into clinically relevant sub-groups based on routine clinical markers. The prevalence of diabetes complications seems to be sub-group specific. Our data suggests the need for a tailored strategy for the treatment of type 2 diabetes....

Clinical capabilities of graduates of an outcomes-based integrated medical program

Directory of Open Access Journals (Sweden)

Scicluna Helen A

2012-06-01

Full Text Available Abstract Background The University of New South Wales (UNSW Faculty of Medicine replaced its old content-based curriculum with an innovative new 6-year undergraduate entry outcomes-based integrated program in 2004. This paper is an initial evaluation of the perceived and assessed clinical capabilities of recent graduates of the new outcomes-based integrated medical program compared to benchmarks from traditional content-based or process-based programs. Method Self-perceived capability in a range of clinical tasks and assessment of medical education as preparation for hospital practice were evaluated in recent graduates after 3 months working as junior doctors. Responses of the 2009 graduates of the UNSW’s new outcomes-based integrated medical education program were compared to those of the 2007 graduates of UNSW’s previous content-based program, to published data from other Australian medical schools, and to hospital-based supervisor evaluations of their clinical competence. Results Three months into internship, graduates from UNSW’s new outcomes-based integrated program rated themselves to have good clinical and procedural skills, with ratings that indicated significantly greater capability than graduates of the previous UNSW content-based program. New program graduates rated themselves significantly more prepared for hospital practice in the confidence (reflective practice, prevention (social aspects of health, interpersonal skills (communication, and collaboration (teamwork subscales than old program students, and significantly better or equivalent to published benchmarks of graduates from other Australian medical schools. Clinical supervisors rated new program graduates highly capable for teamwork, reflective practice and communication. Conclusions Medical students from an outcomes-based integrated program graduate with excellent self-rated and supervisor-evaluated capabilities in a range of clinically-relevant outcomes. The program

Toward Value-Based Pricing to Boost Cancer Research and Innovation.

Science.gov (United States)

Ocana, Alberto; Amir, Eitan; Tannock, Ian F

2016-06-01

The high market price of new anticancer agents has stimulated debate about the long-term sustainability of healthcare systems and whether these new agents can continue to be supported by public healthcare or by private insurers. In addition, some drugs have been approved with limited clinical benefit, raising concerns about setting a minimum requirement for medical benefit. Options to resolve these problems include raising the bar for approval of new drugs and/or pricing of new agents based on the medical benefit that they offer to patients. In this commentary, we suggest that new agents should be marketed in a two-step process that would include first the approval of the new drug by the regulatory agencies and second the introduction of a market price based on the medical benefit that the new intervention offers to patients. Introduction of value-based pricing would maintain the sustainability of health care systems and would improve drug development, as it would pressure pharmaceutical companies to become more innovative and avoid the development of compounds with limited benefit. Value-based pricing could also stimulate the funding of research directed to development of new anticancer drugs with novel mechanisms of action. Cancer Res; 76(11); 3127-9. ©2016 AACR. ©2016 American Association for Cancer Research.

Immunotherapy Combination Approved for Advanced Kidney Cancer

Science.gov (United States)

FDA has approved the combination of the immunotherapy drugs nivolumab (Opdivo) and ipilimumab (Yervoy) as an initial treatment for some patients with advanced kidney cancer. The approval is expected to immediately affect patient care, as this Cancer Currents post explains.

Biological Mesh Implants for Abdominal Hernia Repair: US Food and Drug Administration Approval Process and Systematic Review of Its Efficacy.

Science.gov (United States)

Huerta, Sergio; Varshney, Anubodh; Patel, Prachi M; Mayo, Helen G; Livingston, Edward H

2016-04-01

Expensive biological mesh materials are increasingly used to reinforce abdominal wall hernia repairs. The clinical and cost benefit of these materials are unknown. To review the published evidence on the use of biological mesh materials and to examine the US Food and Drug Administration (FDA) approval history for these devices. Search of multiple electronic databases (Ovid, MEDLINE, EMBASE, Cochrane Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, and Cochrane National Health Service Economic Evaluation Database) to identify articles published between 1948 and June 30, 2015, on the use of biological mesh materials used to reinforce abdominal wall hernia repair. Keywords searched included surgical mesh, abdominal hernia, recurrence, infection, fistula, bioprosthesis, biocompatible materials, absorbable implants, dermis, and collagen. The FDA online database for 510(k) clearances was reviewed for all commercially available biological mesh materials. The median national price for mesh materials was established by a benchmarking query through several Integrated Delivery Network and Group Purchasing Organization tools. Of 274 screened articles, 20 met the search criteria. Most were case series that reported results of convenience samples of patients at single institutions with a variety of clinical problems. Only 3 of the 20 were comparative studies. There were no randomized clinical trials. In total, outcomes for 1033 patients were described. Studies varied widely in follow-up time, operative technique, meshes used, and patient selection criteria. Reported outcomes and clinical outcomes, such as fistula formation and infection, were inconsistently reported across studies. Conflicts of interest were not reported in 16 of the 20 studies. Recurrence rates ranged from 0% to 80%. All biological mesh devices were approved by the FDA based on substantial equivalence to a group of nonbiological predicate

IMPLEMENTATION OF THE PROJECT «CLINICAL BASES OF INTERNSHIP» WHILE PREPARING STUDENTS WITH A SPECIALTY IN «PSYCHOLOGY AND PEDAGOGY OF PRIMARY EDUCATION»

Directory of Open Access Journals (Sweden)

Elena G. Gutsu

2015-01-01

Full Text Available The aim of this work is to test new approaches to the students’practice organization in pedagogical universities on the basis of the competence approach.Methods. Diagnosis of formedness competences is carried out on the basis of the analysis of products of activity during the students’ school internship.Results. Teachers’ experience of Nizhny Novgorod State Pedagogical University of K. Minin on implementation of the innovative project «Clinical Bases of Internship » is presented. The authors have created and approved the program of school internship for the students with specialty in «Psychology and Pedagogics of Primary Education» based on the concept of the integrated clinical practice developed in higher education institution. The program involves organizational, reflexive-analytical, active-practical and project blocks. Features of clinical approach to pedagogical education are considered; requirements to school as the base of clinical practice are listed. The main content of student teaching and its role in professional formation of future elementary school teachers is disclosed. Importance of students’ project group and individual activity (the subject has to correspond to interests of employers and real needs of school are emphasized.Scientific novelty. Specifics of integrated clinical internship as a means of formation of professional metacompetences of undergraduate students are presented. The organization of pedagogical internship is reconsidered; theoretically it has to provide fast professionalizing of training, early immersion into a profession that will promote not only to successful formation of flexible pedagogical thinking, but also growth of professional motivation of students – development in them of the positive relation to work of the teacher, interest in communication with children of younger school age, and aspiration to pedagogical research creativity.Practical significance. The research

Poet Leipsic Approval

Science.gov (United States)

This August 9, 2016 letter from EPA approves,wtih modifications, the petition from Poet Biorefining-Leipsic, LLC, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable fuel (D-code 6) RINs

Guidance for package approvals in the United Kingdom

International Nuclear Information System (INIS)

Morgan-Warren, E.J.

2004-01-01

Approval is required under the transport regulations for a wide range of package designs and operations, and applications for competent authority approval and validation are received from many sources, both in the UK and overseas. To assist package designers and applicants for approval, and to promote consistency in applications and their assessment, the UK Department for Transport issues guidance on the interpretation of the transport regulations and the requirements of an application for approval and its supporting safety case. The general guidance document, known as the Guide to an Application for UK Competent Authority Approval of Radioactive Material in Transport, has been issued for many years and updated to encompass the provisions of each successive edition of the IAEA transport regulations. The guide has been referred to in a number of international fora, including PATRAM, and was cited as a 'good practice' in the report of the IAEA TRANSAS appraisal of the UK in 2002. Specialist guides include the Guide to the Suitability of Elastomeric Seal Materials, which is the subject of a separate paper in this conference, and the Guide to the Approval of Freight Containers as Types IP-2 and IP-3 Packages. This paper discusses the guidance material and summarises the administrative and technical information required in support of applications for approval of package designs, special form and low-dispersible radioactive materials, shipments, special arrangements, modifications and validations. (author)

Pharmacometrics in early clinical drug development

NARCIS (Netherlands)

Keizer, R.J.

2010-01-01

Pharmacometrics, the science of quantitative clinical pharmacology, has been recognized as one of the main research fields able to improve efficiency in drug development, and to reduce attrition rates on the route from drug discovery to approval. This field of drug research, which builds heavily on

Clinical roundtable monograph: new and emerging treatments for advanced prostate cancer.

Science.gov (United States)

George, Daniel J; Kantoff, Philip W; Lin, Daniel W

2011-06-01

Historically, the treatment of metastatic castration-resistant prostate cancer (CRPC) has been limited to chemotherapeutic regimens that did not improve patient survival. In 2004, clinical studies began to demonstrate significant improvements in patient outcomes, including overall survival, with docetaxel versus mitoxantrone chemotherapy. Since these pivotal trials, the combination of docetaxel plus prednisone has become a standard of care for patients with metastatic CRPC. However, the limited survival benefit achieved with this regimen prompted several investigations into the development of alternative therapeutic options. Recent advances have now led to an unprecedented number of new drug approvals within the past year, providing many new treatment options for patients with metastatic CRPC. Sipuleucel-T, considered a new paradigm in cancer treatment, is the first such immunotherapeutic agent approved by the US Food and Drug Administration. Other successes include abiraterone acetate, the first androgen biosynthesis inhibitor, and cabazitaxel, a novel microtubule inhibitor, both of which have demonstrated improved survival following docetaxel failure. The bone-targeting agent denosumab, also recently approved in this setting, offers these patients significant improvement in the prevention of skeletal-related events. The data supporting the approval of each of these agents are described in this monograph, as are current approaches in the treatment of metastatic CRPC and ongoing clinical trials of novel treatments and strategies. The experts also discuss several of the issues regarding the introduction of these novel agents into clinical practice for metastatic CRPC patients.

Development of a Primary Care-Based Clinic to Support Adults With a History of Childhood Cancer: The Tactic Clinic.

Science.gov (United States)

Overholser, Linda S; Moss, Kerry M; Kilbourn, Kristin; Risendal, Betsy; Jones, Alison F; Greffe, Brian S; Garrington, Timothy; Leonardi-Warren, Kristin; Yamashita, Traci E; Kutner, Jean S

2015-01-01

Describe the development and evolution of a primary-care-based, multidisciplinary clinic to support the ongoing care of adult survivors of childhood cancer. A consultative clinic for adult survivors of childhood cancer has been developed that is located in an adult, academic internal medicine setting and is based on a long-term follow-up clinic model available at Children's Hospital Colorado. The clinic opened in July 2008. One hundred thirty-five patients have been seen as of April 2014. Referrals and clinic capacity have gradually increased over time, and a template has been developed in the electronic medical record to help facilitate completion of individualized care plan letters. A primary care-based, multidisciplinary consultative clinic for adults with a history of childhood cancer survivor is feasible and actively engages adult primary care resources to provide risk-based care for long-term pediatric cancer survivors. This model of care planning can help support adult survivors of pediatric cancer and their primary care providers in non-academic, community settings as well. Copyright © 2015 Elsevier Inc. All rights reserved.

FDA Approves Immunotherapy for a Cancer that Affects Infants and Children | Poster

Science.gov (United States)

By Frank Blanchard, Staff Writer The U.S. Food and Drug Administration (FDA) recently approved dinutuximab (ch14.18) as an immunotherapy for neuroblastoma, a rare type of childhood cancer that offers poor prognosis for about half of the children who are affected. The National Cancer Institute’s (NCI) Biopharmaceutical Development Program (BDP) at the Frederick National Laboratory for Cancer Research produced ch14.18 for the NCI-sponsored clinical trials that proved the drug’s effectiveness against the disease.

45 CFR 95.611 - Prior approval conditions.

Science.gov (United States)

2010-10-01

... Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION GENERAL ADMINISTRATION... for Department approval, signed by the appropriate State official, to the Director, Administration for... of procurement activities beyond that approved in the APD; (D) A change in system concept, or a...

A Comparison of Urban School- and Community-Based Dental Clinics

Science.gov (United States)

Larsen, Charles D.; Larsen, Michael D.; Handwerker, Lisa B.; Kim, Maile S.; Rosenthal, Murray

2009-01-01

Background: The objective of the study was to quantitatively compare school- and community-based dental clinics in New York City that provide dental services to children in need. It was hypothesized that the school-based clinics would perform better in terms of several measures. Methods: We reviewed billing and visit data derived from encounter…

8 CFR 207.6 - Control over approved refugee numbers.

Science.gov (United States)

2010-01-01

... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Control over approved refugee numbers. 207... ADMISSION OF REFUGEES § 207.6 Control over approved refugee numbers. Current numerical accounting of approved refugees is maintained for each special group designated by the President. As refugee status is...

Preclinical and Clinical Development of a YFV 17 D-Based Chimeric Vaccine against West Nile Virus

Directory of Open Access Journals (Sweden)

Gustavo H. Dayan

2013-12-01

Full Text Available Substantial success has been achieved in the development and implementation of West Nile (WN vaccines for horses; however, no human WN vaccines are approved. This review focuses on the construction, pre-clinical and clinical characterization of ChimeriVax-WN02 for humans, a live chimeric vaccine composed of a yellow fever (YF 17D virus in which the prM-E envelope protein genes are replaced with the corresponding genes of the WN NY99 virus. Pre-clinical studies demonstrated that ChimeriVax-WN02 was significantly less neurovirulent than YF 17D in mice and rhesus and cynomolgus monkeys. The vaccine elicited neutralizing antibody titers after inoculation in hamsters and monkeys and protected immunized animals from lethal challenge including intracerebral inoculation of high dose of WN NY99 virus. Safety, viremia and immunogenicity of ChimeriVax-WN02 were assessed in one phase I study and in two phase II clinical trials. No safety signals were detected in the three clinical trials with no remarkable differences in incidence of adverse events (AEs between vaccine and placebo recipients. Viremia was transient and the mean viremia levels were low. The vaccine elicited strong and durable neutralizing antibody and cytotoxic T cell responses. WN epidemiology impedes a classical licensure pathway; therefore, innovative licensure strategies should be explored.

47 CFR 400.5 - Approval and award.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Approval and award. 400.5 Section 400.5 Telecommunication NATIONAL TELECOMMUNICATIONS AND INFORMATION ADMINISTRATION, DEPARTMENT OF COMMERCE, AND NATIONAL HIGHWAY TRAFFIC SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION E-911 GRANT PROGRAM § 400.5 Approval...

13 CFR 302.18 - Post-approval requirements.

Science.gov (United States)

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Post-approval requirements. 302.18 Section 302.18 Business Credit and Assistance ECONOMIC DEVELOPMENT ADMINISTRATION, DEPARTMENT OF COMMERCE... Federal cost principles (collectively, “Post-Approval Requirements”). A Recipient's failure to comply with...

Evaluation of Porcine Pancreatic Islets Transplanted in the Kidney Capsules of Diabetic Mice Using a Clinically Approved Superparamagnetic Iron Oxide (SPIO) and a 1.5T MR Scanner

International Nuclear Information System (INIS)

Kim, Hoe Suk; Kim, Hyoung Su; Park, Kyong Soo; Moon, Woo Kyung

2010-01-01

To evaluate transplanted porcine pancreatic islets in the kidney capsules of diabetic mice using a clinically approved superparamagnetic iron oxide (SPIO) and a 1.5T MR scanner. Various numbers of porcine pancreatic islets labeled with Resovist, a carboxydextran-coated SPIO, were transplanted into the kidney capsules of normal mice and imaged with a 3D FIESTA sequence using a 1.5T clinical MR scanner. Labeled (n = 3) and unlabeled (n = 2) islets were transplanted into the kidney capsules of streptozotocin-induced diabetic mice. Blood glucose levels and MR signal intensities were monitored for 30 days post-transplantation. There were no significant differences in viability or insulin secretion between labeled and unlabeled islets. A strong correlation (γ 2 > 0.94) was evident between the number of transplanted islets and T 2 relaxation times quantified by MRI. Transplantation with labeled or unlabeled islets helped restore normal sustained glucose levels in diabetic mice, and nephrectomies induced the recurrence of diabetes. The MR signal intensity of labeled pancreatic islets decreased by 80% over 30 days. The transplantation of SPIO-labeled porcine islets into the kidney capsule of diabetic mice allows to restore normal glucose levels, and these islets can be visualized and quantified using a 1.5T clinical MR scanner

Chloroquine, a FDA-approved Drug, Prevents Zika Virus Infection and its Associated Congenital Microcephaly in Mice.

Science.gov (United States)

Li, Chunfeng; Zhu, Xingliang; Ji, Xue; Quanquin, Natalie; Deng, Yong-Qiang; Tian, Min; Aliyari, Roghiyh; Zuo, Xiangyang; Yuan, Ling; Afridi, Shabbir Khan; Li, Xiao-Feng; Jung, Jae U; Nielsen-Saines, Karin; Qin, Frank Xiao-Feng; Qin, Cheng-Feng; Xu, Zhiheng; Cheng, Genhong

2017-10-01

Zika virus (ZIKV) has become a global public health emergency due to its rapidly expanding range and its ability to cause severe congenital defects such as microcephaly. However, there are no FDA-approved therapies or vaccines against ZIKV infection. Through our screening of viral entry inhibitors, we found that chloroquine (CQ), a commonly used antimalarial and a FDA-approved drug that has also been repurposed against other pathogens, could significantly inhibit ZIKV infection in vitro, by blocking virus internalization. We also demonstrated that CQ attenuates ZIKV-associated morbidity and mortality in mice. Finally, we proved that CQ protects fetal mice from microcephaly caused by ZIKV infection. Our methodology of focusing on previously identified antivirals in screens for effectiveness against ZIKV proved to be a rapid and efficient means of discovering new ZIKV therapeutics. Selecting drugs that were previously FDA-approved, such as CQ, also improves the likelihood that they may more quickly reach stages of clinical testing and use by the public. Copyright © 2017. Published by Elsevier B.V.

12 CFR 614.4470 - Loans subject to bank approval.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Loans subject to bank approval. 614.4470 Section 614.4470 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM LOAN POLICIES AND OPERATIONS Loan Approval Requirements § 614.4470 Loans subject to bank approval. (a) The following loans...

7 CFR 1717.609 - RUS approval of general manager.

Science.gov (United States)

2010-01-01

... 7 Agriculture 11 2010-01-01 2010-01-01 false RUS approval of general manager. 1717.609 Section... Operational Controls § 1717.609 RUS approval of general manager. (a) If a borrower's mortgage or loan contract... general manager of the borrower's system, such approval is hereby granted provided that the borrower is in...

28 CFR 551.11 - Authority to approve a marriage.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Authority to approve a marriage. 551.11... MISCELLANEOUS Marriages of Inmates § 551.11 Authority to approve a marriage. (a) The Warden may approve the marriage of a federal inmate confined in a federal institution. This authority may not be delegated below...

[The historical background and present development of evidence-based healthcare and clinical nursing].

Science.gov (United States)

Tsai, Jung-Mei

2014-12-01

Evidence-based healthcare (EBHC) emphasizes the integration of the best research evidence with patient values, specialist suggestions, and clinical circumstances during the process of clinical decision-making. EBHC is a recognized core competency in modern healthcare. Nursing is a professional discipline of empirical science that thrives in an environment marked by advances in knowledge and technology in medicine as well as in nursing. Clinical nurses must elevate their skills and professional qualifications, provide efficient and quality health services, and promote their proficiency in EBHC. The Institute of Medicine in the United States indicates that evidence-based research results often fail to disseminate efficiently to clinical decision makers. This problem highlights the importance of better promoting the evidence-based healthcare fundamentals and competencies to frontline clinical nurses. This article describes the historical background and present development of evidence-based healthcare from the perspective of modern clinical nursing in light of the importance of evidence-based healthcare in clinical nursing; describes the factors associated with evidence-based healthcare promotion; and suggests strategies and policies that may improve the promotion and application of EBHC in clinical settings. The authors hope that this paper provides a reference for efforts to improve clinical nursing in the realms of EBHC training, promotion, and application.

eLearning techniques supporting problem based learning in clinical simulation.

Science.gov (United States)

Docherty, Charles; Hoy, Derek; Topp, Helena; Trinder, Kathryn

2005-08-01

This paper details the results of the first phase of a project using eLearning to support students' learning within a simulated environment. The locus was a purpose built clinical simulation laboratory (CSL) where the School's philosophy of problem based learning (PBL) was challenged through lecturers using traditional teaching methods. a student-centred, problem based approach to the acquisition of clinical skills that used high quality learning objects embedded within web pages, substituting for lecturers providing instruction and demonstration. This encouraged student nurses to explore, analyse and make decisions within the safety of a clinical simulation. Learning was facilitated through network communications and reflection on video performances of self and others. Evaluations were positive, students demonstrating increased satisfaction with PBL, improved performance in exams, and increased self-efficacy in the performance of nursing activities. These results indicate that eLearning techniques can help students acquire clinical skills in the safety of a simulated environment within the context of a problem based learning curriculum.

Radiotherapy fractionation for the palliation of uncomplicated painful bone metastases – an evidence-based practice guideline

International Nuclear Information System (INIS)

Wu, Jackson Sai-Yiu; Wong, Rebecca KS; Lloyd, Nancy S; Johnston, Mary; Bezjak, Andrea; Whelan, Timothy

2004-01-01

This practice guideline was developed to provide recommendations to clinicians in Ontario on the preferred standard radiotherapy fractionation schedule for the treatment of painful bone metastases. A systematic review and meta-analysis was performed and published elsewhere. The Supportive Care Guidelines Group, a multidisciplinary guideline development panel, formulated clinical recommendations based on their interpretation of the evidence. In addition to evidence from clinical trials, the panel also considered patient convenience and ease of administration of palliative radiotherapy. External review of the draft report by Ontario practitioners was obtained through a mailed survey, and final approval was obtained from the Practice Guidelines Coordinating Committee. Meta-analysis did not detect a significant difference in complete or overall pain relief between single treatment and multifraction palliative radiotherapy for bone metastases. Fifty-nine Ontario practitioners responded to the mailed survey (return rate 62%). Forty-two percent also returned written comments. Eighty-three percent of respondents agreed with the interpretation of the evidence and 75% agreed that the report should be approved as a practice guideline. Minor revisions were made based on feedback from the external reviewers and the Practice Guidelines Coordinating Committee. The Practice Guidelines Coordinating Committee approved the final practice guideline report. For adult patients with single or multiple radiographically confirmed bone metastases of any histology corresponding to painful areas in previously non-irradiated areas without pathologic fractures or spinal cord/cauda equine compression, we conclude that: • Where the treatment objective is pain relief, a single 8 Gy treatment, prescribed to the appropriate target volume, is recommended as the standard dose-fractionation schedule for the treatment of symptomatic and uncomplicated bone metastases. Several factors frequently

2016 in review: FDA approvals of new molecular entities.

Science.gov (United States)

Griesenauer, Rebekah H; Kinch, Michael S

2017-11-01

An overview of drugs approved by FDA in 2016 reveals dramatic disruptions in long-term trends. The number of new molecular entities (NMEs) dropped, reflecting the lowest rate of small-molecule approvals observed in almost five decades. In addition, the pace of industry consolidation slowed substantially. The impact of mergers and acquisitions decreased the total number of organizations with past approval experience and continued research and development (R&D) activities to 102, divided evenly between more established pharmaceutical and newer biotechnology companies. Despite these substantial differences, the industry continued to pursue regulatory incentives, as evidenced by a continued increase in the fraction of NMEs approved using an orphan or priority designation, and almost all oncology drugs approved in 2016 utilized these mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evidence-based medicine: what it can and cannot do

Directory of Open Access Journals (Sweden)

Goffredo Freddi

2011-01-01

Full Text Available Evidence-based medicine (EBM is not a old hat, a "cookbook" medicine perpetrated by arrogant to serve cost cutters to suppress clinical freedom, a mandatory, deterministic, totalitarian practice of medicine, a way to control cost and to ignore patient preferences, a limit to personal/humanistic/individual medicine. EBM is a reference of excellence to guide clinical decisions, the integration of own expertise with others' expertise and patient preferences, a way to improve medical practice and limit the variability and errors created when there is not evidence to identify the gold standard and differentiate among alternatives available. But evidences need to be integrated with a new thinking based on Complexity Science. Health care systems operates as complex adaptative systems rather than rigid, linear or mechanical organizations and innovation is a critical outcome of Complexity Science. How does EBM impact drug innovation? New drug approvals are not keeping pace with rising Research and Development spending, clinical approval success rate for new chemical entities (NCEs is progressively dropping and maybe, through these indicators, we are seeing the worst face of EBM: its limiting, blocking, and controlling side. If that is the case, EBM is the main ally to keep the economy of health systems under control and the great excuse to block the access of the innovation to patients. Certainly not the best way to maximize the benefits of EBM.

Medical imaging in clinical applications algorithmic and computer-based approaches

CERN Document Server

Bhateja, Vikrant; Hassanien, Aboul

2016-01-01

This volume comprises of 21 selected chapters, including two overview chapters devoted to abdominal imaging in clinical applications supported computer aided diagnosis approaches as well as different techniques for solving the pectoral muscle extraction problem in the preprocessing part of the CAD systems for detecting breast cancer in its early stage using digital mammograms. The aim of this book is to stimulate further research in medical imaging applications based algorithmic and computer based approaches and utilize them in real-world clinical applications. The book is divided into four parts, Part-I: Clinical Applications of Medical Imaging, Part-II: Classification and clustering, Part-III: Computer Aided Diagnosis (CAD) Tools and Case Studies and Part-IV: Bio-inspiring based Computer Aided diagnosis techniques. .

42 CFR 482.80 - Condition of participation: Data submission, clinical experience, and outcome requirements for...

Science.gov (United States)

2010-10-01

..., clinical experience, and outcome requirements for initial approval of transplant centers. 482.80 Section... Hospitals Transplant Center Data Submission, Clinical Experience, and Outcome Requirements § 482.80 Condition of participation: Data submission, clinical experience, and outcome requirements for initial...

24 CFR 886.107 - Approval of applications.

Science.gov (United States)

2010-04-01

...) The Owner's Affirmative Fair Housing Marketing Plan is approvable. (b) The HUD-approved unit rents are... climatic or geological conditions or local codes are examples which may justify such variations. (d) A... neighborhood in a substantially adverse manner. Examples of such adverse effects are (1) substantial move-outs...

77 FR 41431 - Proposed Collection; Comment Request: Impact of Clinical Research Training and Medical Education...

Science.gov (United States)

2012-07-13

... Request: Impact of Clinical Research Training and Medical Education at the Clinical Center on Physician Careers in Academia and Clinical Research SUMMARY: In compliance with the requirement of Section 3506(c)(2... approval. Proposed Collection Title: The Impact of Clinical Research Training and Medical Education at the...

New Breast Cancer Treatment Approved | NIH MedlinePlus the Magazine

Science.gov (United States)

... Breast Cancer Treatment Approved Follow us New Breast Cancer Treatment Approved Photo: Wikimedia Commons IN THE NEWS - Breast ... Food and Drug Administration approved a new breast cancer treatment that aims to reduce the risk of the ...

Sonidegib: mechanism of action, pharmacology, and clinical utility for advanced basal cell carcinomas

Directory of Open Access Journals (Sweden)

Jain S

2017-03-01

Full Text Available Sachin Jain,1 Ruolan Song,2 Jingwu Xie2 1Indiana University School of Medicine, 2Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indianapolis, IN, USA Abstract: The Hedgehog (Hh pathway is critical for cell differentiation, tissue polarity, and stem cell maintenance during embryonic development, but is silent in adult tissues under normal conditions. However, aberrant Hh signaling activation has been implicated in the development and promotion of certain types of cancer, including basal cell carcinoma (BCC, medulloblastoma, and gastrointestinal cancers. In 2015, the US Food and Drug Administration (FDA approved sonidegib, a smoothened (SMO antagonist, for treatment of advanced BCC (aBCC after a successful Phase II clinical trial. Sonidegib, also named Odomzo, is the second Hh signaling inhibitor approved by the FDA to treat BCCs following approval of the first SMO antagonist vismodegib in 2012. What are the major features of sonidegib (mechanism of action; metabolic profiles, clinical efficacy, safety, and tolerability profiles? Will the sonidegib experience help other clinical trials using Hh signaling inhibitors in the future? In this review, we will summarize current understanding of BCCs and Hh signaling. We will focus on sonidegib and its use in the clinic, and we will discuss ways to improve its clinical application in cancer therapeutics. Keywords: Hedgehog, smoothened, inhibitor, cancer, basal cell carcinoma, sonidegib

Clinical trials of CAR-T cells in China

OpenAIRE

Bingshan Liu; Yongping Song; Delong Liu

2017-01-01

Abstract Novel immunotherapeutic agents targeting tumor-site microenvironment are revolutionizing cancer therapy. Chimeric antigen receptor (CAR)-engineered T cells are widely studied for cancer immunotherapy. CD19-specific CAR-T cells, tisagenlecleucel, have been recently approved for clinical application. Ongoing clinical trials are testing CAR designs directed at novel targets involved in hematological and solid malignancies. In addition to trials of single-target CAR-T cells, simultaneous...

76 FR 30175 - Draft Guidance for Clinical Investigators, Industry, and FDA Staff: Financial Disclosure by...

Science.gov (United States)

2011-05-24

... consider public release of financial disclosure information related to an approved marketing application...] (Formerly FDA-1999-D-0792) Draft Guidance for Clinical Investigators, Industry, and FDA Staff: Financial... entitled ``Guidance for Clinical Investigators, Industry, and FDA Staff: Financial Disclosure by Clinical...

FDA approves efavirenz. Food and Drug Administration.

Science.gov (United States)

Highleyman, L

1998-10-01

The Food and Drug Administration (FDA) approved DuPont Pharma's new non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (Sustiva, DMP-266). Efavirenz has shown promise in trials with over 2000 participants for up to 24 weeks, and early data suggests it may be as effective as protease inhibitors when used in a combination regimen. It is the first anti-HIV drug approved for once-daily dosing. Efavirenz is well tolerated, and the main side effects reported are dizziness, insomnia, abnormal dreams, and skin rash. Efavirenz has been approved for adults and children, but should not be used by pregnant women. Contact information is provided.

Adequacy of clinical trial evidence of metformin fixed-dose combinations for the treatment of type 2 diabetes mellitus in India.

Science.gov (United States)

Evans, Valerie; Roderick, Peter; Pollock, Allyson M

2018-01-01

There is growing national and international concern about the drug regulatory system in India. Parliamentary reports have highlighted the presence of high numbers of unapproved medicines and irrational combinations of both approved and unapproved drugs in the Indian market-place. Fixed-dose combinations (FDCs) are a peculiar feature of the Indian pharmaceutical landscape. Although metformin is a first-line treatment, FDCs for diabetes in India account for two-thirds of all diabetes medicine sales, and some have not been approved by the Central Drugs Standard Control Organization (CDSCO). This study examines the basis of efficacy and safety of top-selling metformin FDCs in India against four WHO criteria from clinical trials guidelines for the approval of FDCs. Data from a commercial drug sales database (PharmaTrac) were combined with searches through published literature, clinical trial registries, and published and unpublished trial websites of metformin FDCs in adults with type 2 diabetes mellitus. Five metformin FDCs in India from November 2011 to October 2012 accounted for 80% of all metformin FDC sales by value and volume. Although all five had obtained CDSCO approval, three had been sold and marketed prior to receiving this approval. Evaluation of published and unpublished clinical trials of these five FDCs found none provided robust evidence of safety and efficacy for the treatment of type 2 diabetes. Recommendations are made for publishing evidence that underpins drug approvals, marketing bans, greater transparency through updated clinical trials databases and legislative reform in order to prevent irrational FDCs from entering the market.

Advances in the delivery of RNA therapeutics: from concept to clinical reality.

Science.gov (United States)

Kaczmarek, James C; Kowalski, Piotr S; Anderson, Daniel G

2017-06-27

The rapid expansion of the available genomic data continues to greatly impact biomedical science and medicine. Fulfilling the clinical potential of genetic discoveries requires the development of therapeutics that can specifically modulate the expression of disease-relevant genes. RNA-based drugs, including short interfering RNAs and antisense oligonucleotides, are particularly promising examples of this newer class of biologics. For over two decades, researchers have been trying to overcome major challenges for utilizing such RNAs in a therapeutic context, including intracellular delivery, stability, and immune response activation. This research is finally beginning to bear fruit as the first RNA drugs gain FDA approval and more advance to the final phases of clinical trials. Furthermore, the recent advent of CRISPR, an RNA-guided gene-editing technology, as well as new strides in the delivery of messenger RNA transcribed in vitro, have triggered a major expansion of the RNA-therapeutics field. In this review, we discuss the challenges for clinical translation of RNA-based therapeutics, with an emphasis on recent advances in delivery technologies, and present an overview of the applications of RNA-based drugs for modulation of gene/protein expression and genome editing that are currently being investigated both in the laboratory as well as in the clinic.

Post-market clinical research conducted by medical device manufacturers: a cross-sectional survey

Directory of Open Access Journals (Sweden)

Ross JS

2015-05-01

Full Text Available Joseph S Ross, Katrina L Blount, Jessica D Ritchie, Beth Hodshon, Harlan M Krumholz Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, CT, USA Background: In the US, once a medical device is made available for use, several requirements have been established by the US Food and Drug Administration (FDA to ensure ongoing post-market surveillance of device safety and effectiveness. Our objective was to determine how commonly medical device manufacturers initiate post-market clinical studies or augment FDA post-market surveillance requirements for higher-risk devices that are most often approved via the FDA's pre-market approval (PMA pathway. Methods and results: We conducted a cross-sectional survey of 47 manufacturers with operations in California, Minnesota, and Massachusetts who market devices approved via the PMA pathway. Among 22 respondents (response rate =47%, nearly all self-reported conducting post-market clinical research studies, commonly between 1 and 5; only 1 respondent reported never conducting post-market clinical research studies. While manufacturers most often engaged in these studies to satisfy FDA requirements, other reasons were reported, including performance monitoring and surveillance and market acceptance initiatives. Risks of conducting and not conducting post-market clinical research studies were described through open-ended response to questions. Conclusion: Medical device manufacturers commonly initiate post-market clinical studies at the request of the FDA. Clinical data from these studies should be integrated into national post-market surveillance initiatives. Keywords: FDA, PMA pathway, post-market surveillance

14 CFR 21.8 - Approval of articles.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Approval of articles. 21.8 Section 21.8 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT CERTIFICATION PROCEDURES FOR PRODUCTS AND PARTS General § 21.8 Approval of articles. If an article is required to be...

48 CFR 1819.7203 - Mentor approval process.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Mentor approval process... ADMINISTRATION SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS NASA Mentor-Protégé Program 1819.7203 Mentor approval process. (a) An entity seeking to participate as a mentor must apply to the NASA Headquarters...

[Reporting ethics board approval in German medical theses and journals].

Science.gov (United States)

Zenz, Michael; Zenz, Julia; Grieger, Maximilian

2018-06-05

Since 1975, the Declaration of Helsinki of the World Medical Association (WMA) has clearly required ethics committee approval for research into humans. Nevertheless, this Declaration is violated quite often. As many English-language publications have addressed the theme of ethics board approval in theses and other published works, it is now to be investigated in Germany for the first time.From 2013 to 2014, a total of 1,482 medical theses at four selected universities in addition to three German-language scientific journals were reviewed. In 543 theses, reference to ethics approval would have been required according to the criteria of the Declaration of Helsinki.However, ethics approval was stated in only 58.7% of cases, and even less frequently if the prevailing doctoral regulations or instructions did not refer to the necessity of obtaining ethics approval. Theses on pediatrics mentioned ethics approval most frequently (78.6%), whereas the proportion of surgical papers was the lowest (34.9%). Among the journals, Der Nervenarzt mentioned ethics approval most frequently (59.4%) and Der Chirurg least frequently (30%).Our results point to significant deficits in mentioning ethics approval in medical theses and publications. These deficits could easily be compensated for by a thorough approach of the referees of doctoral regulations and by journal reviewers and editors.

27 CFR 4.50 - Certificates of label approval.

Science.gov (United States)

2010-04-01

..., DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF WINE Requirements for Approval of Labels of... of exemption from label approval, as well as appeal procedures, see part 13 of this chapter. [T.D...

The Challenges of First-in-Human Stem Cell Clinical Trials: What Does This Mean for Ethics and Institutional Review Boards?

Directory of Open Access Journals (Sweden)

Roger A. Barker

2018-05-01

Full Text Available Stem cell-based clinical interventions are increasingly advancing through preclinical testing and approaching clinical trials. The complexity and diversity of these approaches, and the confusion created by unproven and untested stem cell-based “therapies,” create a growing need for a more comprehensive review of these early-stage human trials to ensure they place the patients at minimal risk of adverse events but are also based on solid evidence of preclinical efficacy with a clear scientific rationale for that effect. To address this issue and supplement the independent review process, especially that of the ethics and institutional review boards who may not be experts in stem cell biology, the International Society for Stem Cell Research (ISSCR has developed a set of practical questions to cover the major issues for which clear evidence-based answers need to be obtained before approving a stem cell-based trial. Keywords: human stem cell-derived interventions, early phase clinical trials, institutional review and ethics boards, review process, guidelines

Recognition and Evaluation of Clinical Section Headings in Clinical Documents Using Token-Based Formulation with Conditional Random Fields

Directory of Open Access Journals (Sweden)

Hong-Jie Dai

2015-01-01

Full Text Available Electronic health record (EHR is a digital data format that collects electronic health information about an individual patient or population. To enhance the meaningful use of EHRs, information extraction techniques have been developed to recognize clinical concepts mentioned in EHRs. Nevertheless, the clinical judgment of an EHR cannot be known solely based on the recognized concepts without considering its contextual information. In order to improve the readability and accessibility of EHRs, this work developed a section heading recognition system for clinical documents. In contrast to formulating the section heading recognition task as a sentence classification problem, this work proposed a token-based formulation with the conditional random field (CRF model. A standard section heading recognition corpus was compiled by annotators with clinical experience to evaluate the performance and compare it with sentence classification and dictionary-based approaches. The results of the experiments showed that the proposed method achieved a satisfactory F-score of 0.942, which outperformed the sentence-based approach and the best dictionary-based system by 0.087 and 0.096, respectively. One important advantage of our formulation over the sentence-based approach is that it presented an integrated solution without the need to develop additional heuristics rules for isolating the headings from the surrounding section contents.

Considering benefits and harms of duloxetine for treatment of stress urinary incontinence: a meta-analysis of clinical study reports

DEFF Research Database (Denmark)

Maund, Emma; Guski, Louise Schow; Gøtzsche, Peter C.

2017-01-01

BACKGROUND: The European Medicines Agency makes clinical study reports publicly available and publishes reasons for not approving applications for marketing authorization. Duloxetine has been approved in Europe for the treatment of stress urinary incontinence in women. The reported adverse effects...... of duloxetine include mental health problems and suicidality. We obtained clinical study reports from the European Medicines Agency concerning use of this drug for stress urinary incontinence. METHODS: We performed a meta-analysis of 4 randomized placebo-controlled trials of duloxetine (involving a total...... of 1913 patients) submitted to the European Medicines Agency for marketing approval for the indication of stress urinary incontinence in women. We used data from the clinical study reports (totalling 6870 pages and including individual patient data) to assess benefits (including frequency of incontinence...

Evaluating the Status Approvals about Cinema (1989 to 2009

Directory of Open Access Journals (Sweden)

Elahe Dehghan Pishe

2012-06-01

Full Text Available The present study aimed to study and evaluate the state approvals in the field of The cabinet approval in mentioned period 1989 to 2009 in Iran. cinema from which keywords related to cinema is shown in their titles or texts will form this The method of this research is content analysis and the instrument used .research is a checklist with r= 0.91 using Scott formula. The content analysis checklist was constructed based on the model which classified arts policies into four types namely: facilitator, patron, architect and engineer. The findings revealed that in the investigated twenty-year process. the various states having come in 4-year intervals have been different in using the types of arts policies. The state in the first and second presidency of Akbar Hashemi Rafsanjani used the facilitator and engineer types; in the first presidency of Mohammad Khatami used the patron and architect types, in his second presidency the architect type; and finally in the first presidency of Mahmoud Ahmadinejad used the architect and engineer types more than the other types. Although there has been a difference between the types of arts policy in the cinema approvals in different periods of presidency. the architect and engineer types of arts policies have been used more than the facilitator and patron types.

14 CFR 21.609 - Approval for deviation.

Science.gov (United States)

2010-01-01

... deviation. (a) Each manufacturer who requests approval to deviate from any performance standard of a TSO shall show that the standards from which a deviation is requested are compensated for by factors or... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Approval for deviation. 21.609 Section 21...

Ordinal Position, Approval Motivation, and Interpersonal Attraction

Science.gov (United States)

Nowicki, Stephen, Jr.

1971-01-01

Results of the study suggest that birth-order effects might be included within the wider framework of approval-dependency theory. Females tend to account for a significant share of birth-order effects. More particularly, firstborn females accounted for much of the differences in expressed attraction as well as need for social approval. (Author)

The clinical development process for a novel preventive vaccine: An overview

Directory of Open Access Journals (Sweden)

K Singh

2016-01-01

Full Text Available Each novel vaccine candidate needs to be evaluated for safety, immunogenicity, and protective efficacy in humans before it is licensed for use. After initial safety evaluation in healthy adults, each vaccine candidate follows a unique development path. This article on clinical development gives an overview on the development path based on the expectations of various guidelines issued by the World Health Organization (WHO, the European Medicines Agency (EMA, and the United States Food and Drug Administration (USFDA. The manuscript describes the objectives, study populations, study designs, study site, and outcome(s of each phase (Phase I-III of a clinical trial. Examples from the clinical development of a malaria vaccine candidate, a rotavirus vaccine, and two vaccines approved for human papillomavirus (HPV have also been discussed. The article also tabulates relevant guidelines, which can be referred to while drafting the development path of a novel vaccine candidate.

General practice-based clinical trials in Germany - a problem analysis

Directory of Open Access Journals (Sweden)

Hummers-Pradier Eva

2012-11-01

Full Text Available Abstract Background In Germany, clinical trials and comparative effectiveness studies in primary care are still very rare, while their usefulness has been recognised in many other countries. A network of researchers from German academic general practice has explored the reasons for this discrepancy. Methods Based on a comprehensive literature review and expert group discussions, problem analyses as well as structural and procedural prerequisites for a better implementation of clinical trials in German primary care are presented. Results In Germany, basic biomedical science and technology is more reputed than clinical or health services research. Clinical trials are funded by industry or a single national programme, which is highly competitive, specialist-dominated, exclusive of pilot studies, and usually favours innovation rather than comparative effectiveness studies. Academic general practice is still not fully implemented, and existing departments are small. Most general practitioners (GPs work in a market-based, competitive setting of small private practices, with a high case load. They have no protected time or funding for research, and mostly no research training or experience. Good Clinical Practice (GCP training is compulsory for participation in clinical trials. The group defined three work packages to be addressed regarding clinical trials in German general practice: (1 problem analysis, and definition of (2 structural prerequisites and (3 procedural prerequisites. Structural prerequisites comprise specific support facilities for general practice-based research networks that could provide practices with a point of contact. Procedural prerequisites consist, for example, of a summary of specific relevant key measures, for example on a web platform. The platform should contain standard operating procedures (SOPs, templates, checklists and other supporting materials for researchers. Conclusion All in all, our problem analyses revealed that

Right to experimental treatment: FDA new drug approval, constitutional rights, and the public's health.

Science.gov (United States)

Leonard, Elizabeth Weeks

2009-01-01

On May 2, 2006, a divided panel of the U.S. Court of Appeals for the District of Columbia, in a startling opinion, Abigail Alliance for Better Access to Developmental Drugs v. Eschenbach, held that terminally ill patients who have exhausted all other available options have a constitutional right to experimental treatment that FDA has not yet approved. Although ultimately overturned by the full court, Abigail Alliance generated considerable interest from various constituencies. Meanwhile, FDA proposed similar regulatory amendments, as have lawmakers on both sides of the aisle in Congress. But proponents of expanded access fail to consider public health and consumer safety concerns. In particular, allowing patients to try unproven treatments, outside of controlled clinical trials risks both the study's outcome and the health of patients who might benefit from the deliberate, careful process of new drug approval as it currently operates under FDA's auspices.

Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients.

Science.gov (United States)

Schulman, S; Angerås, U; Bergqvist, D; Eriksson, B; Lassen, M R; Fisher, W

2010-01-01

The definition of major bleeding varies between studies on surgical patients, particularly regarding the criteria for surgical wound-related bleeding. This diversity contributes to the difficulties in comparing data between trials. The Scientific and Standardization Committee (SSC), through its subcommittee on Control of Anticoagulation, of the International Society on Thrombosis and Haemostasis has previously published a recommendation for a harmonized definition of major bleeding in non-surgical studies. That definition has been adopted by the European Medicines Agency and is currently used in several non-surgical trials. A preliminary proposal for a parallel definition for surgical studies was presented at the 54(th) Annual Meeting of the SSC in Vienna, July 2008. Based on those discussions and further consultations with European and North American surgeons with experience from clinical trials a definition has been developed that should be applicable to all agents that interfere with hemostasis. The definition and the text that follows have been reviewed and approved by relevant co-chairs of the subcommittee and by the Executive Committee of the SSC. The intention is to seek approval of this definition from the regulatory authorities to enhance its incorporation into future clinical trial protocols.

Biology and clinical application of CAR T cells for B cell malignancies.

Science.gov (United States)

Davila, Marco L; Sadelain, Michel

2016-07-01

Chimeric antigen receptor (CAR)-modified T cells have generated broad interest in oncology following a series of dramatic clinical successes in patients with chemorefractory B cell malignancies. CAR therapy now appears to be on the cusp of regulatory approval as a cell-based immunotherapy. We review here the T cell biology and cell engineering research that led to the development of second generation CARs, the selection of CD19 as a CAR target, and the preclinical studies in animal models that laid the foundation for clinical trials targeting CD19+ malignancies. We further summarize the status of CD19 CAR clinical therapy for non-Hodgkin lymphoma and B cell acute lymphoblastic leukemia, including their efficacy, toxicities (cytokine release syndrome, neurotoxicity and B cell aplasia) and current management in humans. We conclude with an overview of recent pre-clinical advances in CAR design that argues favorably for the advancement of CAR therapy to tackle other hematological malignancies as well as solid tumors.

Drugs Approved for Neuroblastoma

Science.gov (United States)

This page lists cancer drugs approved by the Food and Drug Administration (FDA) for neuroblastoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

42 CFR 102.73 - Approval of benefits.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Approval of benefits. 102.73 Section 102.73 Public... PROGRAM Secretarial Determinations § 102.73 Approval of benefits. When the Secretary has determined that benefits will be paid to a requester and has calculated the type and amount of such benefits, he will...

76 FR 66117 - Projects Approved for Consumptive Uses of Water

Science.gov (United States)

2011-10-25

... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule... notice lists the projects, described below, receiving approval for the consumptive use of water pursuant...

76 FR 53526 - Projects Approved for Consumptive Uses of Water

Science.gov (United States)

2011-08-26

... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule... lists the projects, described below, receiving approval for the consumptive use of water pursuant to the...

76 FR 42159 - Projects Approved for Consumptive Uses of Water

Science.gov (United States)

2011-07-18

... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule... lists the projects, described below, receiving approval for the consumptive use of water pursuant to the...

77 FR 4859 - Projects Approved for Consumptive Uses of Water

Science.gov (United States)

2012-01-31

... SUSQUEHANNA RIVER BASIN COMMISSION Projects Approved for Consumptive Uses of Water AGENCY: Susquehanna River Basin Commission. ACTION: Notice. SUMMARY: This notice lists the projects approved by rule... notice lists the projects, described below, receiving approval for the consumptive use of water pursuant...

Growing insights into the potential benefits and risks of activated protein C administration in sepsis: a review of preclinical and clinical studies

Directory of Open Access Journals (Sweden)

Laith Altaweel

2009-09-01

Full Text Available Laith Altaweel, Daniel Sweeney, Xizhong Cui, Amisha Barochia, Charles Natanson, Peter Q EichackerCritical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, USAAbstract: Recombinant human activated protein C (rhAPC was developed to reduce excessive coagulant and inflammatory activity during sepsis. Basic and clinical research has suggested these pathways contribute to the pathogenesis of this lethal syndrome and are inhibited by rhAPC. Based in large part on the results of a single multicenter randomized controlled trial, rhAPC was first approved in 2001 by the US Food and Drug Administration (FDA as adjunctive therapy in septic patients with a high risk of death. This was followed closely by approval in Europe, Australia, and New Zealand. At the original FDA review of rhAPC, concerns were raised as to whether a confirmatory trial should be done before final regulatory approval because of concerns that rhAPCs bleeding risk might outweigh its potential benefit during clinical use. Since 2001, continuing basic and clinical research has further elucidated the complex role activated protein C may have in both adaptive and maladaptive responses during sepsis. Moreover, subsequent controlled trials in other types of septic patients and observational studies appear to support earlier concerns that the benefit-to-risk ratio of rhAPC may not support its clinical use. This experience has prompted additional trials presently underway, to define whether treatment with rhAPC as it was originally indicated in septic patients with persistent shock, is safe and effective. Until such trials are complete, physicians employing this agent must carefully consider which patients may be appropriate candidates for rhAPC administration.Keywords: rhAPC, treatment, sepsis

Oncogenic human papillomavirus genital infection in southern Iranian women: population-based study versus clinic-based data

Directory of Open Access Journals (Sweden)

Eghbali Seyed

2012-09-01

Full Text Available Abstract Background Epidemiological studies on genital human papilloma viruses infection (HPVs in general population are crucial for the implementation of health policy guidelines for developing the strategies to prevent the primary and secondary cervical cancer. In different parts of Iran, there is a lack of population-based studies to determine the prevalence of HPV in the general population. The aim of this population-based study is to compare the prevalence rate of genital HPV infection among reproductive women with our previous clinic-based data, which showed a prevalence rate of 5% in women in southern Iran. Results Using general primers for all genotypes of HPV, of 799 randomly selected women, five (0.63%, 95% CI 0.23-1.55% tested positive for HPV DNA. Overall, seven different HPV genotypes were detected: six types (16, 18, 31, 33, 51 and 56 were carcinogenic, or “high risk genotypes” and one genotype (HPV-66 was “probably carcinogenic.” Conclusions In a population-based study, the prevalence of HPV infection among southern Iranian women was lower than that observed worldwide. However, our gynaecological clinic-based study on the prevalence of HPV infection showed results comparable with other studies in the Middle East and Persian Gulf countries. Since gynaecological clinic-based data may generally overestimate HPV prevalence, estimates of prevalence according to clinic-based data should be adjusted downward by the population-based survey estimates.

Deterministic versus evidence-based attitude towards clinical diagnosis.

Science.gov (United States)

Soltani, Akbar; Moayyeri, Alireza

2007-08-01

Generally, two basic classes have been proposed for scientific explanation of events. Deductive reasoning emphasizes on reaching conclusions about a hypothesis based on verification of universal laws pertinent to that hypothesis, while inductive or probabilistic reasoning explains an event by calculation of some probabilities for that event to be related to a given hypothesis. Although both types of reasoning are used in clinical practice, evidence-based medicine stresses on the advantages of the second approach for most instances in medical decision making. While 'probabilistic or evidence-based' reasoning seems to involve more mathematical formulas at the first look, this attitude is more dynamic and less imprisoned by the rigidity of mathematics comparing with 'deterministic or mathematical attitude'. In the field of medical diagnosis, appreciation of uncertainty in clinical encounters and utilization of likelihood ratio as measure of accuracy seem to be the most important characteristics of evidence-based doctors. Other characteristics include use of series of tests for refining probability, changing diagnostic thresholds considering external evidences and nature of the disease, and attention to confidence intervals to estimate uncertainty of research-derived parameters.

Drugs Approved for Retinoblastoma

Science.gov (United States)

This page lists cancer drugs approved by the Food and Drug Administration (FDA) for retinoblastoma. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

Blockchain protocols in clinical trials: Transparency and traceability of consent [version 3; referees: 1 approved, 2 approved with reservations, 1 not approved

OpenAIRE

Mehdi Benchoufi; Raphael Porcher; Philippe Ravaud

2017-01-01

Clinical trial consent for protocols and their revisions should be transparent for patients and traceable for stakeholders. Our goal is to implement a process allowing the collection of patients’ informed consent, which is bound to protocol revisions, storing and tracking the consent in a secure, unfalsifiable and publicly verifiable way, and enabling the sharing of this information in real time. For that, we will built a consent workflow using a rising technology called Blockchain. This is a...

Bladder cancer treatment response assessment with radiomic, clinical, and radiologist semantic features

Science.gov (United States)

Gordon, Marshall N.; Cha, Kenny H.; Hadjiiski, Lubomir M.; Chan, Heang-Ping; Cohan, Richard H.; Caoili, Elaine M.; Paramagul, Chintana; Alva, Ajjai; Weizer, Alon Z.

2018-02-01

We are developing a decision support system for assisting clinicians in assessment of response to neoadjuvant chemotherapy for bladder cancer. Accurate treatment response assessment is crucial for identifying responders and improving quality of life for non-responders. An objective machine learning decision support system may help reduce variability and inaccuracy in treatment response assessment. We developed a predictive model to assess the likelihood that a patient will respond based on image and clinical features. With IRB approval, we retrospectively collected a data set of pre- and post- treatment CT scans along with clinical information from surgical pathology from 98 patients. A linear discriminant analysis (LDA) classifier was used to predict the likelihood that a patient would respond to treatment based on radiomic features extracted from CT urography (CTU), a radiologist's semantic feature, and a clinical feature extracted from surgical and pathology reports. The classification accuracy was evaluated using the area under the ROC curve (AUC) with a leave-one-case-out cross validation. The classification accuracy was compared for the systems based on radiomic features, clinical feature, and radiologist's semantic feature. For the system based on only radiomic features the AUC was 0.75. With the addition of clinical information from examination under anesthesia (EUA) the AUC was improved to 0.78. Our study demonstrated the potential of designing a decision support system to assist in treatment response assessment. The combination of clinical features, radiologist semantic features and CTU radiomic features improved the performance of the classifier and the accuracy of treatment response assessment.

The approval mechanism solves the prisoner's dilemma theoretically and experimentally

OpenAIRE

Tatsuyoshi Saijo; Yoshitaka Okano; Takafumi Yamakawa

2015-01-01

Consider a situation where players in a prisoner's dilemma game can approve or reject the other's choice such as cooperation or defection. If both players approve the other's choice, the outcome is the one they chose, whereas if either one rejects the other's choice, the outcome is the one when both defect, which we name the approval mechanism herein (this is inspired by the Cold War doctrine of mutually assured destruction). Experimentally, we find that the cooperation rate with the approval...

Big Data Mining and Adverse Event Pattern Analysis in Clinical Drug Trials.

Science.gov (United States)

Federer, Callie; Yoo, Minjae; Tan, Aik Choon

2016-12-01

Drug adverse events (AEs) are a major health threat to patients seeking medical treatment and a significant barrier in drug discovery and development. AEs are now required to be submitted during clinical trials and can be extracted from ClinicalTrials.gov ( https://clinicaltrials.gov/ ), a database of clinical studies around the world. By extracting drug and AE information from ClinicalTrials.gov and structuring it into a database, drug-AEs could be established for future drug development and repositioning. To our knowledge, current AE databases contain mainly U.S. Food and Drug Administration (FDA)-approved drugs. However, our database contains both FDA-approved and experimental compounds extracted from ClinicalTrials.gov . Our database contains 8,161 clinical trials of 3,102,675 patients and 713,103 reported AEs. We extracted the information from ClinicalTrials.gov using a set of python scripts, and then used regular expressions and a drug dictionary to process and structure relevant information into a relational database. We performed data mining and pattern analysis of drug-AEs in our database. Our database can serve as a tool to assist researchers to discover drug-AE relationships for developing, repositioning, and repurposing drugs.

FDA-approved drugs that are spermatotoxic in animals and the utility of animal testing for human risk prediction.

Science.gov (United States)

Rayburn, Elizabeth R; Gao, Liang; Ding, Jiayi; Ding, Hongxia; Shao, Jun; Li, Haibo

2018-02-01

This study reviews FDA-approved drugs that negatively impact spermatozoa in animals, as well as how these findings reflect on observations in human male gametes. The FDA drug warning labels included in the DailyMed database and the peer-reviewed literature in the PubMed database were searched for information to identify single-ingredient, FDA-approved prescription drugs with spermatotoxic effects. A total of 235 unique, single-ingredient, FDA-approved drugs reported to be spermatotoxic in animals were identified in the drug labels. Forty-nine of these had documented negative effects on humans in either the drug label or literature, while 31 had no effect or a positive impact on human sperm. For the other 155 drugs that were spermatotoxic in animals, no human data was available. The current animal models are not very effective for predicting human spermatotoxicity, and there is limited information available about the impact of many drugs on human spermatozoa. New approaches should be designed that more accurately reflect the findings in men, including more studies on human sperm in vitro and studies using other systems (ex vivo tissue culture, xenograft models, in silico studies, etc.). In addition, the present data is often incomplete or reported in a manner that prevents interpretation of their clinical relevance. Changes should be made to the requirements for pre-clinical testing, drug surveillance, and the warning labels of drugs to ensure that the potential risks to human fertility are clearly indicated.

Gender-specific Regulatory Challenges to Product Approval: a panel discussion.

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McGregor, Alyson J; Barr, Helen; Greenberg, Marna R; Safdar, Basmah; Wildgoose, Peter; Wright, David W; Hollander, Judd E

2014-12-01

On May 13, 2014, a 1-hour panel discussion session titled "Gender-specific Regulatory Challenges to Product Approval" was held during the Academic Emergency Medicine consensus conference, "Gender-specific Research in Emergency Medicine: Investigate, Understand, and Translate How Gender Affects Patient Outcomes." The session sought to bring together leaders in emergency medicine (EM) research, authors, and reviewers in EM research publications, as well as faculty, fellows, residents, and students engaged in research and clinical practice. A panel was convened involving a representative from the Office of Women's Health of the U.S. Food and Drug Administration, two pharmaceutical executives, and a clinical EM researcher. The moderated discussion also involved audience members who contributed significantly to the dialogue. Historical background leading up to the session along with the main themes of the discussion are reproduced in this article. These revolve around sex- and gender-specific research, statistical analysis of sex and gender, clinical practice, financial costs associated with pharmaceutical development, adaptive design, and specific recommendations on the regulatory process as it affects the specialty of EM. © 2014 by the Society for Academic Emergency Medicine.

42 CFR 8.6 - Withdrawal of approval of accreditation bodies.

Science.gov (United States)

2010-10-01

... PROVISIONS CERTIFICATION OF OPIOID TREATMENT PROGRAMS Accreditation § 8.6 Withdrawal of approval of... 42 Public Health 1 2010-10-01 2010-10-01 false Withdrawal of approval of accreditation bodies. 8.6... to establish that the problems that were grounds for withdrawal of approval have been resolved. (2...

Machine learning-based analysis of MR radiomics can help to improve the diagnostic performance of PI-RADS v2 in clinically relevant prostate cancer

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Wang, Jing [CFDA, Center for Medical Device Evaluation, Beijing (China); Wu, Chen-Jiang; Zhang, Jing; Wang, Xiao-Ning; Zhang, Yu-Dong [First Affiliated Hospital with Nanjing Medical University, Department of Radiology, Nanjing, Jiangsu Province (China); Bao, Mei-Ling [First Affiliated Hospital with Nanjing Medical University, Department of Pathology, Nanjing (China)

2017-10-15

To investigate whether machine learning-based analysis of MR radiomics can help improve the performance PI-RADS v2 in clinically relevant prostate cancer (PCa). This IRB-approved study included 54 patients with PCa undergoing multi-parametric (mp) MRI before prostatectomy. Imaging analysis was performed on 54 tumours, 47 normal peripheral (PZ) and 48 normal transitional (TZ) zone based on histological-radiological correlation. Mp-MRI was scored via PI-RADS, and quantified by measuring radiomic features. Predictive model was developed using a novel support vector machine trained with: (i) radiomics, (ii) PI-RADS scores, (iii) radiomics and PI-RADS scores. Paired comparison was made via ROC analysis. For PCa versus normal TZ, the model trained with radiomics had a significantly higher area under the ROC curve (Az) (0.955 [95% CI 0.923-0.976]) than PI-RADS (Az: 0.878 [0.834-0.914], p < 0.001). The Az between them was insignificant for PCa versus PZ (0.972 [0.945-0.988] vs. 0.940 [0.905-0.965], p = 0.097). When radiomics was added, performance of PI-RADS was significantly improved for PCa versus PZ (Az: 0.983 [0.960-0.995]) and PCa versus TZ (Az: 0.968 [0.940-0.985]). Machine learning analysis of MR radiomics can help improve the performance of PI-RADS in clinically relevant PCa. (orig.)

Machine learning-based analysis of MR radiomics can help to improve the diagnostic performance of PI-RADS v2 in clinically relevant prostate cancer

International Nuclear Information System (INIS)

Wang, Jing; Wu, Chen-Jiang; Zhang, Jing; Wang, Xiao-Ning; Zhang, Yu-Dong; Bao, Mei-Ling

2017-01-01

To investigate whether machine learning-based analysis of MR radiomics can help improve the performance PI-RADS v2 in clinically relevant prostate cancer (PCa). This IRB-approved study included 54 patients with PCa undergoing multi-parametric (mp) MRI before prostatectomy. Imaging analysis was performed on 54 tumours, 47 normal peripheral (PZ) and 48 normal transitional (TZ) zone based on histological-radiological correlation. Mp-MRI was scored via PI-RADS, and quantified by measuring radiomic features. Predictive model was developed using a novel support vector machine trained with: (i) radiomics, (ii) PI-RADS scores, (iii) radiomics and PI-RADS scores. Paired comparison was made via ROC analysis. For PCa versus normal TZ, the model trained with radiomics had a significantly higher area under the ROC curve (Az) (0.955 [95% CI 0.923-0.976]) than PI-RADS (Az: 0.878 [0.834-0.914], p < 0.001). The Az between them was insignificant for PCa versus PZ (0.972 [0.945-0.988] vs. 0.940 [0.905-0.965], p = 0.097). When radiomics was added, performance of PI-RADS was significantly improved for PCa versus PZ (Az: 0.983 [0.960-0.995]) and PCa versus TZ (Az: 0.968 [0.940-0.985]). Machine learning analysis of MR radiomics can help improve the performance of PI-RADS in clinically relevant PCa. (orig.)

What to Know About Medicines With New Active Ingredients Approved in FY 2016 / 2016 in Japan and EU: A Brief Comparison of New Medicines Approved in Japan and the EU in 2016.

Science.gov (United States)

Kondo, Hideyuki; Saint-Raymond, Agnès; Yasuda, Naoyuki

2018-03-01

The Pharmaceuticals and Medical Devices Agency (PMDA) in Japan and the European Medicines Agency (EMA) have a long-standing experience of reviews of new medicines, and they meet their target pre-market review periods. In FY 2016 / 2016, 112 and 83 new medicines were approved in Japan and EU, respectively. Out of these medicines, 41 and 27 medicines containing new active ingredients were approved with total pre-market review periods of 209 days and 428 days in Japan and EU, respectively. Approximately one-third of these medicines were reviewed by the Agencies in close timing, within 1 year between pre-market review applications in Japan and in EU. Taking into account the increasing number of global clinical trials and constant number of consultations or scientific advice related to global clinical trials in Japan, it is clear that the importance of the continuous, collaborative relationship between EMA and PMDA is more and more crucial, as it does facilitate close and timely exchange of information and opinions on products and technologies under development. There already are effective collaborative frameworks between PMDA and EMA in addition to daily communication, and our findings support the development and best use of regulatory tools such as consultation services and scientific advice/protocol assistance for the benefit of the pharmaceutical industry but mostly of patients.

Acid-base equilibrium: The best clinical approach

OpenAIRE

Aristizábal-Salazar, Raúl E; Calvo-Torres, L. Felipe; Valencia-Arango, Luis Alfonso; Montoya-Canon, Mauricio; Barbosa-Gantiva, Oscar; Hincapié-Baena, Vanessa

2015-01-01

Acid-base balance disorders can be found in a primary or secondary form in patients with a disease process such as Diabetes Mellitus or acute renal failure, among others. The objective of this article is to explain and guide the correlation ship between the clinical findings in the patient and the parameters of arterial blood gases in a simple and precise manner, in order to make the correct acid-base balance diagnosis and adequate therapeutic interventions. A non-systematic review of the sci...

Poet North Manchester Approval

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This update August 9, 2016 letter from EPA approves, with modifications, the petition from Poet Biorefining-North Manchester, LLC, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable

7 CFR 1717.159 - Applications for RUS approvals of mergers.

Science.gov (United States)

2010-01-01

... 7 Agriculture 11 2010-01-01 2010-01-01 false Applications for RUS approvals of mergers. 1717.159... ELECTRIC LOANS Mergers and Consolidations of Electric Borrowers § 1717.159 Applications for RUS approvals of mergers. If a proposed merger requires RUS approval according to RUS regulations and/or the loan...

7 CFR 4290.510 - Approval of RBIC's Investment Adviser/Manager.

Science.gov (United States)

2010-01-01

... INVESTMENT COMPANY (âRBICâ) PROGRAM Managing the Operations of a RBIC Management and Compensation § 4290.510... approval of the management contract. Approval of an Investment Adviser/Manager for one RBIC does not... 7 Agriculture 15 2010-01-01 2010-01-01 false Approval of RBIC's Investment Adviser/Manager. 4290...

30 CFR 250.119 - Will MMS approve subsurface gas storage?

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Will MMS approve subsurface gas storage? 250....119 Will MMS approve subsurface gas storage? The Regional Supervisor may authorize subsurface storage of gas on the OCS, on and off-lease, for later commercial benefit. To receive MMS approval you must...

A service oriented approach for guidelines-based clinical decision support using BPMN.

Science.gov (United States)

Rodriguez-Loya, Salvador; Aziz, Ayesha; Chatwin, Chris

2014-01-01

Evidence-based medical practice requires that clinical guidelines need to be documented in such a way that they represent a clinical workflow in its most accessible form. In order to optimize clinical processes to improve clinical outcomes, we propose a Service Oriented Architecture (SOA) based approach for implementing clinical guidelines that can be accessed from an Electronic Health Record (EHR) application with a Web Services enabled communication mechanism with the Enterprise Service Bus. We have used Business Process Modelling Notation (BPMN) for modelling and presenting the clinical pathway in the form of a workflow. The aim of this study is to produce spontaneous alerts in the healthcare workflow in the diagnosis of Chronic Obstructive Pulmonary Disease (COPD). The use of BPMN as a tool to automate clinical guidelines has not been previously employed for providing Clinical Decision Support (CDS).

Practical Approach for the Clinical Use of Dopamine Transporter Imaging

International Nuclear Information System (INIS)

Kim, Jae Seung

2008-01-01

Dopamine transporter imaging is useful in the diagnosis of Parkinson's disease and the most successful technique in the clinical use of neuroreceptor imaging. Recently, several radiopharmaceuticals including I-123 FP-CIT, Tc-99m TRODAT, and F-18 FP-CIT for dopamine transporter imaging have been approved for the routine clinical use in several European countries, Taiwan and Korea, respectively. This review summarized the practical issue for the routine clinical examination of dopamine transporter imaging

Study design and rationale for biomedical shirt-based electrocardiography monitoring in relevant clinical situations: ECG-shirt study.

Science.gov (United States)

Balsam, Paweł; Lodziński, Piotr; Tymińska, Agata; Ozierański, Krzysztof; Januszkiewicz, Łukasz; Główczyńska, Renata; Wesołowska, Katarzyna; Peller, Michał; Pietrzak, Radosław; Książczyk, Tomasz; Borodzicz, Sonia; Kołtowski, Łukasz; Borkowski, Mariusz; Werner, Bożena; Opolski, Grzegorz; Grabowski, Marcin

2018-01-01

Today, the main challenge for researchers is to develop new technologies which may help to improve the diagnoses of cardiovascular disease (CVD), thereby reducing healthcare costs and improving the quality of life for patients. This study aims to show the utility of biomedical shirt-based electrocardiography (ECG) monitoring of patients with CVD in different clinical situations using the Nuubo® ECG (nECG) system. An investigator-initiated, multicenter, prospective observational study was carried out in a cardiology (adult and pediatric) and cardiac rehabilitation wards. ECG monitoring was used with the biomedical shirt in the following four independent groups of patients: 1) 30 patients after pulmonary vein isolation (PVI), 2) 30 cardiac resynchronization therapy (CRT) recipients, 3) 120 patients during cardiac rehabilitation after myocardial infarction, and 4) 40 pediatric patients with supraventricular tachycardia (SVT) before electrophysiology study. Approval for all study groups was obtained from the institutional review board. The biomedical shirt captures the electrocardiographic signal via textile electrodes integrated into a garment. The software allows the visualization and analysis of data such as ECG, heart rate, arrhythmia detecting algorithm and relative position of the body is captured by an electronic device. The major advantages of the nECG system are continuous ECG monitoring during daily activities, high quality of ECG recordings, as well as assurance of a proper adherence due to adequate comfort while wearing the shirt. There are only a few studies that have examined wearable systems, especially in pediatric populations. This study is registered in ClinicalTrials.gov: Identifier NCT03068169. (Cardiol J 2018; 25, 1: 52-59).

75 FR 36301 - Review and Approval of Projects

Science.gov (United States)

2010-06-25

... SUSQUEHANNA RIVER BASIN COMMISSION 18 CFR Parts 806 and 808 Review and Approval of Projects AGENCY... document contains proposed rules that would amend the project review regulations of the Susquehanna River... the scope of withdrawals requiring review and approval; improve notice procedures for all project...

Editorial: Ethics approval: responsibilities of journal editors, authors ...

African Journals Online (AJOL)

Meaningful progress of medicine depends on research that must ultimately involve human subjects. Obtaining ethical approval therefore, especially in medical sciences, should be a moral reflex for researchers. This unfortunately is not the case, with numerous researchers bypassing the ethics approval procedure, or simply ...

Building an Undergraduate Book Approval Plan for a Large Academic Library

Directory of Open Access Journals (Sweden)

Denise Koufogiannakis

2007-05-01

Full Text Available The University of Alberta Libraries (UAL, working with two book vendors, created large-scale undergraduate book approval plans to deliver new publications. Detailed selections profiles were created for many subject areas, designed to deliver books that would have been obvious choices by subject selectors. More than 5800 monographs were received through the book approval plans during the pilot period. These volumes proved to be highly relevant to users, showing twice as much circulation as other monographs acquired during the same time period. Goals achieved through this project include: release of selectors’ time from routine work, systematic acquisition of a broadly based high-demand undergraduate collection and faster delivery of undergraduate materials. This successful program will be expanded and incorporated into UAL’s normal acquisitions processes for undergraduate materials.

29 CFR 1952.10 - Requirements for approval of State posters.

Science.gov (United States)

2010-07-01

... 29 Labor 9 2010-07-01 2010-07-01 false Requirements for approval of State posters. 1952.10 Section... and Conditions § 1952.10 Requirements for approval of State posters. (a)(1) In order to inform..., States with approved plans shall develop and require employers to post a State poster meeting the...

42 CFR 422.256 - Review, negotiation, and approval of bids.

Science.gov (United States)

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Review, negotiation, and approval of bids. 422.256... Information and Plan Approval § 422.256 Review, negotiation, and approval of bids. (a) Authority. Subject to... submitted under § 422.252 and conduct negotiations with MA organizations regarding these bids (including the...

Comparison of RNA-seq and microarray-based models for clinical endpoint prediction.

Science.gov (United States)

Zhang, Wenqian; Yu, Ying; Hertwig, Falk; Thierry-Mieg, Jean; Zhang, Wenwei; Thierry-Mieg, Danielle; Wang, Jian; Furlanello, Cesare; Devanarayan, Viswanath; Cheng, Jie; Deng, Youping; Hero, Barbara; Hong, Huixiao; Jia, Meiwen; Li, Li; Lin, Simon M; Nikolsky, Yuri; Oberthuer, André; Qing, Tao; Su, Zhenqiang; Volland, Ruth; Wang, Charles; Wang, May D; Ai, Junmei; Albanese, Davide; Asgharzadeh, Shahab; Avigad, Smadar; Bao, Wenjun; Bessarabova, Marina; Brilliant, Murray H; Brors, Benedikt; Chierici, Marco; Chu, Tzu-Ming; Zhang, Jibin; Grundy, Richard G; He, Min Max; Hebbring, Scott; Kaufman, Howard L; Lababidi, Samir; Lancashire, Lee J; Li, Yan; Lu, Xin X; Luo, Heng; Ma, Xiwen; Ning, Baitang; Noguera, Rosa; Peifer, Martin; Phan, John H; Roels, Frederik; Rosswog, Carolina; Shao, Susan; Shen, Jie; Theissen, Jessica; Tonini, Gian Paolo; Vandesompele, Jo; Wu, Po-Yen; Xiao, Wenzhong; Xu, Joshua; Xu, Weihong; Xuan, Jiekun; Yang, Yong; Ye, Zhan; Dong, Zirui; Zhang, Ke K; Yin, Ye; Zhao, Chen; Zheng, Yuanting; Wolfinger, Russell D; Shi, Tieliu; Malkas, Linda H; Berthold, Frank; Wang, Jun; Tong, Weida; Shi, Leming; Peng, Zhiyu; Fischer, Matthias

2015-06-25

Gene expression profiling is being widely applied in cancer research to identify biomarkers for clinical endpoint prediction. Since RNA-seq provides a powerful tool for transcriptome-based applications beyond the limitations of microarrays, we sought to systematically evaluate the performance of RNA-seq-based and microarray-based classifiers in this MAQC-III/SEQC study for clinical endpoint prediction using neuroblastoma as a model. We generate gene expression profiles from 498 primary neuroblastomas using both RNA-seq and 44 k microarrays. Characterization of the neuroblastoma transcriptome by RNA-seq reveals that more than 48,000 genes and 200,000 transcripts are being expressed in this malignancy. We also find that RNA-seq provides much more detailed information on specific transcript expression patterns in clinico-genetic neuroblastoma subgroups than microarrays. To systematically compare the power of RNA-seq and microarray-based models in predicting clinical endpoints, we divide the cohort randomly into training and validation sets and develop 360 predictive models on six clinical endpoints of varying predictability. Evaluation of factors potentially affecting model performances reveals that prediction accuracies are most strongly influenced by the nature of the clinical endpoint, whereas technological platforms (RNA-seq vs. microarrays), RNA-seq data analysis pipelines, and feature levels (gene vs. transcript vs. exon-junction level) do not significantly affect performances of the models. We demonstrate that RNA-seq outperforms microarrays in determining the transcriptomic characteristics of cancer, while RNA-seq and microarray-based models perform similarly in clinical endpoint prediction. Our findings may be valuable to guide future studies on the development of gene expression-based predictive models and their implementation in clinical practice.

Evaluation of Criteria-Based Clinical Audit in Improving Quality of ...

African Journals Online (AJOL)

Erah

ABSTRACT. Study evaluated criteria–based clinical audit in measuring and improving quality of obstetric care for five life-threatening obstetric complications: obstetric haemorrhage, eclampsia, genital tract infections, obstructed labor and uterine rupture. Clinical management of 65 patients was audited using a 'before.

Global Trends in Alzheimer Disease Clinical Development: Increasing the Probability of Success.

Science.gov (United States)

Sugino, Haruhiko; Watanabe, Akihito; Amada, Naoki; Yamamoto, Miho; Ohgi, Yuta; Kostic, Dusan; Sanchez, Raymond

2015-08-01

Alzheimer disease (AD) is a growing global health and economic issue as elderly populations increase dramatically across the world. Despite the many clinical trials conducted, currently no approved disease-modifying treatment exists. In this commentary, the present status of AD drug development and the grounds for collaborations between government, academia, and industry to accelerate the development of disease-modifying AD therapies are discussed. Official government documents, literature, and news releases were surveyed by MEDLINE and website research. Currently approved anti-AD drugs provide only short-lived symptomatic improvements, which have no effect on the underlying pathogenic mechanisms or progression of the disease. The failure to approve a disease-modifying drug for AD may be because the progression of AD in the patient populations enrolled in clinical studies was too advanced for drugs to demonstrate cognitive and functional improvements. The US Food and Drug Administration and the European Medicines Agency recently published draft guidance for industry which discusses approaches for conducting clinical studies with patients in early AD stages. For successful clinical trials in early-stage AD, however, it will be necessary to identify biomarkers highly correlated with the clinical onset and the longitudinal progress of AD. In addition, because of the high cost and length of clinical AD studies, support in the form of global initiatives and collaborations between government, industry, and academia is needed. In response to this situation, national guidance and international collaborations have been established. Global initiatives are focusing on 2025 as a goal to provide new treatment options, and early signs of success in biomarker and drug development are already emerging. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Efficacy comparison of duloxetine and SSRIs at doses approved in Japan

Directory of Open Access Journals (Sweden)

Harada E

2015-01-01

Full Text Available Eiji Harada,1 Alexander Schacht,2 Tsukasa Koyama,3 Lauren Marangell,4,5 Toshinaga Tsuji,6 Rodrigo Escobar41Medical Science, Eli Lilly Japan K.K, Kobe, Japan; 2Global Statistical Sciences, Eli Lilly and Company, Bad Homburg, Germany; 3Clinical Research Center, Ohyachi Hospital, Sapporo, Japan; 4Eli Lilly and Company, Indianapolis, IN, 5The University of Texas Health Science Center, Houston, TX, USA; 6Medical Affairs, Shionogi & Co Ltd, Osaka, JapanBackground: Approved doses of antidepressants in Japan are usually lower than those in the USA and European Union, but to date meta-analyses comparing antidepressants have all used the higher doses approved in the USA and European Union and often have used indirect comparisons. The purpose of this study was to conduct an integrated database analysis of patient level data to compare the effects of duloxetine with those of selective serotonin reuptake inhibitors (SSRIs at the doses approved in Japan.Methods: Pooled data were analyzed from four randomized, double-blind, placebo-controlled studies that compared duloxetine at the dose range approved in Japan (40–60 mg/day with other SSRIs (paroxetine 20 mg/day or escitalopram 10 mg/day and placebo in patients with major depressive disorder. In total, 1,694 patients were included in the analysis (duloxetine, n=688; selective serotonin reuptake inhibitors, n=690; placebo, n=316. The primary outcome measure was the mean change from baseline at week 8 in 17-item Hamilton Rating Scale for Depression (HAMD17 total and subscale scores.Results: Duloxetine and both selective serotonin reuptake inhibitors were superior to placebo in HAMD17 total score at week 8 in both the all-randomized group and the more severe subgroup (HAMD17 total scores ≥19. Duloxetine was superior to SSRIs in improving the HAMD17 Retardation subscale score (least squares mean difference [95% confidence interval]: all-randomized group, −0.33 [−0.60, −0.07], P=0.015; severe subgroup, �

Glioblastoma update: molecular biology, diagnosis, treatment, response assessment, and translational clinical trials [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Frank Lieberman

2017-10-01

Full Text Available This is an exciting time in neuro-oncology. Discoveries elucidating the molecular mechanisms of oncogenesis and the molecular subtypes of glioblastoma multiforme (GBM have led to new diagnostic and classification schemes with more prognostic power than histology alone. Molecular profiling has become part of the standard neuropathological evaluation of GBM. Chemoradiation followed by adjuvant temozolomide remains the standard therapy for newly diagnosed GBM, but survival remains unsatisfactory. Patients with recurrent GBM continue to have a dismal prognosis, but neuro-oncology centers with active clinical trial programs are seeing a small but increasing cadre of patients with longer survival. Molecularly targeted therapeutics, personalized therapy based on molecular profiling of individual tumors, and immunotherapeutic strategies are all being evaluated and refined in clinical trials. Understanding of the molecular mechanisms of tumor-mediated immunosuppression, and specifically interactions between tumor cells and immune effector cells in the tumor microenvironment, has led to a new generation of immunotherapies, including vaccine and immunomodulatory strategies as well as T-cell-based treatments. Molecularly targeted therapies, chemoradiation, immunotherapies, and anti-angiogenic therapies have created the need to develop more reliable neuroimaging criteria for differentiating the effects of therapy from tumor progression and changes in blood–brain barrier physiology from treatment response. Translational clinical trials for patients with GBM now incorporate quantitative imaging using both magnetic resonance imaging and positron emission tomography techniques. This update presents a summary of the current standards for therapy for newly diagnosed and recurrent GBM and highlights promising translational research.

Approved Drug Products with Therapuetic Equivalence Evaluations (Orange Book)

Data.gov (United States)

U.S. Department of Health & Human Services — The publication Approved Drug Products with Therapeutic Equivalence Evaluations (the List, commonly known as the Orange Book) identifies drug products approved on...

Statistical analysis of MRI-only based dose planning

DEFF Research Database (Denmark)

Korsholm, M. E.; Waring, L. W.; Paulsen, Rasmus Reinhold

2012-01-01

. MRIonly based RT eliminates these errors and reduce the time and costs of a CT scan. The aim of this study is to investigate the dosimetric differences of a treatment plan when the dose calculation is based on MRI as compared to CT. Materials and Methods: Four diagnostic groups are investigated; 12...... as a clinically approved treatment plan. The treatment planning software is Eclipse v.10.0 (Varian Medical Systems). The dose calculation based on MRI data is evaluated in two different ways; a homogeneous density assigned MRI (MRI unit), where the entire body is assigned an HU equal to water and a heterogeneous...... density assigned MRI (MRI bulk) where in addition the CT segmented bone is transferred to the MRI and assigned an age dependent HU based on ICRU report 46. The CT based clinical treatment plan and structure set are registered to the corresponding MRI unit and MRI bulk. The body is outlined on both the MRI...

44 CFR 78.9 - Planning grant approval process.

Science.gov (United States)

2010-10-01

..., DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood Insurance Program FLOOD MITIGATION ASSISTANCE § 78.9 Planning grant approval process. The State POC will evaluate and approve applications for Planning Grants. Funds will be provided only for the flood portion of any mitigation plan, and...

7 CFR 1703.121 - Approved purposes for grants.

Science.gov (United States)

2010-01-01

... Approved purposes for grants. For distance learning and telemedicine projects, grants shall finance only... studies relating to the establishment or expansion of the phase of the project that is being financed with... initial capital assets associated with the project. The following are approved grant purposes: (a...

Dabrafenib Plus Trametinib Approved for Melanoma, Thyroid Cancer

Science.gov (United States)

FDA recently approved the combination of dabrafenib (Taflinar) and trametinib (Mekinist) to treat some patients with melanoma and anaplastic thyroid cancer whose tumors have a mutation in the BRAF gene. As this Cancer Currents blog post explains, this is the first treatment approved specifically for anaplastic thyroid

Browser Based Platform in Maintaining Clinical Activities - Use of The iPads in Head and Neck Clinics

Science.gov (United States)

Yang, W. Y.; Moore, J.; Quon, H.; Evans, K.; Sharabi, A.; Herman, J.; Hacker-Prietz, A.; McNutt, T.

2014-03-01

Purpose: Incompatibility between documentation and clinical workflow causes physician resistance in organized data collection, which in turn complicates the use of data in patient care improvement. To resolve the gap, we developed an iPad compatible in situ browser-based platform that integrates clinical activity with data collection and analysis presentation. The ability to perform in-clinic activities and monitor decision making using the iPad was evaluated. Methods: A browser-based platform that can exchange and present analysed data from the MOSAIQ database was developed in situ, the iPads were distributed in head and neck clinics to present the browser for clinical activities, data collection and assessment monitoring. Performance of the iPads for in-clinic activities was observed. Results: All in-clinic documentation activities can be performed without workstation computers. Accessing patient record and previous assessments was significantly faster without having to open the MOSAIQ application. Patient assessments can be completed with the physician facing the patient. Graphical presentation of toxicity progression and patient radiation plans to the patient can be performed in single interface without patient leaving the seating area. Updates in patient treatment status and medical history were presented in real time without having to move paper charts around. Conclusions: The iPad can be used in clinical activities independent of computer workstations. Improvements in clinical workflow can be critical in reducing physician resistance in data maintenance. Using the iPad in providing real-time quality monitoring is intuitive to both providers and patients.

Drugs Approved for Leukemia

Science.gov (United States)

This page lists cancer drugs approved by the FDA for use in leukemia. The drug names link to NCI's Cancer Drug Information summaries. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

Poet Lake Crystal Approval

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This September 19, 2016 letter from EPA approves the petition from Poet Biorefining-Lake Crystal, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable fuel (D-code 6) RINs under the RFS

76 FR 73634 - Agency Information Collection Activities: Announcement of Board Approval Under Delegated...

Science.gov (United States)

2011-11-29

... securities-based lending from the definition of other consumer loans. \\2\\ The Consolidated Financial... currently approved collections of information. Copies of the PRA submission, supporting statements and... ensure that certain BHCs and nonbank financial companies supervised by the Federal Reserve are subject to...

77 FR 3144 - Approval and Promulgation of Air Quality Implementation Plans; Missouri; Reasonably Available...

Science.gov (United States)

2012-01-23

... comments on this proposal. Therefore, based on the rational stated in the proposal, EPA is approving this..., petitions for judicial review of this action must be filed in the United States Court of Appeals for the...

Extended device profiles and testing procedures for the approval process of integrated medical devices using the IEEE 11073 communication standard.

Science.gov (United States)

Janß, Armin; Thorn, Johannes; Schmitz, Malte; Mildner, Alexander; Dell'Anna-Pudlik, Jasmin; Leucker, Martin; Radermacher, Klaus

2018-02-23

Nowadays, only closed and proprietary integrated operating room systems (IORS) from big manufacturers are available on the market. Hence, the interconnection of components from third-party vendors is only possible with increased time and costs. In the context of the German Federal Ministry of Education and Research (BMBF)-funded project OR.NET (2012-2016), the open integration of medical devices from different manufacturers was addressed. An integrated operating theater based on the open communication standard IEEE 11073 shall give clinical operators the opportunity to choose medical devices independently of the manufacturer. This approach would be advantageous especially for hospital operators and small- and medium-sized enterprises (SME) of medical devices. Actual standards and concepts regarding technical feasibility and the approval process do not cope with the requirements for a modular integration of medical devices in the operating room (OR), based on an open communication standard. Therefore, innovative approval strategies and corresponding certification and test procedures, which cover actual legal and normative standards, have to be developed in order to support the future risk management and the usability engineering process of open integrated medical devices in the OR. The use of standardized device and service profiles and a three-step testing procedure, including conformity, interoperability and integration tests are described in this paper and shall support the manufacturers to integrate their medical devices without disclosing the medical devices' risk analysis and related confidential expertise or proprietary information.

Who is Distressed Applying the Diabetes Related Distress Scale in a Diabetes Clinic

Science.gov (United States)

2017-06-09

59 MDW /SGVU SUBJECT: Professional Presentation Approval 7APR 2017 1. Your paper, entitled Who is Distressed? Applying the Diabetes -Related Distress...Scale in A Diabetes Clinic presented at/published to American Diabetes Association 2017 Meeting, San Francisco, CA (National Conference), 9-16 June...as a publication/presentation, a new 59 MOW Form 3039 must be submitted for review and approval.) Using the Diabetes -Related Distress Scale in

Evaluating approved medications to treat allergic rhinitis in the United States: an evidence-based review of efficacy for nasal symptoms by class.

Science.gov (United States)

Benninger, Michael; Farrar, Judith R; Blaiss, Michael; Chipps, Bradley; Ferguson, Berrylin; Krouse, John; Marple, Bradley; Storms, William; Kaliner, Michael

2010-01-01

To evaluate how well the medications currently approved in the United States for allergic rhinitis (AR) treat nasal symptoms when examined according to Food and Drug Administration-indicated uses and dosages. MEDLINE (1966 onward), EMBASE (1974 onward), and the Cochrane Library (2007) were systematically searched according to the following criteria defined at a roundtable meeting of the authors: randomized controlled trial, at least a 2-week duration, and approved indication and dosage in the United States. Data from studies that met the inclusion criteria were extracted into evidence tables, which were reviewed twice by the full panel of authors. Individual panel members also were asked to comment on abstracts, articles, and summary tables based on their known expertise. The entire faculty approved the selection of studies included in this review. Fifty-four randomized, placebo-controlled studies involving more than 14,000 adults and 1,580 children with AR met the criteria for review: 38 studies of seasonal allergic rhinitis (SAR; n = 11,980 adults and 946 children) and 12 studies of perennial allergic rhinitis (PAR; n = 3,800 adults and 366 children). The median percentage changes from baseline for total nasal symptom score for SAR were as follows: nasal antihistamines, -22.2%; oral antihistamines, -23.5%; intranasal steroids (INSs), -40.7%; and placebo, -15.0%. For PAR, the changes were as follows: oral antihistamines, -51.4%; INSs, -37.3%; and placebo, -24.8%. Data for mediator antagonists were limited. The data, although limited, confirm that INSs produce the greatest improvements in nasal symptoms in patients with SAR. In addition, INSs are effective for PAR, but the data were of variable quality, and oral antihistamines may be equally effective for some patients. The reporting of published data should be standardized to permit better comparisons in future studies.

22 CFR 96.63 - Renewal of accreditation or approval.

Science.gov (United States)

2010-04-01

... for renewal in a timely fashion. Before deciding whether to renew the accreditation or approval of an... accrediting entity or the Secretary during its most current accreditation or approval cycle, the accrediting...

Clone of EPA Approved Regulations in the Texas SIP

Science.gov (United States)

changed name to EPA Approved Regulations in the Texas SIP, Add links to:Texas Read Me; Texas SIP History;Current/Previous SIP-Approved Regulations; Delete regulations--now in /node/191099, removed tables

72/74As-labeling of HPMA based polymers for long-term in vivo PET imaging

DEFF Research Database (Denmark)

Herth, Matthias M; Barz, Matthias; Jahn, Markus

2010-01-01

In the context of molecular imaging, various polymers based on the clinically approved N-(2-hydroxypropyl)-methacrylamide (HPMA) have been radio-labeled using longer-living positron emitters 72As t1/2=26 h or 74As t1/2=17.8 d. This approach may lead to non-invasive determination of the long...

ATTITUDE AND PERCEPTION OF FACULTIES TOWARDS TEACHING EVIDENCE BASED MEDICINE TO PRE - CLINICAL & PARA - CLINICAL MEDICAL STUDENTS

Directory of Open Access Journals (Sweden)

Bhavita Patel

2015-02-01

Full Text Available NTRODUCTION: Evidence - based medicine (EBM is defined as the „conscientious, explicit, and judicious use of current best evidence‟. It i s an important tool for lifelong learning in medicine, and medical students can develop the skills necessary to understand and use EBM. The teaching of EBM in Sumandeep Vidyapeeth is as part of Evidence Based Education System (EBES. The university has imp lemented the 16 hours of teaching with project work on Evidence Based Medicine in 1st MBBS and 2nd MBBS curriculum in addition to MBBS syllabus. AIMS & OBJECTIVES: This study was planned to take feedback from all the faculties those who are involved in Evi dence based Medicine teaching to evaluate their attitude and perception towards this innovative teaching method and to recommend improvements. MATERIAL & METHODS: A Descriptive, self - structured , pilot pretested questionnaire based cross sectional study was conducted in the year 2013 - 2014 among 40 faculties from 7 Departments like Anatomy, Physiology, Biochemistry, Microbiology, Pharmacology, Pathology and Forensic Medicine teaching Evidence Base d Medicine to students at S.B.K.S MI & RC, Sumandeep Vidyapeeth. Data was expressed as percentage. RESULTS: The response rate for the study was 75%. Almost 87% of faculties agreed that teaching EBM is a welcoming development during pre and para clinical ye ars. About 80% faculties agreed that it will help them in future clinical learning. 87% faculties agreed that literature and research searching improves their day to day teaching. About 77% of faculties have attended workshop and training held in Universit y and 83% of faculties agreed that they are interested in more learning and improving skills necessary to incorporate Evidence based medicine into their discipline. Barriers included shortage of time and need for training in teaching EBM. CONCLUSION: Facul ties of this University teaching Pre - clinical and Para - clinical medical students recognized

76 FR 9356 - Intent To Request Approval From OMB of One New Public Collection of Information: Baseline...

Science.gov (United States)

2011-02-17

... (BASE) Program AGENCY: Transportation Security Administration, DHS. ACTION: 60-day notice. SUMMARY: The... of Data Collection TSA's Surface Transportation Security Inspectors (STSIs) conduct BASE reviews... DEPARTMENT OF HOMELAND SECURITY Transportation Security Administration Intent To Request Approval...

OntoCR: A CEN/ISO-13606 clinical repository based on ontologies.

Science.gov (United States)

Lozano-Rubí, Raimundo; Muñoz Carrero, Adolfo; Serrano Balazote, Pablo; Pastor, Xavier

2016-04-01

To design a new semantically interoperable clinical repository, based on ontologies, conforming to CEN/ISO 13606 standard. The approach followed is to extend OntoCRF, a framework for the development of clinical repositories based on ontologies. The meta-model of OntoCRF has been extended by incorporating an OWL model integrating CEN/ISO 13606, ISO 21090 and SNOMED CT structure. This approach has demonstrated a complete evaluation cycle involving the creation of the meta-model in OWL format, the creation of a simple test application, and the communication of standardized extracts to another organization. Using a CEN/ISO 13606 based system, an indefinite number of archetypes can be merged (and reused) to build new applications. Our approach, based on the use of ontologies, maintains data storage independent of content specification. With this approach, relational technology can be used for storage, maintaining extensibility capabilities. The present work demonstrates that it is possible to build a native CEN/ISO 13606 repository for the storage of clinical data. We have demonstrated semantic interoperability of clinical information using CEN/ISO 13606 extracts. Copyright © 2016 Elsevier Inc. All rights reserved.

CORN, LP Goldfield Approval

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This November 19, 2015 letter from EPA approves the petition from CORN, LP, Goldfield facility, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable fuel (D-code 6) RINs under the RFS pro

Korean Clinic Based Outcome Measure Studies

Directory of Open Access Journals (Sweden)

Jongbae Park

2003-02-01

Full Text Available Background: Evidence based medicine has become main tools for medical practice. However, conducting a highly ranked in the evidence hierarchy pyramid is not easy or feasible at all times and places. There remains a room for descriptive clinical outcome measure studies with admitting the limit of the intepretation. Aims: Presents three Korean clinic based outcome measure studies with a view to encouraging Korean clinicians to conduct similar studies. Methods: Three studies are presented briefly here including 1 Quality of Life of liver cancer patients after 8 Constitutional acupuncture; 2 Developing a Korean version of Measuring yourself Medical Outcome profile (MYMOP; and 3 Survey on 5 Shu points: a pilot In the first study, we have included 4 primary or secondary liver cancer patients collecting their diagnostic X-ray film and clinical data f개m their hospital, and asked them to fill in the European Organization Research and Treatment of Cancer, Quality of Life Questionnaire before the commencement of the treatment. The acupuncture treatment is set up format but not disclosed yet. The translation and developing a Korean version of outcome measures that is Korean clinician friendly has been sought for MYMOP is one of the most appropriate one. The permission was granted, the translation into Korean was done, then back translated into English only based on the Korean translation by the researcher who is bilingual in both languages. The back translation was compared by the original developer of MYMOP and confirmed usable. In order to test the existence of acupoints and meridians through popular forms of Korean acupuncture regimes, we aim at collecting opinions from 101 Korean clinicians that have used those forms. The questions asked include most effective symptoms, 5 Shu points, points those are least likely to use due to either adverse events or the lack of effectiveness, theoretical reasons for the above proposals, proposing outcome measures

HSE statement on the approval of dosimetry services

International Nuclear Information System (INIS)

1992-09-01

This statement is intended to assist dosimetry services who may wish to be approved by the U.K. Health and Safety Executive under Regulation 15 of the Ionising Radiations Regulations 1985. It also serves to inform approved dosimetry services of changes in the arrangements which HSE makes for approval and reassessment of dosimetry services. A general description of the administrative arrangements for making application is given and the subsequent processing of such applications by the HSE is outlined. Background notes on the requirements of the Regulations are given in Appendix I. The fees which are chargeable from 20/8/92 are given in Appendix II. (Author)

Evidence-based practice guideline of Chinese herbal medicine for primary open-angle glaucoma (qingfeng -neizhang).

Science.gov (United States)

Yang, Yingxin; Ma, Qiu-Yan; Yang, Yue; He, Yu-Peng; Ma, Chao-Ting; Li, Qiang; Jin, Ming; Chen, Wei

2018-03-01

Primary open angle glaucoma (POAG) is a chronic, progressive optic neuropathy. The aim was to develop an evidence-based clinical practice guideline of Chinese herbal medicine (CHM) for POAG with focus on Chinese medicine pattern differentiation and treatment as well as approved herbal proprietary medicine. The guideline development group involved in various pieces of expertise in contents and methods. Authors searched electronic databases include CNKI, VIP, Sino-Med, Wanfang data, PubMed, the Cochrane Library, EMBASE, as well as checked China State Food and Drug Administration (SFDA) from the inception of these databases to June 30, 2015. Systematic reviews and randomized controlled trials of Chinese herbal medicine treating adults with POAG were evaluated. Risk of bias tool in the Cochrane Handbook and evidence strength developed by the GRADE group were applied for the evaluation, and recommendations were based on the findings incorporating evidence strength. After several rounds of Expert consensus, the final guideline was endorsed by relevant professional committees. CHM treatment principle and formulae based on pattern differentiation together with approved patent herbal medicines are the main treatments for POAG, and the diagnosis and treatment focusing on blood related patterns is the major domain. CHM therapy alone or combined with other conventional treatment reported in clinical studies together with Expert consensus were recommended for clinical practice.

A History of the Sonocare CST-100: The First FDA-approved HIFU Device

Science.gov (United States)

Muratore, Robert

2006-05-01

The Sonocare CST-100 Therapeutic Ultrasound System, designed for the treatment of glaucoma, was developed in the 1980s and became the first high intensity focused ultrasound (HIFU) device to receive Food and Drug Administration approval. The system arose from studies done by F.L. Lizzi, Eng.Sc.D., of Riverside Research Institute and D.J. Coleman, M.D., of Cornell Medical Center/New York Hospital on the safety of ultrasound diagnosis of the eye. As safety limits were probed, therapeutic regimes were discovered. Optimization of operational parameters, clinical experience, and engineering design came together through a spin-off company, Sonocare, Inc., formed to produce and market the ophthalmic device. Various precedents were set during the approval process, including the acceptance by the FDA of radiation momentum imparted to an absorber as a measure of acoustic power. Many devices were sold, but the laser industry, grandfathered into the therapeutic field, eventually out-marketed Sonocare. The CST-100 remains as a model of elegant industrial design, and existing units are used daily in HIFU laboratory experiments.

Avelumab: First Global Approval.

Science.gov (United States)

Kim, Esther S

2017-05-01

Avelumab (Bavencio ® ) is an intravenously administered programmed cell death ligand-1-blocking human antibody initially developed by EMD Serono Inc. (the biopharmaceutical division of Merck KGaA, Darmstadt, Germany) [now jointly developed and commercialized by EMD Serono Inc. and Pfizer] for the treatment of various tumours. It has received accelerated approval in the USA for the treatment of metastatic Merkel cell carcinoma (mMCC) in adults and paediatric patients aged ≥12 years. The marketing authorization application for avelumab in the treatment of mMCC is undergoing regulatory review in the EU, the biologics license application for avelumab in the treatment of urothelial carcinoma is undergoing priority review by the FDA, and avelumab is in various stages of development internationally for a variety of cancers. This article summarizes the milestones in the development of avelumab leading to this first approval for mMCC.

5 CFR 1320.16 - Delegation of approval authority.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Delegation of approval authority. 1320.16... PAPERWORK BURDENS ON THE PUBLIC § 1320.16 Delegation of approval authority. (a) OMB may, after complying... delegation of review authority shall be made unless the agency demonstrates to OMB that the Senior Official...

Waste Feed Delivery Environmental Permits and Approvals Plan

International Nuclear Information System (INIS)

TOLLEFSON, K.S.

2000-01-01

This plan describes the environmental permits approvals, and other requirements that may affect establishment of a waste feed delivery system for the Hanford Site's River Protection Project. This plan identifies and screens environmental standards for potential applicability, outlines alternatives for satisfying applicable standards, and describes preferred permitting and approval approaches

34 CFR 668.144 - Application for test approval.

Science.gov (United States)

2010-07-01

... quantitative skills; (9) If a test has been revised from the most recent edition approved by the Secretary, an... Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY... inquiries; (3) Each edition and form of the test for which the publisher requests approval; (4) The...

50 CFR 37.22 - Approval of exploration plan.

Science.gov (United States)

2010-10-01

... § 37.21(b), the Regional Director shall promptly publish notice of the application and text of the plan... exploration plan shall be approved by the Regional Director if he determines that it satisfies the....11(b), or minimize adverse impacts on subsistence uses, the Regional Director may approve or...

7 CFR 319.8-11 - From approved areas of Mexico.

Science.gov (United States)

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false From approved areas of Mexico. 319.8-11 Section 319.8... Conditions for the Entry of Cotton and Covers from Mexico § 319.8-11 From approved areas of Mexico. (a) Entry... in, and which were produced and handled only in approved areas of Mexico 5 may be authorized through...

Radiotherapy fractionation for the palliation of uncomplicated painful bone metastases – an evidence-based practice guideline

Directory of Open Access Journals (Sweden)

Bezjak Andrea

2004-10-01

Full Text Available Abstract Background This practice guideline was developed to provide recommendations to clinicians in Ontario on the preferred standard radiotherapy fractionation schedule for the treatment of painful bone metastases. Methods A systematic review and meta-analysis was performed and published elsewhere. The Supportive Care Guidelines Group, a multidisciplinary guideline development panel, formulated clinical recommendations based on their interpretation of the evidence. In addition to evidence from clinical trials, the panel also considered patient convenience and ease of administration of palliative radiotherapy. External review of the draft report by Ontario practitioners was obtained through a mailed survey, and final approval was obtained from the Practice Guidelines Coordinating Committee. Results Meta-analysis did not detect a significant difference in complete or overall pain relief between single treatment and multifraction palliative radiotherapy for bone metastases. Fifty-nine Ontario practitioners responded to the mailed survey (return rate 62%. Forty-two percent also returned written comments. Eighty-three percent of respondents agreed with the interpretation of the evidence and 75% agreed that the report should be approved as a practice guideline. Minor revisions were made based on feedback from the external reviewers and the Practice Guidelines Coordinating Committee. The Practice Guidelines Coordinating Committee approved the final practice guideline report. Conclusion For adult patients with single or multiple radiographically confirmed bone metastases of any histology corresponding to painful areas in previously non-irradiated areas without pathologic fractures or spinal cord/cauda equine compression, we conclude that: • Where the treatment objective is pain relief, a single 8 Gy treatment, prescribed to the appropriate target volume, is recommended as the standard dose-fractionation schedule for the treatment of symptomatic and

A Good Year: FDA Approved Nine New Cancer Drugs in 2014

Science.gov (United States)

In 2014, the Food and Drug Administration (FDA) approved 41 drugs that had not been approved previously for any indication, the most in nearly 20 years. Of these 41 novel drugs, 9 were approved for the treatment of cancer or cancer-related conditions.

Intrinsic fluorescence of the clinically approved multikinase inhibitor nintedanib reveals lysosomal sequestration as resistance mechanism in FGFR-driven lung cancer.

Science.gov (United States)

Englinger, Bernhard; Kallus, Sebastian; Senkiv, Julia; Heilos, Daniela; Gabler, Lisa; van Schoonhoven, Sushilla; Terenzi, Alessio; Moser, Patrick; Pirker, Christine; Timelthaler, Gerald; Jäger, Walter; Kowol, Christian R; Heffeter, Petra; Grusch, Michael; Berger, Walter

2017-09-07

Studying the intracellular distribution of pharmacological agents, including anticancer compounds, is of central importance in biomedical research. It constitutes a prerequisite for a better understanding of the molecular mechanisms underlying drug action and resistance development. Hyperactivated fibroblast growth factor receptors (FGFRs) constitute a promising therapy target in several types of malignancies including lung cancer. The clinically approved small-molecule FGFR inhibitor nintedanib exerts strong cytotoxicity in FGFR-driven lung cancer cells. However, subcellular pharmacokinetics of this compound and its impact on therapeutic efficacy remain obscure. 3-dimensional fluorescence spectroscopy was conducted to asses cell-free nintedanib fluorescence properties. MTT assay was used to determine the impact of the lysosome-targeting agents bafilomycin A1 and chloroquine combined with nintedanib on lung cancer cell viability. Flow cytometry and live cell as well as confocal microscopy were performed to analyze uptake kinetics as well as subcellular distribution of nintedanib. Western blot was conducted to investigate protein expression. Cryosections of subcutaneous tumor allografts were generated to detect intratumoral nintedanib in mice after oral drug administration. Here, we report for the first time drug-intrinsic fluorescence properties of nintedanib in living and fixed cancer cells as well as in cryosections derived from allograft tumors of orally treated mice. Using this feature in conjunction with flow cytometry and confocal microscopy allowed to determine cellular drug accumulation levels, impact of the ABCB1 efflux pump and to uncover nintedanib trapping into lysosomes. Lysosomal sequestration - resulting in an organelle-specific and pH-dependent nintedanib fluorescence - was identified as an intrinsic resistance mechanism in FGFR-driven lung cancer cells. Accordingly, combination of nintedanib with agents compromising lysosomal acidification

38 CFR 21.9765 - Program of education approval.

Science.gov (United States)

2010-07-01

... education offered by an institution of higher learning if that program of education is approved under 38 U.S... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Program of education... (CONTINUED) VOCATIONAL REHABILITATION AND EDUCATION Post-9/11 GI Bill Approval of Programs of Education § 21...

Waste Feed Delivery Environmental Permits and Approvals Plan

Energy Technology Data Exchange (ETDEWEB)

TOLLEFSON, K.S.

2000-01-18

This plan describes the environmental permits approvals, and other requirements that may affect establishment of a waste feed delivery system for the Hanford Site's River Protection Project. This plan identifies and screens environmental standards for potential applicability, outlines alternatives for satisfying applicable standards, and describes preferred permitting and approval approaches.

Integrating evidence-based practice into RN-to-BSN clinical nursing education.

Science.gov (United States)

Oh, Eui Geum; Kim, Sunah; Kim, So Sun; Kim, Sue; Cho, Eun Yong; Yoo, Ji-Soo; Kim, Hee Soon; Lee, Ju Hee; You, Mi Ae; Lee, Hyejung

2010-07-01

This study examines the effects of integrating evidence-based practice (EBP) into clinical practicum on EBP efficacy and barriers to research utilization among Korean RN-to-BSN students. A one-group pretest-posttest design was used. Eighty-one students were recruited from a school of nursing in Korea. Evidence-based practice clinical practicum was composed of two consecutive programs during one semester. Lectures, individual mentoring on EBP practicum, small group, and wrap-up conferences were provided. Outcomes of EBP efficacy and barriers to research utilization were analyzed using paired t tests for 74 final participants. Evidence-based practice efficacy scores increased significantly (p effectiveness of EBP education among RN-to-BSN students. These results may help health educators develop effective educational strategies to integrate EBP concepts into a clinical practicum. Copyright 2010, SLACK Incorporated.

Drugs Approved for Rhabdomyosarcoma

Science.gov (United States)

This page lists cancer drugs approved by the Food and Drug Administration (FDA) for rhabdomyosarcoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries. There may be drugs used in rhabdomyosarcoma that are not listed here.

An ethnography of clinic "noise" in a community-based, promotora-centered mental health intervention.

Science.gov (United States)

Getrich, Christina; Heying, Shirley; Willging, Cathleen; Waitzkin, Howard

2007-07-01

Community-based health interventions have emerged as a growing focus for anthropological research. The application of ethnographic approaches in clinical practice settings reveals that community-based interventions must grapple with "noise," or unanticipated factors such as patients' own perceptions of illness and treatment, primary care providers' non-adherence to guidelines-based treatment, the social dynamics of the clinic site itself, and incomplete understanding and acceptance of an intervention by a clinic's staff members. Such noise can influence the implementation and quality of treatment. Thus, identifying clinic-based noise is critical in assessments of fidelity to intervention protocols as well as outcomes of community-based interventions. This paper highlights findings from an evaluation of a mental health intervention focusing on the role of promotoras (briefly trained, non-professional community health workers) as mental health practitioners in two urban New Mexico, USA, community health centers. Our research identified three areas of clinic-based noise: the clinics' physical ability to "absorb" the intervention, the challenges of co-worker instability and interpersonal relationships, and balancing extra workplace demands. The findings demonstrate the value of ethnographic approaches in community-based intervention research.

Correlation of abdominopelvic computed tomography with clinical manifestations in methamphetamine body stuffers.

Science.gov (United States)

Bahrami-Motlagh, Hooman; Hassanian-Moghaddam, Hossein; Zamini, Hedieh; Zamani, Nasim; Gachkar, Latif

2018-02-01

Little is known about methamphetamine body stuffers and correlation of clinical manifestations with imaging studies. Current study was done to determine abdominopelvic computed tomography findings and clinical manifestations in methamphetamine body stuffers. In an IRB-approved routine data base study, demographic characteristics, clinical findings, and CT results of 70 methamphetamine body stuffers were retrieved. According to the clinical manifestations, the patients were categorized into either benign- or severe-outcome group. Also, they were determined to have positive or negative CT results. In the group with positive results, number and place of the baggies were determined, as well. Results of the CT were compared between the two groups. Almost 43% of the patients had positive abdominopelvic CT results. Mean density of the packs was 176.2 ± 152.7 Hounsfield unit. Based on the clinical grounds, 57% of the patients were in the benign- and 33% were in the severe-outcome group. In the benign group, 45% of the patients had positive CTs while in the severe-risk group, this was 40% (p > 0.05). Except variables defined as severe outcome (seizure, intubation, creatinine level, aspartate aminotransferase level, creatine phosphokinase and troponin level), agitation, on-arrival pulse rate, lactate dehydrogenase, bicarbonate, base excess, loss of consciousness and hospitalization period were correlating factors. But in regression analysis, we could not find a significant variable that prognosticate severe outcome. It seems that there is no relationship between the CT findings and clinical manifestations of the methamphetamine body stuffers. Severe outcomes may be observed even in the face of negative CTs.

Impact of clinical pharmacist-based parenteral nutrition service for bone marrow transplantation patients: a randomized clinical trial.

Science.gov (United States)

Mousavi, Maryam; Hayatshahi, Alireza; Sarayani, Amir; Hadjibabaie, Molouk; Javadi, Mohammadreza; Torkamandi, Hassan; Gholami, Kheirollah; Ghavamzadeh, Ardeshir

2013-12-01