Efficacy and safety of oxcarbazepine in the treatment of children with epilepsy: a meta-analysis of randomized controlled trials.

Science.gov (United States)

Geng, Hua; Wang, Chengzhong

2017-01-01

To assess the efficacy and safety of oxcarbazepine (OXC) in the treatment of children with epilepsy. Randomized controlled trials (RCTs) published in PubMed, Embase, Web of Science, Cochrane Library, Scopus, SinoMed (Chinese BioMedical Literature Service System, China), and Chinese National Knowledge Infrastructure (China) database were systematically reviewed. Eligible studies were those that compared the efficacy and safety of OXC with other antiepileptic drugs in epilepsy. Risk ratio (RR) with 95% confidence intervals (95% CIs) was calculated using fixed-effects or random-effects model. Eleven RCTs with a total of 1,241 patients met the inclusion criteria and were included in this meta-analysis. Compared with other antiepileptic drugs (sodium valproate, levetiracetam, phenytoin, and placebo), OXC was associated with similar seizure-free rate (RR =1.06, 95% CI: 0.94, 1.20; P =0.366) and percentage reduction from baseline in seizure frequency (for ≥75% reduction: RR =1.15, 95% CI: 0.88, 1.49; P =0.310; for 50%-75% reduction: RR =1.12, 95% CI: 0.90, 1.39; P =0.301; for effects and safety as other antiepileptic drugs in the treatment of children with epilepsy. Further well-conducted, large-scale RCTs are needed to validate these findings.

[Post-marketing drug safety-risk management plan(RMP)].

Science.gov (United States)

Ezaki, Asami; Hori, Akiko

2013-03-01

The Guidance for Risk Management Plan(RMP)was released by the Ministry of Health, Labour and Welfare in April 2012. The RMP consists of safety specifications, pharmacovigilance plans and risk minimization action plans. In this paper, we outline post-marketing drug safety operations in PMDA and the RMP, with examples of some anticancer drugs.

Advice on drug safety in pregnancy: are there differences between commonly used sources of information?

Science.gov (United States)

Frost Widnes, Sofia K; Schjøtt, Jan

2008-01-01

Safety regarding use in pregnancy is not established for many drugs. Inconsistencies between sources providing drug information can give rise to confusion with possible therapeutic consequences. Therefore, it is important to measure clinically important differences between drug information sources. The objective of this study was to compare two easily accessible Norwegian sources providing advice on drug safety in pregnancy - the product monographs in the Felleskatalog (FK), published by the pharmaceutical companies, and the five regional Drug Information Centres (DICs) in Norway - in addition to assessing the frequency of questions regarding drug safety in pregnancy made to the DICs according to the Anatomical Therapeutic Chemical (ATC) classification system. Advice on drug use in pregnancy provided by the DICs in 2003 and 2005 were compared with advice in the product monographs for the respective drugs in the FK. Comparison of advice was based on categorization to one of four categories: can be used, benefit-risk assessment, should not be used, or no available information. A total of 443 drug advice were categorized. Seven out of ten of drugs frequently enquired about, according to the ATC system, were drugs acting on the nervous system (group N). For 208 (47%) of the drugs, advice differed between the DICs and FK. Advice from the FK was significantly (p drugs that were newly introduced and those that had been on the market for a longer time, advice regarding use of drugs in the first trimester and advice regarding use of drugs in the second or third trimester, or between advice provided during 2003 and during 2005. The results of this study show considerable differences between two Norwegian sources providing advice on the use of drugs in pregnancy. Based on the knowledge that healthcare providers choose sources of information in a random manner, our results may be of clinical importance. We believe that the problem with heterogeneous drug information on this

76 FR 59142 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

Science.gov (United States)

2011-09-23

...] Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk... Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee. General Function of the...., [[Page 59143

78 FR 20327 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

Science.gov (United States)

2013-04-04

... Management Advisory Committee; Amendment of Notice AGENCY: Food and Drug Administration, HHS. ACTION: Notice... of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk Management... Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee...

Level of Evidence Associated with FDA Safety Communications with Drug Labeling Changes: 2010-2014

Directory of Open Access Journals (Sweden)

Benjamin Hixon

2017-02-01

Full Text Available Purpose: Approximately 800,000 safety reports are submitted to the FDA annually, however, only significant issues generate drug safety communications (DSC. The purpose of this study was to determine the type of clinical evidence used to warrant a change in drug labeling for drugs with DSC between January 1, 2010 and December 31, 2014. Methods: Selected data was obtained from the FDA website. The primary endpoint of the study was the frequency of the types of clinical evidence used in FDA communications, as reported through the FDA DSC. Results were evaluated via descriptive statistics, and chi-squared for nominal data. Results: A total of 2521 drug safety labeling changes were identified and 99 (3.9% of safety communications met the inclusion criteria. The majority of the labeling changes were associated with single agents (83.8%. The three most frequently reported labeling changes were warnings (68.7%, precautions (58.6%, and patient package insert/medication guide (23.2%. Case reports resulted in the greatest number of documented literature types (n = 791, followed by randomized controlled trials (n = 76, and case control/cohort studies (n = 74. Significantly more evidence for DSCs were classified as Level of Evidence B (LOE B, 68.6%, compared to LOE A (17.1%, and LOE C (14.1% (p = 0.007. Conclusions: The majority of drug labeling change initiators was associated with LOE equivalent to B. Practitioners should evaluate data associated with labeling changes to determine how to interpret the information for their patients. Conflict of Interest We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received, employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents and royalties.   Type: Original Research

Diabetes Drugs and Cardiovascular Safety

Directory of Open Access Journals (Sweden)

Ji Cheol Bae

2016-06-01

Full Text Available Diabetes is a well-known risk factor of cardiovascular morbidity and mortality, and the beneficial effect of improved glycemic control on cardiovascular complications has been well established. However, the rosiglitazone experience aroused awareness of potential cardiovascular risk associated with diabetes drugs and prompted the U.S. Food and Drug Administration to issue new guidelines about cardiovascular risk. Through postmarketing cardiovascular safety trials, some drugs demonstrated cardiovascular benefits, while some antidiabetic drugs raised concern about a possible increased cardiovascular risk associated with drug use. With the development of new classes of drugs, treatment options became wider and the complexity of glycemic management in type 2 diabetes has increased. When choosing the appropriate treatment strategy for patients with type 2 diabetes at high cardiovascular risk, not only the glucose-lowering effects, but also overall benefits and risks for cardiovascular disease should be taken into consideration.

A Model for Random Student Drug Testing

Science.gov (United States)

Nelson, Judith A.; Rose, Nancy L.; Lutz, Danielle

2011-01-01

The purpose of this case study was to examine random student drug testing in one school district relevant to: (a) the perceptions of students participating in competitive extracurricular activities regarding drug use and abuse; (b) the attitudes and perceptions of parents, school staff, and community members regarding student drug involvement; (c)…

Safety of polyethylene glycol 3350 solution in chronic constipation: randomized, placebo-controlled trial

Directory of Open Access Journals (Sweden)

McGraw T

2016-07-01

Full Text Available Thomas McGraw Global Medical Affairs, Merck & Co., Inc., Kenilworth, NJ, USA Purpose: To evaluate the safety and tolerability of aqueous solution concentrate (ASC of polyethylene glycol (PEG 3350 in patients with functional constipation.Patients and methods: The patients who met Rome III diagnostic criteria for functional constipation were randomized in this multicenter, randomized, placebo-controlled, single-blind study to receive once daily dose of PEG 3350 (17 g ASC or placebo solution for 14 days. The study comprised a screening period (visit 1, endoscopy procedure (visits 2 and 3, and follow-up telephone calls 30 days post-treatment. Safety end points included adverse events (AEs, clinical laboratory evaluations, vital signs, and others. The primary end points were the proportion of patients with abnormalities of the oral and esophageal mucosa, detected by visual and endoscopic examination of the oral cavity and esophagus, respectively, compared with placebo. A secondary objective was to compare the safety and tolerability of ASC by evaluating AEs or adverse drug reactions.Results: A total of 65 patients were enrolled in this study, 31 were randomized to PEG 3350 ASC and 34 were randomized to placebo, of which 62 patients completed the study. No patients in either group showed abnormalities in inflammation of the oral mucosa during visit 2 (before treatment or visit 3 (after treatment. Fewer abnormalities of the esophageal mucosa were observed in the PEG 3350 ASC group than in the placebo group on visit 3, with no significant difference in the proportion of abnormalities between the treatment groups. Overall, 40 treatment-emergent AEs were observed in 48.4% of patients treated with PEG 3350 ASC, and 41 treatment-emergent AEs were observed in 55.9% of patients treated with placebo – nonsignificant difference of -7.5% (95% CI: -21.3, 6.3 between treatment groups. No serious AEs or deaths were reported, and no patient discontinued because

Long-Term Safety of Drug-Eluting and Bare-Metal Stents

DEFF Research Database (Denmark)

Palmerini, Tullio; Benedetto, Umberto; Biondi-Zoccai, Giuseppe

2015-01-01

BACKGROUND: Previous meta-analyses have investigated the relative safety and efficacy profiles of different types of drug-eluting stents (DES) and bare-metal stents (BMS); however, most prior trials in these meta-analyses reported follow-up to only 1 year, and as such, the relative long-term safety....... RESULTS: Fifty-one trials that included a total of 52,158 randomized patients with follow-up duration ≥3 years were analyzed. At a median follow-up of 3.8 years, cobalt-chromium everolimus-eluting stents (EES) were associated with lower rates of mortality, definite stent thrombosis (ST), and myocardial...... infarction than BMS, paclitaxel-eluting stents (PES), and sirolimus-eluting stents (SES) and less ST than BES. Phosphorylcholine-based zotarolimus-eluting stents had lower rates of definite ST than SES and lower rates of myocardial infarction than BMS and PES. The late rates of target...

Drug safety: withdrawn medications are only part of the picture.

Science.gov (United States)

Rawson, Nigel S B

2016-02-13

In a research article published in BMC Medicine, Onakpoya and colleagues provide a historical review of withdrawals of medications for safety reasons. However, withdrawn medications are only one part of the picture about how regulatory agencies manage drug risks. Moreover, medications introduced before the increased pre-marketing regulations and post-marketing monitoring systems instituted after the thalidomide tragedy have little relevance when considering the present drug safety picture because the circumstances under which they were introduced were completely different. To more fully understand drug safety management and regulatory agency actions, withdrawals should be evaluated within the setting and timeframe in which the medications are approved, which requires information about approvals and safety warnings. Studies are needed that provide a more comprehensive current picture of the identification and evaluation of drug safety risks as well as how regulatory agencies deal with them. Please see related research article: http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0553-2.

Safety and efficacy of drugs in pregnancy.

Science.gov (United States)

Knoppert, David

2011-01-01

Although most drugs are used to treat chronic or pregnancy-induced conditions during pregnancy and lactation, very few are studied in pregnant or breastfeeding women. The information we have on drugs taken during pregnancy and lactation is usually obtained after market approval through published case reports or case series and from pregnancy exposure or retrospective birth defect registries. Furthermore, generic drugs approved for use in this vulnerable population may be approved based on results from a male trial population. This disregards the changes that can occur during pregnancy which can affect the pharmacokinetics of drugs. In an effort to improve the information provided to prescribers, in 2008 the United States Food and Drug Administration proposed a change in product labelling where information from pregnancy exposure registries would be required. As of 2009, European Medicines Agency requires additional statements on use during pregnancy within drug labelling information. In Canada, it is anticipated that the efficacy and safety of drugs in pregnancy will be included under the Drug Safety and Effectiveness Network initiative, and that this will offer a unified approach for such assessments. Pregmedic, a non-profit organization for the advancement of safe and effective use of drugs in pregnancy, has presented a number of proposals and draft guidelines to Health Canada on the inclusion of pregnant women in pharmacokinetic studies and the establishment of registries for women who take drugs during pregnancy. Pregmedic advocates for ensuring that drugs indicated for women are studied in women.

A primer of drug safety surveillance: an industry perspective. Part I: Information flow, new drug development, and federal regulations.

Science.gov (United States)

Allan, M C

1992-01-01

To place the fundamentals of clinical drug safety surveillance in a conceptual framework that will facilitate understanding and application of adverse drug event data to protect the health of the public and support a market for pharmaceutical manufacturers' products. Part I of this series provides a background for the discussion of drug safety by defining the basic terms and showing the flow of safety information through a pharmaceutical company. The customers for adverse drug event data are identified to provide a basis for providing quality service. The development of a drug product is briefly reviewed to show the evolution of safety data. Drug development and safety are defined by federal regulations. These regulations are developed by the FDA with information from pharmaceutical manufacturers. The intent of the regulations and the accompanying guidelines is described. An illustration from the news media is cited to show an alternative, positive approach to handling an adverse event report. This review uses primary sources from the federal laws (regulations), commentaries, and summaries. Very complex topics are briefly summarized in the text and additional readings are presented in an appendix. Secondary sources, ranging from newspaper articles to judicial summaries, illustrate the interpretation of adverse drug events and opportunities for drug safety surveillance intervention. The reference materials used were articles theoretically or practically applicable in the day-to-day practice of drug safety surveillance. The role of clinical drug safety surveillance in product monitoring and drug development is described. The process of drug safety surveillance is defined by the Food and Drug Administration regulations, product labeling, product knowledge, and database management. Database management is subdivided into the functions of receipt, retention, retrieval, and review of adverse event reports. Emphasis is placed on the dynamic interaction ;of the components

76 FR 40735 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

Science.gov (United States)

2011-07-11

...] Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk... Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee. General Function of the... East, Adelphi, MD. The conference center telephone number is: 301 985-7300. Contact Person: Kalyani...

75 FR 10490 - Joint Meeting of the Arthritis Drugs Advisory Committee and the Drug Safety and Risk Management...

Science.gov (United States)

2010-03-08

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Joint Meeting of the Arthritis Drugs Advisory Committee and the Drug Safety and Risk Management Advisory... Drug Safety and Risk Management Advisory Committee. General Function of the Committees: To provide...

77 FR 65000 - Drug Safety and Risk Management Advisory Committee; Notice of Meeting

Science.gov (United States)

2012-10-24

...] Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Drug Safety and Risk Management Advisory Committee. General Function of the Committee: To provide... Use (ETASU) before CDER's Drug Safety and Risk Management Advisory Committee (DSaRM). The Agency plans...

78 FR 30929 - Drug Safety and Risk Management Advisory Committee; Notice of Meeting

Science.gov (United States)

2013-05-23

...] Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Drug Safety and Risk Management Advisory Committee. General Function of the Committee: To provide... (REMS) with elements to assure safe use (ETASU) before its Drug Safety and Risk Management Advisory...

78 FR 2677 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

Science.gov (United States)

2013-01-14

...] Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk... Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee. General Function of the... before February 7, 2013. Time allotted for each presentation may be limited. If the number of registrants...

76 FR 59143 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

Science.gov (United States)

2011-09-23

...] Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk... Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee. General Function of the..., Adelphi, MD. The conference center telephone number is 301-985-7300. Contact Person: Kalyani Bhatt, Center...

77 FR 75176 - Drug Safety and Risk Management Advisory Committee; Notice of Meeting

Science.gov (United States)

2012-12-19

...] Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY: Food and Drug... being rescheduled due to the postponement of the October 29-30, 2012, Drug Safety and Risk Management... Committee: Drug Safety and Risk Management Advisory Committee. General Function of the Committee: To provide...

Drug safety data mining with a tree-based scan statistic.

Science.gov (United States)

Kulldorff, Martin; Dashevsky, Inna; Avery, Taliser R; Chan, Arnold K; Davis, Robert L; Graham, David; Platt, Richard; Andrade, Susan E; Boudreau, Denise; Gunter, Margaret J; Herrinton, Lisa J; Pawloski, Pamala A; Raebel, Marsha A; Roblin, Douglas; Brown, Jeffrey S

2013-05-01

In post-marketing drug safety surveillance, data mining can potentially detect rare but serious adverse events. Assessing an entire collection of drug-event pairs is traditionally performed on a predefined level of granularity. It is unknown a priori whether a drug causes a very specific or a set of related adverse events, such as mitral valve disorders, all valve disorders, or different types of heart disease. This methodological paper evaluates the tree-based scan statistic data mining method to enhance drug safety surveillance. We use a three-million-member electronic health records database from the HMO Research Network. Using the tree-based scan statistic, we assess the safety of selected antifungal and diabetes drugs, simultaneously evaluating overlapping diagnosis groups at different granularity levels, adjusting for multiple testing. Expected and observed adverse event counts were adjusted for age, sex, and health plan, producing a log likelihood ratio test statistic. Out of 732 evaluated disease groupings, 24 were statistically significant, divided among 10 non-overlapping disease categories. Five of the 10 signals are known adverse effects, four are likely due to confounding by indication, while one may warrant further investigation. The tree-based scan statistic can be successfully applied as a data mining tool in drug safety surveillance using observational data. The total number of statistical signals was modest and does not imply a causal relationship. Rather, data mining results should be used to generate candidate drug-event pairs for rigorous epidemiological studies to evaluate the individual and comparative safety profiles of drugs. Copyright © 2013 John Wiley & Sons, Ltd.

78 FR 16271 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

Science.gov (United States)

2013-03-14

...] Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk... Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee. General Function of the... presentation may be limited. If the number of registrants requesting to speak is greater than can be reasonably...

Regulatory aspects of oncology drug safety evaluation: Past practice, current issues, and the challenge of new drugs

International Nuclear Information System (INIS)

Rosenfeldt, Hans; Kropp, Timothy; Benson, Kimberly; Ricci, M. Stacey; McGuinn, W. David; Verbois, S. Leigh

2010-01-01

The drug development of new anti-cancer agents is streamlined in response to the urgency of bringing effective drugs to market for patients with limited life expectancy. FDA's regulation of oncology drugs has evolved from the practices set forth in Arnold Lehman's seminal work published in the 1950s through the current drafting of a new International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) safety guidance for anti-cancer drug nonclinical evaluations. The ICH combines the efforts of the regulatory authorities of Europe, Japan, and the United States and the pharmaceutical industry from these three regions to streamline the scientific and technical aspects of drug development. The recent development of new oncology drug classes with novel mechanisms of action has improved survival rates for some cancers but also brings new challenges for safety evaluation. Here we present the legacy of Lehman and colleagues in the context of past and present oncology drug development practices and focus on some of the current issues at the center of an evolving harmonization process that will generate a new safety guidance for oncology drugs, ICH S9. The purpose of this new guidance will be to facilitate oncology drug development on a global scale by standardizing regional safety requirements.

Meta-Analysis of Randomized Clinical Trials Comparing Biodegradable Polymer Drug-Eluting Stent to Second-Generation Durable Polymer Drug-Eluting Stents.

Science.gov (United States)

El-Hayek, Georges; Bangalore, Sripal; Casso Dominguez, Abel; Devireddy, Chandan; Jaber, Wissam; Kumar, Gautam; Mavromatis, Kreton; Tamis-Holland, Jacqueline; Samady, Habib

2017-03-13

The authors sought to perform a meta-analysis of randomized clinical trials (RCTs) comparing the safety and efficacy of biodegradable polymer drug-eluting stents (BP-DES) to second-generation durable polymer drug-eluting stents (DP-DES). Prior meta-analyses have established the superiority of BP-DES over bare-metal stents and first-generation DP-DES; however, their advantage compared with second-generation DP-DES remains controversial. The authors searched PubMed and Scopus databases for RCTs comparing BP-DES to the second-generation DP-DES. Outcomes included target vessel revascularization (TVR) as efficacy outcome and cardiac death, myocardial infarction (MI), and definite or probable stent thrombosis (ST) as safety outcomes. In addition, we performed landmark analysis for endpoints beyond 1 year of follow-up and a subgroup analysis based on the stent characteristics. The authors included 16 RCTs comprising 19,886 patients in the meta-analysis. At the longest available follow-up (mean duration 26 months), we observed no significant differences in TVR (p = 0.62), cardiac death (p = 0.46), MI (p = 0.98), or ST (risk ratio: 0.83, 95% confidence interval: 0.64 to 1.09; p = 0.19). Our landmark analysis showed that BP-DES were not associated with a reduction in the risk of very late ST (risk ratio: 0.87, 95% confidence interval: 0.49 to 1.53; p = 0.62). Similar outcomes were seen regardless of the eluting drug (biolimus vs. sirolimus), the stent platform (stainless steel vs. alloy), the kinetics of polymer degradation or drug release (6 months), the strut thickness of the BP-DES (thin 100 μm), or the DAPT duration (≥6 months vs. ≥12 months). BP-DES have similar safety and efficacy profiles to second-generation DP-DES. Published by Elsevier Inc.

78 FR 36711 - Food and Drug Administration Safety and Innovation Act Title VII-Drug Supply Chain; Standards for...

Science.gov (United States)

2013-06-19

... inspections, and drive safety and quality throughout the supply chain. Implementation of these authorities... authorities granted to FDA under Title VII and their importance in ensuring drug safety, effectiveness, and.... FDA-2013-N-0683, FDA-2013-N-0684, and FDA-2013-N-0685] Food and Drug Administration Safety and...

Mathematical modeling of efficacy and safety for anticancer drugs clinical development.

Science.gov (United States)

Lavezzi, Silvia Maria; Borella, Elisa; Carrara, Letizia; De Nicolao, Giuseppe; Magni, Paolo; Poggesi, Italo

2018-01-01

Drug attrition in oncology clinical development is higher than in other therapeutic areas. In this context, pharmacometric modeling represents a useful tool to explore drug efficacy in earlier phases of clinical development, anticipating overall survival using quantitative model-based metrics. Furthermore, modeling approaches can be used to characterize earlier the safety and tolerability profile of drug candidates, and, thus, the risk-benefit ratio and the therapeutic index, supporting the design of optimal treatment regimens and accelerating the whole process of clinical drug development. Areas covered: Herein, the most relevant mathematical models used in clinical anticancer drug development during the last decade are described. Less recent models were considered in the review if they represent a standard for the analysis of certain types of efficacy or safety measures. Expert opinion: Several mathematical models have been proposed to predict overall survival from earlier endpoints and validate their surrogacy in demonstrating drug efficacy in place of overall survival. An increasing number of mathematical models have also been developed to describe the safety findings. Modeling has been extensively used in anticancer drug development to individualize dosing strategies based on patient characteristics, and design optimal dosing regimens balancing efficacy and safety.

Determining animal drug combinations based on efficacy and safety.

Science.gov (United States)

Kratzer, D D; Geng, S

1986-08-01

A procedure for deriving drug combinations for animal health is used to derive an optimal combination of 200 mg of novobiocin and 650,000 IU of penicillin for nonlactating cow mastitis treatment. The procedure starts with an estimated second order polynomial response surface equation. That surface is translated into a probability surface with contours called isoprobs. The isoprobs show drug amounts that have equal probability to produce maximal efficacy. Safety factors are incorporated into the probability surface via a noncentrality parameter that causes the isoprobs to expand as safety decreases, resulting in lower amounts of drug being used.

75 FR 23782 - Drug Safety and Risk Management Advisory Committee; Notice of Meeting

Science.gov (United States)

2010-05-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Drug Safety and Risk Management Advisory Committee. General Function of the Committee: To provide...

Efficacy and safety of oxcarbazepine in the treatment of children with epilepsy: a meta-analysis of randomized controlled trials

Directory of Open Access Journals (Sweden)

Geng H

2017-03-01

Full Text Available Hua Geng, Chengzhong Wang Department of Pediatrics, Maternal and Child Health Hospital of Yancheng, Yancheng City, People’s Republic of China Background: To assess the efficacy and safety of oxcarbazepine (OXC in the treatment of children with epilepsy.Methods: Randomized controlled trials (RCTs published in PubMed, Embase, Web of Science, Cochrane Library, Scopus, SinoMed (Chinese BioMedical Literature Service System, China, and Chinese National Knowledge Infrastructure (China database were systematically reviewed. Eligible studies were those that compared the efficacy and safety of OXC with other antiepileptic drugs in epilepsy. Risk ratio (RR with 95% confidence intervals (95% CIs was calculated using fixed-effects or random-effects model.Results: Eleven RCTs with a total of 1,241 patients met the inclusion criteria and were included in this meta-analysis. Compared with other antiepileptic drugs (sodium valproate, levetiracetam, phenytoin, and placebo, OXC was associated with similar seizure-free rate (RR =1.06, 95% CI: 0.94, 1.20; P=0.366 and percentage reduction from baseline in seizure frequency (for ≥75% reduction: RR =1.15, 95% CI: 0.88, 1.49; P=0.310; for 50%–75% reduction: RR =1.12, 95% CI: 0.90, 1.39; P=0.301; for <50% reduction: RR =0.79, 95% CI: 0.56, 1.12; P=0.179. Moreover, patients treated with OXC had a comparable incidence of adverse events compared with those treated with other antiepileptic drugs (RR =1.01, 95% CI: 0.92, 1.11; P=0.760.Conclusion: OXC showed similar effects and safety as other antiepileptic drugs in the treatment of children with epilepsy. Further well-conducted, large-scale RCTs are needed to validate these findings. Keywords: epilepsy, children, oxcarbazepine, meta-analysis

Drug research methodology. Volume 2, The identification of drugs of interest in highway safety

Science.gov (United States)

1980-03-01

This report presents findings of a workshop on the identification of drugs that should be the focus of near-term highway safety research. Drugs of interest are those that have a potential to increase the likelihood of traffic crashes and their attend...

Safety of polyethylene glycol 3350 solution in chronic constipation: randomized, placebo-controlled trial.

Science.gov (United States)

McGraw, Thomas

2016-01-01

To evaluate the safety and tolerability of aqueous solution concentrate (ASC) of polyethylene glycol (PEG) 3350 in patients with functional constipation. The patients who met Rome III diagnostic criteria for functional constipation were randomized in this multicenter, randomized, placebo-controlled, single-blind study to receive once daily dose of PEG 3350 (17 g) ASC or placebo solution for 14 days. The study comprised a screening period (visit 1), endoscopy procedure (visits 2 and 3), and followup telephone calls 30 days post-treatment. Safety end points included adverse events (AEs), clinical laboratory evaluations, vital signs, and others. The primary end points were the proportion of patients with abnormalities of the oral and esophageal mucosa, detected by visual and endoscopic examination of the oral cavity and esophagus, respectively, compared with placebo. A secondary objective was to compare the safety and tolerability of ASC by evaluating AEs or adverse drug reactions. A total of 65 patients were enrolled in this study, 31 were randomized to PEG 3350 ASC and 34 were randomized to placebo, of which 62 patients completed the study. No patients in either group showed abnormalities in inflammation of the oral mucosa during visit 2 (before treatment) or visit 3 (after treatment). Fewer abnormalities of the esophageal mucosa were observed in the PEG 3350 ASC group than in the placebo group on visit 3, with no significant difference in the proportion of abnormalities between the treatment groups. Overall, 40 treatment-emergent AEs were observed in 48.4% of patients treated with PEG 3350 ASC, and 41 treatment-emergent AEs were observed in 55.9% of patients treated with placebo - nonsignificant difference of -7.5% (95% CI: -21.3, 6.3) between treatment groups. No serious AEs or deaths were reported, and no patient discontinued because of an AE. PEG 3350 ASC is safe and well tolerated in patients with functional constipation (NCT01885104).

Exploring Machine Learning Techniques Using Patient Interactions in Online Health Forums to Classify Drug Safety

Science.gov (United States)

Chee, Brant Wah Kwong

2011-01-01

This dissertation explores the use of personal health messages collected from online message forums to predict drug safety using natural language processing and machine learning techniques. Drug safety is defined as any drug with an active safety alert from the US Food and Drug Administration (FDA). It is believed that this is the first…

Pooling, meta-analysis, and the evaluation of drug safety

Directory of Open Access Journals (Sweden)

Leizorovicz Alain

2002-03-01

Full Text Available Abstract Background The "integrated safety report" of the drug registration files submitted to health authorities usually summarizes the rates of adverse events observed for a new drug, placebo or active control drugs by pooling the safety data across the trials. Pooling consists of adding the numbers of events observed in a given treatment group across the trials and dividing the results by the total number of patients included in this group. Because it considers treatment groups rather than studies, pooling ignores validity of the comparisons and is subject to a particular kind of bias, termed "Simpson's paradox." In contrast, meta-analysis and other stratified analyses are less susceptible to bias. Methods We use a hypothetical, but not atypical, application to demonstrate that the results of a meta-analysis can differ greatly from those obtained by pooling the same data. In our hypothetical model, a new drug is compared to 1 a placebo in 4 relatively small trials in patients at high risk for a certain adverse event and 2 an active reference drug in 2 larger trials of patients at low risk for this event. Results Using meta-analysis, the relative risk of experiencing the adverse event with the new drug was 1.78 (95% confidence interval [1.02; 3.12] compared to placebo and 2.20 [0.76; 6.32] compared to active control. By pooling the data, the results were, respectively, 1.00 [0.59; 1.70] and 5.20 [2.07; 13.08]. Conclusions Because these findings could mislead health authorities and doctors, regulatory agencies should require meta-analyses or stratified analyses of safety data in drug registration files.

USER S GUIDE FOR THE RANDOM DRUG SCREENING SYSTEM

Energy Technology Data Exchange (ETDEWEB)

McNeany, Karen I [ORNL

2013-12-01

The Random Drug Screening System (RDSS) is a desktop computing application designed to assign nongameable drug testing dates to each member in a population of employees, within a specific time line. The program includes reporting capabilities, test form generation, unique test ID number assignment, and the ability to flag high-risk employees for a higher frequency of drug testing than the general population.

Safety learning from drugs of the same class

DEFF Research Database (Denmark)

Stefansdottir, G; Knol, M J; Arnardottir, A H

2012-01-01

This study was aimed at assessing the extent of safety learning from data pertaining to other drugs of the same class. We studied drug classes for which the first and second drugs were centrally registered in the European Union from 1995 to 2008. We assessed whether adverse drug reactions (ADRs......) associated with one of the drugs also appeared in the Summary of Product Characteristics (SPC) of the other drug, either initially or during the postmarketing phase. We identified 977 ADRs from 19 drug pairs, of which 393 ADRs (40.2%) were listed in the SPCs of both drugs of a pair. Of these 393 that were...... present in both SPCs of a drug pair, 241 (61.3%) were present when the drug entered the market and 152 (30.7%) appeared in the postmarketing phase. The mention of ADRs in the SPCs of both same-class drugs in the postmarketing phase was associated with type A ADRs, marketing in the same regulator country...

Influence of companion diagnostics on efficacy and safety of targeted anti-cancer drugs: systematic review and meta-analyses.

Science.gov (United States)

Ocana, Alberto; Ethier, Josee-Lyne; Díez-González, Laura; Corrales-Sánchez, Verónica; Srikanthan, Amirrtha; Gascón-Escribano, María J; Templeton, Arnoud J; Vera-Badillo, Francisco; Seruga, Bostjan; Niraula, Saroj; Pandiella, Atanasio; Amir, Eitan

2015-11-24

Companion diagnostics aim to identify patients that will respond to targeted therapies, therefore increasing the clinical efficacy of such drugs. Less is known about their influence on safety and tolerability of targeted anti-cancer agents. Randomized trials evaluating targeted agents for solid tumors approved by the US Food and Drug Administration since year 2000 were assessed. Odds ratios (OR) and and 95% confidence intervals (CI) were computed for treatment-related death, treatment-discontinuation related to toxicity and occurrence of any grade 3/4 adverse events (AEs). The 12 most commonly reported individual AEs were also explored. ORs were pooled in a meta-analysis. Analysis comprised 41 trials evaluating 28 targeted agents. Seventeen trials (41%) utilized companion diagnostics. Compared to control groups, targeted drugs in experimental arms were associated with increased odds of treatment discontinuation, grade 3/4 AEs, and toxic death irrespective of whether they utilized companion diagnostics or not. Compared to drugs without available companion diagnostics, agents with companion diagnostics had a lower magnitude of increased odds of treatment discontinuation (OR = 1.12 vs. 1.65, p diagnostics were greatest for diarrhea (OR = 1.29 vs. 2.43, p diagnostics are associated with improved safety, and tolerability. Differences were most marked for gastrointestinal, cutaneous and neurological toxicity.

Review of the Methods to Obtain Paediatric Drug Safety Information: Spontaneous Reporting and Healthcare Databases, Active Surveillance Programmes, Systematic Reviews and Meta-analyses

Science.gov (United States)

Gentili, Marta; Pozzi, Marco; Peeters, Gabrielle; Radice, Sonia; Carnovale, Carla

2018-02-06

Knowledge of drugs safety collected during the pre-marketing phase is inevitably limited because the randomized clinical trials (RCTs) are rarely designed to evaluate safety. The small and selective groups of enrolled individuals and the limited duration of trials may hamper the ability to characterize fully the safety profiles of drugs. Additionally, information about rare adverse drug reactions (ADRs) in special groups is often incomplete or not available for most of the drugs commonly used in the daily clinical practice. In the paediatric setting several highimpact safety issues have emerged. Hence, in recent years, there has been a call for improved post-marketing pharmacoepidemiological studies, in which cohorts of patients are monitored for sufficient time in order to determine the precise risk-benefit ratio. In this review, we discuss the current available strategies enhancing the post-marketing monitoring activities of the drugs in the paediatric setting and define criteria whereby they can provide valuable information to improve the management of therapy in daily clinical practice including both safety and efficacy aspects. The strategies we cover include the signal detection using international pharmacovigilance and/or healthcare databases, the promotion of active surveillance initiatives which can generate complete, informative data sets for the signal detection and systematic review/meta-analysis. Together, these methods provide a comprehensive picture of causality and risk improving the management of therapy in a paediatric setting and they should be considered as a unique tool to be integrated with post-marketing activities. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Drug research methodology. Volume 5, Experimentation in drugs and highway safety : the study of drug effects on skills related to driving

Science.gov (United States)

1980-06-01

This report presents the findings of a workshop on experimental research in the area of drugs and highway safety. Complementing studies of drug use in different driving populations, experimentation here refers to studies performed under controlled co...

FDA drug safety communications: a narrative review and clinical considerations for older adults.

Science.gov (United States)

Marcum, Zachary A; Vande Griend, Joseph P; Linnebur, Sunny A

2012-08-01

The US Food and Drug Administration (FDA) has new regulatory authorities intended to enhance drug safety monitoring in the postmarketing period. This has resulted in an increase in communication from the FDA in recent years about the safety profile of certain drugs. It is important to stay abreast of the current literature on drug risks to effectively communicate these risks to patients, other health care providers, and the general public. To summarize 4 new FDA drug safety communications by describing the evidence supporting the risks and the clinical implications for older adults. The FDA Web site was reviewed for new drug safety communications from May 2011 to April 2012 that would be relevant to older adults. Approved labeling for each drug or class was obtained from the manufacturer, and PubMed was searched for primary literature that supported the drug safety concern. FDA drug safety communications for 4 drugs were chosen because of the potential clinical importance in older adults. A warning for citalopram was made because of potential problems with QT prolongation in patients taking less than 40 mg per day. The evidence suggests minor changes in QT interval. Given the flat dose-response curve in treating depression with citalopram, the new 20-mg/d maximum dose in older adults is sensible. Another warning was made for proton pump inhibitors (PPIs) and an increased risk of Clostridium difficile infection. A dose-response relationship was found for this drug risk. With C. difficile infections on the rise in older adults, along with other safety risks of PPI therapy, PPIs should only be used in older adults indicated for therapy for the shortest duration possible. In addition, a warning about dabigatran was made. There is strong evidence from a large clinical trial, as well as case reports, of increased bleeding risk in older adults taking dabigatran, especially in older adults with decreased renal function. This medication should be used with caution in older

Holes in the safety net: a case study of access to prescription drugs and specialty care.

Science.gov (United States)

Stanley, Ava; Cantor, Joel C; Guarnaccia, Peter

2008-07-01

The health care safety net in the United States is intended to fill gaps in health care services for uninsured and other vulnerable populations. This paper presents a case study of New Brunswick, NJ, a small city rich in safety net resources, to examine the adequacy of the American model of safety net care. We find substantial gaps in access to care despite the presence of a medical school, an abundance of primary care and specialty physicians, two major teaching hospitals, a large federally qualified health center and other safety net resources in this community of about 50,000 residents. Using a blend of random-digit-dial and area probability sampling, a survey of 595 households was conducted in 2001 generating detailed information about the health, access to care, demographic and other characteristics of 1,572 individuals. Confirming the great depth of the New Brunswick health care safety net, the survey showed that more than one quarter of local residents reported a hospital or community clinic as their usual source of care. Still, barriers to prescription drugs were reported for 11.0% of the area population and more than two in five (42.8%) local residents who perceived a need for specialty care reported difficulty getting those services. Bivariate analyses show significantly elevated risk of access problems among Hispanic and black residents, those in poor health, those relying on hospital and community clinics or with no usual source of care, and those living at or below poverty. In multivariate analysis, lack of health insurance was the greatest risk factor associated with both prescription drug and specialty access problems. Few local areas can claim the depth of safety net resources as New Brunswick, NJ, raising serious concerns about the adequacy of the American safety net model, especially for people with complex and chronic health care needs.

Pancreatic Safety of Incretin-Based Drugs - FDA and EMA Assessment

NARCIS (Netherlands)

Egan, Amy G.; Blind, Eberhard; Dunder, Kristina; de Graeff, Pieter A.; Hummer, B. Timothy; Bourcier, Todd; Rosebraugh, Curtis

2014-01-01

After evaluating a safety signal regarding pancreatitis and pancreatic cancer in patients using incretin-based drugs, the Food and Drug Administration and the European Medicines Agency conclude that assertions of a causal association are inconsistent with the data. With approximately 25.8 million

The practice of pre-marketing safety assessment in drug development.

Science.gov (United States)

Chuang-Stein, Christy; Xia, H Amy

2013-01-01

The last 15 years have seen a substantial increase in efforts devoted to safety assessment by statisticians in the pharmaceutical industry. While some of these efforts were driven by regulations and public demand for safer products, much of the motivation came from the realization that there is a strong need for a systematic approach to safety planning, evaluation, and reporting at the program level throughout the drug development life cycle. An efficient process can help us identify safety signals early and afford us the opportunity to develop effective risk minimization plan early in the development cycle. This awareness has led many pharmaceutical sponsors to set up internal systems and structures to effectively conduct safety assessment at all levels (patient, study, and program). In addition to process, tools have emerged that are designed to enhance data review and pattern recognition. In this paper, we describe advancements in the practice of safety assessment during the premarketing phase of drug development. In particular, we share examples of safety assessment practice at our respective companies, some of which are based on recommendations from industry-initiated working groups on best practice in recent years.

Self-Reported Drug and Alcohol Use and Attitudes toward Drug Testing in High Schools with Random Student Drug Testing

Science.gov (United States)

DuPont, Robert L.; Campbell, Michael D.; Campbell, Teresa G.; Shea, Corinne L.; DuPont, Helen S.

2013-01-01

Many schools implement random student drug testing (RSDT) programs as a drug prevention strategy. This study analyzes self-report surveys of students in eight secondary schools with well-established RSDT programs, comparing students who understood they were subject to testing and students who understood they were not subject to testing. Students…

77 FR 10666 - Pipeline Safety: Post Accident Drug and Alcohol Testing

Science.gov (United States)

2012-02-23

... 199 [Docket No. PHMSA-2011-0335] Pipeline Safety: Post Accident Drug and Alcohol Testing AGENCY... operators of Liquefied Natural Gas (LNG) facilities to conduct post- accident drug and alcohol tests of..., operators must drug and alcohol test each covered employee whose performance either contributed to the...

Effects of organizational safety practices and perceived safety climate on PPE usage, engineering controls, and adverse events involving liquid antineoplastic drugs among nurses.

Science.gov (United States)

DeJoy, David M; Smith, Todd D; Woldu, Henok; Dyal, Mari-Amanda; Steege, Andrea L; Boiano, James M

2017-07-01

Antineoplastic drugs pose risks to the healthcare workers who handle them. This fact notwithstanding, adherence to safe handling guidelines remains inconsistent and often poor. This study examined the effects of pertinent organizational safety practices and perceived safety climate on the use of personal protective equipment, engineering controls, and adverse events (spill/leak or skin contact) involving liquid antineoplastic drugs. Data for this study came from the 2011 National Institute for Occupational Safety and Health (NIOSH) Health and Safety Practices Survey of Healthcare Workers which included a sample of approximately 1,800 nurses who had administered liquid antineoplastic drugs during the past seven days. Regression modeling was used to examine predictors of personal protective equipment use, engineering controls, and adverse events involving antineoplastic drugs. Approximately 14% of nurses reported experiencing an adverse event while administering antineoplastic drugs during the previous week. Usage of recommended engineering controls and personal protective equipment was quite variable. Usage of both was better in non-profit and government settings, when workers were more familiar with safe handling guidelines, and when perceived management commitment to safety was higher. Usage was poorer in the absence of specific safety handling procedures. The odds of adverse events increased with number of antineoplastic drugs treatments and when antineoplastic drugs were administered more days of the week. The odds of such events were significantly lower when the use of engineering controls and personal protective equipment was greater and when more precautionary measures were in place. Greater levels of management commitment to safety and perceived risk were also related to lower odds of adverse events. These results point to the value of implementing a comprehensive health and safety program that utilizes available hazard controls and effectively communicates

Trust in the pharmaceutical sector : Analysis of drug safety controversies by means of drug life cycles

NARCIS (Netherlands)

Hernández, J.F.

2015-01-01

Before obtaining a marketing approval, the efficacy and safety profile of drugs is studied in specific populations and under well-controlled circumstances. After marketing approval, the drug is made available and used in ‘real world conditions’, which are known to deviate from the trial setting.

Enabling social listening for cardiac safety monitoring: Proceedings from a drug information association-cardiac safety research consortium cosponsored think tank.

Science.gov (United States)

Seifert, Harry A; Malik, Raleigh E; Bhattacharya, Mondira; Campbell, Kevin R; Okun, Sally; Pierce, Carrie; Terkowitz, Jeffrey; Turner, J Rick; Krucoff, Mitchell W; Powell, Gregory E

2017-12-01

This white paper provides a summary of the presentations and discussions from a think tank on "Enabling Social Listening for Cardiac Safety Monitoring" trials that was cosponsored by the Drug Information Association and the Cardiac Safety Research Consortium, and held at the White Oak headquarters of the US Food and Drug Administration on June 3, 2016. The meeting's goals were to explore current methods of collecting and evaluating social listening data and to consider their applicability to cardiac safety surveillance. Social listening is defined as the act of monitoring public postings on the Internet. It has several theoretical advantages for drug and device safety. First, these include the ability to detect adverse events that are "missed" by traditional sources and the ability to detect adverse events sooner than would be allowed by traditional sources, both by affording near-real-time access to data from culturally and geographically diverse sources. Social listening can also potentially introduce a novel patient voice into the conversation about drug safety, which could uniquely augment understanding of real-world medication use obtained from more traditional methodologies. Finally, it can allow for access to information about drug misuse and diversion. To date, the latter 2 of these have been realized. Although regulators from the Food and Drug Administration and the United Kingdom's Medicines and Healthcare Products Regulatory Agency participated in the think tank along with representatives from industry, academia, and patient groups, this article should not be construed to constitute regulatory guidance. Copyright © 2017 Elsevier Inc. All rights reserved.

Tolerability and safety of antifungal drugs

Directory of Open Access Journals (Sweden)

Francesco Scaglione

2013-08-01

Full Text Available When treating critically ill patients, as those with fungal infections, attention should be focused on the appropriate use of drugs, especially in terms of dose, safety, and tolerability. The fungal infection itself and the concomitant physiological disorders concur to increase the risk of mortality in these patients, therefore the use of any antifungal agent should be carefully evaluated, considering both the direct action on the target fungus and the adverse effects eventually caused. Among antifungal drugs, echinocandins have the greatest tolerability. In fact, unlike amphotericin B, showing nephrotoxicity, and azoles, which are hepatotoxic, the use of echinocandins doesn’t result in major adverse events.http://dx.doi.org/10.7175/rhc.v4i2s.873

Why trash don't pass? pharmaceutical licensing and safety performance of drugs.

Science.gov (United States)

Banerjee, Tannista; Nayak, Arnab

2017-01-01

This paper examines how asymmetric information in pharmaceutical licensing affects the safety standards of licensed drugs. Pharmaceutical companies often license potential drug molecules at different stages of drug development from other pharmaceutical or biotechnology companies and complete the remaining of research stages before submitting the new drug application(NDA) to the food and drug administration. The asymmetric information associated with the quality of licensed molecules might result in the molecules which are less likely to succeed to be licensed out, while those with greater potential of success being held internally for development. We identify the NDAs submitted between 1993 and 2004 where new molecular entities were acquired through licensing. Controlling for other drug area specific and applicant firm specific factors, we investigate whether drugs developed with licensed molecules face higher probability of safety based recall and ultimate withdrawal from the market than drugs developed internally. Results suggest the opposite of Akerlof's (Q J Econ 84:488-500, 1970) lemons problem. Licensed molecules rather have less probability of facing safety based recalls and ultimate withdrawal from the market comparing to internally developed drug molecules. This suggests that biotechnology and small pharmaceutical firms specializing in pharmaceutical research are more efficient in developing good potential molecules because of their concentrated research. Biotechnology firms license out good potential molecules because it increases their market value and reputation. In addition, results suggest that both the number of previous approved drugs in the disease area, and also the applicant firms' total number of previous approvals in all disease areas reduce the probability that an additional approved drug in the same drug area will potentially be harmful.

A primer of drug safety surveillance: an industry perspective. Part II: Product labeling and product knowledge.

Science.gov (United States)

Allan, M C

1992-01-01

To place the fundamentals of clinical drug safety surveillance in a conceptual framework that will facilitate understanding and application of adverse drug event data to protect the health of the public and support a market for pharmaceutical manufacturers' products. Part II of this series discusses specific issues regarding product labeling, such as developing the labeling, changing the labeling, and the legal as well as commercial ramifications of the contents of the labeling. An adverse event report scenario is further analyzed and suggestions are offered for maintaining the product labeling as an accurate reflection of the drug safety surveillance data. This article also emphasizes the necessity of product knowledge in adverse event database management. Both scientific and proprietary knowledge are required. Acquiring product knowledge is a part of the day-to-day activities of drug safety surveillance. A knowledge of the history of the product may forestall adverse publicity, as shown in the illustration. This review uses primary sources from the federal laws (regulations), commentaries, and summaries. Very complex topics are briefly summarized in the text. Secondary sources, ranging from newspaper articles to judicial summaries, illustrate the interpretation of adverse drug events and opportunities for drug safety surveillance intervention. The reference materials used were articles theoretically or practically applicable in the day-to-day practice of drug safety surveillance. The role of clinical drug safety surveillance in product monitoring and drug development is described. The process of drug safety surveillance is defined by the Food and Drug Administration regulations, product labeling, product knowledge, and database management. Database management is subdivided into the functions of receipt, retention, retrieval, and review of adverse event reports. Emphasis is placed on the dynamic interaction of the components of the process. Suggestions are offered

Observational Pharmacoepidemiology in the Drug Safety and Effectiveness Evaluation

Directory of Open Access Journals (Sweden)

José Cabrita

2017-04-01

Full Text Available Observational epidemiological studies have been used in the medicines context for more than 40 years, contributing to characterize drug use patterns and safety, efficacy and effectiveness profiles. Its use has been increased in recognition of the clinical trials limitations to assess the therapeutic and iatrogenic potential of the medicines after its commercialization. The evolution of the regulatory framework for pharmacovigilance, requiring post-marketing studies, post-authorization safety studies (PASS and the post-authorization efficacy studies (PAES to approve certain drugs, reinforced the importance of observational pharmacoepidemiology for the characterization of the medicines safety and effectiveness profiles. Pharmacoepidemiological research can be carried out from field studies designed to obtain the necessary information or in databases with health records of population samples that already contain the information. This 2nd option is more efficient and more and more frequent. Although, observational research from field studies continues to have its space, the increasing availability of databases allowed a new development to observational pharmacoepidemiology. Indeed, access to automated records databases with up-to-date information on medical prescriptions and global health care to representative population samples with long follow-up periods is a valuable tool for the study of drug use patterns and therapeutic and iatrogenic potential in routine clinical practice. In this context, observational pharmacoepidemiology reinforces its role as a scientific area particularly suitable for evaluating the safety and the effectiveness of the medicines in the “real world”, making a relevant contribution to overcome the gap in translating the evidence from the clinical trials for clinical practice.

75 FR 17417 - Joint Meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management...

Science.gov (United States)

2010-04-06

...] Joint Meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory... Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee. This meeting was... Drug Safety and Risk Management Advisory Committee would be held on May 12, 2010. On page 10490, in the...

77 FR 75896 - Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2013

Science.gov (United States)

2012-12-26

...-11213, Notice No. 16] Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2013...., Washington, DC 20590, (telephone 202-493- 1342); or Kathy Schnakenberg, FRA Alcohol/Drug Program Specialist... from FRA's Management Information System, the rail industry's random drug testing positive rate has...

A Randomized, Controlled Clinical Trial Comparing Efficacy, Safety ...

African Journals Online (AJOL)

A Randomized, Controlled Clinical Trial Comparing Efficacy, Safety and Cost Effectiveness of Lornoxicam with Diclofenac Sodium in Patients of Osteoarthritis Knee. ... All patients were assessed with visual analogue scale and 100 meter walking test before starting of therapy, at 15 days and at 1, 2 and 3 months of therapy.

ISSUES OF FETUS DRUG SAFETY

Directory of Open Access Journals (Sweden)

A.V. Ostrovskaya

2010-01-01

Full Text Available The article is focused on the issue of fetus drug safety. Development of a child’s health depends both on hereditary information and environment factors. The reason for deviation from the process of normal prenatal development could be any xenobiotics, physical factors and some medications having a pathogenic effect during pregnancy on the embryo and fetus. Due to that, the physician’s preventive work based on the knowledge of embryogenesis processes and critical development periods. Key words: teratogenic action, medications, prenatal development, congenital malformation, newborns, children.(Pediatric Pharmacology. – 2010; 7(1:25-28

75 FR 79308 - Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2011

Science.gov (United States)

2010-12-20

...-11213, Notice No. 14] Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2011... random testing positive rates were .037 percent for drugs and .014 percent for alcohol. Because the... effective December 20, 2010. FOR FURTHER INFORMATION CONTACT: Lamar Allen, Alcohol and Drug Program Manager...

75 FR 1547 - Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2010

Science.gov (United States)

2010-01-12

...-11213, Notice No. 13] RIN 2130-AA81 Alcohol and Drug Testing: Determination of Minimum Random Testing... percent for alcohol. Because the industry-wide random drug testing positive rate has remained below 1.0... effective upon publication. FOR FURTHER INFORMATION CONTACT: Lamar Allen, Alcohol and Drug Program Manager...

Drug safety: Pregnancy rating classifications and controversies.

Science.gov (United States)

Wilmer, Erin; Chai, Sandy; Kroumpouzos, George

2016-01-01

This contribution consolidates data on international pregnancy rating classifications, including the former US Food and Drug Administration (FDA), Swedish, and Australian classification systems, as well as the evidence-based medicine system, and discusses discrepancies among them. It reviews the new Pregnancy and Lactation Labeling Rule (PLLR) that replaced the former FDA labeling system with narrative-based labeling requirements. PLLR emphasizes on human data and highlights pregnancy exposure registry information. In this context, the review discusses important data on the safety of most medications used in the management of skin disease in pregnancy. There are also discussions of controversies relevant to the safety of certain dermatologic medications during gestation. Copyright © 2016 Elsevier Inc. All rights reserved.

Application of the Pareto principle to identify and address drug-therapy safety issues.

Science.gov (United States)

Müller, Fabian; Dormann, Harald; Pfistermeister, Barbara; Sonst, Anja; Patapovas, Andrius; Vogler, Renate; Hartmann, Nina; Plank-Kiegele, Bettina; Kirchner, Melanie; Bürkle, Thomas; Maas, Renke

2014-06-01

Adverse drug events (ADE) and medication errors (ME) are common causes of morbidity in patients presenting at emergency departments (ED). Recognition of ADE as being drug related and prevention of ME are key to enhancing pharmacotherapy safety in ED. We assessed the applicability of the Pareto principle (~80 % of effects result from 20 % of causes) to address locally relevant problems of drug therapy. In 752 cases consecutively admitted to the nontraumatic ED of a major regional hospital, ADE, ME, contributing drugs, preventability, and detection rates of ADE by ED staff were investigated. Symptoms, errors, and drugs were sorted by frequency in order to apply the Pareto principle. In total, 242 ADE were observed, and 148 (61.2 %) were assessed as preventable. ADE contributed to 110 inpatient hospitalizations. The ten most frequent symptoms were causally involved in 88 (80.0 %) inpatient hospitalizations. Only 45 (18.6 %) ADE were recognized as drug-related problems until discharge from the ED. A limited set of 33 drugs accounted for 184 (76.0 %) ADE; ME contributed to 57 ADE. Frequency-based listing of ADE, ME, and drugs involved allowed identification of the most relevant problems and development of easily to implement safety measures, such as wall and pocket charts. The Pareto principle provides a method for identifying the locally most relevant ADE, ME, and involved drugs. This permits subsequent development of interventions to increase patient safety in the ED admission process that best suit local needs.

Spillover Effects of Drug Safety Warnings on Preventive Health Care Use

DEFF Research Database (Denmark)

Daysal, N. Meltem; Orsini, Chiara

2015-01-01

We examine how new medical information on drug safety impacts preventive health care use. We exploit the release of the findings of the Women’s Health Initiative Study (WHIS) – the largest randomized controlled trial of women’s health – which demonstrated in 2002 the health risks associated...... with the long-term use of hormone replacement therapy (HRT). We first show that, after the release of the WHIS findings, HRT use dropped sharply among post-menopausal women. We then estimate the spillover effects of the WHIS findings on preventive care by means of a difference-in-differences methodology...... comparing changes in preventive care use among 60 to 69 year-old women (who have high rates of HRT use) with the change among women aged 75 and above (who have much lower rates of HRT use). Using data from the Behavioral Risk Factor Surveillance System for the period 1998–2007, we find that women aged 60...

Safety profile of drugs used in the treatment of osteoporosis: a systematical review of the literature

Directory of Open Access Journals (Sweden)

M. Varenna

2013-10-01

Full Text Available The range of osteoporosis treatments is increasingly large and, like any disease, the pharmacological management of patients should involve a risk/benefit evaluation to attain the greatest reduction in risk of fracture with the lowest incidence of adverse events. The aim of this review is to critically appraise the literature about the safety issues of the main pharmacological treatments of osteoporosis. This document is the result of a consensus of experts based on a systematic review of regulatory documents, randomized controlled trials, metaanalyses, pharmacovigilance surveys and case series related to possible adverse drug reactions to osteoporosis treatment with calcium and vitamin D supplements, bisphosphonates, strontium ranelate, selective estrogen receptor modulators, denosumab, and teriparatide. As expected, randomized controlled trials showed only the most common adverse events due to the samples size and the short observation time. Case series and observational studies are able to provide data about uncommon side effects, but in some cases a sure cause-effect relationship needs still to be confirmed. Consistently with methodological limitations, the newer drugs have a tolerance profile that has not been fully explored yet. Osteoporosis treatments showed an overall good tolerance profile with rare serious adverse events that, however, must be well known by the clinician who prescribes these drugs. The concern about possible adverse events should be weighed against the reduction of morbidity and mortality associated with a significant fracture risk reduction.

Systematic review of randomized trials on vasoconstrictor drugs for hepatorenal syndrome

DEFF Research Database (Denmark)

Gluud, Lise L; Christensen, Kurt; Christensen, Erik

2010-01-01

Vasoconstrictor drugs may improve renal function in hepatorenal syndrome (HRS), but the effect on mortality has not been established. We therefore performed a systematic review of randomized trials on vasoconstrictor drugs for type 1 or type 2 HRS. Mortality was the primary outcome measure...

Drug research methodology. Volume 4, Epidemiology in drugs and highway safety : the study of drug use among drivers and its role in traffic crashes

Science.gov (United States)

1980-06-01

This report presents the findings of a workshop on epidemiology in drugs and highway safety. A cross-disciplinary panel of experts (1) identified methodological issues and constraints present in research to define the nature and magnitude of the drug...

76 FR 63929 - Joint Meeting of the Drug Safety and Risk Management Advisory Committee and the Dermatologic and...

Science.gov (United States)

2011-10-14

...] Joint Meeting of the Drug Safety and Risk Management Advisory Committee and the Dermatologic and... Administration (FDA). The meeting will be open to the public. Name of Committees: Drug Safety and Risk Management... Safe Use (ETASU) before its Drug Safety and Risk Management Advisory Committee (DSaRM). On December 1...

The 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE trial: study protocol for a randomized controlled trial

Directory of Open Access Journals (Sweden)

Park Kyung

2012-03-01

Full Text Available Abstract Background Second-generation drug-eluting stents (DES have raised the bar of clinical performance. These stents are mostly made from cobalt chromium alloy. A newer generation DES has been developed from platinum chromium alloy, but clinical data regarding the efficacy and safety of the platinum chromium-based everolimus-eluting stent (PtCr-EES is limited, with no comparison data against the cobalt chromium-based zotarolimus-eluting stent (CoCr-ZES. In addition, an antiplatelet regimen is an integral component of medical therapy after percutaneous coronary intervention (PCI. A 1-week duration of doubling the dose of clopidogrel (double-dose antiplatelet therapy (DDAT was shown to improve outcome at 1 month compared with conventional dose in acute coronary syndrome (ACS patients undergoing PCI. However in Asia, including Korea, the addition of cilostazol (triplet antiplatelet therapy (TAT is used more commonly than doubling the dose of clopidogrel in high-risk patients. Methods In the 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE trial, approximately 3,750 patients are being prospectively and randomly assigned in a 2 × 2 factorial design according to the type of stent (PtCr-EES vs CoCr-ZES and antiplatelet regimen (TAT vs DDAT. The first primary endpoint is target lesion failure at 1 year for the stent comparison, and the second primary endpoint is net clinical outcome at 1 month for comparison of antiplatelet therapy regimen. Discussion The HOST-ASSURE trial is the largest study yet performed to directly compare the efficacy and safety of the PtCr-EES versus CoCr-ZES in an 'all-comers' population. In addition, this study will also compare the clinical outcome of TAT versus DDAT for 1-month post PCI. Trial registration ClincalTrials.gov number NCT01267734.

Safety risks with investigational drugs: Pharmacy practices and perceptions in the veterans affairs health system.

Science.gov (United States)

Cruz, Jennifer L; Brown, Jamie N

2015-06-01

Rigorous practices for safe dispensing of investigational drugs are not standardized. This investigation sought to identify error-prevention processes utilized in the provision of investigational drug services (IDS) and to characterize pharmacists' perceptions about safety risks posed by investigational drugs. An electronic questionnaire was distributed to an audience of IDS pharmacists within the Veteran Affairs Health System. Multiple facets were examined including demographics, perceptions of medication safety, and standard processes used to support investigational drug protocols. Twenty-one respondents (32.8% response rate) from the Northeast, Midwest, South, West, and Non-contiguous United States participated. The mean number of pharmacist full-time equivalents (FTEs) dedicated to the IDS was 0.77 per site with 0.2 technician FTEs. The mean number of active protocols was 22. Seventeen respondents (81%) indicated some level of concern for safety risks. Concerns related to the packaging of medications were expressed, most notably lack of product differentiation, expiration dating, barcodes, and choice of font size or color. Regarding medication safety practices, the majority of sites had specific procedures in place for storing and securing drug supply, temperature monitoring, and prescription labeling. Repackaging bulk items and proactive error-identification strategies were less common. Sixty-seven percent of respondents reported that an independent double check was not routinely performed. Medication safety concerns exist among pharmacists in an investigational drug service; however, a variety of measures have been employed to improve medication safety practices. Best practices for the safe dispensing of investigational medications should be developed in order to standardize these error-prevention strategies.

Analyzing research trends on drug safety using topic modeling.

Science.gov (United States)

Zou, Chen

2018-04-06

Published drug safety data has evolved in the past decade due to scientific and technological advances in the relevant research fields. Considering that a vast amount of scientific literature has been published in this area, it is not easy to identify the key information. Topic modeling has emerged as a powerful tool to extract meaningful information from a large volume of unstructured texts. Areas covered: We analyzed the titles and abstracts of 4347 articles in four journals dedicated to drug safety from 2007 to 2016. We applied Latent Dirichlet allocation (LDA) model to extract 50 main topics, and conducted trend analysis to explore the temporal popularity of these topics over years. Expert Opinion/Commentary: We found that 'benefit-risk assessment and communication', 'diabetes' and 'biologic therapy for autoimmune diseases' are the top 3 most published topics. The topics relevant to the use of electronic health records/observational data for safety surveillance are becoming increasingly popular over time. Meanwhile, there is a slight decrease in research on signal detection based on spontaneous reporting, although spontaneous reporting still plays an important role in benefit-risk assessment. The topics related to medical conditions and treatment showed highly dynamic patterns over time.

Legacy data sharing to improve drug safety assessment: the eTOX project

DEFF Research Database (Denmark)

Sanz, Ferran; Pognan, François; Steger-Hartmann, Thomas

2017-01-01

The sharing of legacy preclinical safety data among pharmaceutical companies and its integration with other information sources offers unprecedented opportunities to improve the early assessment of drug safety. Here, we discuss the experience of the eTOX project, which was established through...

Drug discrimination: A versatile tool for characterization of CNS safety pharmacology and potential for drug abuse.

Science.gov (United States)

Swedberg, Michael D B

2016-01-01

Drug discrimination studies for assessment of psychoactive properties of drugs in safety pharmacology and drug abuse and drug dependence potential evaluation have traditionally been focused on testing novel compounds against standard drugs for which drug abuse has been documented, e.g. opioids, CNS stimulants, cannabinoids etc. (e.g. Swedberg & Giarola, 2015), and results are interpreted such that the extent to which the test drug causes discriminative effects similar to those of the standard training drug, the test drug would be further characterized as a potential drug of abuse. Regulatory guidance for preclinical assessment of abuse liability by the European Medicines Agency (EMA, 2006), the U.S. Food and Drug Administration (FDA, 2010), the International Conference of Harmonization (ICH, 2009), and the Japanese Ministry of Health Education and Welfare (MHLW, 1994) detail that compounds with central nervous system (CNS) activity, whether by design or not, need abuse and dependence liability assessment. Therefore, drugs with peripheral targets and a potential to enter the CNS, as parent or metabolite, are also within scope (see Swedberg, 2013, for a recent review and strategy). Compounds with novel mechanisms of action present a special challenge due to unknown abuse potential, and should be carefully assessed against defined risk criteria. Apart from compounds sharing mechanisms of action with known drugs of abuse, compounds intended for indications currently treated with drugs with potential for abuse and or dependence are also within scope, regardless of mechanism of action. Examples of such compounds are analgesics, anxiolytics, cognition enhancers, appetite control drugs, sleep control drugs and drugs for psychiatric indications. Recent results (Swedberg et al., 2014; Swedberg & Raboisson, 2014; Swedberg, 2015) on the metabotropic glutamate receptor type 5 (mGluR5) antagonists demonstrate that compounds causing hallucinatory effects in humans did not exhibit

10 CFR 26.67 - Random drug and alcohol testing of individuals who have applied for authorization.

Science.gov (United States)

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Random drug and alcohol testing of individuals who have... PROGRAMS Granting and Maintaining Authorization § 26.67 Random drug and alcohol testing of individuals who... other entity relies on drug and alcohol tests that were conducted before the individual applied for...

Exploiting pluripotent stem cell technology for drug discovery, screening, safety, and toxicology assessments.

Science.gov (United States)

McGivern, Jered V; Ebert, Allison D

2014-04-01

In order for the pharmaceutical industry to maintain a constant flow of novel drugs and therapeutics into the clinic, compounds must be thoroughly validated for safety and efficacy in multiple biological and biochemical systems. Pluripotent stem cells, because of their ability to develop into any cell type in the body and recapitulate human disease, may be an important cellular system to add to the drug development repertoire. This review will discuss some of the benefits of using pluripotent stem cells for drug discovery and safety studies as well as some of the recent applications of stem cells in drug screening studies. We will also address some of the hurdles that need to be overcome in order to make stem cell-based approaches an efficient and effective tool in the quest to produce clinically successful drug compounds. Copyright © 2013 Elsevier B.V. All rights reserved.

The principle of safety evaluation in medicinal drug - how can toxicology contribute to drug discovery and development as a multidisciplinary science?

Science.gov (United States)

Horii, Ikuo

2016-01-01

Pharmaceutical (drug) safety assessment covers a diverse science-field in the drug discovery and development including the post-approval and post-marketing phases in order to evaluate safety and risk management. The principle in toxicological science is to be placed on both of pure and applied sciences that are derived from past/present scientific knowledge and coming new science and technology. In general, adverse drug reactions are presented as "biological responses to foreign substances." This is the basic concept of thinking about the manifestation of adverse drug reactions. Whether or not toxic expressions are extensions of the pharmacological effect, adverse drug reactions as seen from molecular targets are captured in the category of "on-target" or "off-target", and are normally expressed as a biological defense reaction. Accordingly, reactions induced by pharmaceuticals can be broadly said to be defensive reactions. Recent molecular biological conception is in line with the new, remarkable scientific and technological developments in the medical and pharmaceutical areas, and the viewpoints in the field of toxicology have shown that they are approaching toward the same direction as well. This paper refers to the basic concept of pharmaceutical toxicology, the differences for safety assessment in each stage of drug discovery and development, regulatory submission, and the concept of scientific considerations for risk assessment and management from the viewpoint of "how can multidisciplinary toxicology contribute to innovative drug discovery and development?" And also realistic translational research from preclinical to clinical application is required to have a significant risk management in post market by utilizing whole scientific data derived from basic and applied scientific research works. In addition, the significance for employing the systems toxicology based on AOP (Adverse Outcome Pathway) analysis is introduced, and coming challenges on precision

Drug packaging in 2014: authorities should direct more efforts towards medication safety.

Science.gov (United States)

2015-05-01

In 2014, Prescrire examined the packaging quality of about 250 drugs. A few advances stand out, mainly involving recent drugs, but on the whole, the situation is worrisome in terms of medication safety. Although pharmaceutical companies and drug regulatory agencies seem to be taking more account of the risk of accidental poisoning in children, the level of protection remains low overall in the absence of stringent measures on the part of the authorities. New drugs too often have poor-quality or even dangerous packaging at the time of their market introduction. And the packaging quality of older drugs is disturbing. Pharmaceutical companies no longer invest in the packaging of these products, and agencies often fail to take advantage of the opportunities provided by their reassessment to improve the situation. The inappropriate labelling of certain injectable drugs remains a source of medication errors, sometimes resulting in very serious consequences. In 2014, signs of progress in the packaging of several drugs show that its role in medication safety is better appreciated. But the persistence of dangers in the pharmaceuticals market, created by "unfinished", overly complex or poor-quality packaging, raises the question of the responsibility of pharmaceutical companies and agencies for past and present accidents.

Drug safety is a barrier to the discovery and development of new androgen receptor antagonists.

Science.gov (United States)

Foster, William R; Car, Bruce D; Shi, Hong; Levesque, Paul C; Obermeier, Mary T; Gan, Jinping; Arezzo, Joseph C; Powlin, Stephanie S; Dinchuk, Joseph E; Balog, Aaron; Salvati, Mark E; Attar, Ricardo M; Gottardis, Marco M

2011-04-01

Androgen receptor (AR) antagonists are part of the standard of care for prostate cancer. Despite the almost inevitable development of resistance in prostate tumors to AR antagonists, no new AR antagonists have been approved for over a decade. Treatment failure is due in part to mutations that increase activity of AR in response to lower ligand concentrations as well as to mutations that result in AR response to a broader range of ligands. The failure to discover new AR antagonists has occurred in the face of continued research; to enable progress, a clear understanding of the reasons for failure is required. Non-clinical drug safety studies and safety pharmacology assays were performed on previously approved AR antagonists (bicalutamide, flutamide, nilutamide), next generation antagonists in clinical testing (MDV3100, BMS-641988), and a pre-clinical drug candidate (BMS-501949). In addition, non-clinical studies with AR mutant mice, and EEG recordings in rats were performed. Non-clinical findings are compared to disclosures of clinical trial results. As a drug class, AR antagonists cause seizure in animals by an off-target mechanism and are found in vitro to inhibit GABA-A currents. Clinical trials of candidate next generation AR antagonists identify seizure as a clinical safety risk. Non-clinical drug safety profiles of the AR antagonist drug class create a significant barrier to the identification of next generation AR antagonists. GABA-A inhibition is a common off-target activity of approved and next generation AR antagonists potentially explaining some side effects and safety hazards of this class of drugs. Copyright © 2010 Wiley-Liss, Inc.

Comparing Safety and Efficacy of "Third-Generation" Antiepileptic Drugs: Long-Term Extension and Post-marketing Treatment.

Science.gov (United States)

Kwok, Charlotte S; Johnson, Emily L; Krauss, Gregory L

2017-11-01

Four "third-generation" antiepileptic drugs (AEDs) were approved for adjunctive treatment of refractory focal onset seizures during the past 10 years. Long-term efficacy and safety of the drugs were demonstrated in large extension studies and in reports of subgroups of patients not studied in pivotal trials. Reviewing extension study and post-marketing outcome series for the four newer AEDs-lacosamide, perampanel, eslicarbazepine acetate and brivaracetam-can guide clinicians in treating and monitoring patients. AED extension studies evaluate treatment retention, drug tolerability, and drug safety during individualized treatment with flexible dosing and thus provide information not available in rigid pivotal trials. Patient retention in the studies ranged from 75 to 80% at 1 year and from 36 to 68% at 2-year treatment intervals. Safety findings were generally similar to those of pivotal trials, with no major safety risks identified and with several specific adverse drug effects, such as hyponatremia, reported. The third-generation AEDs, some through new mechanisms and others with improved tolerability compared to related AEDs, provide new options in efficacy and tolerability.

3-Year Clinical Follow-Up of the RIBS IV Clinical Trial: A Prospective Randomized Study of Drug-Eluting Balloons Versus Everolimus-Eluting Stents in Patients With In-Stent Restenosis in Coronary Arteries Previously Treated With Drug-Eluting Stents.

Science.gov (United States)

Alfonso, Fernando; Pérez-Vizcayno, María José; Cuesta, Javier; García Del Blanco, Bruno; García-Touchard, Arturo; López-Mínguez, José Ramón; Masotti, Mónica; Zueco, Javier; Cequier, Angel; Velázquez, Maite; Moreno, Raúl; Mainar, Vicente; Domínguez, Antonio; Moris, Cesar; Molina, Eduardo; Rivero, Fernando; Jiménez-Quevedo, Pilar; Gonzalo, Nieves; Fernández-Pérez, Cristina

2018-05-28

This study sought to compare the long-term safety and efficacy of drug-eluting balloons (DEB) and everolimus-eluting stents (EES) in patients with in-stent restenosis (ISR) of drug-eluting stents (DES). Treatment of patients with DES-ISR remains a challenge. The RIBS IV (Restenosis Intra-Stent of Drug-Eluting Stents: Drug-Eluting Balloons vs Everolimus-Eluting Stents) trial is a prospective multicenter randomized clinical trial comparing DEB and EES in patients with DES-ISR. The pre-specified comparison of the 3-year clinical outcomes obtained with these interventions is the main objective of the present study. A total of 309 patients with DES-ISR were randomized to DEB (n = 154) or EES (n = 155). At angiographic follow-up, the in-segment minimal lumen diameter was larger in the EES arm (2.03 ± 0.7 mm vs. 1.80 ± 0.6 mm; p 1 year) target lesion revascularization (2.6% vs. 4%) and target vessel revascularization (4% vs. 6.6%) was similar in the 2 arms. Rates of cardiac death (3.9% vs. 3.2%), myocardial infarction (2.6% vs. 4.5%), and stent thrombosis (1.3% vs. 2.6%) at 3 years were also similar in both arms. The 3-year clinical follow-up of this randomized clinical trial demonstrates that in patients with DES-ISR, EES reduce the need for repeat interventions compared with DEB. (Restenosis Intra-Stent of Drug-Eluting Stents: Drug-Eluting Balloons vs Everolimus-Eluting Stents [RIBS IV]; NCT01239940). Published by Elsevier Inc.

Enhancing food safety: the role of the Food and Drug Administration

National Research Council Canada - National Science Library

Wallace, Robert B; Oria, Maria

2010-01-01

.... Food and Drug Administration's abilities to discover potential threats to food safety and prevent outbreaks of foodborne illness are hampered by impediments to efficient use of its limited resources...

A Decade in the MIST: Learnings from Investigations of Drug Metabolites in Drug Development under the "Metabolites in Safety Testing" Regulatory Guidance.

Science.gov (United States)

Schadt, Simone; Bister, Bojan; Chowdhury, Swapan K; Funk, Christoph; Hop, Cornelis E C A; Humphreys, W Griffith; Igarashi, Fumihiko; James, Alexander D; Kagan, Mark; Khojasteh, S Cyrus; Nedderman, Angus N R; Prakash, Chandra; Runge, Frank; Scheible, Holger; Spracklin, Douglas K; Swart, Piet; Tse, Susanna; Yuan, Josh; Obach, R Scott

2018-06-01

Since the introduction of metabolites in safety testing (MIST) guidance by the Food and Drug Administration in 2008, major changes have occurred in the experimental methods for the identification and quantification of metabolites, ways to evaluate coverage of metabolites, and the timing of critical clinical and nonclinical studies to generate this information. In this cross-industry review, we discuss how the increased focus on human drug metabolites and their potential contribution to safety and drug-drug interactions has influenced the approaches taken by industry for the identification and quantitation of human drug metabolites. Before the MIST guidance was issued, the method of choice for generating comprehensive metabolite profile was radio chromatography. The MIST guidance increased the focus on human drug metabolites and their potential contribution to safety and drug-drug interactions and led to changes in the practices of drug metabolism scientists. In addition, the guidance suggested that human metabolism studies should also be accelerated, which has led to more frequent determination of human metabolite profiles from multiple ascending-dose clinical studies. Generating a comprehensive and quantitative profile of human metabolites has become a more urgent task. Together with technological advances, these events have led to a general shift of focus toward earlier human metabolism studies using high-resolution mass spectrometry and to a reduction in animal radiolabel absorption/distribution/metabolism/excretion studies. The changes induced by the MIST guidance are highlighted by six case studies included herein, reflecting different stages of implementation of the MIST guidance within the pharmaceutical industry. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Comparison of the safety information on drug labels in three developed countries: The USA, UK and Canada

Directory of Open Access Journals (Sweden)

Thamir M. Alshammari

2017-12-01

Full Text Available The safety information on drug labels of a company marketing the same drugs in different countries is sometimes different. The aim of the present study is to understand the differences in the volume and content of safety information on the drug labels from the same manufacturers in three developed countries: the United States of America (USA, the United Kingdom (UK and Canada. This study involved the calculation of the proportion of total safety information (PSI and of contraindications (PCI in comparison to all information on the label and the percentage of boxed warnings (PBW among the 100 labels studied from each country. The PSI on the labels of different countries is different with USA labels bearing lesser value PSI and UK labels bearing higher value PSI. The qualitative information provided on these drug labels from each country in ‘contraindications’ sections, ‘boxed/serious warnings’ and ‘overdosage’ sections presented differences in the information provided on most of the labels. We have found distinct differences between the safety information available on drug labels in terms of volume and content. We conclude that the safety information for the same products should be standardised across all countries.

The Expected Net Present Value of Developing Weight Management Drugs in the Context of Drug Safety Litigation.

Science.gov (United States)

Chawla, Anita; Carls, Ginger; Deng, Edmund; Tuttle, Edward

2015-07-01

Following withdrawals, failures, and significant litigation settlements, drug product launches in the anti-obesity category slowed despite a large and growing unmet need. Litigation concerns, a more risk-averse regulatory policy, and the difficulty of developing a product with a compelling risk-benefit profile in this category may have limited innovators' expected return on investment and restricted investment in this therapeutic area. The objective of the study was to estimate perceived manufacturer risk associated with product safety litigation and increased development costs vs. revenue expectations on anticipated return on investment and to determine which scenarios might change a manufacturer's investment decision. Expected net present value of a weight-management drug entering pre-clinical trials was calculated for a range of scenarios representing evolving expectations of development costs, revenue, and litigation risk over the past 25 years. These three factors were based on published estimates, historical data, and analogs from other therapeutic areas. The main driver in expected net present value calculations is expected revenue, particularly if one assumes that litigation risk and demand are positively correlated. Changes in development costs associated with increased regulatory concern with potential safety issues for the past 25 years likely did not impact investment decisions. Regulatory policy and litigation risk both played a role in anti-obesity drug development; however, product revenue-reflecting efficacy at acceptable levels of safety-was by far the most important factor. To date, relatively modest sales associated with recent product introductions suggest that developing a product that is sufficiently efficacious with an acceptable level of safety continues to be the primary challenge in this market.

Thermal safety of ultrasound-enhanced ocular drug delivery: A modeling study

Energy Technology Data Exchange (ETDEWEB)

Nabili, Marjan, E-mail: mnabili@gwmail.gwu.edu [Department of Electrical and Computer Engineering, The George Washington University, 800 22nd Street NW, Room 5000, Washington, DC 20052 (United States); Geist, Craig, E-mail: cgeist@mfa.gwu.edu, E-mail: zderic@gwu.edu [Department of Ophthalmology, The George Washington University, 2150 Pennsylvania Avenue NW, Floor 2A, Washington, DC 20037 (United States); Zderic, Vesna, E-mail: cgeist@mfa.gwu.edu, E-mail: zderic@gwu.edu [Department of Biomedical Engineering, The George Washington University, 800 22nd Street NW, Room 6670, Washington, DC 20052 (United States)

2015-10-15

Purpose: Delivery of sufficient amounts of therapeutic drugs into the eye for treatment of various ocular diseases is often a challenging task. Ultrasound was shown to be effective in enhancing ocular drug delivery in the authors’ previous in vitro and in vivo studies. Methods: The study reported here was designed to investigate the safety of ultrasound application and its potential thermal effects in the eye using PZFlex modeling software. The safety limit in this study was set as a temperature increase of no more than 1.5 °C based on regulatory recommendations and previous experimental safety studies. Acoustic and thermal specifications of different human eye tissues were obtained from the published literature. The tissues of particular interest in this modeling safety study were cornea, lens, and the location of optic nerve in the posterior eye. Ultrasound application was modeled at frequencies of 400 kHz–1 MHz, intensities of 0.3–1 W/cm{sup 2}, and exposure duration of 5 min, which were the parameters used in the authors’ previous drug delivery experiments. The baseline eye temperature was 37 °C. Results: The authors’ results showed that the maximal tissue temperatures after 5 min of ultrasound application were 38, 39, 39.5, and 40 °C in the cornea, 39.5, 40, 42, and 43 °C in the center of the lens, and 37.5, 38.5, and 39 °C in the back of the eye (at the optic nerve location) at frequencies of 400, 600, 800 kHz, and 1 MHz, respectively. Conclusions: The ocular temperatures reached at higher frequencies were considered unsafe based on current recommendations. At a frequency of 400 kHz and intensity of 0.8 W/cm{sup 2} (parameters shown in the authors’ previous in vivo studies to be optimal for ocular drug delivery), the temperature increase was small enough to be considered safe inside different ocular tissues. However, the impact of orbital bone and tissue perfusion should be included in future modeling efforts to determine the safety

Thermal safety of ultrasound-enhanced ocular drug delivery: A modeling study

International Nuclear Information System (INIS)

Nabili, Marjan; Geist, Craig; Zderic, Vesna

2015-01-01

Purpose: Delivery of sufficient amounts of therapeutic drugs into the eye for treatment of various ocular diseases is often a challenging task. Ultrasound was shown to be effective in enhancing ocular drug delivery in the authors’ previous in vitro and in vivo studies. Methods: The study reported here was designed to investigate the safety of ultrasound application and its potential thermal effects in the eye using PZFlex modeling software. The safety limit in this study was set as a temperature increase of no more than 1.5 °C based on regulatory recommendations and previous experimental safety studies. Acoustic and thermal specifications of different human eye tissues were obtained from the published literature. The tissues of particular interest in this modeling safety study were cornea, lens, and the location of optic nerve in the posterior eye. Ultrasound application was modeled at frequencies of 400 kHz–1 MHz, intensities of 0.3–1 W/cm 2 , and exposure duration of 5 min, which were the parameters used in the authors’ previous drug delivery experiments. The baseline eye temperature was 37 °C. Results: The authors’ results showed that the maximal tissue temperatures after 5 min of ultrasound application were 38, 39, 39.5, and 40 °C in the cornea, 39.5, 40, 42, and 43 °C in the center of the lens, and 37.5, 38.5, and 39 °C in the back of the eye (at the optic nerve location) at frequencies of 400, 600, 800 kHz, and 1 MHz, respectively. Conclusions: The ocular temperatures reached at higher frequencies were considered unsafe based on current recommendations. At a frequency of 400 kHz and intensity of 0.8 W/cm 2 (parameters shown in the authors’ previous in vivo studies to be optimal for ocular drug delivery), the temperature increase was small enough to be considered safe inside different ocular tissues. However, the impact of orbital bone and tissue perfusion should be included in future modeling efforts to determine the safety of this

[Evaluation of the safety of innovative drugs against viruses and infectious agents].

Science.gov (United States)

Kobayashi, Tetsu; Yusa, Keisuke; Kawasaki, Nana

2013-01-01

Recently, several novel cellular therapy products and biological drugs are being developed to treat various previously untreatable diseases. One of the most important issues regarding these innovations is how to ensure safety over infectious agents, including viruses and prions, in the earliest treatments with these products. The object of this study is a risk assessment of cases of human infectious with the agents and to present a sample risk management plan based on a collaboration among the National Institute of Health Sciences, universities, marketing authorization holders, and scientific societies. There are three subjects of study: (1) the viral safety of cellular therapy products, (2) the viral safety of biological drugs, and (3) the safety of prions. In this report, we describe the objects of the study, the project members, the study plan outline, and the ongoing plans. The results of the viral risk identification and the risk analysis of cellular therapy products will also be described, based on a review of the literature and case reports obtained during the first year of this project.

Assessment of pharmacovigilance approaches for monitoring the safety of antimalarial drugs in pregnancy

NARCIS (Netherlands)

Dellicour, S.O.M.C.

2014-01-01

Post-marketing surveillance of drugs used in pregnancy is challenging, especially in developing countries where resources for pharmacovigilance are rare. There is a need to establish simple but effective systems to monitor safety of drugs given during pregnancy in resource constrained countries.

Levofloxacin-Induced QTc Prolongation Depends on the Time of Drug Administration

NARCIS (Netherlands)

Kervezee, L; Gotta, V; Stevens, J; Birkhoff, W; Kamerling, Imc; Danhof, M; Meijer, J H; Burggraaf, J

2016-01-01

Understanding the factors influencing a drug's potential to prolong the QTc interval on an electrocardiogram is essential for the correct evaluation of its safety profile. To explore the effect of dosing time on drug-induced QTc prolongation, a randomized, crossover, clinical trial was conducted in

78 FR 77196 - Random Drug and Alcohol Testing Percentage Rates of Covered Aviation Employees for the Period of...

Science.gov (United States)

2013-12-20

... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Random Drug and Alcohol Testing... the minimum random drug and alcohol testing percentage rates for the period January 1, 2014, through... Federal Regulations Title 14, section 120.109(b) (for drug testing), and 120.217(c) (for alcohol testing...

The Patient's Voice in Pharmacovigilance: Pragmatic Approaches to Building a Patient-Centric Drug Safety Organization.

Science.gov (United States)

Smith, Meredith Y; Benattia, Isma

2016-09-01

Patient-centeredness has become an acknowledged hallmark of not only high-quality health care but also high-quality drug development. Biopharmaceutical companies are actively seeking to be more patient-centric in drug research and development by involving patients in identifying target disease conditions, participating in the design of, and recruitment for, clinical trials, and disseminating study results. Drug safety departments within the biopharmaceutical industry are at a similar inflection point. Rising rates of per capita prescription drug use underscore the importance of having robust pharmacovigilance systems in place to detect and assess adverse drug reactions (ADRs). At the same time, the practice of pharmacovigilance is being transformed by a host of recent regulatory guidances and related initiatives which emphasize the importance of the patient's perspective in drug safety. Collectively, these initiatives impact the full range of activities that fall within the remit of pharmacovigilance, including ADR reporting, signal detection and evaluation, risk management, medication error assessment, benefit-risk assessment and risk communication. Examples include the fact that manufacturing authorization holders are now expected to monitor all digital sources under their control for potential reports of ADRs, and the emergence of new methods for collecting, analysing and reporting patient-generated ADR reports for signal detection and evaluation purposes. A drug safety department's ability to transition successfully into a more patient-centric organization will depend on three defining attributes: (1) a patient-centered culture; (2) deployment of a framework to guide patient engagement activities; and (3) demonstrated proficiency in patient-centered competencies, including patient engagement, risk communication and patient preference assessment. Whether, and to what extent, drug safety departments embrace the new patient-centric imperative, and the methods and

Chemical dependency and drug testing in the workplace.

OpenAIRE

Osterloh, J D; Becker, C E

1990-01-01

Urine testing for drug use in the workplace is now widespread, with the prevalence of positive drug tests in the work force being 0% to 15%. The prevalence of marijuana use is highest, and this can be reliably tested. Though it is prudent to rid the workplace of drug use, there is little scientific study on the relationship of drug use and workplace outcomes, such as productivity and safety. Probable-cause testing and preemployment testing are the most common applications. Random testing has ...

75 FR 76069 - Random Drug and Alcohol Testing Percentage Rates of Covered Aviation Employees for the Period of...

Science.gov (United States)

2010-12-07

... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Random Drug and Alcohol Testing... minimum random drug and alcohol testing percentage rates for the period January 1, 2011, through December... Regulations Title 14, section 120.109(b) (for drug testing), and 120.217(c) (for alcohol testing). Issued in...

77 FR 71669 - Random Drug and Alcohol Testing Percentage Rates of Covered Aviation Employees for the Period of...

Science.gov (United States)

2012-12-03

... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Random Drug and Alcohol Testing... the minimum random drug and alcohol testing percentage rates for the period January 1, 2013, through... Regulations Title 14, Sec. Sec. 120.109(b) (for drug testing), and 120.217(c) (for alcohol testing). Issued in...

76 FR 74843 - Random Drug and Alcohol Testing Percentage Rates of Covered Aviation Employees for the Period of...

Science.gov (United States)

2011-12-01

... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Random Drug and Alcohol Testing... the minimum random drug and alcohol testing percentage rates for the period January 1, 2012, through... Regulations Title 14, Sec. 120.109(b) (for drug testing), and 120.217(c) (for alcohol testing). Issued in...

Prescription for antibiotics at drug shops and strategies to improve quality of care and patient safety

DEFF Research Database (Denmark)

Mbonye, Anthony K; Buregyeya, Esther; Rutebemberwa, Elizeus

2016-01-01

OBJECTIVES: The main objective of this study was to assess practices of antibiotic prescription at registered drug shops with a focus on upper respiratory tract infections among children in order to provide data for policy discussions aimed at improving quality of care and patient safety......-line drug for treatment of pneumonia in children according to the guidelines. CONCLUSIONS: There is urgent need to regulate drug shop practices of prescribing and selling antibiotics, for the safety of patients seeking care at these outlets....

76 FR 64354 - Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small...

Science.gov (United States)

2011-10-18

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0529] Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small Business... amounts on small business, as set forth in the FDA Food Safety Modernization Act (FSMA). In particular...

76 FR 45818 - Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small...

Science.gov (United States)

2011-08-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0529] Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small Business... burden of fee amounts on small business, as set forth in the FDA Food Safety Modernization Act (FSMA...

Randomized, Controlled, Multi-center Trial: Comparing the Safety and Efficacy of DA-9701 and Itopride Hydrochloride in Patients With Functional Dyspepsia.

Science.gov (United States)

Choi, Myung-Gyu; Rhee, Poong-Lyul; Park, Hyojin; Lee, Oh Young; Lee, Kwang Jae; Choi, Suck Chei; Seol, Sang Young; Chun, Hoon Jai; Rew, Jong-Sun; Lee, Dong Ho; Song, Geun Am; Jung, Hwoon Yong; Jeong, Hyung Yong; Sung, In Kyung; Lee, Joon Seong; Lee, Soo Teik; Kim, Sung Kook; Shin, Yong Woon

2015-07-30

Therapies of functional dyspepsia (FD) are limited. DA-9701 is a novel prokinetic agent formulated with Pharbitis semen and Corydalis Tuber. We aimed to assess the efficacy of DA-9701 compared with itopride in FD patients. Patients with FD randomly received either itopride 50 mg or DA-9701 30 mg t.i.d after a 2-week baseline period. After 4 weeks of treatment, 2 primary efficacy endpoints were analyzed: the change from baseline in composite score of the 8 dyspep-tic symptoms and the overall treatment effect. Impact on patients' quality of life was assessed using the Nepean Dyspepsia Index (NDI) questionnaire. We randomly assigned 464 patients with 455 having outcome data. The difference of the composite score change of the 8 symptoms between the 2 groups was 0.62, indicating that DA-9701 was not inferior to itopride. The overall treatment effect response rate was not different between the groups. When responder was defined as ≥ 5 of the 7 Likert scale, responder rates were 37% of DA-9701 and 36% of itopride group. Patients receiving DA-9701 experienced similar mean percentage of days with adequate relief during the 4-week treatment period compared with those receiving itopride (56.8% vs 59.1%). Both drugs increased the NDI score of 5 domains without any difference in change of the NDI score between the groups. The safety profile of both drugs was comparable. DA-9701 significantly improves symptoms in patients with FD. DA-9701 showed non-inferior efficacy to itopride with com-parable safety.

Safety and efficacy of generic drugs with respect to brand formulation

OpenAIRE

Gallelli, Luca; Palleria, Caterina; De Vuono, Antonio; Mumoli, Laura; Vasapollo, Piero; Piro, Brunella; Russo, Emilio

2013-01-01

Generic drugs are equivalent to the brand formulation if they have the same active substance, the same pharmaceutical form and the same therapeutic indications and a similar bioequivalence respect to the reference medicinal product. The use of generic drugs is indicated from many countries in order to reduce medication price. However some points, such as bioequivalence and the role of excipients, may be clarified regarding the clinical efficacy and safety during the switch from brand to gener...

Safety and efficacy of generic drugs with respect to brand formulation.

Science.gov (United States)

Gallelli, Luca; Palleria, Caterina; De Vuono, Antonio; Mumoli, Laura; Vasapollo, Piero; Piro, Brunella; Russo, Emilio

2013-12-01

Generic drugs are equivalent to the brand formulation if they have the same active substance, the same pharmaceutical form and the same therapeutic indications and a similar bioequivalence respect to the reference medicinal product. The use of generic drugs is indicated from many countries in order to reduce medication price. However some points, such as bioequivalence and the role of excipients, may be clarified regarding the clinical efficacy and safety during the switch from brand to generic formulations. In conclusion, the use of generic drugs could be related with an increased days of disease (time to relapse) or might lead to a therapeutic failure; on the other hand, a higher drug concentration might expose patients to an increased risk of dose-dependent side-effects.

Type I error probability spending for post-market drug and vaccine safety surveillance with binomial data.

Science.gov (United States)

Silva, Ivair R

2018-01-15

Type I error probability spending functions are commonly used for designing sequential analysis of binomial data in clinical trials, but it is also quickly emerging for near-continuous sequential analysis of post-market drug and vaccine safety surveillance. It is well known that, for clinical trials, when the null hypothesis is not rejected, it is still important to minimize the sample size. Unlike in post-market drug and vaccine safety surveillance, that is not important. In post-market safety surveillance, specially when the surveillance involves identification of potential signals, the meaningful statistical performance measure to be minimized is the expected sample size when the null hypothesis is rejected. The present paper shows that, instead of the convex Type I error spending shape conventionally used in clinical trials, a concave shape is more indicated for post-market drug and vaccine safety surveillance. This is shown for both, continuous and group sequential analysis. Copyright © 2017 John Wiley & Sons, Ltd.

Efficacy and safety of immunomodulatory drugs in patients with anterior uveitis

Science.gov (United States)

Gómez-Gómez, Alejandro; Loza, Estíbaliz; Rosario, Maria Piedad; Espinosa, Gerard; de Morales, José M. García Ruiz; Herreras, Jose M.; Muñoz-Fernández, Santiago; Cordero-Coma, Miguel

2017-01-01

Abstract Background: To assess the efficacy and safety of immunomodulatory drugs in patients with noninfectious anterior uveitis (AU). Methods: Systematic review of studies were retrieved from Medline (1961 to March 2016), Embase (1961 to March 2016), and Cochrane Library (up to March 2016), and a complementary hand search was also performed. The selection criteria were as follows: (population) noninfectious AU patients, adults; (intervention) immunomodulatory drugs (any dose, regimen, route of administration, duration of treatment); (outcome) control of inflammation, steroid-sparing effect, AU flares, adverse events, and so on; (study design) systematic literature reviews, randomized controlled trials, and observational studies. The study quality was assessed using the Jadad scale and according to The Oxford Centre for Evidence-based Medicine (update 2009). Results: We included 13 studies of moderate-poor quality, with a mean duration from 5 months to 20 years, and number of AU patients ranging from 9 to 274. Patient's demographic and clinical characteristics were very heterogeneous. In most cases, uveitis anatomic classification criteria and outcomes definitions were unclear. Some of the studies only included AU patients with a systemic disease associated, mostly spondyloarthritis, others, mixed populations (idiopathic and systemic disease associated patients), and in some articles this data is not described. We found that methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might prevent AU flares, improve ocular inflammation and visual acuity, and decrease systemic steroids doses. Conclusions: Although there is a lack of robust evidence, methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might be effective in AU patients. PMID:29049193

A Copula Based Approach for Design of Multivariate Random Forests for Drug Sensitivity Prediction.

Science.gov (United States)

Haider, Saad; Rahman, Raziur; Ghosh, Souparno; Pal, Ranadip

2015-01-01

Modeling sensitivity to drugs based on genetic characterizations is a significant challenge in the area of systems medicine. Ensemble based approaches such as Random Forests have been shown to perform well in both individual sensitivity prediction studies and team science based prediction challenges. However, Random Forests generate a deterministic predictive model for each drug based on the genetic characterization of the cell lines and ignores the relationship between different drug sensitivities during model generation. This application motivates the need for generation of multivariate ensemble learning techniques that can increase prediction accuracy and improve variable importance ranking by incorporating the relationships between different output responses. In this article, we propose a novel cost criterion that captures the dissimilarity in the output response structure between the training data and node samples as the difference in the two empirical copulas. We illustrate that copulas are suitable for capturing the multivariate structure of output responses independent of the marginal distributions and the copula based multivariate random forest framework can provide higher accuracy prediction and improved variable selection. The proposed framework has been validated on genomics of drug sensitivity for cancer and cancer cell line encyclopedia database.

Documentation of pediatric drug safety in manufacturers' product monographs: a cross-sectional evaluation of the canadian compendium of pharmaceuticals and specialities.

Science.gov (United States)

Uppal, Navjeet K; Dupuis, Lee L; Parshuram, Christopher S

2008-01-01

To describe the provision of pediatric drug safety information in a national formulary of manufacturers' drug product monographs. We performed a cross-sectional evaluation of comprehensive product monographs contained in the 2005 Canadian Compendium of Pharmaceuticals and Specialities (CPS). We abstracted data describing indications for prescription, statements about pediatric safety, available preparations, and provision of dosing guidelines. For each monograph we classified pediatric safety data as either present, present but limited or absent. We then described the pediatric safety data in CPS monographs for drugs listed in the published formulary of the Hospital for Sick Children, Toronto, Ontario, Canada. A total of 2232 product monographs were screened; 684 were excluded and 1548 (66%) were further analyzed. 1462 (94%) had indications that did not exclude children. Pediatric safety information was present in 592 (38%), present but limited in 148 (10%), and absent in 808 (52%) drug monographs. Safety statements were absent in 224 (14%) drug monographs that provided both dosing guidelines and formulations suitable for administration to children, and in 214 (52%) of 411 drugs in the pediatric hospital formulary. We evaluated a widely available national source of pediatric prescribing information. Safety data for children was not mentioned in more than half of the product monographs. Moreover, the provision of safety data was discordant with indications for prescription, the availability of pediatric formulations, and dosing guidelines within the monographs, and with inclusion in a pediatric hospital formulary. Our study suggests that the presentation of pediatric safety data in drug product monographs can be improved to better inform prescribing and to optimize pharmacotherapy in children.

Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: myocardial and infectious adverse reactions as application cases.

Science.gov (United States)

Wang, Kejian; Weng, Zuquan; Sun, Liya; Sun, Jiazhi; Zhou, Shu-Feng; He, Lin

2015-02-13

Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure-activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. In the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. Copyright © 2015 Elsevier Inc. All rights reserved.

Efficacy and safety of oral tinidazole and metronidazole in treatment of bacterial vaginosis: a randomized control trial

Directory of Open Access Journals (Sweden)

Zahra Abbaspoor

2014-05-01

Full Text Available Aims: Oral metronidazole 500 mg twice a day for one week is currently the treatment of choice for bacterial vaginosis (BV. Complete treatment by this regimen takes time and occurs less often. This drug has significant side effects too. Using a drug in the shortest treatment course may increases the success of treatment. To evaluate the effectiveness and safety of oral tinidazole compare to metronidazole in treatment of BV.Methods: In this randomized, controlled, double-blind, comparative, clinical trial, 110 non-pregnant women aged between 15-45 years with confirmed diagnosis of BV by Amsels criteria were randomly assigned to receive either 2 g tinidazole tablet once daily for 2 days (n=55 or 500 mg metronidazole table twice daily for 7 days (n=55.The cure and recurrence rate were evaluated in both groups after 2 and 4 weeks follow up visits. For statistical analysis t-test,   test, fisher's exact test and Mann-Whitney test were used.Results: The results showed that cure rate after 2 weeks in tinidazole tablet group was 84.6٪ and in metronidazole group was 85.4٪ (p=0.9, and after 4 weeks recurrence rate in tinidazole and metronidazole groups was 6.9٪and 12.1٪respectively (P=0.3.Conclusions: Tinidazole table 2 g once daily for 2 days is as effective as metronidazole tablet 500 mg twice a day for 7 days in treatment of BV.

The Influence of Safety, Efficacy, and Medical Condition Severity on Natural versus Synthetic Drug Preference.

Science.gov (United States)

Meier, Brian P; Lappas, Courtney M

2016-11-01

Research indicates that there is a preference for natural v. synthetic products, but the influence of this preference on drug choice in the medical domain is largely unknown. We present 5 studies in which participants were asked to consider a hypothetical situation in which they had a medical issue requiring pharmacological therapy. Participants ( N = 1223) were asked to select a natural, plant-derived, or synthetic drug. In studies 1a and 1b, approximately 79% of participants selected the natural v. synthetic drug, even though the safety and efficacy of the drugs were identical. Furthermore, participants rated the natural drug as safer than the synthetic drug, and as that difference increased, the odds of choosing the natural over synthetic drug increased. In studies 2 and 3, approximately 20% of participants selected the natural drug even when they were informed that it was less safe (study 2) or less effective (study 3) than the synthetic drug. Finally, in study 4, approximately 65% of participants chose a natural over synthetic drug regardless of the severity of a specific medical condition (mild v. severe hypertension), and this choice was predicted by perceived safety and efficacy differences. Overall, these data indicate that there is a bias for natural over synthetic drugs. This bias could have implications for drug choice and usage. © The Author(s) 2015.

The impact of assay technology as applied to safety assessment in reducing compound attrition in drug discovery.

Science.gov (United States)

Thomas, Craig E; Will, Yvonne

2012-02-01

Attrition in the drug industry due to safety findings remains high and requires a shift in the current safety testing paradigm. Many companies are now positioning safety assessment at each stage of the drug development process, including discovery, where an early perspective on potential safety issues is sought, often at chemical scaffold level, using a variety of emerging technologies. Given the lengthy development time frames of drugs in the pharmaceutical industry, the authors believe that the impact of new technologies on attrition is best measured as a function of the quality and timeliness of candidate compounds entering development. The authors provide an overview of in silico and in vitro models, as well as more complex approaches such as 'omics,' and where they are best positioned within the drug discovery process. It is important to take away that not all technologies should be applied to all projects. Technologies vary widely in their validation state, throughput and cost. A thoughtful combination of validated and emerging technologies is crucial in identifying the most promising candidates to move to proof-of-concept testing in humans. In spite of the challenges inherent in applying new technologies to drug discovery, the successes and recognition that we cannot continue to rely on safety assessment practices used for decades have led to rather dramatic strategy shifts and fostered partnerships across government agencies and industry. We are optimistic that these efforts will ultimately benefit patients by delivering effective and safe medications in a timely fashion.

An extended car-following model considering random safety distance with different probabilities

Science.gov (United States)

Wang, Jufeng; Sun, Fengxin; Cheng, Rongjun; Ge, Hongxia; Wei, Qi

2018-02-01

Because of the difference in vehicle type or driving skill, the driving strategy is not exactly the same. The driving speeds of the different vehicles may be different for the same headway. Since the optimal velocity function is just determined by the safety distance besides the maximum velocity and headway, an extended car-following model accounting for random safety distance with different probabilities is proposed in this paper. The linear stable condition for this extended traffic model is obtained by using linear stability theory. Numerical simulations are carried out to explore the complex phenomenon resulting from multiple safety distance in the optimal velocity function. The cases of multiple types of safety distances selected with different probabilities are presented. Numerical results show that the traffic flow with multiple safety distances with different probabilities will be more unstable than that with single type of safety distance, and will result in more stop-and-go phenomena.

Safety and improvement of movement function after stroke with atomoxetine: A pilot randomized trial

Science.gov (United States)

Ward, Andrea; Carrico, Cheryl; Powell, Elizabeth; Westgate, Philip M.; Nichols, Laurie; Fleischer, Anne; Sawaki, Lumy

2016-01-01

Background: Intensive, task-oriented motor training has been associated with neuroplastic reorganization and improved upper extremity movement function after stroke. However, to optimize such training for people with moderate-to-severe movement impairment, pharmacological modulation of neuroplasticity may be needed as an adjuvant intervention. Objective: Evaluate safety, as well as improvement in movement function, associated with motor training paired with a drug to upregulate neuroplasticity after stroke. Methods: In this double-blind, randomized, placebo-controlled study, 12 subjects with chronic stroke received either atomoxetine or placebo paired with motor training. Safety was assessed using vital signs. Upper extremity movement function was assessed using Fugl-Meyer Assessment, Wolf Motor Function Test, and Action Research Arm Test at baseline, post-intervention, and 1-month follow-up. Results: No significant between-groups differences were found in mean heart rate (95% CI, –12.4–22.6; p = 0.23), mean systolic blood pressure (95% CI, –1.7–29.6; p = 0.21), or mean diastolic blood pressure (95% CI, –10.4–13.3; p = 0.08). A statistically significant between-groups difference on Fugl-Meyer at post-intervention favored the atomoxetine group (95% CI, 1.6–12.7; p = 0.016). Conclusion: Atomoxetine combined with motor training appears safe and may optimize motor training outcomes after stroke. PMID:27858723

The neuropharmacology of ADHD drugs in vivo: insights on efficacy and safety.

Science.gov (United States)

Heal, D J; Cheetham, S C; Smith, S L

2009-12-01

Results from in vivo techniques, especially intracerebral microdialysis in freely-moving rats, have provided insights into potential mechanisms responsible for the efficacy and safety of catecholaminergic drugs for ADHD treatment. The drugs reviewed come from distinct pharmacological classes: psychostimulant releasing agents, eg d-amphetamine; psychostimulant reuptake inhibitors, eg dl-threo-methylphenidate (dl-MPH), and non-stimulant reuptake inhibitors, eg atomoxetine. Psychostimulants, which currently deliver the best efficacy in treating ADHD, exhibit the following characteristics on extraneuronal catecholamine concentrations in rodent brain in vivo: 1) They enhance the efflux and function of both noradrenaline and dopamine in the central nervous system. 2) The increase of dopamine efflux that they produce is not limited to cortical regions. 3) They have a rapid onset of action with no ceiling on drug effect. d-Amphetamine has a mechanism independent of neuronal firing rate, displacing intraneuronal stores of catecholamines, delaying their reuptake and inhibiting catabolism by monoamine oxidase. dl-MPH has an enigmatic, extraneuronal action that is neuronal firing rate-dependent and reuptake transporter-mediated, yet paradoxically, almost as powerful as that of d-amphetamine. In safety terms, these powerful catecholaminergic effects also make the psychostimulants liable for abuse. Since efficacy and safety derive from the same pharmacological mechanisms, it has not yet been possible to separate these two components. However, the development of once-daily psychostimulant formulations and a prodrug, lisdexamfetamine, has improved patient compliance and markedly reduced scope for their diversion/abuse. This review will discuss the in vivo pharmacological profiles of approved catecholaminergic drugs for treatment of ADHD and implications for their clinical efficacy and abuse liability.

Investigating drug repositioning opportunities in FDA drug labels through topic modeling.

Science.gov (United States)

Bisgin, Halil; Liu, Zhichao; Kelly, Reagan; Fang, Hong; Xu, Xiaowei; Tong, Weida

2012-01-01

Drug repositioning offers an opportunity to revitalize the slowing drug discovery pipeline by finding new uses for currently existing drugs. Our hypothesis is that drugs sharing similar side effect profiles are likely to be effective for the same disease, and thus repositioning opportunities can be identified by finding drug pairs with similar side effects documented in U.S. Food and Drug Administration (FDA) approved drug labels. The safety information in the drug labels is usually obtained in the clinical trial and augmented with the observations in the post-market use of the drug. Therefore, our drug repositioning approach can take the advantage of more comprehensive safety information comparing with conventional de novo approach. A probabilistic topic model was constructed based on the terms in the Medical Dictionary for Regulatory Activities (MedDRA) that appeared in the Boxed Warning, Warnings and Precautions, and Adverse Reactions sections of the labels of 870 drugs. Fifty-two unique topics, each containing a set of terms, were identified by using topic modeling. The resulting probabilistic topic associations were used to measure the distance (similarity) between drugs. The success of the proposed model was evaluated by comparing a drug and its nearest neighbor (i.e., a drug pair) for common indications found in the Indications and Usage Section of the drug labels. Given a drug with more than three indications, the model yielded a 75% recall, meaning 75% of drug pairs shared one or more common indications. This is significantly higher than the 22% recall rate achieved by random selection. Additionally, the recall rate grows rapidly as the number of drug indications increases and reaches 84% for drugs with 11 indications. The analysis also demonstrated that 65 drugs with a Boxed Warning, which indicates significant risk of serious and possibly life-threatening adverse effects, might be replaced with safer alternatives that do not have a Boxed Warning. In

76 FR 23324 - Endocrinologic and Metabolic Drugs Advisory Committee; Notice of Meeting

Science.gov (United States)

2011-04-26

... for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 31, rm... Cardiovascular Risk in Diabetes-Lipid (ACCORD Lipid) trial as they relate to the efficacy and safety of the... cholesterol goal. The ACCORD Lipid study was a randomized, double-blind, placebo- controlled add-on trial...

Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: Myocardial and infectious adverse reactions as application cases

International Nuclear Information System (INIS)

Wang, Kejian; Weng, Zuquan; Sun, Liya; Sun, Jiazhi; Zhou, Shu-Feng; He, Lin

2015-01-01

Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure–activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. In the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. - Highlights: • Drugs causing common toxicity lead to similar in vitro gene expression changes. • We built a model to predict drug toxicity with drug-specific expression profiles. • Drugs with FDA black box warnings were effectively identified by our model. • In vitro assay can detect severe toxicity in the early stage of drug development

Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: Myocardial and infectious adverse reactions as application cases

Energy Technology Data Exchange (ETDEWEB)

Wang, Kejian, E-mail: kejian.wang.bio@gmail.com [Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai (China); Weng, Zuquan [Japan National Institute of Occupational Safety and Health, Kawasaki (Japan); Sun, Liya [Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai (China); Sun, Jiazhi; Zhou, Shu-Feng [Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL (United States); He, Lin, E-mail: helin@Bio-X.com [Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai (China)

2015-02-13

Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure–activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. In the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. - Highlights: • Drugs causing common toxicity lead to similar in vitro gene expression changes. • We built a model to predict drug toxicity with drug-specific expression profiles. • Drugs with FDA black box warnings were effectively identified by our model. • In vitro assay can detect severe toxicity in the early stage of drug development.

78 FR 78275 - Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2014

Science.gov (United States)

2013-12-26

...-11213, Notice No. 17] Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2014... December 26, 2013. FOR FURTHER INFORMATION CONTACT: Jerry Powers, FRA Drug and Alcohol Program Manager, W38...-493-6313); or Sam Noe, FRA Drug and Alcohol Program Specialist, (telephone 615-719- 2951). Issued in...

The algorithmic performance of J-Tpeak for drug safety clinical trial.

Science.gov (United States)

Chien, Simon C; Gregg, Richard E

The interval from J-point to T-wave peak (JTp) in ECG is a new biomarker able to identify drugs that prolong the QT interval but have different ion channel effects. If JTp is not prolonged, the prolonged QT may be associated with multi ion channel block that may have low torsade de pointes risk. From the automatic ECG measurement perspective, accurate and repeatable measurement of JTp involves different challenges than QT. We evaluated algorithm performance and JTp challenges using the Philips DXL diagnostic 12/16/18-lead algorithm. Measurement of JTp represents a different use model. Standard use of corrected QT interval is clinical risk assessment on patients with cardiac disease or suspicion of heart disease. Drug safety trials involve a very different population - young healthy subjects - who commonly have J-waves, notches and slurs. Drug effects include difficult and unusual morphology such as flat T-waves, gentle notches, and multiple T-wave peaks. The JTp initiative study provided ECGs collected from 22 young subjects (11 males and females) in randomized testing of dofetilide, quinidine, ranolazine, verapamil and placebo. We compare the JTp intervals between DXL algorithm and the FDA published measurements. The lead wise, vector-magnitude (VM), root-mean-square (RMS) and principal-component-analysis (PCA) representative beats were used to measure JTp and QT intervals. We also implemented four different methods for T peak detection for comparison. We found that JTp measurements were closer to the reference for combined leads RMS and PCA than individual leads. Differences in J-point location led to part of the JTp measurement difference because of the high prevalence of J-waves, notches and slurs. Larger differences were noted for drug effect causing multiple distinct T-wave peaks (Tp). The automated algorithm chooses the later peak while the reference was the earlier peak. Choosing among different algorithmic strategies in T peak measurement results in the

Safety Profile of the Newest Antiepileptic Drugs: A Curated Literature Review.

Science.gov (United States)

Palleria, Caterina; Cozza, Giuseppe; Khengar, Rajeshree; Libri, Vincenzo; De Sarro, Giovambattista

2017-01-01

Despite the introduction of new antiepileptic drugs (AEDs), the quality of life and therapeutic response for patients with epilepsy remain unsatisfactory. In addition, whilst several antiepileptic drugs (AEDs) have been approved and consequently marketed in recent years, little is known about their long-term safety and tolerability. Availability of the newest AEDs, characterized by improved pharmacokinetic profiles, has positively impacted the treatment approach for patients with partial seizures in clinical practice. However, the main cause of treatment failure is still poor patient compliance due to the occurrence of adverse drug reactions (ADRs) that lead to treatment withdrawal in about 25% of cases before achieving maximal efficacy, and is associated with increasing health care costs. In this Review, we conducted an online database search using Medline, PubMed, Embase, and the Cochrane Online Library to review the available studies highlighting the clinical relevance of side effects, pharmacological interactions, safety and tolerability of the newest AEDs: Brivaracetam (BRV), Cannabidiol (CBD), Eslicarbazepine acetate (ESL), Lacosamide (LCM), and Perampanel (PER). The principal benefit of the newest AEDs, in addition to reduced frequency and seizure severity, is the low number and severity of ADRs reported compared to more historic drugs. Early detection of ADRs could lead to an improvement in patients' quality of life, therefore it is important to monitor ADRs and to adequately perform post marketing surveillance in the clinical practice setting. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Does the Early Adopter of Drugs Exist? A Population Based Study of General Practitioners’ Prescribing of New Drugs.20 th International Conference on Pharmacoepiemiology and Risk Management. Bordeaux, France. Pharmacoepidemiology and Drug Safety, 2004;13:Sl 1:158

DEFF Research Database (Denmark)

Dybdahl, Torben; Andersen, Morten; Søndergaard, Jens

2004-01-01

20 th International Conference on Pharmacoepiemiology and Risk Management. Bordeaux, France. Pharmacoepidemiology and Drug Safety, 2004;13:Sl 1:158......20 th International Conference on Pharmacoepiemiology and Risk Management. Bordeaux, France. Pharmacoepidemiology and Drug Safety, 2004;13:Sl 1:158...

How do pharmaceutical companies handle consumer adverse drug reaction reports? An overview based on a survey of French drug safety managers and officers.

Science.gov (United States)

Fleuranceau-Morel, P

2002-01-01

It is surprising to see how consumer Adverse Drug Reaction (ADR) reports have been continuously increasing for the last few years in Europe. This probably results from the influence of United States (US) market where the patients feels justified in telephoning the pharmaceutical companies directly with queries regarding their treatment. The growing number of alternative sources of information (e.g. health and popular magazines, spots on radio and TV etc.) to which a consumer is exposed has added to this growth too. The changing relationship between patients and doctors may also contribute to this phenomenon. It is then interesting to evaluate the way pharmaceutical companies currently deal with consumer ADR reports. The management of consumer ADR reporting was investigated by means of a questionnaire sent to 46 French drug safety managers and drug safety officers (DSOs) of multinational pharmaceutical companies. The analysis of the survey stressed the fact that pharmaceutical companies should be prepared to face up to an increase in the number of consumer ADR reports. It clearly appears that the consumers who telephone to register side-effects should be forwarded to a trained DSO with medical or pharmaceutical background and the communication skills acquired through specific training. This person should also be able to release adequate product information validated by his/her own company. The influence of the US market seems to be changing the way pharmaceutical companies deal with consumer ADR reports. Nowadays, these reports are entered into a drug safety database by most of the companies without previously having contacted the patient's general practitioner (GP) or specialist for medical confirmation. Lastly, the drug safety managers and DSOs consulted have divided opinions about the usefulness of call centres and e-mails as tools for ADR reporting. But both tools are globally rejected by the pharmaceutical companies as a reliable means of reporting. As stated

Drug Safety Monitoring in Children: Performance of Signal Detection Algorithms and Impact of Age Stratification

NARCIS (Netherlands)

O.U. Osokogu (Osemeke); C. Dodd (Caitlin); A.C. Pacurariu (Alexandra C.); F. Kaguelidou (Florentia); D.M. Weibel (Daniel); M.C.J.M. Sturkenboom (Miriam)

2016-01-01

textabstractIntroduction: Spontaneous reports of suspected adverse drug reactions (ADRs) can be analyzed to yield additional drug safety evidence for the pediatric population. Signal detection algorithms (SDAs) are required for these analyses; however, the performance of SDAs in the pediatric

Efficacy, safety and tolerability of sildenafil in Brazilian hypertensive patients on multiple antihypertensive drugs

Directory of Open Access Journals (Sweden)

Denilson C. Albuquerque

2005-08-01

Full Text Available OBJECTIVE: To evaluate the efficacy, safety and tolerability of sildenafil among Brazilian patients with hypertension treated with combinations of anti-hypertensive drugs. MATERIALS AND METHODS: One hundred twenty hypertensive men aged 30 to 81 years old under treatment with 2 or more anti-hypertensive drugs and with erectile dysfunction (ED lasting for at least 6 months were enrolled at 7 research centers in Brazil. Patients were randomized to receive treatment with either sildenafil or placebo taken 1 hour before sexual intercourse (initial dose of 50 mg, adjusted to 25 mg or 100 mg according to efficacy and toxicity. During the following 8 weeks, patients were evaluated regarding vital signs, adverse events, therapeutic efficacy, satisfaction with treatment and use of concurrent medications. RESULTS: The primary evaluation of efficacy, which was based on responses to questions 3 and 4 of the International Index of Erectile Function, showed significant differences regarding treatment with sildenafil (p = 0.0002 and p < 0.0001, respectively. In the assessment of global efficacy, 87% of the patients treated with sildenafil reported improved erections, as compared with 37% of patients given placebos (p < 0.0001. The other secondary evaluations supported the results favoring sildenafil. The most frequent adverse events among patients treated with sildenafil were headaches (11.4%, vasodilation (11.4% and dyspepsia (6.5%. There were no significant changes in blood pressure measurements in both groups. CONCLUSION: Sildenafil is efficacious and safe for the treatment of hypertensive patients with ED who receive concurrent combinations of anti-hypertensive drugs.

From Drug Safety to Drug Security: A Contemporary Shift in the Policing of Health.

Science.gov (United States)

Hornberger, Julia

2018-01-29

The counterfeiting of medication is increasingly seen as a major threat to health, especially in the light of both the everyday reliance on and a broadening of world-wide access to pharmaceuticals. Exaggerated or real, this threat has inaugurated, this article argues, a shift from a drug safety regime to a drug security regime that governs the flow of pharmaceuticals and brings together markets, police, and health actors in new ways. This entails a shift from soft disciplinary means aimed at incremental and continued inclusion of defaulters, to one of drastically sovereign measures of exclusion and banishment aimed at fake goods and the people associated with them, in the name of health. Through a multi-sited ethnographic study, this article shows how such new drug security efforts play themselves out especially in (South) Africa, highlighting a modus operandi of spectacular performativity and of working through suspicion and association rather than factuality, producing value less so for those in need of health than for a petty security industry itself. © 2018 by the American Anthropological Association.

Open-label extension studies: do they provide meaningful information on the safety of new drugs?

Science.gov (United States)

Day, Richard O; Williams, Kenneth M

2007-01-01

The number of open-label extension studies being performed has increased enormously in recent years. Often it is difficult to differentiate between these extension studies and the double-blind, controlled studies that preceded them. If undertaken primarily to gather more patient-years of exposure to the new drug in order to understand and gain confidence in its safety profile, open-label extension studies can play a useful and legitimate role in drug development and therapeutics. However, this can only occur if the open-label extension study is designed, executed, analysed and reported competently. Most of the value accrued in open-label extension studies is gained from a refinement in the perception of the expected incidence of adverse effects that have most likely already been identified as part of the preclinical and clinical trial programme. We still have to rely heavily on post-marketing safety surveillance systems to alert us to type B (unpredictable) adverse reactions because open-label extension studies are unlikely to provide useful information about these types of often serious and relatively rare adverse reactions. Random allocation into test and control groups is needed to produce precise incidence data on pharmacologically expected, or type A, adverse effects. Some increased confidence about incidence rates might result from the open-label extension study; however, as these studies are essentially uncontrolled and biased, the data are not of great value. Other benefits have been proposed to be gained from open-label extension studies. These include ongoing access to an effective but otherwise unobtainable medicine by the volunteers who participated in the phase III pivotal trials. However, there are unappreciated ethical issues about the appropriateness of enrolling patients whose response to previous treatment is uncertain, largely because treatment allocation in the preceding randomised, double-blind, controlled trial has not been revealed at the

A phase 1–2, prospective, double blind, randomized study of the safety and efficacy of Sulfasalazine for the treatment of progressing malignant gliomas: study protocol of [ISRCTN45828668

International Nuclear Information System (INIS)

Robe, Pierre A; Martin, Didier; Albert, Adelin; Deprez, Manuel; Chariot, Alain; Bours, Vincent

2006-01-01

The prognosis of patients suffering from WHO grade 3 and 4 astrocytic glioma remains poor despite surgery, radiation therapy and the use of current chemotherapy regimen. Indeed, the median survival of glioblastoma multiforme (WHO grade 4) patients is at best 14.6 month with only 26.5 percents of the patients still alive after 2 years and the median survival of anaplastic astrocytomas (WHO grade 3) is 19.2 month. Recent evidence suggests that the transcription factor NF-kappaB is constitutively expressed in malignant gliomas and that its inhibition by drugs like Sulfasalazine may block the growth of astrocytic tumors in vitro and in experimental models of malignant gliomas. ULg-GBM-04/1 is a prospective, randomized, double blind single-center phase 1–2 study. A total of twenty patients with progressive malignant glioma despite surgery, radiation therapy and a first line of chemotherapy will be recruited and assigned to four dosage regimen of Sulfasalazine. This medication will be taken orally t.i.d. at a daily dose of 1.5–3–4 or 6 g, continuously until complete remission, evidence of progression or drug intolerance. Primary endpoints are drug safety in the setting of malignant gliomas and tumor response as measured according to MacDonald's criteria. An interim analysis of drug safety will be conducted after the inclusion of ten patients. The complete evaluation of primary endpoints will be conducted two years after the enrolment of the last patient or after the death of the last patient should this occur prematurely. The aim of this study is to evaluate the safety and efficacy of Sulfasalazine as a treatment for recurring malignant gliomas. The safety and efficacy of this drug are analyzed as primary endpoints. Overall survival and progression-free survival are secondary endpoint

Safety of Etoricoxib, Celecoxib, and Nonselective Nonsteroidal Antiinflammatory Drugs in Ankylosing Spondylitis and Other Spondyloarthritis Patients

DEFF Research Database (Denmark)

Kristensen, L E; Jakobsen, A K; Askling, J

2015-01-01

OBJECTIVE: Safety data regarding the use of etoricoxib and other nonsteroidal antiinflammatory drugs (NSAIDs) in ankylosing spondylitis (AS) and other spondyloarthritis (SpA) patients are rather limited. Our objective was to estimate and compare rates of gastrointestinal, renovascular, and cardio......OBJECTIVE: Safety data regarding the use of etoricoxib and other nonsteroidal antiinflammatory drugs (NSAIDs) in ankylosing spondylitis (AS) and other spondyloarthritis (SpA) patients are rather limited. Our objective was to estimate and compare rates of gastrointestinal, renovascular...

Online availability and safety of drugs in shortage: a descriptive study of internet vendor characteristics.

Science.gov (United States)

Liang, Bryan A; Mackey, Tim K

2012-02-09

Unprecedented drug shortages announced by the US Food and Drug Administration (FDA) have severely affected therapeutic access, patient safety, and public health. With continued shortages, patients may seek drugs online. To assess the prevalence of online marketing for current FDA shortage drugs and potential patient safety risks. We performed a descriptive study of the prevalence of online marketing for shortage drugs-that is, offers for sale of each drug, including characteristics of online drug sellers and intermediary sites marketing these drugs. Of the 72 FDA shortage-listed drugs, 68 (94%) were offered for sale online. We found 291 offers for these drugs, the vast majority (n = 207, 71.1%) by online drug sellers selling direct to consumers. Intermediary sites included data aggregators (n = 22, 8%), forum links (n = 23, 8%), and personal page data links (n = 34, 12%), as well as Flickr social media links (n = 5, 2%), all advertising drugs without a prescription. Of the 91 online drug sellers identified, 31 (34%) had more than 1 shortage drug offered for sale, representing most (n = 148, 71%) of all online drug seller sales offers. The majority of these online drug sellers (n = 21, 68%) were on the National Association of Boards of Pharmacy (NABP) Not Recommended Sites list. Finally, for shortage drugs with an online drug seller (n = 58, 85%), 53 (91%) had at least one site on the Not Recommended list and 21 (36%) had only sites on the Not Recommended list. FDA shortage drugs are widely marketed over the Internet. Suspect online drug sellers and intermediaries dominate these sales offers. As a critical risk management issue, patients, providers, and policymakers should be extremely cautious in procuring shortage drugs through Internet sourcing.

Effect and Safety of Shihogyejitang for Drug Resistant Childhood Epilepsy

Directory of Open Access Journals (Sweden)

Jinsoo Lee

2016-01-01

Full Text Available Objective. Herbal medicine has been widely used to treat drug resistant epilepsy. Shihogyejitang (SGT has been commonly used to treat epilepsy. We investigated the effect and safety of SGT in children with drug resistant epilepsy. Design. We reviewed medical records of 54 patients with epilepsy, who failed to respond to at least two antiepileptic drugs and have been treated with SGT between April 2006 and June 2014 at the Department of Pediatric Neurology, I-Tomato Hospital, Korea. Effect was measured by the response rate, seizure-free rate, and retention rate at six months. We also checked adverse events, change in antiepileptic drugs use, and the variables related to the outcome. Results. Intent-to-treat analysis showed that, after six months, 44.4% showed a >50% seizure reduction, 24.1% including seizure-free, respectively, and 53.7% remained on SGT. Two adverse events were reported, mild skin rash and fever. Focal seizure type presented significantly more positive responses when compared with other seizure types at six months (p=0.0284, Fisher’s exact test. Conclusion. SGT is an effective treatment with excellent tolerability for drug resistant epilepsy patients. Our data provide evidence that SGT may be used as alternative treatment option when antiepileptic drug does not work in epilepsy children.

Safety of diabetes drugs in patients with heart failure.

Science.gov (United States)

Carrasco-Sánchez, F J; Ostos-Ruiz, A I; Soto-Martín, M

2018-03-01

Heart failure (HF) and diabetes mellitus are 2 clinical conditions that often coexist, particularly in patients older than 65 years. Diabetes mellitus promotes the development of HF and confers a poorer prognosis. Hypoglycaemic agents (either by their mechanism of action, hypoglycaemic action or adverse effects) can be potentially dangerous for patients with HF. In this study, we performed a review of the available evidence on the safety of diabetes drugs in HF, focused on the main observational and experimental studies. Recent studies on cardiovascular safety have evaluated, although as a secondary objective, the impact of new hypoglycaemic agents on HF, helping us understand the neutrality, risks and potential benefits of these agents. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Online Availability and Safety of Drugs in Shortage: A Descriptive Study of Internet Vendor Characteristics

Science.gov (United States)

Mackey, Tim K

2012-01-01

Background Unprecedented drug shortages announced by the US Food and Drug Administration (FDA) have severely affected therapeutic access, patient safety, and public health. With continued shortages, patients may seek drugs online. Objective To assess the prevalence of online marketing for current FDA shortage drugs and potential patient safety risks. Methods We performed a descriptive study of the prevalence of online marketing for shortage drugs—that is, offers for sale of each drug, including characteristics of online drug sellers and intermediary sites marketing these drugs. Results Of the 72 FDA shortage-listed drugs, 68 (94%) were offered for sale online. We found 291 offers for these drugs, the vast majority (n = 207, 71.1%) by online drug sellers selling direct to consumers. Intermediary sites included data aggregators (n = 22, 8%), forum links (n = 23, 8%), and personal page data links (n = 34, 12%), as well as Flickr social media links (n = 5, 2%), all advertising drugs without a prescription. Of the 91 online drug sellers identified, 31 (34%) had more than 1 shortage drug offered for sale, representing most (n = 148, 71%) of all online drug seller sales offers. The majority of these online drug sellers (n = 21, 68%) were on the National Association of Boards of Pharmacy (NABP) Not Recommended Sites list. Finally, for shortage drugs with an online drug seller (n = 58, 85%), 53 (91%) had at least one site on the Not Recommended list and 21 (36%) had only sites on the Not Recommended list. Conclusions FDA shortage drugs are widely marketed over the Internet. Suspect online drug sellers and intermediaries dominate these sales offers. As a critical risk management issue, patients, providers, and policymakers should be extremely cautious in procuring shortage drugs through Internet sourcing. PMID:22321731

Efficacy and safety of anakinra for the treatment of rheumatoid arthritis: an update of the Oregon Drug  Effectiveness Review Project

Directory of Open Access Journals (Sweden)

Kylie Thaler

2009-11-01

Full Text Available Kylie Thaler1, Divya V Chandiramani2, Richard A Hansen2, Gerald Gartlehner11Department for Evidence-based Medicine and Clinical Epidemiology, Danube University Krems, Krems, Austria; 2UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAObjective: To systematically review the general and comparative efficacy and safety of anakinra for rheumatoid arthritis.Methods: We searched MEDLINE®, Embase, The Cochrane Library, and the International Pharmaceutical Abstracts from 1980 to April 2009. We manually searched reference lists of pertinent review articles and explored the Center for Drug Evaluation and Research database. For efficacy we included randomized controlled trials (RCTs comparing anakinra with placebo or other biologics. For safety both experimental and observational studies were eligible. Two persons independently reviewed abstracts and full text articles and extracted relevant data.Results: We included data from 3 RCTs comparing anakinra with placebo for rheumatoid arthritis (RA. The pooled relative risk (RR of an ACR50 (American College of Rheumatology response for anakinra compared with placebo is 2.28 (95% CI 1.41 to 3.67. Adjusted indirect comparisons of ACR50 response rates of anakinra and anti-TNF agents showed a RR of 0.67 (95% CI 0.38 to 1.17 favoring the anti-TNF drugs. This result did not reach statistical significance. For safety, we included 9 experimental and observational studies of 24 weeks to 3 years duration. Up to 30% of patients withdrew from the studies due to adverse events. 67.2% (95% CI 38.7 to 95.7 of patients experienced an injection site reaction.Conclusions: Anakinra is an effective drug for treating RA. Indirect comparisons with adalimumab, etanercept and infliximab, however, showed a trend towards greater efficacy for the anti-TNF drugs. Anakinra also seems to be associated with comparably high rates of injection site reactions. These results should be taken into

Efficacy and safety of tolvaptan in heart failure patients with volume overload despite the standard treatment with conventional diuretics: a phase III, randomized, double-blind, placebo-controlled study (QUEST study).

Science.gov (United States)

Matsuzaki, Masunori; Hori, Masatsugu; Izumi, Tohru; Fukunami, Masatake

2011-12-01

Diuretics are recommended to treat volume overload with heart failure (HF), however, they may cause serum electrolyte imbalance, limiting their use. Moreover, patients with advanced HF could poorly respond to these diuretics. In this study, we evaluated the efficacy and safety of Tolvaptan, a competitive vasopressin V2-receptor antagonist developed as a new drug to treat volume overload in HF patients. A phase III, multicenter, randomized, double-blind, placebo-controlled parallel study was performed to assess the efficacy and safety of tolvaptan in treating HF patients with volume overload despite the use of conventional diuretics. One hundred and ten patients were randomly assigned to receive either placebo or 15 mg/day tolvaptan for 7 consecutive days. Compared with placebo, tolvaptan administered for 7 days significantly reduced body weight and improved symptoms associated with volume overload. The safety profile of tolvaptan was considered acceptable for clinical use with minimal adverse effects. Tolvaptan reduced volume overload and improved congestive symptoms associated with HF by a potent water diuresis (aquaresis).

Phase 1 Safety, Pharmacokinetics, and Pharmacodynamics of Dapivirine and Maraviroc Vaginal Rings: A Double-Blind Randomized Trial.

Science.gov (United States)

Chen, Beatrice A; Panther, Lori; Marzinke, Mark A; Hendrix, Craig W; Hoesley, Craig J; van der Straten, Ariane; Husnik, Marla J; Soto-Torres, Lydia; Nel, Annalene; Johnson, Sherri; Richardson-Harman, Nicola; Rabe, Lorna K; Dezzutti, Charlene S

2015-11-01

Variable adherence limits effectiveness of daily oral and intravaginal tenofovir-containing pre-exposure prophylaxis. Monthly vaginal antiretroviral rings are one approach to improve adherence and drug delivery. MTN-013/IPM 026, a multisite, double-blind, randomized, placebo-controlled trial in 48 HIV-negative US women, evaluated vaginal rings containing dapivirine (DPV) (25 mg) and maraviroc (MVC) (100 mg), DPV only, MVC only, and placebo used continuously for 28 days. Safety was assessed by adverse events. Drug concentrations were quantified in plasma, cervicovaginal fluid (CVF), and cervical tissue. Cervical biopsy explants were challenged with HIV ex vivo to evaluate pharmacodynamics. There was no difference in related genitourinary adverse events between treatment arms compared with placebo. DPV and MVC concentrations rose higher initially before falling more rapidly with the combination ring compared with relatively stable concentrations with the single-drug rings. DPV concentrations in CVF were 1 and 5 log10 greater than cervical tissue and plasma for both rings. MVC was consistently detected only in CVF. DPV and MVC CVF and DPV tissue concentrations dropped rapidly after ring removal. Cervical tissue showed a significant inverse linear relationship between HIV replication and DPV levels. In this first study of a combination microbicide vaginal ring, all 4 rings were safe and well tolerated. Tissue DPV concentrations were 1000 times greater than plasma concentrations and single drug rings had more stable pharmacokinetics. DPV, but not MVC, demonstrated concentration-dependent inhibition of HIV-1 infection in cervical tissue. Because MVC concentrations were consistently detectable only in CVF and not in plasma, improved drug release of MVC rings is needed.

Efficacy and Safety of Nitazoxanide, Albendazole, and Nitazoxanide-Albendazole against Trichuris trichiura Infection: A Randomized Controlled Trial

Science.gov (United States)

Speich, Benjamin; Ame, Shaali M.; Ali, Said M.; Alles, Rainer; Hattendorf, Jan; Utzinger, Jürg; Albonico, Marco; Keiser, Jennifer

2012-01-01

Background The currently used anthelmintic drugs, in single oral application, have low efficacy against Trichuris trichiura infection, and hence novel anthelmintic drugs are needed. Nitazoxanide has been suggested as potential drug candidate. Methodology The efficacy and safety of a single oral dose of nitazoxanide (1,000 mg), or albendazole (400 mg), and a nitazoxanide-albendazole combination (1,000 mg–400 mg), with each drug administered separately on two consecutive days, were assessed in a double-blind, randomized, placebo-controlled trial in two schools on Pemba, Tanzania. Cure and egg reduction rates were calculated by per-protocol analysis and by available case analysis. Adverse events were assessed and graded before treatment and four times after treatment. Principal Findings Complete data for the per-protocol analysis were available from 533 T. trichiura-positive children. Cure rates against T. trichiura were low regardless of the treatment (nitazoxanide-albendazole, 16.0%; albendazole, 14.5%; and nitazoxanide, 6.6%). Egg reduction rates were 54.9% for the nitazoxanide-albendazole combination, 45.6% for single albendazole, and 13.4% for single nitazoxanide. Similar cure and egg reduction rates were calculated using the available case analysis. Children receiving nitazoxanide had significantly more adverse events compared to placebo recipients. Most of the adverse events were mild and had resolved within 24 hours posttreatment. Conclusions/Significance Nitazoxanide shows no effect on T. trichiura infection. The low efficacy of albendazole against T. trichiura in the current setting characterized by high anthelmintic drug pressure is confirmed. There is a pressing need to develop new anthelmintics against trichuriasis. Trial Registration Controlled-Trials.com ISRCTN08336605 PMID:22679525

Anti-Obesity Drugs: A Review about Their Effects and Safety

Directory of Open Access Journals (Sweden)

Jun Goo Kang

2012-02-01

Full Text Available The current recommendations for the treatment of obese people include increased physical activity and reduced calories intake. When the behavioral approach is not sufficient, a pharmacologic treatment is recommended. In past years, numerous drugs have been approved for the treatment of obesity; however, most of them have been withdrawn from the market because of their adverse effects. In fact, amphetamine, rimonabant and sibutramine licenses have been withdrawn due to an increased risk of psychiatric disorders and non-fatal myocardial infarction or stroke. Even if orlistat is not as effective as other drugs in reducing body weight, orlistat is presently the only available choice for the treatment of obesity because of its safety for cardiovascular events and positive effects on diabetic control. Hopefully, more effective and better tolerated anti-obesity drugs will be developed through an improved understanding of the multiple mechanisms and complex physiological systems targeting appetite.

Use of nonsteroidal anti-inflammatory drugs among healthy people and specific cerebrovascular safety

DEFF Research Database (Denmark)

Fosbøl, Emil L; Olsen, Anne-Marie Schjerning; Olesen, Jonas Bjerring

2014-01-01

BACKGROUND: Nonsteroidal anti-inflammatory drugs can increase bleeding and thrombosis, but little is known about the cerebrovascular safety of these drugs, especially among healthy people. AIMS: The aim of this study was to examine the risk of ischemic and hemorrhagic stroke associated with the use...... stroke). RESULTS: We selected 1,028,437 healthy individuals (median age 39 years). At least one nonsteroidal anti-inflammatory drug was claimed by 44·7% of the study population, and the drugs were generally used for a short period of time and in low doses. High-dose ibuprofen and diclofenac were......·35-3·42)]. CONCLUSIONS: In healthy individuals, use of commonly available nonsteroidal anti-inflammatory drugs such as ibuprofen, diclofenac, and naproxen was associated with increased risk of stroke....

Erlotinib 150 mg daily plus chemotherapy in advanced pancreatic cancer: an interim safety analysis of a multicenter, randomized, cross-over phase III trial of the 'Arbeitsgemeinschaft Internistische Onkologie'.

Science.gov (United States)

Boeck, Stefan; Vehling-Kaiser, Ursula; Waldschmidt, Dirk; Kettner, Erika; Märten, Angela; Winkelmann, Cornelia; Klein, Stefan; Kojouharoff, Georgi; Gauler, Thomas; Fischer von Weikersthal, Ludwig; Clemens, Michael R; Geissler, Michael; Greten, Tim F; Hegewisch-Becker, Susanna; Neugebauer, Sascha; Heinemann, Volker

2010-01-01

To date, only limited toxicity data are available for the combination of erlotinib with either capecitabine or gemcitabine as front-line therapy for advanced pancreatic cancer. Within a randomized phase III trial, 281 treatment-naive patients were randomly assigned between capecitabine (2000 mg/m/day, for 14 days, once every 3 weeks) plus erlotinib (150 mg/day, arm A) and gemcitabine (1000 mg/m as a 30-min infusion) plus erlotinib (150 mg/day, arm B). In case of treatment failure, patients were crossed over to a second-line treatment with the comparator cytostatic drug without erlotinib. The primary study endpoint was the time to treatment failure of second-line therapy (TTF2). This interim analysis of toxicity contains safety data from the first 127 randomized patients. During first-line therapy, patients received a median number of three treatment cycles (range 0-13) in both the arms. Regarding chemotherapy, a treatment delay was observed in 12% of the cycles in arm A and in 22% of the cycles in arm B. Dose reductions of the cytostatic drug were performed in 18 and 27% of treatment cycles, respectively. Erlotinib dose reductions were performed in 6 and 11% of all cycles. Grade 3/4 hematological toxicity was arms; major grade 3/4 toxicities in arms A and B were diarrhea (9 vs. 7%), skin rash (4 vs. 12%), and hand-foot syndrome (7 vs. 0%). No treatment-related death was observed. In conclusion, this interim safety analysis suggests that treatment with erlotinib 150 mg/day is feasible in combination with capecitabine or gemcitabine.

Safety of polyethylene glycol 3350 solution in chronic constipation: randomized, placebo-controlled trial

OpenAIRE

McGraw, Thomas

2016-01-01

Thomas McGraw Global Medical Affairs, Merck & Co., Inc., Kenilworth, NJ, USA Purpose: To evaluate the safety and tolerability of aqueous solution concentrate (ASC) of polyethylene glycol (PEG) 3350 in patients with functional constipation.Patients and methods: The patients who met Rome III diagnostic criteria for functional constipation were randomized in this multicenter, randomized, placebo-controlled, single-blind study to receive once daily dose of PEG 3350 (17 g) ASC or ...

75 FR 36427 - Joint Meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management...

Science.gov (United States)

2010-06-25

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Joint Meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice...

Safety, pharmacokinetic, and functional effects of the nogo-a monoclonal antibody in amyotrophic lateral sclerosis: a randomized, first-in-human clinical trial.

Directory of Open Access Journals (Sweden)

Vincent Meininger

Full Text Available The neurite outgrowth inhibitor, Nogo-A, has been shown to be overexpressed in skeletal muscle in amyotrophic lateral sclerosis (ALS; it is both a potential biomarker and therapeutic target. We performed a double-blind, two-part, dose-escalation study, in subjects with ALS, assessing safety, pharmacokinetics (PK and functional effects of ozanezumab, a humanized monoclonal antibody against Nogo-A. In Part 1, 40 subjects were randomized (3∶1 to receive single dose intravenous ozanezumab (0.01, 0.1, 1, 5, or 15 mg/kg or placebo. In Part 2, 36 subjects were randomized (3∶1 to receive two repeat doses of intravenous ozanezumab (0.5, 2.5, or 15 mg/kg or placebo, approximately 4 weeks apart. The primary endpoints were safety and tolerability (adverse events [AEs], vital signs, electrocardiogram (ECG, and clinical laboratory tests. Secondary endpoints included PK, immunogenicity, functional endpoints (clinical and electrophysiological, and biomarker parameters. Overall, ozanezumab treatment (0.01-15 mg/kg was well tolerated. The overall incidence of AEs in the repeat dose 2.5 mg/kg and 15 mg/kg ozanezumab groups was higher than in the repeat dose placebo group and repeat dose 0.5 mg/kg ozanezumab group. The majority were considered not related to study drug by the investigators. Six serious AEs were reported in three subjects receiving ozanezumab; none were considered related to study drug. No study drug-related patterns were identified for ECG, laboratory, or vital signs parameters. One subject (repeat dose 15 mg/kg ozanezumab showed a weak, positive anti-ozanezumab-antibody result. PK results were generally consistent with monoclonal antibody treatments. No apparent treatment effects were observed for functional endpoints or muscle biomarkers. Immunohistochemical staining showed dose-dependent co-localization of ozanezumab with Nogo-A in skeletal muscle. In conclusion, single and repeat dose ozanezumab treatment was well tolerated and demonstrated

Safety and efficacy of tamsulosin, alfuzosin or silodosin as monotherapy for LUTS in BPH - a double-blind randomized trial.

Science.gov (United States)

Manohar, Chikka Moga Siddaiah; Nagabhushana, Mahadevappa; Karthikeyan, Vilvapathy Senguttuvan; Sanjay, Ramachandra Pudakalkatti; Kamath, Ananth Janardhan; Keshavamurthy, Ramaiah

2017-06-30

Currently alpha1-adrenoceptor blockers (AB) are widely used as first-line therapy to improve lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). We compared the efficacy and safety profile of tamsulosin, alfuzosin and silodosin in LUTS due to BPH. Consecutive consenting male patients (N = 269) undergoing medical management of BPH with AB from February 2012 to October 2015 were enrolled. Patients were randomized to a 0.4 mg tamsulosin (group T), 10 mg alfuzosin (group A) or a 8 mg silodosin (group S) by double-blind randomization. All patients were assessed for improvements and post-void residual urine (PVR) and for adverse drug events (ADE). IPSS showed significant improvement in Group S at the first week (11.7 ±4.18, p = 0.027) and at 3 months (7.97 ±3.84, p = 0.020). QOL showed significant improvement at 1 (2.2 ±0.76, p = 0.020), 4 (1.47 ±0.63, p BPH and objectively improves maximum flow rate. However, silodosin has more adverse events when compared to tamsulosin and alfuzosin.

Just don`t do it: zero tolerance alcohol and drug policy in place

Energy Technology Data Exchange (ETDEWEB)

Anon.

1997-10-01

Safety policies in effect on the Hibernia offshore platform in the Hibernia Field, 300 km off the Newfoundland coast, were described, especially with regard to alcohol and drugs. No alcohol of any type is allowed on the platform. Each employee departing for the platform must take a breathalyzer test prior to boarding the helicopter. The tolerance level at the heliport is .05 per cent and anyone exceeding that is not permitted to board the aircraft. Employees must also be drug-free to be permitted to travel offshore. There is a policy of random testing on the platform for illicit or `recreational` drugs. All employees must agree in writing to taking these tests through provision of a urine sample on demand, as a condition of employment. The use of alcohol offshore or the detection of illegal drugs through the random testing program are grounds for dismissal, although team leaders have some discretion to judge each situation on its own set of circumstances. The company also has the right to search individuals, their sleeping quarters, lockers and other property for alcohol, drugs or other controlled substances in situations where reasonable doubt exists. To date there has been very little resistance within Hibernia to its random testing and zero tolerance policies. Employees understand that this is a safety issue and that they serve to protect everyone who works on the offshore platform.

Evaluating a Website to Teach Children Safety with Dogs: A Randomized Controlled Trial

Directory of Open Access Journals (Sweden)

David C. Schwebel

2016-12-01

Full Text Available Dog bites represent a significant threat to child health. Theory-driven interventions scalable for broad dissemination are sparse. A website was developed to teach children dog safety via increased knowledge, improved cognitive skills in relevant domains, and increased perception of vulnerability to bites. A randomized controlled trial was conducted with 69 children aged 4–5 randomly assigned to use the dog safety website or a control transportation safety website for ~3 weeks. Assessment of dog safety knowledge and behavior plus skill in three relevant cognitive constructs (impulse control, noticing details, and perspective-taking was conducted both at baseline and following website use. The dog safety website incorporated interactive games, instructional videos including testimonials, a motivational rewards system, and messaging to parents concerning child lessons. Our results showed that about two-thirds of the intervention sample was not adherent to website use at home, so both intent-to-treat and per-protocol analyses were conducted. Intent-to-treat analyses yielded mostly null results. Per-protocol analyses suggested children compliant to the intervention protocol scored higher on knowledge and recognition of safe behavior with dogs following the intervention compared to the control group. Adherent children also had improved scores post-intervention on the cognitive skill of noticing details compared to the control group. We concluded that young children’s immature cognition can lead to dog bites. Interactive eHealth training on websites shows potential to teach children relevant cognitive and safety skills to reduce risk. Compliance to website use is a challenge, and some relevant cognitive skills (e.g., noticing details may be more amenable to computer-based training than others (e.g., impulse control.

Suspected adverse drug reactions in elderly patients reported to the Committee on Safety of Medicines.

OpenAIRE

Castleden, C M; Pickles, H

1988-01-01

1. Spontaneous reports of suspected adverse drug reactions (ADRs) reported to the Committee on Safety of Medicines (CSM) have been studied in relation to patient age. 2. The proportion of reports received for the elderly increased between 1965 and 1983. 3. There was a correlation between the use of drugs and the number of ADR reports. Thus age-related prescription figures for two non-steroidal anti-inflammatory drugs (NSAI) and co-trimoxazole matched ADR reports for each drug in each age grou...

76 FR 20686 - Draft Guidance for Industry on Safety Labeling Changes; Implementation of the Federal Food, Drug...

Science.gov (United States)

2011-04-13

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0164] Draft Guidance for Industry on Safety Labeling Changes; Implementation of the Federal Food, Drug, and Cosmetic Act; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and...

The role of the Australian Adverse Drug Reactions Advisory Committee (ADRAC) in monitoring drug safety

International Nuclear Information System (INIS)

Boyd, Ian W.

2002-01-01

The Australian adverse drug reaction reporting system is acknowledged as one of the best in the world. Despite its small population of less than 20 million people, Australia's current ADR reporting rate of over 12000 reports per year places it in the top few nations in terms of reports per capita. The ADRAC program has been in operation for over 30 years. Australia was a founding member of the WHO International Drug Monitoring Programme which commenced in 1968 and currently there are about 153000 reports in the ADRAC database. Reports from health professionals have uncovered a number of significant safety problems over the years. Of particular importance are flucloxacillin-induced hepatitis, amoxycillin/clavulanate-induced hepatitis, and the association of cystitis with tiaprofenic acid. The number and quality of the reports has allowed an understanding of the characteristics of the reactions and, using ADRAC reporters as a major source of cases, case-control studies have been completed which have identified risk factors. ADRAC's review of Australian reports has highlighted many important associations that have been disseminated through the Australian Adverse Drug Reactions Bulletin

A randomized controlled trial to evaluate the Make Safe Happen® app-a mobile technology-based safety behavior change intervention for increasing parents' safety knowledge and actions.

Science.gov (United States)

McKenzie, Lara B; Roberts, Kristin J; Clark, Roxanne; McAdams, Rebecca; Abdel-Rasoul, Mahmoud; Klein, Elizabeth G; Keim, Sarah A; Kristel, Orie; Szymanski, Alison; Cotton, Christopher G; Shields, Wendy C

2018-03-12

Many unintentional injuries that occur in and around the home can be prevented through the use of safety equipment and by consistently following existing safety recommendations. Unfortunately, uptake of these safety behaviors is unacceptably low. This paper describes the design of the Make Safe Happen® smartphone application evaluation study, which aims to evaluate a mobile technology-based safety behavior change intervention on parents' safety knowledge and actions. Make Safe Happen® app evaluation study is a randomized controlled trial. Participants will be parents of children aged 0-12 years who are recruited from national consumer online survey panels. Parents will complete a pretest survey, and will be randomized to receive the Make Safe Happen® app or a non-injury-related app, and then complete a posttest follow-up survey after 1 week. Primary outcomes are: (1) safety knowledge; (2) safety behaviors; (3) safety device acquisition and use, and (4) behavioral intention to take safety actions. Anticipated study results are presented. Wide-reaching interventions, to reach substantial parent and caregiver audiences, to effectively reduce childhood injuries are needed. This study will contribute to the evidence-base about how to increase safety knowledge and actions to prevent home-related injuries in children. NCT02751203 ; Pre-results.

Drug-eluting stents for acute coronary syndrome: a meta-analysis of randomized controlled trials.

Directory of Open Access Journals (Sweden)

Lishan Wang

Full Text Available Drug-eluting stents (DES are increasingly used for treatment of acute coronary syndrome (ACS. However, clinical efficacy and safety of various types of DES is not well established in these subjects. We therefore evaluated clinical utility of second-generation and first-generation DES in patients with ACS by conducting a meta-analysis.A search of Medline, Embase, the Cochrane databases, and Web of Science was made. Randomized controlled trials (RCTs which compared second-generation DES (everolimus-eluting stents [EES] or zotarolimus-eluting stents [ZES] versus first-generation DES (sirolimus-eluting stents [SES] or paclitaxe-eluting stents [PES] in patients with ACS and provided data on clinical efficacy or safety endpoints were included. Pooled estimates were calculated using random-effects model.A total of 2,757 participants with ACS in 6 RCTs were included. Compared with first-generation one, second-generation DES trended to be associated with the decreased incidence of definite or probable stent thrombosis in ACS patients (risk ratio [RR]  = 0.60, 95% confidence intervals [CI] 0.33 to 1.07, p = 0.09. However, the rate of target lesion revascularization (TLR significantly increased in second-generation DES (RR = 2.08, 95%CI 1.25 to 3.47, p = 0.005. There were no significant differences in the incidence of major adverse cardiac events (MACEs, all-cause death, cardiac death, and recurrent myocardial infarction between the two arms (all p>0.10. The second-generation EES showed a tendency towards lower risk of MACEs (p = 0.06 and a beneficial effect on reducing stent thrombosis episodes (p = 0.009, while the second-generation ZES presented an increased occurrence of MACEs (p = 0.02 and TLR (p = 0.003.Second-generation DES, especially EES, appeared to present a lower risk of stent thrombosis, whereas second-generation ZES might increase the need for repeat revascularization in ACS patients. During coronary

A Randomized Controlled Trial for Veterans with PTSD and Substance Use Disorder: Creating Change versus Seeking Safety.

Science.gov (United States)

Najavits, Lisa M; Krinsley, Karen; Waring, Molly E; Gallagher, Matthew W; Skidmore, Christopher

2018-02-20

Posttraumatic stress disorder (PTSD) and substance use disorder (SUD) co-occur in military veterans and other populations. To conduct a randomized controlled trial to compare a new past-focused treatment (Creating Change; CC), to a well-established, evidence-based present-focused treatment for PTSD/SUD (Seeking Safety; SS), on symptoms of both disorders. CC guides patients to process the past through exploration of PTSD/SUD life themes and memories whereas SS focuses on coping skills in the present. Fifty-two male and female veterans with current PTSD/SUD were randomized (n = 26 per treatment) and assessed at baseline, end-of-treatment and 3-month follow-up. They received 17 individual one-hour sessions. Intent-to-treat analyses indicated that both conditions improved over time, with no difference between conditions, on PTSD, alcohol use, and drug use (our primary outcomes) as well as mental health symptoms, quality of life, self-efficacy, and SUD cognitions. Effect sizes were medium except for alcohol use, which was large. Change over time reflected improvement from baseline to end-of-treatment, with gains sustained at follow-up, although alcohol use showed continued improvement from end-of-treatment to follow-up. Both treatments evidenced a strong safety profile; and attendance, alliance, and treatment satisfaction were also very strong. Conclusions/importance: CC has promise as a PTSD/SUD therapy with strong public health relevance and the potential to fill important gaps in the field. We used minimal exclusionary criteria to obtain a real-world sample, which was severe-predominantly substance-dependent with chronic PTSD and additional psychiatric diagnoses. Future research is warranted, especially on nonveteran samples and treatment mechanisms of action.

Efficacy and safety of parecoxib in the treatment of acute renal colic: a randomized clinical trial

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Sidney Glina

2011-12-01

Full Text Available PURPOSE: Although nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs and opioids are effective treatments for acute renal colic, they are associated with adverse events (AEs. As cyclooxygenase-2 selective NSAIDs may provide a safer alternative, we compared the efficacy and safety of parecoxib versus an nsNSAID in subjects with acute renal colic. MATERIALS AND METHODS: Phase IV., multicenter, double-blind, noninferiority, active-controlled study: 338 subjects with acute renal colic were randomized to parecoxib 40 mg i.v. plus placebo (n = 174 or ketoprofen 100 mg IV plus placebo (n = 164. 338 subjects with acute renal colic were randomized to parecoxib 40 mg IV (n = 174 or ketoprofen 100 mg IV(n = 164 plus placebo. Subjects were evaluated 15, 30, 45, 60, 90 and 120 minutes after treatment start and 24 hours after discharge. Primary endpoint was the mean pain intensity difference (PID at 30 minutes by visual analog scale (VAS (per-protocol population. An ANCOVA model was used with treatment group, country, and baseline score as covariates. Non-inferiority of parecoxib to ketoprofen was declared if the lower bound of the 95% confidence interval (CI for the difference between the two groups excluded the pre-established margin of 10 mm for the primary endpoint. RESULTS: Baseline demographics were similar. The mean (SD mPID30 min was 33.84 (24.61 and 35.16 (26.01 for parecoxib and ketoprofen, respectively. For treatment difference (parecoxib-ketoprofen the lower bound of the 95% CI was 6.53. The mean change from baseline in VAS 30 minutes after study medication was ~43 mm; AEs were comparable between treatments. CONCLUSIONS: Parecoxib is as effective as ketoprofen in the treatment of pain due to acute renal colic, is well tolerated, and has a comparable safety profile.

Characteristics of men with substance use disorder consequent to illicit drug use: comparison of a random sample and volunteers.

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Reynolds, Maureen D; Tarter, Ralph E; Kirisci, Levent

2004-09-06

Men qualifying for substance use disorder (SUD) consequent to consumption of an illicit drug were compared according to recruitment method. It was hypothesized that volunteers would be more self-disclosing and exhibit more severe disturbances compared to randomly recruited subjects. Personal, demographic, family, social, substance use, psychiatric, and SUD characteristics of volunteers (N = 146) were compared to randomly recruited (N = 102) subjects. Volunteers had lower socioceconomic status, were more likely to be African American, and had lower IQ than randomly recruited subjects. Volunteers also evidenced greater social and family maladjustment and more frequently had received treatment for substance abuse. In addition, lower social desirability response bias was observed in the volunteers. SUD was not more severe in the volunteers; however, they reported a higher lifetime rate of opiate, diet, depressant, and analgesic drug use. Volunteers and randomly recruited subjects qualifying for SUD consequent to illicit drug use are similar in SUD severity but differ in terms of severity of psychosocial disturbance and history of drug involvement. The factors discriminating volunteers and randomly recruited subjects are well known to impact on outcome, hence they need to be considered in research design, especially when selecting a sampling strategy in treatment research.

What can nanosafety learn from drug development? The feasibility of “safety by design”

DEFF Research Database (Denmark)

Hjorth, Rune; van Hove, Lilian; Wickson, Fern

2017-01-01

“Safety by design” (SbD) is an intuitively appealing concept that is on the rise within nanotoxicology and nanosafety research, as well as within nanotechnology research policy. It leans on principles established within drug discovery and development (DDD) and seeks to address safety early, as well...... as throughout product development. However, it remains unclear what the concept of SbD exactly entails for engineered nanomaterials (ENMs) or how it is envisioned to be implemented. Here, we review the concept as it is emerging in European research and compare its resemblance with the safety testing...

[Investigation of the cognition and behavior on drug safety in Beijing middle school students].

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Cheng, Y C; Pan, Y P; Zhang, Y; Pan, Y T; Ding, C Y; Cao, Y; Zhuo, L; Fang, R F; Gao, A Y; Guo, J; Li, A J; Fu, Q; Ma, J; Zhan, S Y

2017-12-18

To understand the cognition and behavior of drug safety in Beijing middle school students and provide advice for relevant education. A cross-sectional survey using paper questionnaires was carried out on the student body of nine Beijing middle schools. Multi-stage proportionate stratified cluster sampling was adopted to enroll participants. In addition to demographic questions, the questionnaire included 17 questions assessing the cognition and behavior of safe drug use, prioritizing questions that aligned with the health education guideline for primary and secondary school students from Chinese Ministry of Education. Descriptive statistical methods were applied using the SAS 9.2 software. Of the 4 220 students investigated, 2 097(49.7%) were males and 2 123(50.3%) were females. The average age was (14.3±1.7) years. 2 030(48.1%) students were from downtown areas, 1 511(35.8%) were from urban-rural linking areas and 679(16.1%) were from rural areas. Half (51.5%) of the respondents were junior high school students, and the others were from senior high schools (34.2%) and vocational high schools (14.3%). Most of the students (89.6%) lived off campus. The awareness rate of drug safety knowledge was 74.4%, the median score of drug safety behavior was 4 points (full score was 5 points) and there was a statistically positive correlation between the two (Spearman's correlation coefficient was 0.156, Pmiddle school students is good, but problems still exist in medication adherence, the management of expired drugs and the antibiotics cognition, which need to be fixed through specific, pointed way of education. And more efforts should be made to improve the cognition in rural regions, vocational high schools and on campus students.

Types, frequencies, and burden of nonspecific adverse events of drugs: analysis of randomized placebo-controlled clinical trials.

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Mahr, Alfred; Golmard, Clara; Pham, Emilie; Iordache, Laura; Deville, Laure; Faure, Pierre

2017-07-01

Scarce studies analyzing adverse event (AE) data from randomized placebo-controlled clinical trials (RPCCTs) of selected illnesses suggested that a substantial proportion of collected AEs are unrelated to the drug taken. This study analyzed the nonspecific AEs occurring with active-drug exposure in RPCCTs for a large range of medical conditions. Randomized placebo-controlled clinical trials published in five prominent medical journals during 2006-2012 were searched. Only trials that evaluated orally or parenterally administered active drugs versus placebo in a head-to-head setting were selected. For AEs reported from ≥10 RPCCTs, Pearson's correlation coefficients (r) were calculated to determine the relationship between AE rates in placebo and active-drug recipients. Random-effects meta-analyses were used to compute proportions of nonspecific AEs, which were truncated at a maximum of 100%, in active-drug recipients. We included 231 trials addressing various medical domains or healthy participants. For the 88 analyzed AE variables, AE rates for placebo and active-drug recipients were in general strongly correlated (r > 0.50) or very strongly correlated (r > 0.80). The pooled proportions of nonspecific AEs for the active-drug recipients were 96.8% (95%CI: 95.5-98.1) for any AEs, 100% (97.9-100) for serious AEs, and 77.7% (72.7-83.2) for drug-related AEs. Results were similar for individual medical domains and healthy participants. The pooled proportion of nonspecificity of 82 system organ class and individual AE types ranged from 38% to 100%. The large proportion of nonspecific AEs reported in active-drug recipients of RPCCTs, including serious and drug-related AEs, highlights the limitations of clinical trial data to determine the tolerability of drugs. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Best practices: an electronic drug alert program to improve safety in an accountable care environment.

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Griesbach, Sara; Lustig, Adam; Malsin, Luanne; Carley, Blake; Westrich, Kimberly D; Dubois, Robert W

2015-04-01

The accountable care organization (ACO), one of the most promising and talked about new models of care, focuses on improving communication and care transitions by tying potential shared savings to specific clinical and financial benchmarks. An important factor in meeting these benchmarks is an ACO's ability to manage medications in an environment where medical and pharmacy care has been integrated. The program described in this article highlights the critical components of Marshfield Clinic's Drug Safety Alert Program (DSAP), which focuses on prioritizing and communicating safety issues related to medications with the goal of reducing potential adverse drug events. Once the medication safety concern is identified, it is reviewed to evaluate whether an alert warrants sending prescribers a communication that identifies individual patients or a general communication to all physicians describing the safety concern. Instead of basing its decisions regarding clinician notification about drug alerts on subjective criteria, the Marshfield Clinic's DSAP uses an internally developed scoring system. The scoring system includes criteria developed from previous drug alerts, such as level of evidence, size of population affected, severity of adverse event identified or targeted, litigation risk, available alternatives, and potential for duration of medication use. Each of the 6 criteria is assigned a weight and is scored based upon the content and severity of the alert received.  In its first 12 months, the program targeted 6 medication safety concerns involving the following medications: topiramate, glyburide, simvastatin, citalopram, pioglitazone, and lovastatin. Baseline and follow-up prescribing data were gathered on the targeted medications. Follow-up review of prescribing data demonstrated that the DSAP provided quality up-to-date safety information that led to changes in drug therapy and to decreases in potential adverse drug events. In aggregate, nearly 10,000 total

Involving fathers in teaching youth about farm tractor seatbelt safety--a randomized control study.

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Jinnah, Hamida Amirali; Stoneman, Zolinda; Rains, Glen

2014-03-01

Farm youth continue to experience high rates of injury and deaths as a result of agricultural activities. Farm machinery, especially tractors, is the most common cause of casualties to youth. A Roll-Over Protection Structure (ROPS) along with a fastened seatbelt can prevent almost all injuries and fatalities from tractor overturns. Despite this knowledge, the use of seatbelts by farmers on ROPS tractors remains low. This study treats farm safety as a family issue and builds on the central role of parents as teachers and role models of farm safety for youth. This research study used a longitudinal, repeated-measures, randomized-control design in which youth 10-19 years of age were randomly assigned to either of two intervention groups (parent-led group and staff-led group) or the control group. Fathers in the parent-led group were less likely to operate ROPS tractors without a seatbelt compared with other groups. They were more likely to have communicated with youth about the importance of wearing seatbelts on ROPS tractors. Consequently, youth in the parent-led group were less likely to operate a ROPS tractor without a seatbelt than the control group at post-test. This randomized control trial supports the effectiveness of a home-based, father-led farm safety intervention as a promising strategy for reducing youth as well as father-unsafe behaviors (related to tractor seatbelts) on the farm. This intervention appealed to fathers' strong motivation to practice tractor safety for the sake of their youth. Involving fathers helped change both father as well as youth unsafe tractor-seatbelt behaviors. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Safety, efficacy, and drug survival of biologics and biosimilars for moderate-to-severe plaque psoriasis

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Egeberg, A; Ottosen, M B; Gniadecki, R

2018-01-01

BACKGROUND: Real-life data on newer biologic and biosimilar agents for moderate-to-severe psoriasis are lacking. OBJECTIVES: To examine safety, efficacy, and time to discontinuation (drug survival) of biologics (adalimumab, etanercept, infliximab, secukinumab, and ustekinumab) and compare origina...... the long-term safety of novel biologics for psoriasis. This article is protected by copyright. All rights reserved....

A comparative analysis of drug safety withdrawals in the UK and the US (1971-1992): implications for current regulatory thinking and policy.

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Abraham, John; Davis, Courtney

2005-09-01

By going beyond individual case studies and solely quantitative surveys, this paper systematically examines why there were over twice as many new prescription drugs withdrawn from the market on grounds of safety in the UK as there were in the US between 1971 and 1992. Drawing on interviews with regulators, industry scientists and others involved, and on regulatory data never before accessed outside governments and companies, five key hypotheses which might explain this difference in drug safety withdrawals are analysed. These are: (1) simply because the UK approved more new drugs than the US; (2) because of an industrial corporate strategy to seek approval of 'less safe' drugs in the UK earlier; (3) because British regulators were more vigilant at spotting post-marketing safety problems than their US counterparts; (4) because the slowness of the US in approving new drugs enabled regulators there to learn from, and avoid, safety problems that had already emerged in the UK or European market; and (5) because more stringent regulation in the US meant that they approved fewer unsafe drugs on to the market in the first place. It is concluded that the main explanation for fewer drug safety withdrawals in the US is that the regulatory agency there applied more stringent pre-market review and/or standards, which took longer than UK regulatory checks, but prevented unsafe drugs marketed in the UK from entering the US market. Contrary to the claims frequently made by the pharmaceutical industry and regulatory agencies on both sides of the Atlantic, these results imply that it is likely that acceleration of regulatory review times in the US and the UK since the early 1990s is compromising drug safety.

Drug safety alerts of pharmacovigilance programme of India: A scope for targeted spontaneous reporting in India

Directory of Open Access Journals (Sweden)

Prasad Thota

2018-01-01

Conclusion: In India, spontaneous reporting of ADRs existed since 1998 under passive surveillance method, but there is an urgent need to initiate TSR, which is a complementary method to spontaneous reporting on these drug safety alerts for further regulatory action by Central Drugs Standard Control Organization.

Systematic Review of Efficacy and Safety of Newer Antidiabetic Drugs Approved from 2013 to 2017 in Controlling HbA1c in Diabetes Patients

Directory of Open Access Journals (Sweden)

Sivanandy Palanisamy

2018-06-01

Full Text Available Type 2 Diabetes Mellitus (T2DM is the most common form of diabetes mellitus and accounts for about 95% of all diabetes cases. Many newer oral as well as parenteral antidiabetic drugs have been introduced in to the market in recent years to control hyperglycemic conditions in diabetes patients and many of these drugs produce potential side effects in diabetes patients. Hence, this systematic review was aimed to analyze and compare the efficacy and safety of oral antidiabetic agents in controlling HbA1c in T2DM patients, that were approved by the United States-Food and Drug Administration (US-FDA from 2013 to 2017. All randomized controlled, double-blind trials published in English during the search period involving the newer antidiabetic agents were selected. In the outcome assessment comparison, semaglutide demonstrated the highest efficacy in lowering HbA1c, with a 1.6% reduction (p < 0.0001 when given at a dose of 1.0 mg. The safety profile of all the agents as compared to placebo or control were similar, with no or slight increase in the occurrence of adverse events (AEs but no fatal reaction was reported. The most common AEs of all the antidiabetic agents were gastrointestinal in nature, with several cases of hypoglycemic events. However, among all these agents, semaglutide seems to be the most efficacious drug to improve glycemic control in terms of HbA1c. Alogliptin has the least overall frequency of AEs compared to other treatment groups.

Preventing errors in administration of parenteral drugs: the results of a four-year national patient safety program.

NARCIS (Netherlands)

Blok, C. de; Schilp, J.; Wagner, C.

2013-01-01

Objectives: To evaluate the implementation of a four-year national patient safety program concerning the parenteral drug administration process in the Netherlands. Methods: Structuring the preparation and administration process of parenteral drugs reduces the number of medication errors. A

Searches for Randomized Controlled Trials of Drugs in MEDLINE and EMBASE Using Only Generic Drug Names Compared with Searches Applied in Current Practice in Systematic Reviews

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Waffenschmidt, Siw; Guddat, Charlotte

2015-01-01

Background: It is unclear which terms should be included in bibliographic searches for randomized controlled trials (RCTs) of drugs, and identifying relevant drug terms can be extremely laborious. The aim of our analysis was to determine whether a bibliographic search using only the generic drug name produces sufficient results for the generation…

Sponsors’ and investigative staffs' perceptions of the current investigational new drug safety reporting process in oncology trials

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Perez, Raymond; Archdeacon, Patrick; Roach, Nancy; Goodwin, Robert; Jarow, Jonathan; Stuccio, Nina; Forrest, Annemarie

2017-01-01

Background/aims: The Food and Drug Administration’s final rule on investigational new drug application safety reporting, effective from 28 March 2011, clarified the reporting requirements for serious and unexpected suspected adverse reactions occurring in clinical trials. The Clinical Trials Transformation Initiative released recommendations in 2013 to assist implementation of the final rule; however, anecdotal reports and data from a Food and Drug Administration audit indicated that a majority of reports being submitted were still uninformative and did not result in actionable changes. Clinical Trials Transformation Initiative investigated remaining barriers and potential solutions to full implementation of the final rule by polling and interviewing investigators, clinical research staff, and sponsors. Methods: In an opinion-gathering effort, two discrete online surveys designed to assess challenges and motivations related to management of expedited (7- to 15-day) investigational new drug safety reporting processes in oncology trials were developed and distributed to two populations: investigators/clinical research staff and sponsors. Data were collected for approximately 1 year. Twenty-hour-long interviews were also conducted with Clinical Trials Transformation Initiative–nominated interview participants who were considered as having extensive knowledge of and experience with the topic. Interviewees included 13 principal investigators/study managers/research team members and 7 directors/vice presidents of pharmacovigilance operations from 5 large global pharmaceutical companies. Results: The investigative site’s responses indicate that too many individual reports are still being submitted, which are time-consuming to process and provide little value for patient safety assessments or for informing actionable changes. Fewer but higher quality reports would be more useful, and the investigator and staff would benefit from sponsors’“filtering” of

Sponsors' and investigative staffs' perceptions of the current investigational new drug safety reporting process in oncology trials.

Science.gov (United States)

Perez, Raymond; Archdeacon, Patrick; Roach, Nancy; Goodwin, Robert; Jarow, Jonathan; Stuccio, Nina; Forrest, Annemarie

2017-06-01

The Food and Drug Administration's final rule on investigational new drug application safety reporting, effective from 28 March 2011, clarified the reporting requirements for serious and unexpected suspected adverse reactions occurring in clinical trials. The Clinical Trials Transformation Initiative released recommendations in 2013 to assist implementation of the final rule; however, anecdotal reports and data from a Food and Drug Administration audit indicated that a majority of reports being submitted were still uninformative and did not result in actionable changes. Clinical Trials Transformation Initiative investigated remaining barriers and potential solutions to full implementation of the final rule by polling and interviewing investigators, clinical research staff, and sponsors. In an opinion-gathering effort, two discrete online surveys designed to assess challenges and motivations related to management of expedited (7- to 15-day) investigational new drug safety reporting processes in oncology trials were developed and distributed to two populations: investigators/clinical research staff and sponsors. Data were collected for approximately 1 year. Twenty-hour-long interviews were also conducted with Clinical Trials Transformation Initiative-nominated interview participants who were considered as having extensive knowledge of and experience with the topic. Interviewees included 13 principal investigators/study managers/research team members and 7 directors/vice presidents of pharmacovigilance operations from 5 large global pharmaceutical companies. The investigative site's responses indicate that too many individual reports are still being submitted, which are time-consuming to process and provide little value for patient safety assessments or for informing actionable changes. Fewer but higher quality reports would be more useful, and the investigator and staff would benefit from sponsors'"filtering" of reports and increased sponsor communication. Sponsors

Treatment options for nonalcoholic steatohepatitis - a safety evaluation.

Science.gov (United States)

Issa, Danny; Wattacheril, Julia; Sanyal, Arun J

2017-08-01

There is an urgent as yet unmet need to develop highly effective and safe therapeutics for nonalcoholic fatty liver disease (NAFLD). The remarkable progress in understanding NAFLD pathogenesis allowed the identification of injury pathways which may be recruited as therapy targets. Areas covered: This article reviews the safety and tolerability data of the NAFLD therapies and explains the mechanistic basis for each of the established and investigational drugs. Treatment targets include: weight loss, anti-metabolic agents such as lipid lowering and anti-diabetic drugs, inflammation, fibrosis and others such as targeting gut microbiota, immune modulation and apoptosis. Expert opinion: Current therapies continue to remain suboptimal. Weight loss is effective but hard to achieve. Traditional and endoscopic bariatric procedures are promising although more randomized trials are needed and the long-term safety remains to be established. Clinical trials have demonstrated the efficacy of several drugs for the treatment of NASH. Of these, there remains some uncertainty about the long-term safety of vitamin E. Pioglitazone is associated with osteopenia, fluid retention and weight gain. Obeticholic acid causes pruritus in a substantial proportion of subjects and elafibranor has been associated with transient rises in creatinine. Several exciting therapies are under development and results of clinical and post-marketing trials will help elucidate their safety.

Evaluation of Pre-marketing Factors to Predict Post-marketing Boxed Warnings and Safety Withdrawals.

Science.gov (United States)

Schick, Andreas; Miller, Kathleen L; Lanthier, Michael; Dal Pan, Gerald; Nardinelli, Clark

2017-06-01

An important goal in drug regulation is understanding serious safety issues with new drugs as soon as possible. Achieving this goal requires us to understand whether information provided during the Food and Drug Administration (FDA) drug review can predict serious safety issues that are usually identified after the product is approved. However, research on this topic remains understudied. In this paper, we examine whether any pre-marketing drug characteristics are associated with serious post-marketing safety actions. We study this question using an internal FDA database containing every new small molecule drug submitted to the FDA's Center for Drug Evaluation and Research (CDER) on or after November 21, 1997, and approved and commercially launched before December 31, 2009. Serious post-marketing safety actions include whether these drugs ever experienced either a post-marketing boxed warning or a withdrawal from the market due to safety concerns. A random effects logistic regression model was used to test whether any pre-marketing characteristics were associated with either post-marketing safety action. A total of 219 new molecular entities were analyzed. Among these drugs, 11 experienced a safety withdrawal and 30 received boxed warnings by July 31, 2016. Contrary to prevailing hypotheses, we find that neither clinical trial sample sizes nor review time windows are associated with the addition of a post-marketing boxed warning or safety withdrawal. However, we do find that new drugs approved with either a boxed warning or priority review are more likely to experience post-marketing boxed warnings. Furthermore, drugs approved with boxed warnings tend to receive post-marketing boxed warnings resulting from new safety information that are unrelated to the original warning. Drugs approved with a boxed warning are 3.88 times more likely to receive a post-marketing boxed warning, while drugs approved with a priority review are 3.51 times more likely to receive a post

Food and Drug Administration Evaluation and Cigarette Smoking Risk Perceptions

Science.gov (United States)

Kaufman, Annette R.; Waters, Erika A.; Parascandola, Mark; Augustson, Erik M.; Bansal-Travers, Maansi; Hyland, Andrew; Cummings, K. Michael

2011-01-01

Objectives: To examine the relationship between a belief about Food and Drug Administration (FDA) safety evaluation of cigarettes and smoking risk perceptions. Methods: A nationally representative, random-digit-dialed telephone survey of 1046 adult current cigarette smokers. Results: Smokers reporting that the FDA does not evaluate cigarettes for…

A Randomized Trial of Probation Case Management for Drug-Involved Women Offenders

Science.gov (United States)

Guydish, Joseph; Chan, Monica; Bostrom, Alan; Jessup, Martha A.; Davis, Thomas B.; Marsh, Cheryl

2011-01-01

This article reports findings from a clinical trial of a probation case management (PCM) intervention for drug-involved women offenders. Participants were randomly assigned to PCM (n = 92) or standard probation (n = 91) and followed for 12 months using measures of substance abuse, psychiatric symptoms, social support, and service utilization.…

Nonsteroidal anti-inflammatory drug gastropathy: new avenues for safety.

Science.gov (United States)

Roth, Sanford H

2011-01-01

Chronic oral or systemic nonselective nonsteroidal anti-inflammatory drug (NSAID) therapy, ubiquitously used by physicians to treat osteoarthritis-associated pain, is associated with a wide range of symptomatic adverse events, the most frequent and serious of which is gastropathy. Although cardiovascular and renal problems are a very real concern, they are significantly less frequent. These complications can be life-threatening in at-risk populations such as older adults, who are common users of long-term oral systemic NSAID therapy. Topical NSAID formulations deliver effective doses of analgesics directly to the affected joints, thereby limiting systemic exposure and potentially the risk of systemic adverse events, such as gastropathy and serious cardiovascular events. There are currently two topical NSAIDs approved by the US Food and Drug Administration for osteoarthritis-associated pain, as well as for the signs and symptoms of osteoarthritis. This review discusses the relative safety, and the gastrointestinal, cardiovascular, and renal risks of chronic oral or systemic NSAID therapy and topical NSAID formulations in patients with osteoarthritis.

The nuts and bolts of pills and portions: the functions of a drug safety working group.

Science.gov (United States)

Nath, Noleen S; Jones, Ellen H; Stride, Peter; Premaratne, Manuja; Thaker, Darshit; Lim, Ivan

2011-11-01

Hospitalised patients commonly experience adverse drug events (ADEs) and medication errors. Runciman reported that ADEs in hospitals account for 20% of reported adverse events and contribute to 27% of deaths where death followed an adverse event. Hughes recommends multidisciplinary hospital drug committees to assess performance and raise standards. The new Code of Conduct of the Medical Board of Australia recommends participation in systems for surveillance and monitoring of adverse events, and to improve patient safety. We describe the functions and role of a Drug Safety Working Group (DSWG) in a suburban hospital, which aims to audit and promote a culture of prescribing and medication administration that is prudent and cautious to minimise the risk of harm to patients. We believe that regular prescription monitoring and feedback to Resident Medical Officers (RMOs) improves medication management in our hospital.

The importance of Pharmacovigilance for the drug safety: Focus on cardiovascular profile of incretin-based therapy.

Science.gov (United States)

Sportiello, Liberata; Rafaniello, Concetta; Scavone, Cristina; Vitale, Cristiana; Rossi, Francesco; Capuano, Annalisa

2016-01-01

With the recent introduction of the new European Pharmacovigilance legislation, all new drugs must be carefully monitored after admission on the European market, in order to assess the long safety profile. Currently, special attention is given to several hypoglycemic agents with recent market approval (agonists of glucagon-like peptide-1 [GLP-1] receptor and dipeptidyl peptidase 4 inhibitors [DPP-4i]), which act through the potentiation of incretin hormone signaling. Their inclusion in European additional monitoring is also due to safety problems, which seem to characterize their pharmacological class. In fact, these drugs initially showed a good tolerability profile with mainly gastrointestinal adverse events, low risk of hypoglycemia and minor effects on body weight. But, new concerns such as infections, pancreatitis, pancreatic cancer and above all cardiovascular events (especially risk of heart failure requiring hospitalization) are now arising. In this review, we highlighted aspects of the new Pharmacovigilance European dispositions, and then we investigated the tolerability profile of incretin-based therapies, in particular DPP-4 inhibitors. Notably, we focused our attention on new safety concerns, which are emerging mostly in the post-marketing period, as the cardiovascular risk profile. Evidence in literature and opinions of regulatory agencies (e.g., European Medicines Agency and Food and Drug Administration) about risks of incretin-based therapies are yet controversial, and there are many open questions in particular on cancer and cardiovascular effects. Thus, it is important to continue to monitor closely the use of these drugs in clinical practice to improve the knowledge on their long-term safety and their place in diabetes therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Safety of Bifidobacterium animalis subsp. lactis (B. lactis) strain BB-12-supplemented yogurt in healthy adults on antibiotics: a phase I safety study.

Science.gov (United States)

Merenstein, Daniel J; Tan, Tina P; Molokin, Aleksey; Smith, Keisha Herbin; Roberts, Robert F; Shara, Nawar M; Mete, Mihriye; Sanders, Mary Ellen; Solano-Aguilar, Gloria

2015-01-01

Probiotics are live microorganisms that, when administered in sufficient doses, provide health benefits on the host. The United States Food and Drug Administration (FDA) requires phase I safety studies for probiotics when the intended use of the product is as a drug. The purpose of the study was to determine the safety of Bifidobacterium animalis subsp lactis (B. lactis) strain BB-12 (BB-12)-supplemented yogurt when consumed by a generally healthy group of adults who were prescribed a 10-day course of antibiotics for a respiratory infection. Secondary aims were to assess the ability of BB-12 to affect the expression of whole blood immune markers associated with cell activation and inflammatory response. A phase I, double-blinded, randomized controlled study was conducted in compliance with FDA guidelines for an Investigational New Drug (IND). Forty participants were randomly assigned to consume 4 ounces of either BB-12 -supplemented yogurt or non-supplemented control yogurt daily for 10 d. The primary outcome was to assess safety and tolerability, assessed by the number of reported adverse events. A total of 165 non-serious adverse events were reported, with no differences between the control and BB-12 groups. When compared to the control group, B lactis fecal levels were modestly higher in the BB-12-supplemented group. In a small subset of patients, changes in whole blood expression of genes associated with regulation and activation of immune cells were detected in the BB-12-supplemented group. BB-12-supplemented yogurt is safe and well tolerated when consumed by healthy adults concurrently taking antibiotics. This study will form the basis for future randomized clinical trials investigating the potential immunomodulatory effects of BB-12-supplemented yogurt in a variety of disease states.

Voluntary, Randomized, Student Drug-Testing: Impact in a Rural, Low-Income, Community

Science.gov (United States)

Barrington, Kyle D.

2008-01-01

Illegal drug use and abuse by the nation's secondary school students is a continuing public health issue and this is especially true for students living in rural, low-income areas where access to intervention and treatment services is often limited. To address this issue, some school districts have implemented voluntary, randomized, student …

Insomnia From Drug Treatments: Evidence From Meta-analyses of Randomized Trials and Concordance With Prescribing Information.

Science.gov (United States)

Doufas, Anthony G; Panagiotou, Orestis A; Panousis, Periklis; Wong, Shane Shucheng; Ioannidis, John P A

2017-01-01

To determine whether drugs used to treat diverse conditions cause insomnia symptoms and whether their prescription information is concordant with this evidence. We conducted a survey of meta-analyses (Cochrane Database of Systematic Reviews) and comparisons with package inserts compiled in the Physicians' Desk Reference (PDR). We identified randomized controlled trials (RCTs) in which any drug had been evaluated vs placebo and sleep had been assessed. We collectively referred to insomnia-related outcomes as sleep disturbance. We also searched the PDR to identify any insomnia symptoms listed for drugs with RCT evidence available. Seventy-four Cochrane systematic reviews corresponding to 274 RCTs assessed 88 drugs in 27 different conditions, providing evidence on 109 drug-condition pairs. Of these 88 drugs, 5 decreased sleep problems and 19 increased sleep problems; 64 drugs had no nominally statistically significant effect on sleep. Acetylcholinesterase inhibitors, dopamine agonists, and selective serotonin reuptake inhibitors were the drug classes most importantly associated with sleep disturbance. Of 35 drugs that included disturbed sleep as an adverse effect in the PDR, only 14 had RCT evidence supporting such effect, and 2 had evidence of increasing and decreasing sleep problems in RCTs, although this was not shown in the PDR. We identified weak concordance between the PDR and RCTs (weighted κ=0.31; P<.001). The RCTs offer substantial evidence about the common effects of drugs on the risk of sleep disturbance; currently, prescription information only partially agrees with the available randomized evidence. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Network meta-analysis of randomized trials in multiple myeloma: efficacy and safety in relapsed/refractory patients.

Science.gov (United States)

Botta, Cirino; Ciliberto, Domenico; Rossi, Marco; Staropoli, Nicoletta; Cucè, Maria; Galeano, Teresa; Tagliaferri, Pierosandro; Tassone, Pierfrancesco

2017-02-28

Despite major therapeutic advancements, multiple myeloma (MM) is still incurable and relapsed/refractory multiple myeloma (RRMM) remains a challenge; the rational choice of the most appropriate regimen in this setting is currently undefined. We performed a systematic review and 2 standard pairwise meta-analyses to evaluate the efficacy of regimens that have been directly compared with bortezomib or immunomodulatory imide drugs (IMiDs) in head-to-head clinical trials and a network meta-analysis (NMA) to determine the relevance of each regimen on the basis of all the available direct and indirect evidence. Sixteen trials were included in the pairwise meta-analyses, and 18 trials were included in the NMA. Pairwise meta-analyses showed that a 3-drug regimen (bortezomib- or IMiD-based) was superior to a 2-drug regimen in progression-free-survival (PFS) and overall response rate (ORR). NMA showed that an IMiD backbone associated with anti-MM monoclonal antibodies (mAbs) (preferably) or proteasome inhibitors had the highest probability of being the most effective regimen with the lowest toxicity. The combination of daratumumab, lenalidomide, and dexamethasone ranked as the first regimen in terms of activity, efficacy, and tolerability according to the average value between surface under the cumulative ranking curve of PFS, overall survival, ORR, complete response rate, and safety. This is the first NMA comparing all currently available regimens evaluated in published randomized trials for the treatment of RRMM, but our results need to be interpreted taking into account differences in their patient populations. Our analysis suggests that IMiDs plus new anti-MM mAb-containing regimens are the most active therapeutic option in RRMM.

Random safety auditing, root cause analysis, failure mode and effects analysis.

Science.gov (United States)

Ursprung, Robert; Gray, James

2010-03-01

Improving quality and safety in health care is a major concern for health care providers, the general public, and policy makers. Errors and quality issues are leading causes of morbidity and mortality across the health care industry. There is evidence that patients in the neonatal intensive care unit (NICU) are at high risk for serious medical errors. To facilitate compliance with safe practices, many institutions have established quality-assurance monitoring procedures. Three techniques that have been found useful in the health care setting are failure mode and effects analysis, root cause analysis, and random safety auditing. When used together, these techniques are effective tools for system analysis and redesign focused on providing safe delivery of care in the complex NICU system. Copyright 2010 Elsevier Inc. All rights reserved.

Social Media Impact of the Food and Drug Administration's Drug Safety Communication Messaging About Zolpidem: Mixed-Methods Analysis.

Science.gov (United States)

Sinha, Michael S; Freifeld, Clark C; Brownstein, John S; Donneyong, Macarius M; Rausch, Paula; Lappin, Brian M; Zhou, Esther H; Dal Pan, Gerald J; Pawar, Ajinkya M; Hwang, Thomas J; Avorn, Jerry; Kesselheim, Aaron S

2018-01-05

The Food and Drug Administration (FDA) issues drug safety communications (DSCs) to health care professionals, patients, and the public when safety issues emerge related to FDA-approved drug products. These safety messages are disseminated through social media to ensure broad uptake. The objective of this study was to assess the social media dissemination of 2 DSCs released in 2013 for the sleep aid zolpidem. We used the MedWatcher Social program and the DataSift historic query tool to aggregate Twitter and Facebook posts from October 1, 2012 through August 31, 2013, a period beginning approximately 3 months before the first DSC and ending 3 months after the second. Posts were categorized as (1) junk, (2) mention, and (3) adverse event (AE) based on a score between -0.2 (completely unrelated) to 1 (perfectly related). We also looked at Google Trends data and Wikipedia edits for the same time period. Google Trends search volume is scaled on a range of 0 to 100 and includes "Related queries" during the relevant time periods. An interrupted time series (ITS) analysis assessed the impact of DSCs on the counts of posts with specific mention of zolpidem-containing products. Chow tests for known structural breaks were conducted on data from Twitter, Facebook, and Google Trends. Finally, Wikipedia edits were pulled from the website's editorial history, which lists all revisions to a given page and the editor's identity. In total, 174,286 Twitter posts and 59,641 Facebook posts met entry criteria. Of those, 16.63% (28,989/174,286) of Twitter posts and 25.91% (15,453/59,641) of Facebook posts were labeled as junk and excluded. AEs and mentions represented 9.21% (16,051/174,286) and 74.16% (129,246/174,286) of Twitter posts and 5.11% (3,050/59,641) and 68.98% (41,138/59,641) of Facebook posts, respectively. Total daily counts of posts about zolpidem-containing products increased on Twitter and Facebook on the day of the first DSC; Google searches increased on the week of the

Clinical Trial Electronic Portals for Expedited Safety Reporting: Recommendations from the Clinical Trials Transformation Initiative Investigational New Drug Safety Advancement Project.

Science.gov (United States)

Perez, Raymond P; Finnigan, Shanda; Patel, Krupa; Whitney, Shanell; Forrest, Annemarie

2016-12-15

Use of electronic clinical trial portals has increased in recent years to assist with sponsor-investigator communication, safety reporting, and clinical trial management. Electronic portals can help reduce time and costs associated with processing paperwork and add security measures; however, there is a lack of information on clinical trial investigative staff's perceived challenges and benefits of using portals. The Clinical Trials Transformation Initiative (CTTI) sought to (1) identify challenges to investigator receipt and management of investigational new drug (IND) safety reports at oncologic investigative sites and coordinating centers and (2) facilitate adoption of best practices for communicating and managing IND safety reports using electronic portals. CTTI, a public-private partnership to improve the conduct of clinical trials, distributed surveys and conducted interviews in an opinion-gathering effort to record investigator and research staff views on electronic portals in the context of the new safety reporting requirements described in the US Food and Drug Administration's final rule (Code of Federal Regulations Title 21 Section 312). The project focused on receipt, management, and review of safety reports as opposed to the reporting of adverse events. The top challenge investigators and staff identified in using individual sponsor portals was remembering several complex individual passwords to access each site. Also, certain tasks are time-consuming (eg, downloading reports) due to slow sites or difficulties associated with particular operating systems or software. To improve user experiences, respondents suggested that portals function independently of browsers and operating systems, have intuitive interfaces with easy navigation, and incorporate additional features that would allow users to filter, search, and batch safety reports. Results indicate that an ideal system for sharing expedited IND safety information is through a central portal used by

Partial safety factor calibration from stochastic finite element computation of welded joint with random geometries

International Nuclear Information System (INIS)

Schoefs, Franck; Chevreuil, Mathilde; Pasqualini, Olivier; Cazuguel, Mikaël

2016-01-01

Welded joints are used in various structures and infrastructures like bridges, ships and offshore structures, and are submitted to cyclic stresses. Their fatigue behaviour is an industrial key issue to deal with and still offers original research subjects. One of the available methods relies on the computing of the stress concentration factor. Even if some studies were previously driven to evaluate this factor onto some cases of welded structures, the shape of the weld joint is generally idealized through a deterministic parametric geometry. Previous experimental works however have shown that this shape plays a key role in the lifetime assessment. We propose in this paper a methodology for computing the stress concentration factor in presence of random geometries of welded joints. In view to make the results available by engineers, this method merges stochastic computation and semi-probabilistic analysis by computing partial safety factors with a dedicated method. - Highlights: • Numerical computation of stress concentration factor with random geometry of weld. • Real data are used for probabilistic modelling. • Identification of partial safety factor from SFEM computation in case of random geometries.

Efficacy and safety of immunomodulatory drugs in patients with anterior uveitis: A systematic literature review.

Science.gov (United States)

Gómez-Gómez, Alejandro; Loza, Estíbaliz; Rosario, Maria Piedad; Espinosa, Gerard; Morales, José M García Ruiz de; Herreras, Jose M; Muñoz-Fernández, Santiago; Cordero-Coma, Miguel

2017-10-01

To assess the efficacy and safety of immunomodulatory drugs in patients with noninfectious anterior uveitis (AU). Systematic review of studies were retrieved from Medline (1961 to March 2016), Embase (1961 to March 2016), and Cochrane Library (up to March 2016), and a complementary hand search was also performed. The selection criteria were as follows: (population) noninfectious AU patients, adults; (intervention) immunomodulatory drugs (any dose, regimen, route of administration, duration of treatment); (outcome) control of inflammation, steroid-sparing effect, AU flares, adverse events, and so on; (study design) systematic literature reviews, randomized controlled trials, and observational studies. The study quality was assessed using the Jadad scale and according to The Oxford Centre for Evidence-based Medicine (update 2009). We included 13 studies of moderate-poor quality, with a mean duration from 5 months to 20 years, and number of AU patients ranging from 9 to 274. Patient's demographic and clinical characteristics were very heterogeneous. In most cases, uveitis anatomic classification criteria and outcomes definitions were unclear. Some of the studies only included AU patients with a systemic disease associated, mostly spondyloarthritis, others, mixed populations (idiopathic and systemic disease associated patients), and in some articles this data is not described. We found that methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might prevent AU flares, improve ocular inflammation and visual acuity, and decrease systemic steroids doses. Although there is a lack of robust evidence, methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might be effective in AU patients.

77 FR 72905 - Pipeline Safety: Random Drug Testing Rate; Contractor MIS Reporting; and Obtaining DAMIS Sign-In...

Science.gov (United States)

2012-12-06

... DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety Administration [Docket ID... DAMIS Sign-In Information AGENCY: Pipeline and Hazardous Materials Safety Administration (PHMSA), DOT..., hazardous liquid, and carbon dioxide pipelines and operators of liquefied natural gas facilities must...

Pregnant womens' concerns when invited to a randomized trial: a qualitative case control study

NARCIS (Netherlands)

Oude Rengerink, Katrien; Logtenberg, Sabine; Hooft, Lotty; Bossuyt, Patrick M.; Mol, Ben Willem

2015-01-01

Pregnant women were excluded from clinical trials until the 1990s, but the Food and Drug Administration nowadays allows--and even encourages--responsible inclusion of pregnant women in trials with adequate safety monitoring. Still, randomized trials in pregnant women face specific enrolment

Pregnant womens' concerns when invited to a randomized trial : a qualitative case control study

NARCIS (Netherlands)

Oude Rengerink, Katrien; Logtenberg, Sabine; Hooft, Lotty; Bossuyt, Patrick M; Mol, Ben Willem; Oude Rengerink, K

2015-01-01

BACKGROUND: Pregnant women were excluded from clinical trials until the 1990s, but the Food and Drug Administration nowadays allows--and even encourages--responsible inclusion of pregnant women in trials with adequate safety monitoring. Still, randomized trials in pregnant women face specific

Efficacy and safety of rabeprazole in non-steroidal anti-inflammatory drug-induced ulcer in Japan.

Science.gov (United States)

Mizokami, Yuji

2009-10-28

To investigate the efficacy and safety of rabeprazole under continuous non-steroidal anti-inflammatory drug (NSAID) administration for NSAID-induced ulcer in Japan. Subjects comprised patients undergoing NSAID treatment in whom upper gastrointestinal endoscopy revealed an ulcerous lesion (open ulcer) with diameter > or = 3 mm, who required continuous NSAID treatment. Endoscopies were performed at the start of treatment, during the treatment period, and at the conclusion (or discontinuation) of treatment. Findings were evaluated as size (maximum diameter) and stage based on the Sakita-Miwa classification. An ulcer was regarded as cured when the "white coating" was seen to have disappeared under endoscopy. As criteria for evaluating safety, all medically untoward symptoms and signs (adverse events, laboratory abnormalities, accidental symptoms, etc.) occurring after the start of rabeprazole treatment were handled as adverse events. Endoscopic cure rate in 38 patients in the efficacy analysis (endoscopic evaluation) was 71.1% (27/38). Among those 38 patients, 35 had gastric ulcer with a cure rate of 71.4% (25/35), and 3 had duodenal ulcer with a cure rate of 66.7% (2/3). Three adverse drug reactions were reported from 64 patients in the safety analysis (interstitial pneumonia, low white blood cell count and pruritus); thus, the incidence rate for adverse drug reactions was 4.7% (3/64). The treatment efficacy of rabeprazole for NSAID-induced ulcer under continuous NSAID administration was confirmed.

The safety, efficacy and regulatory triangle in drug development: Impact for animal models and the use of animals.

Science.gov (United States)

van Meer, Peter J K; Graham, Melanie L; Schuurman, Henk-Jan

2015-07-15

Nonclinical studies in animals are conducted to demonstrate proof-of-concept, mechanism of action and safety of new drugs. For a large part, in particular safety assessment, studies are done in compliance with international regulatory guidance. However, animal models supporting the initiation of clinical trials have their limitations, related to uncertainty regarding the predictive value for a clinical condition. The 3Rs principles (refinement, reduction and replacement) are better applied nowadays, with a more comprehensive application with respect to the original definition. This regards also regulatory guidance, so that opportunities exist to revise or reduce regulatory guidance with the perspective that the optimal balance between scientifically relevant data and animal wellbeing or a reduction in animal use can be achieved. In this manuscript we review the connections in the triangle between nonclinical efficacy/safety studies and regulatory aspects, with focus on in vivo testing of drugs. These connections differ for different drugs (chemistry-based low molecular weight compounds, recombinant proteins, cell therapy or gene therapy products). Regarding animal models and their translational value we focus on regulatory aspects and indications where scientific outcomes warrant changes, reduction or replacement, like for, e.g., biosimilar evaluation and safety testing of monoclonal antibodies. On the other hand, we present applications where translational value has been clearly demonstrated, e.g., immunosuppressives in transplantation. Especially for drugs of more recent date like recombinant proteins, cell therapy products and gene therapy products, a regulatory approach that allows the possibility to conduct combined efficacy/safety testing in validated animal models should strengthen scientific outcomes and improve translational value, while reducing the numbers of animals necessary. Copyright © 2015 Elsevier B.V. All rights reserved.

Efficacy and safety of gemcitabine-fluorouracil combination therapy in the management of advanced pancreatic cancer: a meta-analysis of randomized controlled trials.

Directory of Open Access Journals (Sweden)

Qin Li

Full Text Available Gemcitabine (GEM is the standard first-line chemotherapy that provides limited clinical benefits for patients with locally advanced/metastatic pancreatic adenocarcinoma (LA/MPC. However, the fluorouracil derivatives (CAP and S-1 show promising efficacy in these patients. This study compared the efficacy and safety of GEM with GEM plus fluorouracil drugs in the treatment of LA/MPC.Pubmed, EMBASE and Cochrane Library databases were searched for relevant randomized controlled trials published on or before January 2014. The Cochrane Collaboration's tool was used to assess the risk of bias in randomized trials. The primary end point was overall survival (OS; the secondary end points were one-year survival rate, objective response rate (ORR and toxicity rates (TRs.A total of 8 randomized controlled trials involving 2,126 patients were included in the systematic evaluation. The results showed that OS was significantly improved (HR 0.83, P<0.01; HR 0.87, P = 0.03; HR 0.80, P = 0.01; respectively and ORR was significantly increased (OR 0.51, P<0.01; OR 0.66, P = 0.03; OR 0.35, P<0.01; respectively in the GEM+5-FU/CAP/S-1, GEM+CAP and GEM+S-1 groups compared to the GEM alone group. In addition, the one-year survival rate was significantly increased (OR 0.78 P = 0.01; OR 0.47, P = 0.04; respectively in the GEM+5-FU/CAP/S-1 and GEM+S-1 groups compared to the GEM alone group. The frequency of grade 3/4 TRs were higher in GEM+5-FU/CAP/S-1 group, the significant increase of grade 3/4 neutropenia, thrombocytopenia and diarrhea were observed.GEM combined with fluorouracil drugs significantly improved OS and increased one-year survival rate and ORR compared to GEM alone in LA/MPC patients. GEM combined with fluorouracil drugs may be considered as an acceptable alternative treatment for LA/MPC patients.

Challenges and strategies to facilitate formulation development of pediatric drug products: Safety qualification of excipients.

Science.gov (United States)

Buckley, Lorrene A; Salunke, Smita; Thompson, Karen; Baer, Gerri; Fegley, Darren; Turner, Mark A

2018-02-05

A public workshop entitled "Challenges and strategies to facilitate formulation development of pediatric drug products" focused on current status and gaps as well as recommendations for risk-based strategies to support the development of pediatric age-appropriate drug products. Representatives from industry, academia, and regulatory agencies discussed the issues within plenary, panel, and case-study breakout sessions. By enabling practical and meaningful discussion between scientists representing the diversity of involved disciplines (formulators, nonclinical scientists, clinicians, and regulators) and geographies (eg, US, EU), the Excipients Safety workshop session was successful in providing specific and key recommendations for defining paths forward. Leveraging orthogonal sources of data (eg. food industry, agro science), collaborative data sharing, and increased awareness of the existing sources such as the Safety and Toxicity of Excipients for Paediatrics (STEP) database will be important to address the gap in excipients knowledge needed for risk assessment. The importance of defining risk-based approaches to safety assessments for excipients vital to pediatric formulations was emphasized, as was the need for meaningful stakeholder (eg, patient, caregiver) engagement. Copyright © 2017 Elsevier B.V. All rights reserved.

Drug Safety: Managing Multiple Drugs

Science.gov (United States)

... This series is produced by Consumers Union and Consumer Reports Best Buy Drugs , a public information project sup- ported by grants from the Engelberg Foundation and the National Library of Medicine of ... Consumer and Prescriber Education Grant Program which is funded ...

Levofloxacin?Induced QTc Prolongation Depends on the Time of Drug Administration

OpenAIRE

Kervezee, L; Gotta, V; Stevens, J; Birkhoff, W; Kamerling, IMC; Danhof, M; Meijer, JH; Burggraaf, J

2016-01-01

Understanding the factors influencing a drug's potential to prolong the QTc interval on an electrocardiogram is essential for the correct evaluation of its safety profile. To explore the effect of dosing time on drug-induced QTc prolongation, a randomized, crossover, clinical trial was conducted in which 12 healthy male subjects received levofloxacin at 02:00, 06:00, 10:00, 14:00, 18:00, and 22:00. Using a pharmacokinetic-pharmacodynamic (PK-PD) modeling approach to account for variations in ...

‘Zero Tolerance’ Drug Driving Laws in Australia: A Gap Between Rationale and Form?

Directory of Open Access Journals (Sweden)

Julia Ann Quilter

2017-08-01

Full Text Available Legislation in all Australian states and territories creates offences and provides for police roadside testing in relation to ‘drug driving’. Ostensibly motivated by the same road safety objectives and impairment paradigm as drink driving laws, drug driving laws adopt a significantly different approach. Whereas random breath testing tests for all forms of alcohol and is designed to determine whether there is a sufficient concentration of alcohol in the driver’s body that s/he should be deemed to be impaired, random drug testing typically tests for the presence of any quantity of only the three most widely used illicit drugs—cannabis, methamphetamine and ecstasy—in the driver’s oral fluids, without reference to what is known about the different pharmacokinetic and pharmacodynamic qualities of different drugs. This article examines this idiosyncratic approach to the criminalisation of drug driving, highlighting its weak correlation with the important road safety objective of deterring substance-impaired driving, and the risks of both over- and under-criminalisation that it creates. It argues that public policy on the prohibition of certain drugs and the criminalisation of their use should be disentangled from public policy on impaired driving. It recommends that drug driving laws in all Australian jurisdictions should be brought back into line with drink driving laws, via legislation and testing practices that turn on substance-specific prescribed concentrations for all drugs (illicit and licit that have the potential to impair drivers.

Clinical efficacy and safety of cisapride and clebopride in the management of chronic functional dyspepsia: a double-blind, randomized study.

Science.gov (United States)

Sabbatini, F; Minieri, M; Manzi, G; Piai, G; D'Angelo, V; Mazzacca, G

1991-01-01

The clinical efficacy and the safety of chronic oral administration of cisapride, a new gastrointestinal prokinetic agent, (10 mg tid) and clebopride (0.5 mg tid) was assayed in 48 outpatients affected with functional dyspepsia, in a randomized double-blind study. Each of the drugs induced a significant reduction in dyspeptic symptoms after 2 and 4 weeks (p less than 0.001). Two patients, given clebopride, dropped out of the study because of severe side effects during the first week of treatment. Mild adverse reactions were reported in 6 out of 23 cisapride-treated patients and in 10 out of 20 clebopride-treated patients who completed the study. The most common side effect of cisapride was diarrhoea and that of clebopride was drowsiness. Cisapride appears to be as effective as clebopride in reducing dyspeptic symptoms and seems to induce less severe side effects.

Radioiodine therapy versus antithyroid drugs in Graves' disease: a meta-analysis of randomized controlled trials

Science.gov (United States)

Qin, Lan

2016-01-01

Objective: This meta-analysis was performed to compare radioiodine therapy with antithyroid drugs in terms of clinical outcomes, including development or worsening of ophthalmopathy, hyperthyroid cure rate, hypothyroidism, relapse rate and adverse events. Methods: Randomized controlled trials (RCTs) published in PubMed, Embase, Web of Science, SinoMed and National Knowledge Infrastructure, China, were systematically reviewed to compare the effects of radioiodine therapy with antithyroid drugs in patients with Graves' disease. Results were expressed as risk ratio with 95% confidence intervals (CIs) and weighted mean differences with 95% CIs. Pooled estimates were performed using a fixed-effects model or random-effects model, depending on the heterogeneity among studies. Results: 17 RCTs involving 4024 patients met the inclusion criteria and were included. Results showed that radioiodine treatment has increased risk in new ophthalmopathy, development or worsening of ophthalmopathy and hypothyroidism. Whereas, compared with antithyroid drugs, radioiodine treatment seems to have a higher hyperthyroid cure rate, lower recurrence rate and lower incidence of adverse events. Conclusion: Radioiodine therapy is associated with a higher hyperthyroid cure rate and lower relapse rate compared with antithyroid drugs. However, it also increases the risk of ophthalmopathy and hypothyroidism. Advances in knowledge: Considering that antithyroid drug treatment can be associated with unsatisfactory control of hyperthyroidism, we would recommend radioiodine therapy as the treatment of choice for patients with Graves' disease. PMID:27266544

Determination of Initial Conditions for the Safety Analysis by Random Sampling of Operating Parameters

International Nuclear Information System (INIS)

Jeong, Hae-Yong; Park, Moon-Ghu

2015-01-01

In most existing evaluation methodologies, which follow a conservative approach, the most conservative initial conditions are searched for each transient scenario through tremendous assessment for wide operating windows or limiting conditions for operation (LCO) allowed by the operating guidelines. In this procedure, a user effect could be involved and a remarkable time and human resources are consumed. In the present study, we investigated a more effective statistical method for the selection of the most conservative initial condition by the use of random sampling of operating parameters affecting the initial conditions. A method for the determination of initial conditions based on random sampling of plant design parameters is proposed. This method is expected to be applied for the selection of the most conservative initial plant conditions in the safety analysis using a conservative evaluation methodology. In the method, it is suggested that the initial conditions of reactor coolant flow rate, pressurizer level, pressurizer pressure, and SG level are adjusted by controlling the pump rated flow, setpoints of PLCS, PPCS, and FWCS, respectively. The proposed technique is expected to contribute to eliminate the human factors introduced in the conventional safety analysis procedure and also to reduce the human resources invested in the safety evaluation of nuclear power plants

Determination of safety margins for whole blood concentrations of alcohol and nineteen drugs in driving under the influence cases.

Science.gov (United States)

Kristoffersen, Lena; Strand, Dag Helge; Liane, Veronica Horpestad; Vindenes, Vigdis; Tvete, Ingunn Fride; Aldrin, Magne

2016-02-01

Legislative limits for driving under the influence of 20 non-alcohol drugs were introduced in Norway in February 2012. Per se limits corresponding to blood alcohol concentrations (BAC) of 0.2g/kg were established for 20 psychoactive drugs, and limits for graded sanctions corresponding to BACs of 0.5 and 1.2g/kg were determined for 13 of these drugs. This new legislation made it possible for the courts to make sentences based on the analytical results, similar to the situation for alcohol. To ensure that the reported concentration is as least as high as the true concentration, with a 99% safety level, safety margins had to be calculated for each of the substances. Diazepam, tetrahydrocannabinol (THC) and alcohol were used as model substances to establish a new model for estimating the safety margins. The model was compared with a previous used model established several years ago, by a similar yet much simpler model, and they were found to be in agreement. The measurement uncertainties depend on the standard batch used, the work list and the measurements' replicate. A Bayesian modelling approach was used to determine the parameters in the model, using a dataset of 4700 diazepam positive specimens and 5400 THC positive specimens. Different safety margins were considered for low and high concentration levels of diazepam (≤2μM (0.6mg/L) and >2μM) and THC (≤0.01μM (0.003mg/L) and >0.01μM). The safety margins were for diazepam 19.5% (≤2μM) and 34% (>2μM), for THC 19.5% (≤0.01μM) and 24.9% (>0.01μM). Concentration dependent safety margins for BAC were based on a dataset of 29500 alcohol positive specimens, and were in the range 10.4% (0.1g/kg) to 4.0% (4.0g/kg) at a 99% safety level. A simplified approach was used to establish safety margins for the compounds amphetamine, MDMA, methamphetamine, alprazolam, phenazepam, flunitrazepam, clonazepam, nitrazepam, oxazepam, buprenorphine, GHB, methadone, ketamine, cocaine, morphine, zolpidem and zopiclone. The

Specialty pharmacies and other restricted drug distribution systems: financial and safety considerations for patients and health-system pharmacists.

Science.gov (United States)

Kirschenbaum, Bonnie E

2009-12-15

To discuss the role of restricted drug distribution systems in the implementation of risk evaluation and mitigation strategies (REMS), health-system pharmacists' concerns associated with the use of specialty pharmacies and other restricted drug distribution systems, reimbursement policies for high-cost specialty drugs, supply chain models for traditional and specialty drugs, and emerging trends in the management of and reimbursement for specialty pharmaceuticals. Restricted drug distribution systems established by pharmaceutical manufacturers, specialty pharmacies, or other specialty suppliers may be a component of REMS, which are required by the Food and Drug Administration for the management of known or potential serious risks from certain drugs. Concerns of health-system pharmacists using specialty suppliers include access to pharmaceuticals, operational challenges, product integrity, financial implications, continuity of care, and patient safety. An ambulatory care patient taking a specialty drug product from home to a hospital outpatient clinic or inpatient setting for administration, a practice known as "brown bagging," raises concerns about product integrity and institutional liability. An institution's finances, tolerance for liability, and ability to skillfully manage the processes involved often determine its choice between an approach that prohibits brown bagging but is costly and one that permits the practice under certain conditions and is less costly. The recent shift from a traditional supply chain model to a specialty pharmacy supply chain model for high-cost pharmaceuticals has the potential to increase pharmaceutical costs for health systems. A dialogue is needed between health-system pharmacists and group purchasing organizations to address the latter's role in mitigating the financial implications of this change and to help clarify the safety issues. Some health plans have shifted part of the cost of expensive drugs to patients by establishing a

Pharmacokinetics and Safety of DW1029M, a Botanical Drug for the Treatment of Diabetic Nephropathy, Following Single Doses in Healthy Subjects.

Science.gov (United States)

Kim, Yunjeong; Jeon, Ji-Young; Kim, Eun-Young; Lim, Cheol-Hee; Jang, Hwan Bong; Kim, Min-Gul

2017-09-01

DW1029M is a botanical extract of Morus albalinne root bark and Puerariae radix that is used for the treatment of diabetic nephropathy. This study evaluated the safety and pharmacokinetics of DW1029M following its administration in healthy Korean subjects. We conducted a randomized, open-label, single-dose, crossover phase 1 clinical study. During each period, subjects received 300, 600, or 1200 mg oral doses of DW1029M. Plasma concentrations of puerarin, daidzin, and daidzein were analyzed using a liquid chromatography-tandem mass spectrometry. Six healthy male subjects completed the study. The maximum concentration of the drug in the plasma (C max ) and area under the plasma drug concentration-time curve to the last measurable concentration (AUC last ) for puerarin, daidzin, and daidzein were assessed after oral administration of DW1029M. No serious adverse events or clinically or statistically significant adverse events associated with any of the drug levels were observed. The results of the measurement of vital signs, electrocardiogram, laboratory tests, and physical examinations indicated that no clinically significant changes occurred during this study. The DW1029M tablet was safe and well tolerated over a single dose range of 300-1200 mg. This pharmacokinetic study of a botanical drug may aid in the development of DW1029M. © 2017, The American College of Clinical Pharmacology.

A tailored online safety and health intervention for women experiencing intimate partner violence: the iCAN Plan 4 Safety randomized controlled trial protocol

Directory of Open Access Journals (Sweden)

Marilyn Ford-Gilboe

2017-03-01

Full Text Available Abstract Background Intimate partner violence (IPV threatens the safety and health of women worldwide. Safety planning is a widely recommended, evidence-based intervention for women experiencing IPV, yet fewer than 1 in 5 Canadian women access safety planning through domestic violence services. Rural, Indigenous, racialized, and immigrant women, those who prioritize their privacy, and/or women who have partners other than men, face unique safety risks and access barriers. Online IPV interventions tailored to the unique features of women’s lives, and to maximize choice and control, have potential to reduce access barriers, and improve fit and inclusiveness, maximizing effectiveness of these interventions for diverse groups. Methods/Design In this double blind randomized controlled trial, 450 Canadian women who have experienced IPV in the previous 6 months will be randomized to either a tailored, interactive online safety and health intervention (iCAN Plan 4 Safety or general online safety information (usual care. iCAN engages women in activities designed to increase their awareness of safety risks, reflect on their plans for their relationships and priorities, and create a personalize action plan of strategies and resources for addressing their safety and health concerns. Self-reported outcome measures will be collected at baseline and 3, 6, and 12 months post-baseline. Primary outcomes are depressive symptoms (Center for Epidemiological Studies Depression Scale, Revised and PTSD Symptoms (PTSD Checklist, Civilian Version. Secondary outcomes include helpful safety actions, safety planning self-efficacy, mastery, and decisional conflict. In-depth qualitative interviews with approximately 60 women who have completed the trial and website utilization data will be used to explore women’s engagement with the intervention and processes of change. Discussion This trial will contribute timely evidence about the effectiveness of online safety and

Reliability assessment for safety critical systems by statistical random testing

International Nuclear Information System (INIS)

Mills, S.E.

1995-11-01

In this report we present an overview of reliability assessment for software and focus on some basic aspects of assessing reliability for safety critical systems by statistical random testing. We also discuss possible deviations from some essential assumptions on which the general methodology is based. These deviations appear quite likely in practical applications. We present and discuss possible remedies and adjustments and then undertake applying this methodology to a portion of the SDS1 software. We also indicate shortcomings of the methodology and possible avenues to address to follow to address these problems. (author). 128 refs., 11 tabs., 31 figs

Reliability assessment for safety critical systems by statistical random testing

Energy Technology Data Exchange (ETDEWEB)

Mills, S E [Carleton Univ., Ottawa, ON (Canada). Statistical Consulting Centre

1995-11-01

In this report we present an overview of reliability assessment for software and focus on some basic aspects of assessing reliability for safety critical systems by statistical random testing. We also discuss possible deviations from some essential assumptions on which the general methodology is based. These deviations appear quite likely in practical applications. We present and discuss possible remedies and adjustments and then undertake applying this methodology to a portion of the SDS1 software. We also indicate shortcomings of the methodology and possible avenues to address to follow to address these problems. (author). 128 refs., 11 tabs., 31 figs.

Efficacy and safety of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Asian patients with hypertension: a randomized, double-blind, placebo-controlled study.

Science.gov (United States)

Kario, Kazuomi; Sun, Ningling; Chiang, Fu-Tien; Supasyndh, Ouppatham; Baek, Sang Hong; Inubushi-Molessa, Akiko; Zhang, Ying; Gotou, Hiromi; Lefkowitz, Martin; Zhang, Jack

2014-04-01

LCZ696 (Japanese adopted name: sucabitril valsartan sodium hydrate), a first-in-class angiotensin receptor neprilysin inhibitor, concomitantly inhibits neprilysin and blocks angiotensin type 1 receptor. This randomized, double-blind, placebo-controlled study, the first in Asia for this drug, evaluated the dose-related efficacy and safety of LCZ696 in patients with hypertension using 24-hour ambulatory blood pressure (BP) monitoring. Asian patients aged ≥18 years (n=389) with hypertension were randomized to receive LCZ696 100 mg (n=100), 200 mg (n=101), 400 mg (n=96), or placebo (n=92) for 8 weeks. The primary end point was mean difference across the 3 single-dose pairwise comparisons of LCZ696 versus placebo in clinic diastolic BP after 8-week treatment. Key secondary efficacy variables included changes in clinic systolic BP and pulse pressure and changes in 24-hour, daytime, and nighttime ambulatory BPs and pulse pressure. Safety assessments included recording all adverse events and serious adverse events. A total of 362 patients completed the study. Reductions in clinic systolic BP, diastolic BP (Phypertension in Asian population and, in general, is safe and well tolerated. Clinical Trial Information- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01193101.

Safety and performance of the second generation EnligHTN™ Renal Denervation System in patients with drug-resistant, uncontrolled hypertension.

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Worthley, Stephen G; Wilkins, Gerard T; Webster, Mark W; Montarello, Joseph K; Delacroix, Sinny; Whitbourn, Robert J; Warren, Roderic J

2017-07-01

Catheter-based renal denervation for the treatment of drug-resistant hypertension has been intensively investigated in recent years. To date, only limited data have been published using multi-electrode radiofrequency ablation systems that can deliver lesions with a pre-determined pattern. This study was designed to evaluate the safety and performance of the second generation EnligHTN™ Renal Denervation System. This first-in-human, prospective, multi-center, non-randomized study included 39 patients (62% male, mean age 63 years, and mean baseline office blood pressure 174/93 mmHg) with drug-resistant hypertension. The primary safety and performance objectives were to characterize, from baseline to 6 months post procedure, the rate of serious procedural and device related adverse events, as adjudicated by an independent Clinical Events Committee, and the reduction of office systolic blood pressure. Renal artery denervation, using the second generation EnligHTN multi-electrode system significantly reduced office blood pressure from baseline to 1, 3, 6, 12, 18 and 24 months by 19/7, 26/9, 25/7, 23/7, 25/8 and 27/9 mmHg, respectively (p ≤ 0.0005). No serious device or procedure related adverse events affecting the renal arteries or renal function occurred through 24 months of follow-up. Renal sympathetic denervation using the second generation EnligHTN Renal Denervation System resulted in safe, rapid, and significant mean office blood pressure reduction that was sustained through 24 months. Future studies will need to address the utility of this system against an appropriate sham based comparator. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Interventional procedures and future drug therapy for hypertension

Science.gov (United States)

Lobo, Melvin D.; Sobotka, Paul A.; Pathak, Atul

2017-01-01

Hypertension management poses a major challenge to clinicians globally once non-drug (lifestyle) measures have failed to control blood pressure (BP). Although drug treatment strategies to lower BP are well described, poor control rates of hypertension, even in the first world, suggest that more needs to be done to surmount the problem. A major issue is non-adherence to antihypertensive drugs, which is caused in part by drug intolerance due to side effects. More effective antihypertensive drugs are therefore required which have excellent tolerability and safety profiles in addition to being efficacious. For those patients who either do not tolerate or wish to take medication for hypertension or in whom BP control is not attained despite multiple antihypertensives, a novel class of interventional procedures to manage hypertension has emerged. While most of these target various aspects of the sympathetic nervous system regulation of BP, an additional procedure is now available, which addresses mechanical aspects of the circulation. Most of these new devices are supported by early and encouraging evidence for both safety and efficacy, although it is clear that more rigorous randomized controlled trial data will be essential before any of the technologies can be adopted as a standard of care. PMID:27406184

Efficacy and Safety of Ivermectin Against Trichuris trichiura in Preschool- and School-Aged Children: A Randomized Controlled Dose-Finding Trial.

Science.gov (United States)

Wimmersberger, David; Coulibaly, Jean T; Schulz, Jessica; Puchkow, Maxim; Huwyler, Jörg; N'Gbesso, Yves; Hattendorf, Jan; Keiser, Jennifer

2018-03-30

Although trichuriasis affects millions of children worldwide, recommended drugs lack efficacy and new treatment options are urgently needed. Ivermectin has promising potential to complement the anthelminthic armamentarium. A randomized placebo-controlled trial was conducted in rural Côte d'Ivoire to provide evidence on the efficacy and safety of ascending oral ivermectin dosages in preschool-aged children and in schoolchildren infected with Trichuris trichiura. Primary outcome was cure rate on T. trichiura infection and secondary outcomes were safety, egg-reduction rates against T. trichiura infection, and cure and egg-reduction rates against other soil-transmitted helminth species. 126 preschool-aged and 166 school-aged children were included in an available case analysis. In preschool-aged children efficacy against T. trichiura did not differ between 200 µg/kg ivermectin and placebo as expressed in cure rates (20.9% [95% CI 11.9-52.8%] vs. 19.5% [95% CI 10.4-49.9%]) and geometric mean egg-reduction rates (78.6% [95% CI 60.1-89.5%] vs. 68.2% [95% CI 40.5 to 84.8%]). In school-aged children even a dose of 600 µg/kg ivermectin revealed a low cure rate (12.2% [95% CI 4.8-32.3%] and moderate egg-reduction rate (66.3% [95% CI 43.8-80.2%]. Only mild adverse events and no organ toxicity based on serum biomarkers was observed. Ivermectin can be administered safely to preschool-aged children suffering from trichuriasis. Given the low efficacy of ivermectin monotherapy against T. trichiura infection further research should investigate the optimal drug combinations and dosages with ivermectin against soil-transmitted helminthiasis. The trial is registered at www.isrctn.com, number ISRCTN15871729.

Efficacy and Safety of Levosulpiride Versus Haloperidol Injection in Patients With Acute Psychosis: A Randomized Double-Blind Study.

Science.gov (United States)

Lavania, Sagar; Praharaj, Samir Kumar; Bains, Hariender Singh; Sinha, Vishal; Kumar, Abhinav

2016-01-01

Injectable antipsychotics are frequently required for controlling agitation and aggression in acute psychosis. No study has examined the use of injectable levosulpiride for this indication. To compare the efficacy and safety of injectable levosulpiride and haloperidol in patients with acute psychosis. This was a randomized, double-blind, parallel-group study in which 60 drug-naive patients having acute psychosis were randomly assigned to receive either intramuscular haloperidol (10-20 mg/d) or levosulpiride (25-50 mg/d) for 5 days. All patients were rated on Brief Psychiatric Rating Scale (BPRS), Overt Agitation Severity Scale (OASS), Overt Aggression Scale-Modified (OAS-M) scores, Simpson Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS). Repeated-measures ANOVA for BPRS scores showed significant effect of time (P haloperidol group as shown by group × time interaction (P = 0.076). Repeated-measures ANOVA for OASS showed significant effect of time (P haloperidol group as shown by group × time interaction (P = 0.032). Lorazepam requirement was much lower in haloperidol group as compared with those receiving levosulpiride (P = 0.022). Higher rates of akathisia and extrapyramidal symptoms were noted in the haloperidol group. Haloperidol was more effective than levosulpiride injection for psychotic symptoms, aggression, and severity of agitation in acute psychosis, but extrapyramidal adverse effects were less frequent with levosulpiride as compared with those receiving haloperidol.

Suspected adverse drug reactions in elderly patients reported to the Committee on Safety of Medicines.

Science.gov (United States)

Castleden, C M; Pickles, H

1988-10-01

1. Spontaneous reports of suspected adverse drug reactions (ADRs) reported to the Committee on Safety of Medicines (CSM) have been studied in relation to patient age. 2. The proportion of reports received for the elderly increased between 1965 and 1983. 3. There was a correlation between the use of drugs and the number of ADR reports. Thus age-related prescription figures for two non-steroidal anti-inflammatory drugs (NSAI) and co-trimoxazole matched ADR reports for each drug in each age group. 4. The reported ADR was more likely to be serious or fatal in the elderly. 5. The commonest ADRs reported for the elderly affected the gastrointestinal (GIT) and haemopoietic systems, where more reports were received than would be expected from prescription figures. 6. The drug suspected of causing a GIT reaction was a NSAI in 75% of the reports. 7. Ninety-one per cent of fatal reports of GIT bleeds and perforations associated with NSAI drugs were in patients over 60 years of age.

A novel algorithm for analyzing drug-drug interactions from MEDLINE literature.

Science.gov (United States)

Lu, Yin; Shen, Dan; Pietsch, Maxwell; Nagar, Chetan; Fadli, Zayd; Huang, Hong; Tu, Yi-Cheng; Cheng, Feng

2015-11-27

Drug-drug interaction (DDI) is becoming a serious clinical safety issue as the use of multiple medications becomes more common. Searching the MEDLINE database for journal articles related to DDI produces over 330,000 results. It is impossible to read and summarize these references manually. As the volume of biomedical reference in the MEDLINE database continues to expand at a rapid pace, automatic identification of DDIs from literature is becoming increasingly important. In this article, we present a random-sampling-based statistical algorithm to identify possible DDIs and the underlying mechanism from the substances field of MEDLINE records. The substances terms are essentially carriers of compound (including protein) information in a MEDLINE record. Four case studies on warfarin, ibuprofen, furosemide and sertraline implied that our method was able to rank possible DDIs with high accuracy (90.0% for warfarin, 83.3% for ibuprofen, 70.0% for furosemide and 100% for sertraline in the top 10% of a list of compounds ranked by p-value). A social network analysis of substance terms was also performed to construct networks between proteins and drug pairs to elucidate how the two drugs could interact.

A primary care, electronic health record-based strategy to promote safe drug use: study protocol for a randomized controlled trial.

Science.gov (United States)

Przytula, Kamila; Bailey, Stacy Cooper; Galanter, William L; Lambert, Bruce L; Shrestha, Neeha; Dickens, Carolyn; Falck, Suzanne; Wolf, Michael S

2015-01-27

The Northwestern University Center for Education and Research on Therapeutics (CERT), funded by the Agency for Healthcare Research and Quality, is one of seven such centers in the USA. The thematic focus of the Northwestern CERT is 'Tools for Optimizing Medication Safety.' Ensuring drug safety is essential, as many adults struggle to take medications, with estimates indicating that only half of adults take drugs as prescribed. This report describes the methods and rationale for one innovative project within the CERT: the 'Primary Care, Electronic Health Record-Based Strategy to Promote Safe and Appropriate Drug Use'. The overall objective of this 5-year study is to evaluate a health literacy-informed, electronic health record-based strategy for promoting safe and effective prescription medication use in a primary care setting. A total of 600 English and Spanish-speaking patients with diabetes will be consecutively recruited to participate in the study. Patients will be randomized to receive either usual care or the intervention; those in the intervention arm will receive a set of print materials designed to support medication use and prompt provider counseling and medication reconciliation. Participants will be interviewed in person after their index clinic visit and again one month later. Process outcomes related to intervention delivery will be recorded. A medical chart review will be performed at 6 months. Patient outcome measures include medication understanding, adherence and clinical measures (hemoglobin A1c, blood pressure, and cholesterol; exploratory outcomes only). Through this study, we will be able to examine the impact of a health literacy-informed, electronic health record-based strategy on medication understanding and adherence among diabetic primary care patients. The measurement of process outcomes will help inform how the strategy might ultimately be refined and disseminated to other sites. Strategies such as these are needed to address the

Nonsteroidal anti-inflammatory drug gastropathy: new avenues for safety

Directory of Open Access Journals (Sweden)

Roth SH

2011-05-01

Full Text Available Sanford H RothArizona Research and Education, Arthritis Laboratory, Arizona State University, Phoenix, AZ, USAAbstract: Chronic oral or systemic nonselective nonsteroidal anti-inflammatory drug (NSAID therapy, ubiquitously used by physicians to treat osteoarthritis-associated pain, is associated with a wide range of symptomatic adverse events, the most frequent and serious of which is gastropathy. Although cardiovascular and renal problems are a very real concern, they are significantly less frequent. These complications can be life-threatening in at-risk populations such as older adults, who are common users of long-term oral systemic NSAID therapy. Topical NSAID formulations deliver effective doses of analgesics directly to the affected joints, thereby limiting systemic exposure and potentially the risk of systemic adverse events, such as gastropathy and serious cardiovascular events. There are currently two topical NSAIDs approved by the US Food and Drug Administration for osteoarthritis-associated pain, as well as for the signs and symptoms of osteoarthritis. This review discusses the relative safety, and the gastrointestinal, cardiovascular, and renal risks of chronic oral or systemic NSAID therapy and topical NSAID formulations in patients with osteoarthritis.Keywords: NSAIDs, osteoarthritis, topical administration, synovial fluid, peptic ulcer, Helicobacter pylori

Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis.

Science.gov (United States)

Trelle, Sven; Reichenbach, Stephan; Wandel, Simon; Hildebrand, Pius; Tschannen, Beatrice; Villiger, Peter M; Egger, Matthias; Jüni, Peter

2011-01-11

To analyse the available evidence on cardiovascular safety of non-steroidal anti-inflammatory drugs. Network meta-analysis. Bibliographic databases, conference proceedings, study registers, the Food and Drug Administration website, reference lists of relevant articles, and reports citing relevant articles through the Science Citation Index (last update July 2009). Manufacturers of celecoxib and lumiracoxib provided additional data. All large scale randomised controlled trials comparing any non-steroidal anti-inflammatory drug with other non-steroidal anti-inflammatory drugs or placebo. Two investigators independently assessed eligibility. The primary outcome was myocardial infarction. Secondary outcomes included stroke, death from cardiovascular disease, and death from any cause. Two investigators independently extracted data. 31 trials in 116 429 patients with more than 115 000 patient years of follow-up were included. Patients were allocated to naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, lumiracoxib, or placebo. Compared with placebo, rofecoxib was associated with the highest risk of myocardial infarction (rate ratio 2.12, 95% credibility interval 1.26 to 3.56), followed by lumiracoxib (2.00, 0.71 to 6.21). Ibuprofen was associated with the highest risk of stroke (3.36, 1.00 to 11.6), followed by diclofenac (2.86, 1.09 to 8.36). Etoricoxib (4.07, 1.23 to 15.7) and diclofenac (3.98, 1.48 to 12.7) were associated with the highest risk of cardiovascular death. Although uncertainty remains, little evidence exists to suggest that any of the investigated drugs are safe in cardiovascular terms. Naproxen seemed least harmful. Cardiovascular risk needs to be taken into account when prescribing any non-steroidal anti-inflammatory drug.

[Drug supply chain safety in hospitals: current data and experience of the Grenoble university hospital].

Science.gov (United States)

Bedouch, P; Baudrant, M; Detavernier, M; Rey, C; Brudieu, E; Foroni, L; Allenet, B; Calop, J

2009-01-01

Drug supply chain safety has become a priority for public health which implies a collective process. This process associates all health professionals including the pharmacist who plays a major role. The objective of this present paper is to describe the several approaches proven effective in the reduction of drug-related problem in hospital, illustrated by the Grenoble University Hospital experience. The pharmacist gets involved first in the general strategy of hospital drug supply chain, second by his direct implication in clinical activities. The general strategy of drug supply chain combines risk management, coordination of the Pharmacy and Therapeutics Committee, selection and purchase of drugs and organisation of drug supply chain. Computer management of drug supply chain is a major evolution. Nominative drug delivering has to be a prior objective and its implementation modalities have to be defined: centralized or decentralized in wards, manual or automated. Also, new technologies allow the automation of overall drug distribution from central pharmacy and the implementation of automated drug dispensing systems into wards. The development of centralised drug preparation allows a safe compounding of high risk drugs, like cytotoxic drugs. The pharmacist should develop his clinical activities with patients and other health care professionals in order to optimise clinical decisions (medication review, drug order analysis) and patients follow-up (therapeutic monitoring, patient education, discharge consultation).

Effect of sanhuangwuji powder, anti-rheumatic drugs, and ginger-partitioned acupoint stimulation on the treatment of rheumatoid arthritis with peptic ulcer: a randomized controlled study.

Science.gov (United States)

Liu, Defang; Guo, Mingyang; Hu, Yonghe; Liu, Taihua; Yan, Jiao; Luo, Yong; Yun, Mingdong; Yang, Min; Zhang, Jun; Guo, Linglin

2015-06-01

To observe the efficacy and safety of oral sanhuangwuji powder, anti-rheumatic drugs (ARDs), and ginger-partitioned acupoint stimulation at zusanli (ST 36) on the treatment of rheumatoid arthritis (RA) complicated by peptic ulcer. This prospective randomized controlled study included 180 eligible inpatients and outpatients randomly assigned to an ARD treatment (n.= 60), ginger-partitioned stimulation (n = 60), or combination treatment (n = 60). Patients assigned to the ARD group were given oral celecoxib, methotrexate, and esomeprazole. Patients assigned to the ginger-partitioned stimulation group were given ginger-partitioned acupoint stimulation at zusanli (ST 36) in addition to the ARDs. Patients in the combination treatment group were given oral sanhuangwuji powder, ginger-partitioned acupoint stimulation at susanli (ST 36), and ARDs. All patients were followed up for 2 months to evaluate clinical effects and safety. The study was registered in the World Health Organization database at the General Hospital of Chengdu Military Area Command Chinese People's Liberation Army (ChiCTR-TCC12002824). The combination treatment group had significantly greater improvements in RA symptoms, laboratory outcomes, and gastrointestinal symptom scores, compared with the other groups (P ginger-partitioned stimulation group (χ2= 6.171, P ginger-partitioned acupoint stimulation at zusanli (ST 36), oral sanhuangwuji powder, and ARDs had a better clinical effect for RA with complicated peptic ulcer, compared with ARD treatmentalone or in combination with ginger-partitioned acupoint stimulation.

COMPARATIVE STUDY OF NEW DRUG OF LONG ACTING METOPROLOL TARTRATE - EGILOK RETARD AND ORIGINAL DRUG OF METOPROLOL SUCCINATE – BETALOC ZOK IN PATIENTS WITH MILD TO MODERATE ARTERIAL HYPERTENSION

Directory of Open Access Journals (Sweden)

J. V. Lukina

2015-12-01

Full Text Available Aim. To study efficiency and safety of new drug of long acting metoprolol tartrate, “Egilok retard” (ER in patients with mild to moderate arterial hypertension (AH in comparison with the original drug of metoprolol succinat, “Betaloc ZOK” (BZ, possibility of reaching target blood pressure (BP level with treatment with each drug.Material and methods. 30 patients (11 men and 19 women with mild to moderate AH took part in randomized, open, cross over study. Previous antihypertensive treatment had been canceled for all the patients 10-14 days before the study started. Each patient by turns was treated during 6 weeks with ER and BZ 50-100 mg daily. After cancellation of the previous antihypertensive therapy, BZ and ER were prescribed (according to the randomization table in dose 50 mg daily. Drugs were taken once per day. 29 patients completed therapy with the first drug of randomization, 25 patients – with the second. After 2 weeks efficiency of treatment was assessed by target BP level achievement (< 140/90 mmHg. If efficiency of beta-adrenoblocker (BB was not sufficient, the dose of the drug was doubled to 100 mg daily, if target level was reached – the dose remained unchanged. Treatment with the settled dose was held within next 4 weeks. After 6-week treatment with the first randomized drug antihypertensive therapy was canceled for 10-14 days depending on the BB dose. At each visit office BP and heart rate were assessed, EKG was registered. Side-effects were registered according to the self-control diary, questionnaire results, examination and EKG data.Results. After 6-week treatment with ER and BZ average level of systolic BP reduced by 15,7 and 15,2 mmHg, of diastolic BP – by 8,0 and 4,5 mmHg, heart rate – by 4,1 and 4,3 beat/min respectively. Differences between antihypertensive and heart rate lowering effect of the studied drugs were not significant. Target BP level with treatment with both drugs was reached in approximately

COMPARATIVE STUDY OF NEW DRUG OF LONG ACTING METOPROLOL TARTRATE - EGILOK RETARD AND ORIGINAL DRUG OF METOPROLOL SUCCINATE – BETALOC ZOK IN PATIENTS WITH MILD TO MODERATE ARTERIAL HYPERTENSION

Directory of Open Access Journals (Sweden)

J. V. Lukina

2005-01-01

Full Text Available Aim. To study efficiency and safety of new drug of long acting metoprolol tartrate, “Egilok retard” (ER in patients with mild to moderate arterial hypertension (AH in comparison with the original drug of metoprolol succinat, “Betaloc ZOK” (BZ, possibility of reaching target blood pressure (BP level with treatment with each drug.Material and methods. 30 patients (11 men and 19 women with mild to moderate AH took part in randomized, open, cross over study. Previous antihypertensive treatment had been canceled for all the patients 10-14 days before the study started. Each patient by turns was treated during 6 weeks with ER and BZ 50-100 mg daily. After cancellation of the previous antihypertensive therapy, BZ and ER were prescribed (according to the randomization table in dose 50 mg daily. Drugs were taken once per day. 29 patients completed therapy with the first drug of randomization, 25 patients – with the second. After 2 weeks efficiency of treatment was assessed by target BP level achievement (< 140/90 mmHg. If efficiency of beta-adrenoblocker (BB was not sufficient, the dose of the drug was doubled to 100 mg daily, if target level was reached – the dose remained unchanged. Treatment with the settled dose was held within next 4 weeks. After 6-week treatment with the first randomized drug antihypertensive therapy was canceled for 10-14 days depending on the BB dose. At each visit office BP and heart rate were assessed, EKG was registered. Side-effects were registered according to the self-control diary, questionnaire results, examination and EKG data.Results. After 6-week treatment with ER and BZ average level of systolic BP reduced by 15,7 and 15,2 mmHg, of diastolic BP – by 8,0 and 4,5 mmHg, heart rate – by 4,1 and 4,3 beat/min respectively. Differences between antihypertensive and heart rate lowering effect of the studied drugs were not significant. Target BP level with treatment with both drugs was reached in approximately

Drug safety evaluation of defibrotide.

Science.gov (United States)

Richardson, Paul G; Corbacioglu, Selim; Ho, Vincent Trien-Vinh; Kernan, Nancy A; Lehmann, Leslie; Maguire, Craig; Maglio, Michelle; Hoyle, Margaret; Sardella, Marco; Giralt, Sergio; Holler, Ernst; Carreras, Enric; Niederwieser, Dietger; Soiffer, Robert

2013-01-01

Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of chemotherapeutic conditioning used in preparation for hematopoietic stem-cell transplantation (SCT). Defibrotide (DF) has been shown in Phase II and III trials to improve complete response in patients with severe VOD (sVOD). None of the articles, to date, provide a comprehensive review of the safety of DF in VOD and/or a range of other conditions. This article reviews current clinical findings on DF, primarily in terms of safety for use in treatment and prophylaxis of VOD, and relevant safety data for its use in other diseases. The literature review was conducted using a PubMed search with the fixed term 'defibrotide' in combination with ≥ 1 of 'safety', 'veno-occlusive disease' (with and without 'treatment', 'prevention'), 'oncology', 'myeloma', 'microangiopathy', 'anti-thrombotic' and 'peripheral vascular disorder'. Related articles from the EBMT and ASH conference websites were also included. DF was well tolerated in majority of the studies. The safety profile of DF is largely favourable with toxicities comparable to control populations in the setting of SCT complicated by sVOD.

Randomized Controlled Evaluation of the "Too Good for Drugs" Prevention Program: Impact on Adolescents at Different Risk Levels for Drug Use

Science.gov (United States)

Hall, Bruce W.; Bacon, Tina P.; Ferron, John M.

2013-01-01

Sixth graders participating in the "Too Good for Drugs" (TGFD) prevention program in comparison to 6th graders not participating show different results by student risk level. Sixth graders from 20 middle schools were randomly assigned to receive the intervention and those from 20 paired middle schools assigned to serve as controls (N =…

Safety and effectiveness of drug therapy for the acutely agitated patient (Part 2

Directory of Open Access Journals (Sweden)

Gianluca Airoldi

2013-04-01

Full Text Available Acute agitation occurs in a variety of medical and psychiatric conditions, and the management of agitated, abusive, or violent patients is a common problem in the emergency department. Rapid control of potentially dangerous behaviors by physical restraint and pharmacologic tranquillization is crucial to ensure the safety of the patient and health-care personnel and to allow diagnostic procedures and treatment of the underlying condition. The purpose of this article (the second in a 2-part series is to review published data on the efficacy and safety of antipsychotic medications currently available for managing situations of this type. Arrhythmias caused by QT-prolonging drugs occur infrequently, and multiple factors are often involved, including concomitant use of other drugs affecting the same pathway (most antipsychotic drugs prolong the QT interval by blocking potassium IKr current in HERG channels of myocardial cells, electrolyte disorders and, possibly, genetic predisposition. Judicious use of typical antipsychotics (mainly haloperidol and benzodiazepines (mainly lorazepam, given intramuscularly alone or in combination, has proved to be safe and effective for controlling acute motor agitation related to psychiatric illness; cocaine, methamphetamine, and ethanol toxicity; ethanol withdrawal; and other factors. They are still widely used and are particularly useful when limited data are available on the patient’s history of cardiovascular disease, current use of medication, and/or the likelihood of illicit drug or alcohol intoxication; when the diagnosis involves medical comorbidity or intoxication; or when there is no specific treatment (e.g., personality disorders, learning disabilities, mental retardation, organic brain damage. If rapid tranquillization is necessary before a formal diagnosis can be made and there are uncertainties regarding the patient’s medical history, lorazepam is often considered the first-line drug of choice. In

Efficacy and Safety of Cerebrolysin for Acute Ischemic Stroke: A Meta-Analysis of Randomized Controlled Trials

Directory of Open Access Journals (Sweden)

Danfeng Zhang

2017-01-01

Full Text Available Cerebrolysin was reported to be effective in the neurological improvement of patients with acute ischemic stroke (AIS in experimental models, while data from clinical trials were inconsistent. We performed a meta-analysis to explore the efficacy and safety of cerebrolysin for AIS. PubMed, EMBASE, and Cochrane Library were searched for randomized controlled trials, which intervened within 72 hours after the stroke onset. We investigated the efficacy and safety outcomes, respectively. Risk ratios and mean differences were pooled with fixed-effects model or random-effects model. Seven studies were identified, involving 1779 patients with AIS. The summary results failed to demonstrate significant superiority of cerebrolysin in the assessment of efficacy outcomes of mRS and BI. Similarly, administration of cerebrolysin had neutral effects on safety outcomes compared with placebo, including mortality and SAE. However, the number of included studies was small, especially in the analysis of efficacy outcomes, which might cause publication bias and inaccurate between-studies variance in the meta-analysis. Conclusively, although it seemed to be safe, routine use of cerebrolysin to improve the long-term rehabilitation after stroke could not be supported by available evidence.

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.

Safety and Efficacy of Catheter Direct Thrombolysis in Management of Acute Iliofemoral Deep Vein Thrombosis: A Systematic Review.

Science.gov (United States)

Elbasty, Ahmed; Metcalf, James

2017-12-01

Catheter direct thrombolysis (CDT) has been shown to be an effective treatment for deep venous thrombosis. The objective of the review is to improve safety and efficacy of the CDT by using ward based protocol, better able to predict complications and treatment outcome through monitoring of haemostatic parameters and clinical observation during thrombolysis procedure. MEDLINE, EMBASE, CENTRAL and Web of Science were searched for all articles on deep venous thrombosis, thrombolysis and correlations of clinical events (bleeding, successful thrombolysis) during thrombolysis with hemostatic parameters to March 2016. The risk of bias in included studies was assessed by Cochrane Collaboration's tool and Cochrane Risk of Bias Assessment Tool: for Non-Randomized Studies of Interventions. Twenty-four studies were included in the review and we found that improving safety and efficacy of CDT by using ward based protocol depending on eight factors; strict patient selection criteria, types of fibrinolytic drugs, mode of fibrinolytic drug injection, biochemical markers monitoring (fibrinogen, D-dimer, activated partial thromboplastin time, plasminogen activator inhibitor-1), timing of intervention, usage of intermittent pneumatic calf, ward monitoring and thrombolysis imaging assessment (intravascular ultrasound). These factors may help to improve safety and efficacy by reducing total thrombolytic drug dosage and at the same time ensure successful lysis. There is a marked lack of randomized controlled trials discussing the safety and efficacy of catheter direct thrombolysis. CDT can be performed safely and efficiently in clinical ward, providing that careful nursing, biochemical monitoring, proper selection and mode of infusion of fibrinolytic drugs, usage of Intermittent pneumatic calf and adequate thrombolysis imaging assessment are ensured.

Epigenetics and cancer: implications for drug discovery and safety assessment

International Nuclear Information System (INIS)

Moggs, Jonathan G.; Goodman, Jay I.; Trosko, James E.; Roberts, Ruth A.

2004-01-01

It is necessary to determine whether chemicals or drugs have the potential to pose a threat to human health. Research conducted over the last two decades has led to the paradigm that chemicals can cause cancer either by damaging DNA or by altering cellular growth, probably via receptor-mediated changes in gene expression. However, recent evidence suggests that gene expression can be altered markedly via several diverse epigenetic mechanisms that can lead to permanent or reversible changes in cellular behavior. Key molecular events underlying these mechanisms include the alteration of DNA methylation and chromatin, and changes in the function of cell surface molecules. Thus, for example, DNA methyltransferase enzymes together with chromatin-associated proteins such as histone modifying enzymes and remodelling factors can modify the genetic code and contribute to the establishment and maintenance of altered epigenetic states. This is relevant to many types of toxicity including but not limited to cancer. In this paper, we describe the potential for interplay between genetic alteration and epigenetic changes in cell growth regulation and discuss the implications for drug discovery and safety assessment

Analysis of physicochemical properties of ternary systems of oxaprozin with randomly methylated-ß-cyclodextrin and l-arginine aimed to improve the drug solubility.

Science.gov (United States)

Mennini, Natascia; Maestrelli, Francesca; Cirri, Marzia; Mura, Paola

2016-09-10

The influence of l-arginine on the complexing and solubilizing power of randomly-methylated-β-cyclodextrin (RameβCD) towards oxaprozin, a very poorly soluble anti-inflammatory drug, was examined. The interactions between the components were investigated both in solution, by phase-solubility analysis, and in the solid state, by differential scanning calorimetry, FTIR and X-ray powder diffractometry. The morphology of the solid products was examined by Scanning Electron Microscopy. Results of phase-solubility studies indicated that addition of arginine enhanced the RameβCD complexing and solubilizing power of about 3.0 and 4.5 times, respectively, in comparison with the binary complex (both at pH≈6.8). The effect of arginine was not simply additive, but synergistic, being the ternary system solubility higher than the sum of those of the respective drug-CD and drug-arginine binary systems. Solid equimolar ternary systems were prepared by physical mixing, co-grinding, coevaporation and kneading techniques, to explore the effect of the preparation method on the physicochemical properties of the final products. The ternary co-ground product exhibited a dramatic increase in both drug dissolution efficiency and percent dissolved at 60min, whose values (83.6 and 97.1, respectively) were about 3 times higher than the sum of those given by the respective drug-CD and drug-aminoacid binary systems. Therefore, the ternary co-ground system with arginine and RameβCD appears as a very valuable product for the development of new more effective delivery systems of oxaprozin, with improved safety and bioavailability. Copyright © 2016 Elsevier B.V. All rights reserved.

Efficacy and safety of oral antidiabetic drugs in comparison to insulin in treating gestational diabetes mellitus: a meta-analysis.

Directory of Open Access Journals (Sweden)

Nalinee Poolsup

Full Text Available OBJECTIVE: To assess the efficacy and safety of oral antidiabetic drugs (OADs in gestational diabetes mellitus (GDM in comparison to insulin. METHODS: A meta-analysis of randomized controlled trials was conducted. The efficacy and safety of OADs in comparison to insulin in GDM patients were explored. Studies were identified by conducting a literature search using the electronic databases of Medline, CENTRAL, CINAHL, LILACS, Scopus and Web of Science in addition to conducting hand search of relevant journals from inception until October 2013. RESULTS: Thirteen studies involving 2,151 patients met the inclusion criteria. These studies were randomized controlled trials of metformin and glyburide in comparison to insulin therapy. Our results indicated a significant increase in the risk for preterm births (RR, 1.51; 95% CI, 1.04-2.19, p = 0.03 with metformin compared to insulin. However, a significant decrease in the risk for gestational hypertension (RR, 0.54; 95% CI, 0.31-0.91, p = 0.02 was found. Postprandial glucose levels also decreased significantly in patients receiving metformin (MD, -2.47 mg/dL; 95% CI, -4.00, -0.94, p = 0.002. There was no significant difference between the two groups for the remaining outcomes. There were significant increases in the risks of macrosomia (RR, 2.34; 95% CI, 1.18-4.63, p = 0.03 and neonatal hypoglycemia (RR, 2.06; 95% CI, 1.27-3.34, p = 0.005 in the glyburide group compared to insulin whereas results for the other analyzed outcomes remained non-significant. CONCLUSION: The available evidence suggests favorable effects of metformin in treating GDM patients. Metformin seems to be an efficacious alternative to insulin and a better choice than glyburide especially those with mild form of disease.

Strategies to reduce safety violations for working from heights in construction companies: study protocol for a randomized controlled trial.

Science.gov (United States)

van der Molen, Henk F; Frings-Dresen, Monique H W

2014-05-31

Safety measures should be applied to reduce work-related fatal and non-fatal fall injuries. However, according to the labor inspectorate, more than 80% of Dutch construction sites violate safety regulations for working from heights. To increase compliance with safety regulations, employers and workers have to select, implement and monitor safety measures. To facilitate this behavioral change, stimulating knowledge awareness and personalized feedback are frequently advocated behavior change techniques. For this study, two behavior change strategies have been developed in addition to the announcement of safety inspections by the labor inspectorate. These strategies consist of 1) face-to-face contacts with safety consultants and 2) direct mail with access to internet facilities. The objective of this study is to evaluate the effectiveness of these two strategies on the safety violations for working from heights, the process and the cost measures. This study is a block randomized intervention trial in 27 cities to establish the effects of the face-to-face guidance strategy (N = 9), a direct mailing strategy (N = 9) and a control condition of no guidance (N = 9) on safety violations to record by labor inspectors after three months. A process evaluation for both strategies will be performed to determine program implementation (reach, dose delivered and dose received), satisfaction, knowledge and perceived safety behavior. A cost analysis will be performed to establish the financial costs for both strategies. The present study is in accordance with the CONSORT statement. This study increases insight into performing practice-based randomized controlled trials. The outcome will help to evaluate the effect of two guidance strategies on safety violations. If these strategies are effective, implementation of these strategies through the national institute of safety and health or labor inspectorate can take place to guide construction companies in complying with

Identifying co-targets to fight drug resistance based on a random walk model

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Chen Liang-Chun

2012-01-01

Full Text Available Abstract Background Drug resistance has now posed more severe and emergent threats to human health and infectious disease treatment. However, wet-lab approaches alone to counter drug resistance have so far still achieved limited success due to less knowledge about the underlying mechanisms of drug resistance. Our approach apply a heuristic search algorithm in order to extract active network under drug treatment and use a random walk model to identify potential co-targets for effective antibacterial drugs. Results We use interactome network of Mycobacterium tuberculosis and gene expression data which are treated with two kinds of antibiotic, Isoniazid and Ethionamide as our test data. Our analysis shows that the active drug-treated networks are associated with the trigger of fatty acid metabolism and synthesis and nicotinamide adenine dinucleotide (NADH-related processes and those results are consistent with the recent experimental findings. Efflux pumps processes appear to be the major mechanisms of resistance but SOS response is significantly up-regulation under Isoniazid treatment. We also successfully identify the potential co-targets with literature confirmed evidences which are related to the glycine-rich membrane, adenosine triphosphate energy and cell wall processes. Conclusions With gene expression and interactome data supported, our study points out possible pathways leading to the emergence of drug resistance under drug treatment. We develop a computational workflow for giving new insights to bacterial drug resistance which can be gained by a systematic and global analysis of the bacterial regulation network. Our study also discovers the potential co-targets with good properties in biological and graph theory aspects to overcome the problem of drug resistance.

Effectiveness of web-based tailored advice on parents' child safety behaviors: randomized controlled trial.

Science.gov (United States)

van Beelen, Mirjam Elisabeth Johanna; Beirens, Tinneke Monique Jozef; den Hertog, Paul; van Beeck, Eduard Ferdinand; Raat, Hein

2014-01-24

Injuries at home are a major cause of death, disability, and loss of quality of life among young children. Despite current safety education, required safety behavior of parents is often lacking. To prevent various childhood disorders, the application of Web-based tools has increased the effectiveness of health promotion efforts. Therefore, an intervention with Web-based, tailored, safety advice combined with personal counseling (E-Health4Uth home safety) was developed and applied. To evaluate the effect of E-Health4Uth home safety on parents' safety behaviors with regard to the prevention of falls, poisoning, drowning, and burns. A randomized controlled trial was conducted (2009-2011) among parents visiting well-baby clinics in the Netherlands. Parents were randomly assigned to the intervention group (E-Health4Uth home safety intervention) or to the control condition consisting of usual care. Parents in the intervention condition completed a Web-based safety behavior assessment questionnaire; the resulting tailored safety advice was discussed with their child health care professional at a well-baby visit (age approximately 11 months). Parents in the control condition received counseling using generic safety information leaflets at this well-baby visit. Parents' child safety behaviors were derived from self-report questionnaires at baseline (age 7 months) and at follow-up (age 17 months). Each specific safety behavior was classified as safe/unsafe and a total risk score was calculated. Logistic and linear regression analyses were used to reveal differences in safety behavior between the intervention and the control condition at follow-up. A total of 1292 parents (response rate 44.79%) were analyzed. At follow-up, parents in the intervention condition (n=643) showed significantly less unsafe behavior compared to parents in the control condition (n=649): top of staircase (23.91% vs. 32.19%; OR 0.65, 95% CI 0.50-0.85); bottom of staircase (63.53% vs. 71.94%; OR 0

Randomized trial of switching from prescribed non-selective non-steroidal anti-inflammatory drugs to prescribed celecoxib

DEFF Research Database (Denmark)

Macdonald, Thomas M; Hawkey, Chris J; Ford, Ian

2017-01-01

BACKGROUND: Selective cyclooxygenase-2 inhibitors and conventional non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) have been associated with adverse cardiovascular (CV) effects. We compared the CV safety of switching to celecoxib vs. continuing nsNSAID therapy in a European setting...

Predictive toxicology in drug safety

National Research Council Canada - National Science Library

Xu, Jinghai J; Urban, Laszlo

2011-01-01

.... It provides information on the present knowledge of drug side effects and their mitigation strategy during drug discovery, gives guidance for risk assessment, and promotes evidence-based toxicology...

Safety of Therapeutic Fever Induction in Cancer Patients Using Approved PAMP Drugs

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Uwe Rudolf Max Reuter

2018-04-01

Full Text Available William Coley, between 1895 and 1936, treated hundreds of cancer patients using infusions of fever inducing bacerial extracts. Similar experiments were done by Klyuyeva and co-workers in the 1940ies in Russia using trypanosoma extracts. Many remissions and cures were reported. We have conjectured that pathogen associated molecular pattern substances (PAMP are the molecular explanation for the beneficial treatments in both groups. We could show that a combination of PAMP can eradicate solid tumours in cancer mice if applied several times. Accordingly, we suggested to combine PAMP containing approved drugs to treat cancer patients using a protocol similar to the old fever induction regimen. In this retrospective phase-1 study we report on the fever induction capacity and safety of applications of bacterial extracts, combinations of bacterial extracts with approved drugs, and combinations of approved drugs in 131 mainly cancer patients. Adverse reactions were those which can be expected during a feverish infection and mild. Over 523 fever inductions, no severe adverse reaction was observed.

Non-clinical studies in the process of new drug development - Part II: Good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies.

Science.gov (United States)

Andrade, E L; Bento, A F; Cavalli, J; Oliveira, S K; Schwanke, R C; Siqueira, J M; Freitas, C S; Marcon, R; Calixto, J B

2016-12-12

The process of drug development involves non-clinical and clinical studies. Non-clinical studies are conducted using different protocols including animal studies, which mostly follow the Good Laboratory Practice (GLP) regulations. During the early pre-clinical development process, also known as Go/No-Go decision, a drug candidate needs to pass through several steps, such as determination of drug availability (studies on pharmacokinetics), absorption, distribution, metabolism and elimination (ADME) and preliminary studies that aim to investigate the candidate safety including genotoxicity, mutagenicity, safety pharmacology and general toxicology. These preliminary studies generally do not need to comply with GLP regulations. These studies aim at investigating the drug safety to obtain the first information about its tolerability in different systems that are relevant for further decisions. There are, however, other studies that should be performed according to GLP standards and are mandatory for the safe exposure to humans, such as repeated dose toxicity, genotoxicity and safety pharmacology. These studies must be conducted before the Investigational New Drug (IND) application. The package of non-clinical studies should cover all information needed for the safe transposition of drugs from animals to humans, generally based on the non-observed adverse effect level (NOAEL) obtained from general toxicity studies. After IND approval, other GLP experiments for the evaluation of chronic toxicity, reproductive and developmental toxicity, carcinogenicity and genotoxicity, are carried out during the clinical phase of development. However, the necessity of performing such studies depends on the new drug clinical application purpose.

Exploiting heterogeneous publicly available data sources for drug safety surveillance: computational framework and case studies.

Science.gov (United States)

Koutkias, Vassilis G; Lillo-Le Louët, Agnès; Jaulent, Marie-Christine

2017-02-01

Driven by the need of pharmacovigilance centres and companies to routinely collect and review all available data about adverse drug reactions (ADRs) and adverse events of interest, we introduce and validate a computational framework exploiting dominant as well as emerging publicly available data sources for drug safety surveillance. Our approach relies on appropriate query formulation for data acquisition and subsequent filtering, transformation and joint visualization of the obtained data. We acquired data from the FDA Adverse Event Reporting System (FAERS), PubMed and Twitter. In order to assess the validity and the robustness of the approach, we elaborated on two important case studies, namely, clozapine-induced cardiomyopathy/myocarditis versus haloperidol-induced cardiomyopathy/myocarditis, and apixaban-induced cerebral hemorrhage. The analysis of the obtained data provided interesting insights (identification of potential patient and health-care professional experiences regarding ADRs in Twitter, information/arguments against an ADR existence across all sources), while illustrating the benefits (complementing data from multiple sources to strengthen/confirm evidence) and the underlying challenges (selecting search terms, data presentation) of exploiting heterogeneous information sources, thereby advocating the need for the proposed framework. This work contributes in establishing a continuous learning system for drug safety surveillance by exploiting heterogeneous publicly available data sources via appropriate support tools.

Safety of a silicone elastomer vaginal ring as potential microbicide delivery method in African women: A Phase 1 randomized trial.

Science.gov (United States)

Nel, Annaléne; Martins, Janine; Bekker, Linda-Gail; Ramjee, Gita; Masenga, Gileard; Rees, Helen; van Niekerk, Neliëtte

2018-01-01

Women in sub-Saharan Africa are in urgent need of female-initiated human immunodeficiency virus (HIV) preventative methods. Vaginal rings are one dosage form in development for delivery of HIV microbicides. However, African women have limited experience with vaginal rings. This Phase I, randomized, crossover trial assessed and compared the safety, acceptability and adherence of a silicone elastomer placebo vaginal ring, intended as a microbicide delivery method, inserted for a 12-week period in healthy, HIV-negative, sexually active women in South Africa and Tanzania. 170 women, aged 18 to 35 years were enrolled with 88 women randomized to Group A, using a placebo vaginal ring for 12 weeks followed by a 12-week safety observation period. 82 women were randomized to Group B and observed for safety first, followed by a placebo vaginal ring for 12 weeks. Safety was assessed by clinical laboratory assessments, pelvic/colposcopy examinations and adverse events. Possible carry-over effect was addressed by ensuring no signs or symptoms of genital irritation at crossover. No safety concerns were identified for any safety variables assessed during the trial. No serious adverse events were reported considered related to the placebo vaginal ring. Vaginal candidiasis was the most common adverse event occurring in 11% of participants during each trial period. Vaginal discharge (2%), vaginal odour (2%), and bacterial vaginitis (2%) were assessed as possibly or probably related to the vaginal ring. Thirty-four percent of participants had sexually transmitted infections (STIs) at screening, compared to 12% of participants who tested positive for STIs at crossover and the final trial visit. Three participants (2%) tested HIV positive during the trial. The silicone elastomer vaginal ring had no safety concerns, demonstrating a profile favorable for further development for topical release of antiretroviral-based microbicides.

Computer-delivered indirect screening and brief intervention for drug use in the perinatal period: A randomized trial.

Science.gov (United States)

Ondersma, Steven J; Svikis, Dace S; Thacker, Casey; Resnicow, Ken; Beatty, Jessica R; Janisse, James; Puder, Karoline

2018-04-01

Under-reporting of drug use in the perinatal period is well-documented, and significantly limits the reach of proactive intervention approaches. The Wayne Indirect Drug Use Screener (WIDUS) focuses on correlates of drug use rather than use itself. This trial tested a computer-delivered, brief intervention designed for use with indirect screen-positive cases, seeking to motivate reductions in drug use without presuming its presence. Randomized clinical trial with 500 WIDUS-positive postpartum women recruited between August 14, 2012 and November 19, 2014. Participants were randomly assigned to either a time control condition or a single-session, tailored, indirect brief intervention. The primary outcome was days of drug use over the 6-month follow-up period; secondary outcomes included urine and hair analyses results at 3- and 6-month follow-up. All outcomes were measured by blinded evaluators. Of the 500 participants (252 intervention and 248 control), 36.1% of participants acknowledged drug use in the 3 months prior to pregnancy, but 89% tested positive at the 6-month follow-up. Participants rated the intervention as easy to use (4.9/5) and helpful (4.4/5). Analyses revealed no between-group differences in drug use (52% in the intervention group, vs. 53% among controls; OR 1.03). Exploratory analyses also showed that intervention effects were not moderated by baseline severity, WIDUS score, or readiness to change. The present trial showed no evidence of efficacy for an indirect, single-session, computer-delivered, brief intervention designed as a complement to indirect screening. More direct approaches that still do not presume active drug use may be possible and appropriate. Copyright © 2018 Elsevier B.V. All rights reserved.

Smart pumps and random safety audits in a Neonatal Intensive Care Unit: a new challenge for patient safety.

Science.gov (United States)

Bergon-Sendin, Elena; Perez-Grande, Carmen; Lora-Pablos, David; Moral-Pumarega, María Teresa; Melgar-Bonis, Ana; Peña-Peloche, Carmen; Diezma-Rodino, Mercedes; García-San Jose, Lidia; Cabañes-Alonso, Esther; Pallas-Alonso, Carmen Rosa

2015-12-11

Random safety audits (RSA) are a safety tool enabling prevention of adverse events, but they have not been widely used in hospitals. The aim of this study was to use RSAs to assess and compare the frequency of appropriate use of infusion pump safety systems in a Neonatal Intensive Care Unit (NICU) before and after quality improvement interventions and to analyse the intravenous medication programming data. Prospective, observational study comparing the frequency of appropriate use of Alaris® CC smart pumps through RSAs over two periods, from 1 January to 31 December 2012 and from 1 November 2014 to 31 January 2015. Appropriate use was defined as all evaluated variables being correctly programmed into the same device. Between the two periods they were established interventions to improve the use of pumps. The information recorded at the pumps with the new security system, also extracted for one year. Fifty-two measurements were collected during the first period and 160 measurements during the second period. The frequency of appropriate use was 73.13 % (117/160) in the second period versus 0 % (0/52) in the first period (p pumps in the NICU. The improvement strategies were effective for improving appropriate use and programming of the intravenous medication infusion pumps in our NICU.

78 FR 23273 - Determination That the OXYCONTIN (Oxycodone Hydrochloride) Drug Products Covered by New Drug...

Science.gov (United States)

2013-04-18

... mitigation strategy (REMS) http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationfor... Blueprint for Prescriber Education for Extended- Release and Long-Acting Opioid Analgesics'' ( http://www...

Random Forest Segregation of Drug Responses May define Regions of Biological Significance

Directory of Open Access Journals (Sweden)

Qasim eBukhari

2016-03-01

Full Text Available The ability to assess brain responses in unsupervised manner based on fMRI measure has remained a challenge. Here we have applied the Random Forest (RF method to detect differences in the pharmacological MRI (phMRI response in rats to treatment with an analgesic drug (buprenorphine as compared to control (saline. Three groups of animals were studied: two groups treated with different doses of the opioid buprenorphine, low (LD and high dose (HD, and one receiving saline. PhMRI responses were evaluated in 45 brain regions and RF analysis was applied to allocate rats to the individual treatment groups. RF analysis was able to identify drug effects based on differential phMRI responses in the hippocampus, amygdala, nucleus accumbens, superior colliculus and the lateral and posterior thalamus for drug vs. saline. These structures have high levels of mu opioid receptors. In addition these regions are involved in aversive signaling, which is inhibited by mu opioids. The results demonstrate that buprenorphine mediated phMRI responses comprise characteristic features that allow an unsupervised differentiation from placebo treated rats as well as the proper allocation to the respective drug dose group using the RF method, a method that has been successfully applied in clinical studies.

Multisite Randomized Trial of Behavioral Interventions for Women with Co-Occurring PTSD and Substance Use Disorders

Science.gov (United States)

Hien, Denise A.; Wells, Elizabeth A.; Jiang, Huiping; Suarez-Morales, Lourdes; Campbell, Aimee N. C.; Cohen, Lisa R.; Miele, Gloria M.; Killeen, Therese; Brigham, Gregory S.; Zhang, Yulei; Hansen, Cheri; Hodgkins, Candace; Hatch-Maillette, Mary; Brown, Chanda; Kulaga, Agatha; Kristman-Valente, Allison; Chu, Melissa; Sage, Robert; Robinson, James A.; Liu, David; Nunes, Edward V.

2009-01-01

The authors compared the effectiveness of the Seeking Safety group, cognitive-behavioral treatment for substance use disorder and posttraumatic stress disorder (PTSD), to an active comparison health education group (Women's Health Education [WHE]) within the National Institute on Drug Abuse's Clinical Trials Network. The authors randomized 353…

Efficacy and safety profile of linezolid in the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis: a systematic review and meta-analysis.

Science.gov (United States)

Agyeman, Akosua Adom; Ofori-Asenso, Richard

2016-06-22

Treatment options for drug-resistant tuberculosis are still limited. Linezolid has been recommended for treatment of patients with multidrug-resistant (MDR) or extensively-drug-resistant (XDR) tuberculosis, although uncertainties remain regarding its safety and tolerability in these circumstances. To systematically evaluate the existing evidence regarding the efficacy and tolerability of linezolid in the treatment of MDR or XDR tuberculosis. We conducted a systematic review and meta-analysis in accordance with the PRISMA guidelines. Searches were conducted in PubMed, Web of Science and EMBASE followed by direct search of abstracts in the International Journal of Tuberculosis and Lung Disease to retrieve primary studies published between January 2000 and January 2016 assessing linezolid efficacy and safety in the treatment of drug-resistant TB. We evaluated the occurrence of outcomes including culture conversion, treatment success and incidence of adverse events such as myelosuppression and neuropathy. Twenty-three (23) studies conducted in fourteen (14) countries and involving 507 patients were retrieved. Only 1 randomized controlled trial was identified and none of the identified studies involved participants from Africa. The pooled proportion for treatment success was 77.36 % (95 % CI = 71.38-82.83 %, I(2) = 37.6 %) with culture conversion rate determined as 88.45 % (95 % CI = 83.82-92.38 %, I(2) = 45.4 %). There was no strong evidence for both culture conversion (p = 0.0948) and treatment success (p = 0.0695) between linezolid daily doses ≤ 600 and > 600 mg. Only myelosuppression showed a strong statistical significance (p linezolid also showed no significance upon dose comparisons (p = 0.3213, p = 0.9050 respectively). Available evidence presents Linezolid as a viable option in the treatment of MDR/XDR TB although patients ought to be monitored closely for the incidence of major adverse events such as myelosuppression and

Pharmacovigilance and drug safety in Calabria (Italy): 2012 adverse events analysis.

Science.gov (United States)

Giofrè, Chiara; Scicchitano, Francesca; Palleria, Caterina; Mazzitello, Carmela; Ciriaco, Miriam; Gallelli, Luca; Paletta, Laura; Marrazzo, Giuseppina; Leporini, Christian; Ventrice, Pasquale; Carbone, Claudia; Saullo, Francesca; Rende, Pierandrea; Menniti, Michele; Mumoli, Laura; Chimirri, Serafina; Patanè, Marinella; Esposito, Stefania; Cilurzo, Felisa; Staltari, Orietta; Russo, Emilio; De Sarro, Giovambattista

2013-12-01

Pharmacovigilance (PV) is designed to monitor drugs continuously after their commercialization, assessing and improving their safety profile. The main objective is to increase the spontaneous reporting of adverse drug reactions (ADRs), in order to have a wide variety of information. The Italian Drug Agency (Agenzia Italiana del Farmaco [AIFA]) is financing several projects to increase reporting. In Calabria, a PV information center has been created in 2010. We obtained data using the database of the National Health Information System AIFA relatively to Italy and Calabria in the year 2012. Descriptive statistics were performed to analyze the ADRs. A total number of 461 ADRs have been reported in the year 2012 with an increase of 234% compared with 2011 (138 reports). Hospital doctors are the main source of this reporting (51.62%). Sorafenib (Nexavar(®)), the combination of amoxicillin/clavulanic acid and ketoprofen represent the drugs most frequently reported causing adverse reactions. Adverse events in female patients (61.83%) were more frequently reported, whereas the age groups "41-65" (39.07%) and "over 65" (27.9%) were the most affected. Calabria has had a positive increase in the number of ADRs reported, although it has not yet reached the gold standard set by World Health Organization (about 600 reports), the data have shown that PV culture is making inroads in this region and that PV projects stimulating and increasing PV knowledge are needed.

Pharmacovigilance and drug safety 2011 in Calabria (Italy: Adverse events analysis

Directory of Open Access Journals (Sweden)

Francesca Scicchitano

2012-01-01

Full Text Available Background : Pharmacovigilance assesses the safety profile of drugs. Its main aim is the increase of spontaneous reporting of adverse drug reactions (ADRs. The Italian Drug Agency (AIFA; Agenzia Italiana del Farmaco is financing several projects to the aim of increasing reporting, and in Calabria a Pharmacovigilance Information Centre has been created. Materials and Methods: We analyzed the AIFA database relatively to Calabria in the year 2011 and we have analyzed ADRs using descriptive statistics. We have also collected a questionnaire-based interview in order to describe the background knowledge in the field. Results : Regarding the number of AIFA reported ADRs from Calabria, a 38% increase (138 vs. 100 in comparison to 2010 was evidenced. Hospital Doctors represent the main source of signaling (71.7 %. Ketoprofene and the combination amoxicillin/clavulanic acid represent the most frequently reported drugs causing ADRs. Our questionnaires indicated that despite the health professionals have met at least once an ADR only a small percentage of them was reported to the authorities (37%. There is a very good knowledge of the ADR concept and reporting system (90% of interviewed distinguish an ADR and knows how to report it, and there is a strong interest in participating to training courses in the field (95% are interested. Conclusions : Despite Calabria has had a positive increase in the number of reported ADRs, the total number is very low and the pharmacovigilance culture is far from being achieved in this region.

Pharmacovigilance and drug safety 2011 in Calabria (Italy): Adverse events analysis.

Science.gov (United States)

Scicchitano, Francesca; Giofrè, Chiara; Palleria, Caterina; Mazzitello, Carmela; Ciriaco, Miriam; Gallelli, Luca; Paletta, Laura; Marrazzo, Giuseppina; De Fazio, Salvatore; Menniti, Michele; Curia, Rubens; Arena, Concetta; Chimirri, Serafina; Patanè, Marinella; Esposito, Stefania; Cilurzo, Felisa; Staltari, Orietta; Russo, Emilio; De Sarro, Giovambattista

2012-09-01

Pharmacovigilance assesses the safety profile of drugs. Its main aim is the increase of spontaneous reporting of adverse drug reactions (ADRs). The Italian Drug Agency (AIFA; Agenzia Italiana del Farmaco) is financing several projects to the aim of increasing reporting, and in Calabria a Pharmacovigilance Information Centre has been created. We analyzed the AIFA database relatively to Calabria in the year 2011 and we have analyzed ADRs using descriptive statistics. We have also collected a questionnaire-based interview in order to describe the background knowledge in the field. Regarding the number of AIFA reported ADRs from Calabria, a 38% increase (138 vs. 100) in comparison to 2010 was evidenced. Hospital Doctors represent the main source of signaling (71.7 %). Ketoprofene and the combination amoxicillin/clavulanic acid represent the most frequently reported drugs causing ADRs. Our questionnaires indicated that despite the health professionals have met at least once an ADR only a small percentage of them was reported to the authorities (37%). There is a very good knowledge of the ADR concept and reporting system (90% of interviewed distinguish an ADR and knows how to report it), and there is a strong interest in participating to training courses in the field (95% are interested). Despite Calabria has had a positive increase in the number of reported ADRs, the total number is very low and the pharmacovigilance culture is far from being achieved in this region.

Safety of Flibanserin in Women Treated With Antidepressants: A Randomized, Placebo-Controlled Study.

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Clayton, Anita H; Croft, Harry A; Yuan, James; Brown, Louise; Kissling, Robert

2018-01-01

Depression is often associated with sexual dysfunction, and pharmacologic treatment for hypoactive sexual desire disorder can be considered in women receiving treatment for depression. To evaluate the safety of flibanserin in women treated for depression with selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors. In this double-blinded, randomized, placebo-controlled trial, women with remitted or mild depression treated with selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors who were not postmenopausal and were experiencing symptoms of hypoactive sexual desire disorder (ie, decreased sexual desire and related distress) received flibanserin 50 mg at bedtime (qhs) for 2 weeks and up-titrated to 100 mg qhs, flibanserin 100 mg qhs for the entire treatment period, or placebo for up to 12 weeks. Safety assessment included adverse events and symptoms of depression and anxiety. 73 patients were randomly assigned to flibanserin (both dose groups combined) and 38 to placebo. The sponsor terminated the study early at discontinuation of the development of flibanserin. Treatment duration was at least 8 weeks for 84.9% and 94.7% of patients in the flibanserin and placebo groups, respectively. The most common adverse events (incidence ≥ 2% in the flibanserin group and higher than that in the placebo group) included dry mouth (5.5% for flibanserin vs 2.6% for placebo), insomnia (5.5% vs 2.6%), back pain (4.1% vs 2.6%), and dizziness (4.1% vs 0.0%). There were no serious adverse events and no instances of suicidal ideation or behavior. The proportions of patients with symptom worsening in the flibanserin and placebo groups, respectively, were 6.9% and 21.6% for depression and 1.4% and 2.7% for anxiety. Remission of depression at study end point, as measured by the Quick Inventory of Depressive Symptomatology-Self Report, was experienced by 19.4% of flibanserin-treated patients and 10.8% of patients

78 FR 63479 - Meta-Analyses of Randomized Controlled Clinical Trials (RCTs) for the Evaluation of Risk To...

Science.gov (United States)

2013-10-24

... pharmaceutical industry and health care organizations, and others from the general public, about the use of meta-analyses of randomized trials as a tool for safety assessment in the regulation of pharmaceutical products... PDUFA Goals Letter, titled ``Enhancing Regulatory Science and Expediting Drug Development,'' includes an...

Open-label, randomized, multicenter, phase III study to evaluate the safety and efficacy of benzoyl peroxide gel in long-term use in patients with acne vulgaris: A secondary publication.

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Kawashima, Makoto; Nagare, Toshitaka; Katsuramaki, Tsuneo

2017-06-01

An open-label, randomized, multicenter study was conducted to evaluate the safety and efficacy of long-term use of 2.5% and 5% benzoyl peroxide (BPO) gels administrated once daily for 52 weeks to Japanese patients with acne vulgaris. The efficacy of the study drugs was evaluated by counting inflammatory lesions and non-inflammatory lesions. Safety was evaluated based on adverse events, local skin tolerability scores and laboratory test values. In total, 458 subjects were included in the efficacy and safety analyses. The total lesion count, the efficacy end-point, was similarly changed both in the 2.5% and 5% BPO groups over the course of the study. The median rates of reduction from baseline to week 12 were approximately 65%. Thereafter, the counts were maintained at a reduced level without increasing until week 52. The median rates at week 52 were approximately 80%. Similar trends were observed for inflammatory and non-inflammatory lesion counts. Bacteriological evaluation indicated similar distribution of the minimum inhibitory concentration of each of the antibacterial drugs against Propionibacterium acnes between the values at baseline and at week 52, suggesting that long-term use did not result in changes in the drug sensitivity. The incidence of adverse events was 84.0% in the 2.5% BPO group and 87.2% in the 5% BPO group. Many of the adverse events occurred within the first month and were mild or moderate in severity and transient. The results suggest that both 2.5% and 5% BPO gels are effective and safe for long-term treatment of patients with acne vulgaris. © 2017 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.

EFFICIENCY AND SAFETY ASSESSMENT OF GENERIC ATORVASTATINE IN PATIENTS WITH HYPERLIPIDEMIA

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J. E. Semyonova

2015-12-01

Full Text Available Aim. To assess in a short-term study efficiency and safety of hypolipidemic therapy with atorvastatine generic, Tulip, in comparison with simvastatine generic, Vasilip, in hyperlipidemic patients.Material and methods. Open, randomized, comparative, cross over study included 87 patients with hyperlipidemia, who didn’t receive hypolipidemic drugs within 6 weeks, or followed hypolipidemic diet for 4 weeks. Each patient received therapy with one of the studied drugs within 6 weeks. Then after 4-week wash-out period the second therapy with the other drug was held. Consequence of courses with each drug was set by randomization. Initial dose of both drugs was 10 mg daily. Dose was adjusted after 3 weeks. The dose was increased to 20 mg daily if cholesterol of low density lipoproteid (CLDL hadn’t reached target level (< 115 mg/dl. of Treatment safety was assessed on the basis of clinical data, hepatic enzymes activity and creatine phosphokinase levels.Results. It is shown, that to reach target figures of plasma lipid spectrum, Vasilip dose was increased significantly more often, than Tulip dose. Average Tulip dose after titration was 14,8 mg daily, Vasilip dose – 15,6 mg daily. Patients with initially higher level of triglycerides (TG > 170 mg/dl after 6 weeks with Tulip treatment showed TG reduction by 38% and with Vasilip treatment – by 20%. Both drugs showed good tolerance, no significant differences in number of side-effects were observed.Conclusion. 6-week treatment with atorvastatine generic Tulip shows significant hypolipidemic effect, which appears in significant reduction of CLDL, total cholesterol, TG compared to the initial levels. Degree of total cholesterol reduction is significantly higher with Tulip treatment compared to Vasilip treatment. Analyses shown that target levels of the assessed figures were reached in more patients, treated with Tulip. Side-effects in Tulip treatment were not severe.

EFFICIENCY AND SAFETY ASSESSMENT OF GENERIC ATORVASTATINE IN PATIENTS WITH HYPERLIPIDEMIA

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J. E. Semyonova

2005-01-01

Full Text Available Aim. To assess in a short-term study efficiency and safety of hypolipidemic therapy with atorvastatine generic, Tulip, in comparison with simvastatine generic, Vasilip, in hyperlipidemic patients.Material and methods. Open, randomized, comparative, cross over study included 87 patients with hyperlipidemia, who didn’t receive hypolipidemic drugs within 6 weeks, or followed hypolipidemic diet for 4 weeks. Each patient received therapy with one of the studied drugs within 6 weeks. Then after 4-week wash-out period the second therapy with the other drug was held. Consequence of courses with each drug was set by randomization. Initial dose of both drugs was 10 mg daily. Dose was adjusted after 3 weeks. The dose was increased to 20 mg daily if cholesterol of low density lipoproteid (CLDL hadn’t reached target level (< 115 mg/dl. of Treatment safety was assessed on the basis of clinical data, hepatic enzymes activity and creatine phosphokinase levels.Results. It is shown, that to reach target figures of plasma lipid spectrum, Vasilip dose was increased significantly more often, than Tulip dose. Average Tulip dose after titration was 14,8 mg daily, Vasilip dose – 15,6 mg daily. Patients with initially higher level of triglycerides (TG > 170 mg/dl after 6 weeks with Tulip treatment showed TG reduction by 38% and with Vasilip treatment – by 20%. Both drugs showed good tolerance, no significant differences in number of side-effects were observed.Conclusion. 6-week treatment with atorvastatine generic Tulip shows significant hypolipidemic effect, which appears in significant reduction of CLDL, total cholesterol, TG compared to the initial levels. Degree of total cholesterol reduction is significantly higher with Tulip treatment compared to Vasilip treatment. Analyses shown that target levels of the assessed figures were reached in more patients, treated with Tulip. Side-effects in Tulip treatment were not severe.

Efficacy and safety of a vaginal medicinal product containing three strains of probiotic bacteria: a multicenter, randomized, double-blind, and placebo-controlled trial.

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Tomusiak, Anna; Strus, Magdalena; Heczko, Piotr B; Adamski, Paweł; Stefański, Grzegorz; Mikołajczyk-Cichońska, Aleksandra; Suda-Szczurek, Magdalena

2015-01-01

The main objective of this study was to evaluate whether vaginal administration of probiotic Lactobacillus results in their colonization and persistence in the vagina and whether Lactobacillus colonization promotes normalization and maintenance of pH and Nugent score. The study was a multicenter, randomized, double-blind, and placebo-controlled trial. Altogether, 376 women were assessed for eligibility, and signed informed consent. One hundred and sixty eligible women with abnormal, also called intermediate, vaginal microflora, as indicated by a Nugent score of 4-6 and pH >4.5 and zero or low Lactobacillus count, were randomized. Each participant was examined four times during the study. Women were randomly allocated to receive either the probiotic preparation inVag(®), or a placebo (one capsule for seven consecutive days vaginally). The product inVag includes the probiotic strains Lactobacillus fermentum 57A, Lactobacillus plantarum 57B, and Lactobacillus gasseri 57C. We took vaginal swabs during visits I, III, and IV to determine the presence and abundance of bacteria from the Lactobacillus genus, measure the pH, and estimate the Nugent score. Drug safety evaluation was based on analysis of the types and occurrence of adverse events. Administration of inVag contributed to a significant decrease (between visits) in both vaginal pH (Pvaginal microbiota, as demonstrated by predominance of the Lactobacillus bacteria in vaginal microbiota.

Metformin efficacy and safety for colorectal polyps: a double-blind randomized controlled trial

International Nuclear Information System (INIS)

Higurashi, Takuma; Fujisawa, Nobutaka; Uchiyama, Shiori; Ezuka, Akiko; Nagase, Hajime; Kessoku, Takaomi; Matsuhashi, Nobuyuki; Yamanaka, Shoji; Inayama, Yoshiaki; Morita, Satoshi; Nakajima, Atsushi; Takahashi, Hirokazu; Endo, Hiroki; Hosono, Kunihiro; Yamada, Eiji; Ohkubo, Hidenori; Sakai, Eiji; Uchiyama, Takashi; Hata, Yasuo

2012-01-01

Colorectal cancer is one of the major neoplasms and a leading cause of cancer death worldwide, and new preventive strategies are needed to lower the burden of this disease. Metformin, a biguanide, which is widely used for treating diabetes mellitus, has recently been suggestive to have a suppressive effect on tumorigenesis and cancer cell growth. In a previous study conducted in non-diabetic subjects, we showed that oral short-term low-dose metformin suppressed the development of colorectal aberrant crypt foci (ACF). ACF have been considered as a useful surrogate biomarker of CRC, although the biological significance of these lesions remains controversial. We devised a prospective randomized controlled trial to evaluate the chemopreventive effect of metformin against metachronous colorectal polyps and the safety of this drug in non-diabetic post-polypectomy patients. This study is a multi-center, double-blind, placebo-controlled, randomized controlled trial to be conducted in non-diabetic patients with a recent history of undergoing colorectal polypectomy. All adult patients visiting the Yokohama City University hospital or affiliated hospitals for polypectomy shall be recruited for the study. Eligible patients will then be allocated randomly into either one of two groups: the metformin group and the placebo group. Patients in the metformin group shall receive oral metformin at 250 mg per day, and those in the placebo group shall receive an oral placebo tablet. At the end of 1 year of administration of metformin/placebo, colonoscopy will be performed to evaluate the polyp formation. This is the first study proposed to explore the effect of metformin against colorectal polyp formation. Metformin activates AMPK, which inhibits the mammalian target of rapamycin (mTOR) pathway. The mTOR pathway plays an important role in the cellular protein translational machinery and cell proliferation. Patients with type 2 diabetes taking under treatment with metformin have been

Metformin efficacy and safety for colorectal polyps: a double-blind randomized controlled trial

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Higurashi Takuma

2012-03-01

Full Text Available Abstract Background Colorectal cancer is one of the major neoplasms and a leading cause of cancer death worldwide, and new preventive strategies are needed to lower the burden of this disease. Metformin, a biguanide, which is widely used for treating diabetes mellitus, has recently been suggestive to have a suppressive effect on tumorigenesis and cancer cell growth. In a previous study conducted in non-diabetic subjects, we showed that oral short-term low-dose metformin suppressed the development of colorectal aberrant crypt foci (ACF. ACF have been considered as a useful surrogate biomarker of CRC, although the biological significance of these lesions remains controversial. We devised a prospective randomized controlled trial to evaluate the chemopreventive effect of metformin against metachronous colorectal polyps and the safety of this drug in non-diabetic post-polypectomy patients. Methods/Design This study is a multi-center, double-blind, placebo-controlled, randomized controlled trial to be conducted in non-diabetic patients with a recent history of undergoing colorectal polypectomy. All adult patients visiting the Yokohama City University hospital or affiliated hospitals for polypectomy shall be recruited for the study. Eligible patients will then be allocated randomly into either one of two groups: the metformin group and the placebo group. Patients in the metformin group shall receive oral metformin at 250 mg per day, and those in the placebo group shall receive an oral placebo tablet. At the end of 1 year of administration of metformin/placebo, colonoscopy will be performed to evaluate the polyp formation. Discussion This is the first study proposed to explore the effect of metformin against colorectal polyp formation. Metformin activates AMPK, which inhibits the mammalian target of rapamycin (mTOR pathway. The mTOR pathway plays an important role in the cellular protein translational machinery and cell proliferation. Patients with

The Internet and drug safety: what are the implications for pharmacovigilance?

Science.gov (United States)

Cobert, B; Silvey, J

1999-02-01

Use of the Internet is becoming widespread throughout the world. Its use in the domain of drug safety and pharmacovigilance is spreading rapidly. Governments and industry have taken the lead in developing extensive web sites. The US Food and Drug Administration (FDA), the European Agency for the Evaluation of Medicinal Products (EMEA) and other agencies have developed sites containing enormous amounts of information both on pharmacovigilance in general and on specific drugs in particular. Under the US 'Freedom of Information Act' the FDA has put major parts of its adverse event database on line. Regulatory documents are also available from the FDA site or from hyperlinks described in the site. The US Center for Drug Evaluation and Research updates its site most days and maintains a free automated e-mail announcement service of these updates. Similarly, the EMEA updates its site frequently and publishes extensive material including regulatory documents, guidelines, European Public Assessment Reports on newly approved medications and other useful information. A free update service by e-mail is also available. Although English is the primary language used on the EMEA site, some of the information is available in other languages. Pharmaceutical companies are not using the Internet for pharmacovigilance yet. Rather, the Internet is being used for promotion of their products and for informing consumers on general information on diseases, for financial and investor data and for employment opportunities, etc. Other organisations such as lobbies, consumer groups and medical journals are also beginning to use the Internet. The electronic transmission of safety information, using the standards developed by the International Conference on Harmonization, is currently being tested for the transmission of individual patient adverse event information between companies and governments. In addition, the FDA has begun to accept adverse events from healthcare providers and consumers

Planning the Safety of Atrial Fibrillation Ablation Registry Initiative (SAFARI) as a Collaborative Pan-Stakeholder Critical Path Registry Model: a Cardiac Safety Research Consortium "Incubator" Think Tank.

Science.gov (United States)

Al-Khatib, Sana M; Calkins, Hugh; Eloff, Benjamin C; Packer, Douglas L; Ellenbogen, Kenneth A; Hammill, Stephen C; Natale, Andrea; Page, Richard L; Prystowsky, Eric; Jackman, Warren M; Stevenson, William G; Waldo, Albert L; Wilber, David; Kowey, Peter; Yaross, Marcia S; Mark, Daniel B; Reiffel, James; Finkle, John K; Marinac-Dabic, Danica; Pinnow, Ellen; Sager, Phillip; Sedrakyan, Art; Canos, Daniel; Gross, Thomas; Berliner, Elise; Krucoff, Mitchell W

2010-01-01

Atrial fibrillation (AF) is a major public health problem in the United States that is associated with increased mortality and morbidity. Of the therapeutic modalities available to treat AF, the use of percutaneous catheter ablation of AF is expanding rapidly. Randomized clinical trials examining the efficacy and safety of AF ablation are currently underway; however, such trials can only partially determine the safety and durability of the effect of the procedure in routine clinical practice, in more complex patients, and over a broader range of techniques and operator experience. These limitations of randomized trials of AF ablation, particularly with regard to safety issues, could be addressed using a synergistically structured national registry, which is the intention of the SAFARI. To facilitate discussions about objectives, challenges, and steps for such a registry, the Cardiac Safety Research Consortium and the Duke Clinical Research Institute, Durham, NC, in collaboration with the US Food and Drug Administration, the American College of Cardiology, and the Heart Rhythm Society, organized a Think Tank meeting of experts in the field. Other participants included the National Heart, Lung and Blood Institute, the Centers for Medicare and Medicaid Services, the Agency for Healthcare Research and Quality, the Society of Thoracic Surgeons, the AdvaMed AF working group, and additional industry representatives. The meeting took place on April 27 to 28, 2009, at the US Food and Drug Administration headquarters in Silver Spring, MD. This article summarizes the issues and directions presented and discussed at the meeting. Copyright 2010 Mosby, Inc. All rights reserved.

Design of Probabilistic Random Forests with Applications to Anticancer Drug Sensitivity Prediction.

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Rahman, Raziur; Haider, Saad; Ghosh, Souparno; Pal, Ranadip

2015-01-01

Random forests consisting of an ensemble of regression trees with equal weights are frequently used for design of predictive models. In this article, we consider an extension of the methodology by representing the regression trees in the form of probabilistic trees and analyzing the nature of heteroscedasticity. The probabilistic tree representation allows for analytical computation of confidence intervals (CIs), and the tree weight optimization is expected to provide stricter CIs with comparable performance in mean error. We approached the ensemble of probabilistic trees' prediction from the perspectives of a mixture distribution and as a weighted sum of correlated random variables. We applied our methodology to the drug sensitivity prediction problem on synthetic and cancer cell line encyclopedia dataset and illustrated that tree weights can be selected to reduce the average length of the CI without increase in mean error.

Permitting product liability litigation for FDA-approved drugs and devices promotes patient safety.

Science.gov (United States)

Kesselheim, A S

2010-06-01

In 2008 and 2009, the Supreme Court reviewed the question of whether patients injured by dangerous prescription drugs or medical devices can bring tort lawsuits against pharmaceutical and device manufacturers. The Court ruled that claims against device manufacturers were preempted while claims against pharmaceutical manufacturers were not. The threat of product liability lawsuits promotes patient safety by encouraging manufacturers to take greater responsibility in providing clear warnings about known adverse effects of their products.

Portraying mental illness and drug addiction as treatable health conditions: effects of a randomized experiment on stigma and discrimination.

Science.gov (United States)

McGinty, Emma E; Goldman, Howard H; Pescosolido, Bernice; Barry, Colleen L

2015-02-01

Despite significant advances in treatment, stigma and discrimination toward persons with mental illness and drug addiction have remained constant in past decades. Prior work suggests that portraying other stigmatized health conditions (i.e., HIV/AIDS) as treatable can improve public attitudes toward those affected. Our study compared the effects of vignettes portraying persons with untreated and symptomatic versus successfully treated and asymptomatic mental illness and drug addiction on several dimensions of public attitudes about these conditions. We conducted a survey-embedded randomized experiment using a national sample (N = 3940) from an online panel. Respondents were randomly assigned to read one of ten vignettes. Vignette one was a control vignette, vignettes 2-5 portrayed individuals with untreated schizophrenia, depression, prescription pain medication addiction and heroin addiction, and vignettes 6-10 portrayed successfully treated individuals with the same conditions. After reading the randomly assigned vignette, respondents answered questions about their attitudes related to mental illness or drug addiction. Portrayals of untreated and symptomatic schizophrenia, depression, and heroin addiction heightened negative public attitudes toward persons with mental illness and drug addiction. In contrast, portrayals of successfully treated schizophrenia, prescription painkiller addiction, and heroin addiction led to less desire for social distance, greater belief in the effectiveness of treatment, and less willingness to discriminate against persons with these conditions. Portrayal of persons with successfully treated mental illness and drug addiction is a promising strategy for reducing stigma and discrimination toward persons with these conditions and improving public perceptions of treatment effectiveness. Copyright © 2014 Elsevier Ltd. All rights reserved.

Safety aspects of protease inhibitors for chronic hepatitis C: adverse events and drug-to-drug interactions

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Rosângela Teixeira

Full Text Available The standard of care therapy of chronic hepatitis C with the combination of pegylated interferon and ribavirin for 24 or 48 weeks was a remarkable accomplishment of the past decade. However, sustained virological responses rates of about 80% (genotypes 2-3 and 50% (geno 3 type 1 were not satisfactory especially for patients infected with genotype 1. Important advances in the biology of HCV have made possible the development of the direct-acting antiviral agents boceprevir and telaprevir with substantial increase in the rates of sustained virological response with shorter duration of therapy for a large number of patients. However, the complexity of triple therapy is higher and several new side effects are expected suggesting greater expertise in the patient management. Anemia and disgeusia are frequent with boceprevir while cutaneous rash, ranging from mild to severe, is expected with telaprevir. Higher risk of drug-drug interactions demand further clinical consideration of the previous well-known adverse events of pegylated interferon and ribavirin. Identification and prompt management of these potential new problems with boceprevir and telaprevir are crucial in clinical practice for optimizing treatment and assuring safety outcomes to HCV-genotype 1 patients.

Safety aspects of protease inhibitors for chronic hepatitis C: adverse events and drug-to-drug interactions

Directory of Open Access Journals (Sweden)

Rosângela Teixeira

2013-04-01

Full Text Available The standard of care therapy of chronic hepatitis C with the combination of pegylated interferon and ribavirin for 24 or 48 weeks was a remarkable accomplishment of the past decade. However, sustained virological responses rates of about 80% (genotypes 2-3 and 50% (geno 3 type 1 were not satisfactory especially for patients infected with genotype 1. Important advances in the biology of HCV have made possible the development of the direct-acting antiviral agents boceprevir and telaprevir with substantial increase in the rates of sustained virological response with shorter duration of therapy for a large number of patients. However, the complexity of triple therapy is higher and several new side effects are expected suggesting greater expertise in the patient management. Anemia and disgeusia are frequent with boceprevir while cutaneous rash, ranging from mild to severe, is expected with telaprevir. Higher risk of drug-drug interactions demand further clinical consideration of the previous well-known adverse events of pegylated interferon and ribavirin. Identification and prompt management of these potential new problems with boceprevir and telaprevir are crucial in clinical practice for optimizing treatment and assuring safety outcomes to HCV-genotype 1 patients.

Evaluation of Electronic Healthcare Databases for Post-Marketing Drug Safety Surveillance and Pharmacoepidemiology in China.

Science.gov (United States)

Yang, Yu; Zhou, Xiaofeng; Gao, Shuangqing; Lin, Hongbo; Xie, Yanming; Feng, Yuji; Huang, Kui; Zhan, Siyan

2018-01-01

Electronic healthcare databases (EHDs) are used increasingly for post-marketing drug safety surveillance and pharmacoepidemiology in Europe and North America. However, few studies have examined the potential of these data sources in China. Three major types of EHDs in China (i.e., a regional community-based database, a national claims database, and an electronic medical records [EMR] database) were selected for evaluation. Forty core variables were derived based on the US Mini-Sentinel (MS) Common Data Model (CDM) as well as the data features in China that would be desirable to support drug safety surveillance. An email survey of these core variables and eight general questions as well as follow-up inquiries on additional variables was conducted. These 40 core variables across the three EHDs and all variables in each EHD along with those in the US MS CDM and Observational Medical Outcomes Partnership (OMOP) CDM were compared for availability and labeled based on specific standards. All of the EHDs' custodians confirmed their willingness to share their databases with academic institutions after appropriate approval was obtained. The regional community-based database contained 1.19 million people in 2015 with 85% of core variables. Resampled annually nationwide, the national claims database included 5.4 million people in 2014 with 55% of core variables, and the EMR database included 3 million inpatients from 60 hospitals in 2015 with 80% of core variables. Compared with MS CDM or OMOP CDM, the proportion of variables across the three EHDs available or able to be transformed/derived from the original sources are 24-83% or 45-73%, respectively. These EHDs provide potential value to post-marketing drug safety surveillance and pharmacoepidemiology in China. Future research is warranted to assess the quality and completeness of these EHDs or additional data sources in China.

Complicating factors in safety testing of drug metabolites: Kinetic differences between generated and preformed metabolites

International Nuclear Information System (INIS)

Prueksaritanont, Thomayant; Lin, Jiunn H.; Baillie, Thomas A.

2006-01-01

This paper aims to provide a scientifically based perspective on issues surrounding the proposed toxicology testing of synthetic drug metabolites as a means of ensuring adequate nonclinical safety evaluation of drug candidates that generate metabolites considered either to be unique to humans or are present at much higher levels in humans than in preclinical species. We put forward a number of theoretical considerations and present several specific examples where the kinetic behavior of a preformed metabolite given to animals or humans differs from that of the corresponding metabolite generated endogenously from its parent. The potential ramifications of this phenomenon are that the results of toxicity testing of the preformed metabolite may be misleading and fail to characterize the true toxicological contribution of the metabolite when formed from the parent. It is anticipated that such complications would be evident in situations where (a) differences exist in the accumulation of the preformed versus generated metabolites in specific tissues, and (b) the metabolite undergoes sequential metabolism to a downstream product that is toxic, leading to differences in tissue-specific toxicity. Owing to the complex nature of this subject, there is a need to treat drug metabolite issues in safety assessment on a case-by-case basis, in which a knowledge of metabolite kinetics is employed to validate experimental paradigms that entail administration of preformed metabolites to animal models

The therapeutic workplace to promote treatment engagement and drug abstinence in out-of-treatment injection drug users: a randomized controlled trial.

Science.gov (United States)

Holtyn, August F; Koffarnus, Mikhail N; DeFulio, Anthony; Sigurdsson, Sigurdur O; Strain, Eric C; Schwartz, Robert P; Leoutsakos, Jeannie-Marie S; Silverman, Kenneth

2014-11-01

Determine if employment-based reinforcement can increase methadone treatment engagement and drug abstinence in out-of-treatment injection drug users. This study was conducted from 2008 to 2012 in a therapeutic workplace in Baltimore, MD. After a 4-week induction, participants (N=98) could work and earn pay for 26 weeks and were randomly assigned to Work Reinforcement, Methadone & Work Reinforcement, and Abstinence, Methadone & Work Reinforcement conditions. Work Reinforcement participants had to work to earn pay. Methadone & Work Reinforcement and Abstinence, Methadone, & Work Reinforcement participants had to enroll in methadone treatment to work and maximize pay. Abstinence, Methadone, & Work Reinforcement participants had to provide opiate- and cocaine-negative urine samples to maximize pay. Most participants (92%) enrolled in methadone treatment during induction. Drug abstinence increased as a graded function of the addition of the methadone and abstinence contingencies. Abstinence, Methadone & Work Reinforcement participants provided significantly more urine samples negative for opiates (75% versus 54%) and cocaine (57% versus 32%) than Work Reinforcement participants. Methadone & Work Reinforcement participants provided significantly more cocaine-negative samples than Work Reinforcement participants (55% versus 32%). The therapeutic workplace can promote drug abstinence in out-of-treatment injection drug users. Clinical trial registration number: NCT01416584. Copyright © 2014 Elsevier Inc. All rights reserved.

Ayurpharmacoepidemiology en Route to Safeguarding Safety and Efficacy of Ayurvedic Drugs in Global Outlook

Science.gov (United States)

Debnath, Parikshit; Banerjee, Subhadip; Adhikari, Anjan; Debnath, Pratip K.

2016-01-01

Ayurpharmacoepidemiology is a new field developed by synergy of the fields of clinical pharmacology, epidemiology, and ayurveda. It will use the effects of ayurvedic medicinal products on large populations to describe and analyze the practices, evaluate the safety and efficacy, and carry out medicoeconomic evaluations. Good pharmacoepidemiology practices in ayurveda is projected to assist with issues of ayurpharmacoepidemiologic research. The embraced good pharmacoepidemiology practices guideline in this viewpoint will be able to provide valuable evidence about the health effects of ayurvedic herbs/drugs and consider different fields like pharmacovigilance, pharmacoeconomics, and drug discovery with ayurvedic reverse pharmacology approach, also pass out significant data for further basic sciences study in ayurveda biology, ayurgenomics, ayurnutrigenomics, and systems biology. Several unanswered questions about ayurvedic drug use and informed interventions or policies that can be addressed by informatics database, which will eventually demonstrate the credibility and rationality of ayurceuticals in the future. PMID:26721554

Safety and effectiveness of drug therapy for the acutely agitated patient (Part I

Directory of Open Access Journals (Sweden)

Gianluca Airoldi

2013-04-01

Full Text Available Acute agitation occurs in a variety of medical and psychiatric conditions, and the management of agitated, abusive, or violent patients is a common problem in the emergency department. Rapid control of potentially dangerous behaviors by physical restraint and pharmacologic tranquillization is crucial to ensure the safety of the patient and health-care personnel and to allow diagnostic procedures and treatment of the underlying condition. The purpose of this article (the first in a 2-part series is to review the extensive safety data published on the antipsychotic medications currently available for managing situations of this type, including older neuroleptics like haloperidol, chlorpromazine, and pimozide as well as a number of the newer atypical antipsychotics (olanzapine, risperidone, ziprasidone. Particular attention is focused on the ability of these drugs to lengthen the QT interval in surface electrocardiograms. This adverse effect is of major concern, especially in light of the reported relation between QT interval and the risk of sudden death. In patients with the congenital long-QT syndrome, a long QT interval is associated with a fatal paroxysmal ventricular arrhythmia knownas torsades de pointes. Therefore, careful evaluation of the QT-prolonging properties and arrhythmogenic potential of antipsychotic drugs is urgently needed. Clinical assessment of drug-induced QT-interval prolongation is strictly dependent on the quality of electrocardiographic data and the appropriateness of electrocardiographic analyses. Unfortunately, measurement imprecision and natural variability preclude a simple use of the actually measured QT interval as a surrogate marker of drug-induced proarrhythmia. Because the QT interval changes with heart rate, a rate-corrected QT interval (QTc is commonly used when evaluating a drug’s effect. In clinical settings, themost widely used formulas for rate-correction are those of Bazett (QTc=QT/RR^0.5 and Fridericia

Sleep-Related Safety Behaviors and Dysfunctional Beliefs Mediate the Efficacy of Online CBT for Insomnia: A Randomized Controlled Trial.

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Lancee, Jaap; Eisma, Maarten C; van Straten, Annemieke; Kamphuis, Jan H

2015-01-01

Several trials have demonstrated the efficacy of online cognitive behavioral therapy (CBT) for insomnia. However, few studies have examined putative mechanisms of change based on the cognitive model of insomnia. Identification of modifiable mechanisms by which the treatment works may guide efforts to further improve the efficacy of insomnia treatment. The current study therefore has two aims: (1) to replicate the finding that online CBT is effective for insomnia and (2) to test putative mechanism of change (i.e., safety behaviors and dysfunctional beliefs). Accordingly, we conducted a randomized controlled trial in which individuals with insomnia were randomized to either online CBT for insomnia (n = 36) or a waiting-list control group (n = 27). Baseline and posttest assessments included questionnaires assessing insomnia severity, safety behaviors, dysfunctional beliefs, anxiety and depression, and a sleep diary. Three- and six-month assessments were administered to the CBT group only. Results show moderate to large statistically significant effects of the online treatment compared to the waiting list on insomnia severity, sleep measures, sleep safety behaviors, and dysfunctional beliefs. Furthermore, dysfunctional beliefs and safety behaviors mediated the effects of treatment on insomnia severity and sleep efficiency. Together, these findings corroborate the efficacy of online CBT for insomnia, and suggest that these effects were produced by changing maladaptive beliefs, as well as safety behaviors. Treatment protocols for insomnia may specifically be enhanced by more focused attention on the comprehensive fading of sleep safety behaviors, for instance through behavioral experiments.

The complications of controlling agency time discretion: FDA review deadlines and postmarket drug safety.

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Carpenter, Daniel; Chattopadhyay, Jacqueline; Moffitt, Susan; Nall, Clayton

2012-01-01

Public agencies have discretion on the time domain, and politicians deploy numerous policy instruments to constrain it. Yet little is known about how administrative procedures that affect timing also affect the quality of agency decisions. We examine whether administrative deadlines shape decision timing and the observed quality of decisions. Using a unique and rich dataset of FDA drug approvals that allows us to examine decision timing and quality, we find that this administrative tool induces a piling of decisions before deadlines, and that these “just-before-deadline” approvals are linked with higher rates of postmarket safety problems (market withdrawals, severe safety warnings, safety alerts). Examination of data from FDA advisory committees suggests that the deadlines may impede quality by impairing late-stage deliberation and agency risk communication. Our results both support and challenge reigning theories about administrative procedures, suggesting they embody expected control-expertise trade-offs, but may also create unanticipated constituency losses.

Effectiveness of multi-drug regimen chemotherapy treatment in osteosarcoma patients: a network meta-analysis of randomized controlled trials.

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Wang, Xiaojie; Zheng, Hong; Shou, Tao; Tang, Chunming; Miao, Kun; Wang, Ping

2017-03-29

Osteosarcoma is the most common malignant bone tumour. Due to the high metastasis rate and drug resistance of this disease, multi-drug regimens are necessary to control tumour cells at various stages of the cell cycle, eliminate local or distant micrometastases, and reduce the emergence of drug-resistant cells. Many adjuvant chemotherapy protocols have shown different efficacies and controversial results. Therefore, we classified the types of drugs used for adjuvant chemotherapy and evaluated the differences between single- and multi-drug chemotherapy regimens using network meta-analysis. We searched electronic databases, including PubMed (MEDLINE), EmBase, and the Cochrane Library, through November 2016 using the keywords "osteosarcoma", "osteogenic sarcoma", "chemotherapy", and "random*" without language restrictions. The major outcome in the present analysis was progression-free survival (PFS), and the secondary outcome was overall survival (OS). We used a random effect network meta-analysis for mixed multiple treatment comparisons. We included 23 articles assessing a total of 5742 patients in the present systematic review. The analysis of PFS indicated that the T12 protocol (including adriamycin, bleomycin, cyclophosphamide, dactinomycin, methotrexate, cisplatin) plays a more critical role in osteosarcoma treatment (surface under the cumulative ranking (SUCRA) probability 76.9%), with a better effect on prolonging the PFS of patients when combined with ifosfamide (94.1%) or vincristine (81.9%). For the analysis of OS, we separated the regimens to two groups, reflecting the disconnection. The T12 protocol plus vincristine (94.7%) or the removal of cisplatinum (89.4%) is most likely the best regimen. We concluded that multi-drug regimens have a better effect on prolonging the PFS and OS of osteosarcoma patients, and the T12 protocol has a better effect on prolonging the PFS of osteosarcoma patients, particularly in combination with ifosfamide or vincristine

Drug monitoring in child and adolescent psychiatry for improved efficacy and safety of psychopharmacotherapy

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Fegert Jörg M

2009-04-01

Full Text Available Abstract Most psychotropic drugs used in the treatment of children and adolescents are applied "off label" with a direct risk of under- or overdosing and a delayed risk of long-term side effects. The selection of doses in paediatric psychiatric patients requires a consideration of pharmacokinetic parameters and the development of central nervous system, and warrants specific studies in children and adolescents. Because these are lacking for most of the psychotropic drugs applied in the Child and Adolescent and Psychiatry, therapeutic drug monitoring (TDM is a valid tool to optimise pharmacotherapy and to enable to adjust the dosage of drugs according to the characteristics of the individual patient. Multi-centre TDM studies enable the identification of age- and development-dependent therapeutic ranges of blood concentrations and facilitate a highly qualified standardized documentation in the child and adolescent health care system. In addition, they will provide data for future research on psychopharmacological treatment in children and adolescents, as a baseline for example for clinically relevant interactions with various co-medications. Therefore, a German-Austrian-Swiss "Competence Network on Therapeutic Drug Monitoring in Child and Adolescent Psychiatry" was founded 1 introducing a comprehensive internet data base for the collection of demographic, safety and efficacy data as well as blood concentrations of psychotropic drugs in children and adolescents.

Predicting Drug Safety and Communicating Risk: Benefits of a Bayesian Approach.

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Lazic, Stanley E; Edmunds, Nicholas; Pollard, Christopher E

2018-03-01

Drug toxicity is a major source of attrition in drug discovery and development. Pharmaceutical companies routinely use preclinical data to predict clinical outcomes and continue to invest in new assays to improve predictions. However, there are many open questions about how to make the best use of available data, combine diverse data, quantify risk, and communicate risk and uncertainty to enable good decisions. The costs of suboptimal decisions are clear: resources are wasted and patients may be put at risk. We argue that Bayesian methods provide answers to all of these problems and use hERG-mediated QT prolongation as a case study. Benefits of Bayesian machine learning models include intuitive probabilistic statements of risk that incorporate all sources of uncertainty, the option to include diverse data and external information, and visualizations that have a clear link between the output from a statistical model and what this means for risk. Furthermore, Bayesian methods are easy to use with modern software, making their adoption for safety screening straightforward. We include R and Python code to encourage the adoption of these methods.

The nature of the scientific evidence leading to drug withdrawals for pharmacovigilance reasons in France.

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Olivier, Pascale; Montastruc, Jean-Louis

2006-11-01

Because of design, objectives and number of included subjects, clinical studies are insufficient to assess the safety of new drugs. Sometimes, serious adverse drug reactions (ADRs) led to withdrawal of the drug from the market after their approval. The objective of our study was to determine the scientific evidences leading to drug withdrawal for pharmacovigilance reasons in France. Data coming from French Health Products Safety Agency, literature and Toulouse Pharmacovigilance Center allowed to identify all drugs withdrawn from the French market for pharmacovigilance reasons from 1998 to 2004. We classified data according to their study design (Randomized Clinical Trial [RCT], case serie or case report, case-control study, cohort study, observational study, animal study), the organ/system affected and the type of ADR. A total of 21 drugs were withdrawn for safety reasons between 1998 and 2004 in France. The most frequent ADRs were hepatic (n = 7), cardiovascular (n = 4) or neurological (n = 3) ones. Eleven withdrawals were due to type-B ('unexpected') reactions (52%). For 19 out of 21 drugs, scientific evidence leading to drug withdrawal came from spontaneous case reports (or case series). Among these, case reports were the sole evidence in 12 cases. Withdrawals were based on evidence from case reports in combination with case-control or cohort study in four cases, in combination with observational study in two cases or in combination with animal study in two other cases. In only one case, a RCT supported the decision. This study underlines the importance of spontaneous case reports in detecting signals and supporting withdrawal of drug for pharmacovigilance reasons in France. Health authorities suffer from lack of comparative data resource. In this perspective, a pharmaco-epidemiological population-based database could represent a helpful tool to both generate and test safety hypotheses.

Effect of Safety Issues with HIV Drugs on the Approval Process of Other Drugs in the Same Class An Analysis of European Public Assessment Reports : an analysis of European public assessment reports

NARCIS (Netherlands)

Arnardottir, Arna H.; Haaijer-Ruskamp, Flora M.; Straus, Sabine M. J.; de Graeff, Pieter A.; Mol, Peter G. M.

2011-01-01

Background: Knowledge on the safety of new medicines is limited at the time of market entry. Nearly half of all drugs used to treat HIV registered in the EU required >= 1 Direct Healthcare Professional Communication (DHPC) in the past 10 years for safety issues identified post-approval. Objective:

Efficacy and safety of escitalopram versus desvenlafaxine in the treatment of major depression: A preliminary 1-year prospective randomized open label comparative trial

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Brij Mohan Gupta

2016-01-01

Full Text Available Aim and Objective: To compare efficacy and safety of escitalopram with desvenlafaxine in the treatment of major depression.Materials and Methods: A total of 60 patients of depression were randomized into two groups after meeting inclusion criterion. In the first 3 weeks, escitalopram 10 mg/day was given and then 20 mg/day for the next 3 weeks in group 1 (n = 30. Desvenlafaxine in the first 3 weeks was given 50 mg/day and 100 mg/day for the next 3 weeks in group 2 (n = 30. The parameters evaluated during the study were efficacy assessments byHamilton Scale of Rating Depression (HAM-D, Hamilton Rating Scale of Anxiety (HAM-A, and Clinical Global Impression (CGI. Safety assessments were done by UKU-scale. Results: Escitalopram and desvenlafaxine significantly (P < 0.001, reduced HAM-D, HAM-A, and CGI scores from their respective base lines. However, on comparison failed show any statistical difference at 3 and 6 weeks of treatment. Escitalopram and desvenlafaxine were both found to be safe and well-tolerated and there was not much difference between the two groups as evident from UKU Scale and their effect on various biochemical parameters. Conclusion: The present study demonstrated similar efficacy and safety in reducing depression and anxiety with both escitalopram and desvenlafaxine, but clinical superiority of one drug over the other cannot be concluded due to limitations of the small sample size.

Randomized clinical trial on the use of antispasmodic drugs in barium enema: impact on radiological practice

International Nuclear Information System (INIS)

Goei, Reginald; Kessels, Alphons H.; Nix, Maarten; Knipschild, Paul G.

2000-01-01

Purpose: To assess the willingness of radiologists to change their practice when the results of a randomized clinical trial (RCT) on the use of antispasmodic drugs in barium enema are presented. Materials and Methods: During the years 1994 and 1995 two postal questionnaires were sent to 481 practicing radiologists who were all members of the Netherlands Society of Radiology. In the first questionnaire the respondents were asked to give the characteristics of their practices in performing daily barium enema. The data from this questionnaire was used as a reference. The second questionnaire was sent to the respondents together with an abstract on the randomized clinical trial supporting the use of antispasmodic drugs in barium enema. We also indicated a preference for Buscopan over Glucagon as the antispasmodic drug. The willingness to change prescription habits was measured by comparing the data of the two questionnaires. Results: Of 481 practicing radiologists, 312 responded to the first questionnaire and gave information of their prescription habits (response rate 64%). These 312 responders were sent an abstract of the RCT and were asked to fill out a second questionnaire to determine their willingness to change their practice. Two hundred and sixty-seven radiologists responded (response rate 86%). A significant number of 119 (51%) were willing to increase the use of antispasmodic drugs. A significant number of 128 (55%) chose to increase the use of Buscopan, while a significant number of 81 (32%) were willing to decrease the use of Glucagon. Conclusion: Direct exposure to the results of an RCT recommending the use of antispasmodic drugs in barium enema, especially Buscopan, is likely to increase its use by practicing radiologists

Post-marketing safety and effectiveness evaluation of the intravenous anti-influenza neuraminidase inhibitor peramivir (I): a drug use investigation.

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Komeda, Takuji; Ishii, Shingo; Itoh, Yumiko; Ariyasu, Yasuyuki; Sanekata, Masaki; Yoshikawa, Takayoshi; Shimada, Jingoro

2014-11-01

Peramivir is the only intravenous formulation among anti-influenza neuraminidase inhibitors currently available. Peramivir was approved for manufacturing and marketing in Japan in January 2010. We conducted a drug use investigation of peramivir from October 2010 to February 2012 and evaluated its safety and effectiveness under routine clinical settings. We collected data of 1309 patients from 189 facilities across Japan and examined safety in 1174 patients and effectiveness in 1158 patients. In total, 143 adverse events were observed with an incidence rate of 7.33% (86/1174). Of these, 78 events were adverse drug reactions (ADRs) with an incidence rate of 4.34% (51/1174). The most frequently reported ADRs were diarrhea, vomiting, and nausea, with incidence rates of 1.87% (22/1174), 0.85% (10/1174), and 0.68% (8/1174), respectively. Moreover, no ADR was reported as serious. ADR onset was within 3 days after the start of peramivir administration in 91.0% (71 events) of the 78 ADRs, and ADRs were resolved or improved within 7 days after onset in 96.2% (75 events) of the 78 ADRs. Neither patient characteristics nor treatment factors appeared to significantly affect drug safety. With regard to effectiveness, the median time to alleviation of both influenza symptoms and fever was 3 days, including the first day of administration. The present study demonstrates the safety and effectiveness of peramivir under routine clinical settings. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Human rights vs. Public safety -- When can you test your workers for drugs?

Energy Technology Data Exchange (ETDEWEB)

Kossowan, B. L.

2002-06-01

Legislative and regulatory aspects of drug testing of employees vs. public safety are discussed. While in Canada federal and provincial laws concerning human rights take precedence over public safety issues, laws and regulations vary from province to province, therefore there is good reason for concern about uncertainty. To compound the uncertainty, certain relevant laws of the United States are different (generally more stringent than corresponding Canadian laws), consequently there is the possibility that certain American companies might feel justified in refusing to do business with Canadian firms that do not follow their rigid standards. The conclusion is that while the situation may be clear enough in a legal situation, it does not always work equally well in practice. Unfortunately, at the present time there is not a whole lot of guidance available for companies to manage the workplace in a practical sense.

Considerations for the nonclinical safety evaluation of antibody drug conjugates for oncology.

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Roberts, Stanley A; Andrews, Paul A; Blanset, Diann; Flagella, Kelly M; Gorovits, Boris; Lynch, Carmel M; Martin, Pauline L; Kramer-Stickland, Kimberly; Thibault, Stephane; Warner, Garvin

2013-12-01

Antibody drug conjugates (ADCs) include monoclonal antibodies that are linked to cytotoxic small molecules. A number of these agents are currently being developed as anti-cancer agents designed to improve the therapeutic index of the cytotoxin (i.e., cytotoxic small molecule or cytotoxic agent) by specifically delivering it to tumor cells. This paper presents primary considerations for the nonclinical safety evaluation of ADCs and includes strategies for the evaluation of the entire ADC or the various individual components (i.e., antibody, linker or the cytotoxin). Considerations are presented on how to design a nonclinical safety assessment program to identify the on- and off-target toxicities to enable first-in-human (FIH) studies. Specific discussions are also included that provide details as to the need and how to conduct the studies for evaluating ADCs in genetic toxicology, tissue cross-reactivity, safety pharmacology, carcinogenicity, developmental and reproductive toxicology, biotransformation, toxicokinetic monitoring, bioanalytical assays, immunogenicity testing, test article stability and the selection of the FIH dose. Given the complexity of these molecules and our evolving understanding of their properties, there is no single all-encompassing nonclinical strategy. Instead, each ADC should be evaluated on a case-by-case scientifically-based approach that is consistent with ICH and animal research guidelines. Copyright © 2013 Elsevier Inc. All rights reserved.

75 FR 56548 - Joint Meeting of the Peripheral and Central Nervous System Drugs Advisory Committee and the Drug...

Science.gov (United States)

2010-09-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Joint Meeting of the Peripheral and Central Nervous System Drugs Advisory Committee and the Drug Safety... and Central Nervous System Drugs Advisory Committee and the Drug Safety and Risk Management Advisory...

Travoprost 0.004%/timolol 0.5%-fixed combination with and without benzalkonium chloride: a prospective, randomized, doubled-masked comparison of safety and efficacy.

Science.gov (United States)

Kitazawa, Y; Smith, P; Sasaki, N; Kotake, S; Bae, K; Iwamoto, Y

2011-09-01

The purpose of this study is to compare the safety and intraocular pressure (IOP)-lowering efficacy of travoprost/timolol in a benzalkonium chloride (BAK)-free fixed combination preserved with polyquaternium-1 (TRA/TIM BAK-free), with travoprost/timolol-fixed combination preserved with BAK (TRA/TIM), in patients with open-angle glaucoma or ocular hypertension. In this prospective randomized controlled trial, subjects with IOP of at least 22  mm Hg in one or both eyes at 0900  h, and IOP of at least 21  mm Hg in one or both eyes at 1100  h and 1600  h at two eligibility visits were randomly assigned to receive either TRA/TIM BAK-free (n=195) or TRA/TIM (n=193), dosed once daily in the morning (0900  h) for 6 weeks. IOP was assessed at 0900  h, 1100  h, and 1600  h at each scheduled visit (baseline, 2 and 6 weeks after randomization). Mean IOP reduction across all visits and time points was 8.0  mm Hg in the TRA/TIM BAK-free group and 8.4  mm Hg in the TRA/TIM group (P=0.0943). The difference in mean IOP between groups ranged from 0.2 to 0.7  mm Hg across visits and time points, with a mean pooled difference of 0.4  mm Hg (95% CI: -0.1 to 0.8), demonstrating equivalence of the two formulations. The most common drug-related adverse event was hyperemia of the eye (ocular hyperemia and conjunctival hyperemia combined), occurring in 11.8% of the TRA/TIM BAK-free group and 13.0% of the TRA/TIM group. Travoprost/timolol BAK-free demonstrated equivalence to travoprost/timolol preserved with BAK in efficacy. No clinically relevant differences in the safety profiles of travoprost/timolol BAK-free and travoprost/timolol preserved with BAK were identified.

Opioid analgesics-related pharmacokinetic drug interactions: from the perspectives of evidence based on randomized controlled trials and clinical risk management

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Feng XQ

2017-05-01

Full Text Available Xiu-qin Feng,1 Ling-ling Zhu,2 Quan Zhou3 1Nursing Administration Office, Division of Nursing, 2VIP Care Ward, Division of Nursing, 3Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China Background: Multimorbidity results in complex polypharmacy which may bear a risk of drug interactions. A better understanding of opioid analgesics combination therapy used for pain management could help warrant medication safety, efficacy, and economic relevance. Until now there has been no review summarizing the opioid analgesics-related pharmacokinetic drug interactions from the perspective of evidence based on randomized controlled trials (RCTs. Method: A literature search was performed using PubMed, MEDLINE, and the Cochrane Library, using a PRISMA flowchart. Results: Fifty-two RCTs were included for data interpretation. Forty-two RCTs (80.8% were conducted in healthy volunteers, whereas 10 RCTs (19.2% enrolled true patients. None of the opioid–drug/herb pairs was listed as contraindications of opioids involved in this review. Circumstances in which opioid is comedicated as a precipitant drug include morphine–P2Y12 inhibitors, morphine–gabapentin, and methadone–zidovudine. Circumstances in which opioid is comedicated as an object drug include rifampin–opioids (morphine, tramadol, oxycodone, methadone, quinidine–opioids (morphine, fentanyl, oxycodone, codeine, dihydrocodeine, methadone, antimycotics–opioids (buprenorphine, fentanyl, morphine, oxycodone, methadone, tilidine, tramadol, protease inhibitors–opioids (ritonavir, ritonavir/lopinavir–oxycodone, ritonavir–fentanyl, ritonavir–tilidine, grapefruit juice–opioids (oxycodone, fentanyl, methadone, antidepressants–opioids (paroxetine–tramadol, paroxetine–hydrocodone, paroxetine–oxycodone, escitalopram–tramadol, metoclopramide–morphine, amantadine–morphine, sumatriptan�

Prescription Drugs, Over-the-Counter Drugs, Supplements and Herbal Products

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... at risk? Zika virus and pregnancy Folic acid Medicine safety and pregnancy Birth defects prevention Learn how ... the-counter drugs, supplements and herbal products Prescription drugs, over-the-counter drugs, supplements and herbal products ...

Clinical Relation Extraction Toward Drug Safety Surveillance Using Electronic Health Record Narratives: Classical Learning Versus Deep Learning.

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Munkhdalai, Tsendsuren; Liu, Feifan; Yu, Hong

2018-04-25

Medication and adverse drug event (ADE) information extracted from electronic health record (EHR) notes can be a rich resource for drug safety surveillance. Existing observational studies have mainly relied on structured EHR data to obtain ADE information; however, ADEs are often buried in the EHR narratives and not recorded in structured data. To unlock ADE-related information from EHR narratives, there is a need to extract relevant entities and identify relations among them. In this study, we focus on relation identification. This study aimed to evaluate natural language processing and machine learning approaches using the expert-annotated medical entities and relations in the context of drug safety surveillance, and investigate how different learning approaches perform under different configurations. We have manually annotated 791 EHR notes with 9 named entities (eg, medication, indication, severity, and ADEs) and 7 different types of relations (eg, medication-dosage, medication-ADE, and severity-ADE). Then, we explored 3 supervised machine learning systems for relation identification: (1) a support vector machines (SVM) system, (2) an end-to-end deep neural network system, and (3) a supervised descriptive rule induction baseline system. For the neural network system, we exploited the state-of-the-art recurrent neural network (RNN) and attention models. We report the performance by macro-averaged precision, recall, and F1-score across the relation types. Our results show that the SVM model achieved the best average F1-score of 89.1% on test data, outperforming the long short-term memory (LSTM) model with attention (F1-score of 65.72%) as well as the rule induction baseline system (F1-score of 7.47%) by a large margin. The bidirectional LSTM model with attention achieved the best performance among different RNN models. With the inclusion of additional features in the LSTM model, its performance can be boosted to an average F1-score of 77.35%. It shows that

Zero-inflated Poisson model based likelihood ratio test for drug safety signal detection.

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Huang, Lan; Zheng, Dan; Zalkikar, Jyoti; Tiwari, Ram

2017-02-01

In recent decades, numerous methods have been developed for data mining of large drug safety databases, such as Food and Drug Administration's (FDA's) Adverse Event Reporting System, where data matrices are formed by drugs such as columns and adverse events as rows. Often, a large number of cells in these data matrices have zero cell counts and some of them are "true zeros" indicating that the drug-adverse event pairs cannot occur, and these zero counts are distinguished from the other zero counts that are modeled zero counts and simply indicate that the drug-adverse event pairs have not occurred yet or have not been reported yet. In this paper, a zero-inflated Poisson model based likelihood ratio test method is proposed to identify drug-adverse event pairs that have disproportionately high reporting rates, which are also called signals. The maximum likelihood estimates of the model parameters of zero-inflated Poisson model based likelihood ratio test are obtained using the expectation and maximization algorithm. The zero-inflated Poisson model based likelihood ratio test is also modified to handle the stratified analyses for binary and categorical covariates (e.g. gender and age) in the data. The proposed zero-inflated Poisson model based likelihood ratio test method is shown to asymptotically control the type I error and false discovery rate, and its finite sample performance for signal detection is evaluated through a simulation study. The simulation results show that the zero-inflated Poisson model based likelihood ratio test method performs similar to Poisson model based likelihood ratio test method when the estimated percentage of true zeros in the database is small. Both the zero-inflated Poisson model based likelihood ratio test and likelihood ratio test methods are applied to six selected drugs, from the 2006 to 2011 Adverse Event Reporting System database, with varying percentages of observed zero-count cells.

The impact of medicinal drugs on traffic safety: a systematic review of epidemiological studies.

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Orriols, Ludivine; Salmi, Louis-Rachid; Philip, Pierre; Moore, Nicholas; Delorme, Bernard; Castot, Anne; Lagarde, Emmanuel

2009-08-01

To evaluate the quality of epidemiological research into effects of medicinal drugs on traffic safety and the current knowledge in this area. The bibliographic search was done in Medline electronic database using the keywords: ((accident* or crash*) and traffic and drug*) leading to 1141 references. Additional references were retrieved from the Safetylit website and the reference lists of selected studies. Original articles published in English or French, between 1 April 1979 and 31 July 2008, were considered for inclusion. We excluded descriptive studies, studies limited to alcohol or illicit drug involvement and investigations of injuries other than from traffic crashes. Studies based on laboratory tests, driving simulators or on-the-road driving tests were also excluded. Eligible studies had to evaluate the causal relationship between the use of medicinal drugs and the risk of traffic crashes. Study quality was assessed by two independent experts, according to a grid adapted from the strengthening the reporting of observational studies in epidemiology (STROBE) statement. Twenty two studies of variable methodological quality were included. Definition of drug exposure varied across studies and depended on the data sources. Potential confounding due to the interaction between the effects of the medicinal drug and disease-related symptoms was often not controlled. The risk of motor-vehicle crashes related to benzodiazepines has been amply studied and demonstrated. Results for other medicinal drugs remain controversial. There is a need for large studies, investigating the role of individual substances in the risk of road traffic crashes. Copyright 2009 John Wiley & Sons, Ltd.

A randomized, controlled intervention of machine guarding and related safety programs in small metal-fabrication businesses.

Science.gov (United States)

Parker, David L; Brosseau, Lisa M; Samant, Yogindra; Xi, Min; Pan, Wei; Haugan, David

2009-01-01

Metal fabrication employs an estimated 3.1 million workers in the United States. The absence of machine guarding and related programs such as lockout/tagout may result in serious injury or death. The purpose of this study was to improve machine-related safety in small metal-fabrication businesses. We used a randomized trial with two groups: management only and management-employee. We evaluated businesses for the adequacy of machine guarding (machine scorecard) and related safety programs (safety audit). We provided all businesses with a report outlining deficiencies and prioritizing their remediation. In addition, the management-employee group received four one-hour interactive training sessions from a peer educator. We evaluated 40 metal-fabrication businesses at baseline and 37 (93%) one year later. Of the three nonparticipants, two had gone out of business. More than 40% of devices required for adequate guarding were missing or inadequate, and 35% of required safety programs and practices were absent at baseline. Both measures improved significantly during the course of the intervention. No significant differences in changes occurred between the two intervention groups. Machine-guarding practices and programs improved by up to 13% and safety audit scores by up to 23%. Businesses that added safety committees or those that started with the lowest baseline measures showed the greatest improvements. Simple and easy-to-use assessment tools allowed businesses to significantly improve their safety practices, and safety committees facilitated this process.

Safety studies of homoeopathic drugs in acute, sub-acute and chronic toxicity in rats

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Surender Singh

2017-01-01

Full Text Available Background: Homoeopathic drugs are frequently recommended in day to day life as therapeutic agents by homoeopathic practitioners. However, safety of homoeopathic drugs remains a challenge because of the high variability of chemical components involved. Aim: The objective of the present study was to investigate the acute, subacute, and chronic oral toxicity of different homoeopathic drugs (Ferrum phosphoricum 3X, Ferrum phosphoricum 6X, Calcarea phosphoricum 6X, and Magnesium phosphoricum 6X in experimental models. Materials and Methods: In acute oral toxicity study, homoeopathic drugs were administered orally at 2000mg/kg body weight, and animals were observed for toxic symptoms till 10 days as per the OECD guidelines. For subacute and chronic toxicity study, homoeopathic drugs were administered for 28 and 180 days, respectively, as per the OECD guidelines. At the end of 28 and 180 days, the animals were sacrificed and toxicity parameters were assessed. Histopathological evaluation of different organs was also performed to assess any toxicity. Results: In acute toxicity study, no mortality was found at a dose of 2000 mg/kg which indicates that oral LD50of homoeopathic drugs were more than 2000 mg/kg. The administration of drugs at a dose of 70 mg/kg body weight for 28 and 180 days did not produce any significant change in haematological and biochemical parameters of male and female rats as compared to normal control group. No pathological changes were observed in histology of various organs of treated rats as compared to normal control animals. Conclusion: These homoeopathic drugs are safe & produce no toxicity when administered for longer duration.

77 FR 44256 - Draft Guidance for Industry and Food and Drug Administration Staff; Safety Considerations for 510...

Science.gov (United States)

2012-07-27

...] Draft Guidance for Industry and Food and Drug Administration Staff; Safety Considerations for 510(k... serious and sometimes fatal consequences to patients. This guidance provides recommendations to 510(k... unintended connections between enteral and nonenteral devices. This draft guidance is not final nor is it in...

Applications of Dynamic Clamp to Cardiac Arrhythmia Research: Role in Drug Target Discovery and Safety Pharmacology Testing

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Francis A. Ortega

2018-01-01

Full Text Available Dynamic clamp, a hybrid-computational-experimental technique that has been used to elucidate ionic mechanisms underlying cardiac electrophysiology, is emerging as a promising tool in the discovery of potential anti-arrhythmic targets and in pharmacological safety testing. Through the injection of computationally simulated conductances into isolated cardiomyocytes in a real-time continuous loop, dynamic clamp has greatly expanded the capabilities of patch clamp outside traditional static voltage and current protocols. Recent applications include fine manipulation of injected artificial conductances to identify promising drug targets in the prevention of arrhythmia and the direct testing of model-based hypotheses. Furthermore, dynamic clamp has been used to enhance existing experimental models by addressing their intrinsic limitations, which increased predictive power in identifying pro-arrhythmic pharmacological compounds. Here, we review the recent advances of the dynamic clamp technique in cardiac electrophysiology with a focus on its future role in the development of safety testing and discovery of anti-arrhythmic drugs.

Data-driven drug safety signal detection methods in pharmacovigilance using electronic primary care records: A population based study

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Shang-Ming Zhou

2017-04-01

Data-driven analytic methods are a valuable aid to signal detection of ADEs from large electronic health records for drug safety monitoring. This study finds the methods can detect known ADE and so could potentially be used to detect unknown ADE.

[HERA-QUEST: HTA evaluation of generic pharmaceutical products to improve quality, economic efficiency, patient safety and transparency in drug product changes in hospitals].

Science.gov (United States)

Gyalrong-Steur, Miriam; Kellermann, Anita; Bernard, Rudolf; Berndt, Georg; Bindemann, Meike; Nusser-Rothermundt, Elfriede; Amann, Steffen; Brakebusch, Myga; Brüggmann, Jörg; Tydecks, Eva; Müller, Markus; Dörje, Frank; Kochs, Eberhard; Riedel, Rainer

2017-04-01

In view of the rising cost pressure and an increasing number of drug shortages, switches between generic drug preparations have become a daily routine in hospitals. To ensure consistently high treatment quality and best possible patient safety, the equivalence of the new and the previous drug preparation must be ensured before any change in the purchase of pharmaceutical products takes place. So far, no easily usable, transparent and standardized instrument for this kind of comparison between generic drug products has been available. A group of pharmaceutical experts has developed the drug HTA (health technology assessment) model "HERA" (HTA Evaluation of geneRic phArmaceutical products) through a multi-step process. The instrument is designed to perform both a qualitative and economic comparison of equivalent drug preparations ("aut idem" substitution) before switching products. The economic evaluation does not only consider unit prices and consumption quantity, but also the processing costs associated with a product change process. The qualitative comparison is based on the evaluation of 34 quality criteria belonging to six evaluation fields (e.g., approval status, practical handling, packaging design). The objective evaluation of the quality criteria is complemented by an assessment of special features of the individual hospital for complex drug switches, including the feedback of the physicians utilizing the drug preparation. Thus potentially problematic switches of pharmaceutical products can be avoided at the best possible rate, contributing to the improvement of patient safety. The novel drug HTA model HERA is a tool used in clinical practice that can add to an increase in quality, therapeutic safety and transparency of drug use while simultaneously contributing to the economic optimization of drug procurement in hospitals. Combining these two is essential for hospitals facing the tension between rising cost pressure and at the same time increasing demands

Effectiveness of the 'Healthy School and Drugs' prevention programme on adolescents' substance use: a randomized clustered trial

NARCIS (Netherlands)

Malmberg, M.; Kleinjan, M.; Overbeek, G.; Vermulst, A.; Monshouwer, K.; Lammers, J.; Vollebergh, W.A.M.; Engels, R.C.M.E.

2014-01-01

Aim: To evaluate the effectiveness of the Healthy School and Drugs programme on alcohol, tobacco and marijuana use among Dutch early adolescents. Design: Randomized clustered trial with two intervention conditions (i.e. e-learning and integral). Setting: General population of 11-15-year-old

Effectiveness of the 'Healthy School and Drugs' prevention programme on adolescents' substance use : A randomized clustered trial

NARCIS (Netherlands)

Malmberg, Monique; Kleinjan, Marloes; Overbeek, Geertjan; Vermulst, Ad; Monshouwer, Karin; Lammers, Jeroen; Vollebergh, Wilma A M; Engels, Rutger C M E

2014-01-01

Aim: To evaluate the effectiveness of the Healthy School and Drugs programme on alcohol, tobacco and marijuana use among Dutch early adolescents. Design: Randomized clustered trial with two intervention conditions (i.e. e-learning and integral). Setting: General population of 11-15-year-old

Effectiveness of the 'Healthy School and Drugs' prevention programme on adolescents' substance use: a randomized clustered trial

NARCIS (Netherlands)

Malmberg, M.; Kleinjan, M.; Overbeek, G.J.; Vermulst, A.A.; Monshouwer, K.; Lammers, J.; Vollebergh, W.A.M.; Engels, R.C.M.E.

2014-01-01

Aim To evaluate the effectiveness of the Healthy School and Drugs programme on alcohol, tobacco and marijuana use among Dutch early adolescents. Design Randomized clustered trial with two intervention conditions (i.e. e-learning and integral). Setting General population of 11-15-year-old adolescents

A Cost Analysis of Hospitalizations for Infections Related to Injection Drug Use at a County Safety-Net Hospital in Miami, Florida

OpenAIRE

Tookes, Hansel; Diaz, Chanelle; Li, Hua; Khalid, Rafi; Doblecki-Lewis, Susanne

2015-01-01

Background Infections related to injection drug use are common. Harm reduction strategies such as syringe exchange programs and skin care clinics aim to prevent these infections in injection drug users (IDUs). Syringe exchange programs are currently prohibited by law in Florida. The goal of this study was to estimate the mortality and cost of injection drug use-related bacterial infections over a 12-month period to the county safety-net hospital in Miami, Florida. Additionally, the prevalence...

Randomized, parallel-group, double-blind, controlled study to evaluate the efficacy and safety of carbohydrate-derived fulvic acid in topical treatment of eczema

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Gandy JJ

2011-09-01

Full Text Available Justin J Gandy, Jacques R Snyman, Constance EJ van RensburgDepartment of Pharmacology, Faculty of Health Sciences, University of Pretoria, Pretoria, South AfricaBackground: The purpose of this study was to evaluate the efficacy and safety of carbohydrate-derived fulvic acid (CHD-FA in the treatment of eczema in patients two years and older.Methods: In this single-center, double-blind, placebo-controlled, parallel-group comparative study, 36 volunteers with predetermined eczema were randomly assigned to receive either the study drug or placebo twice daily for four weeks.Results: All safety parameters remained within normal limits, with no significant differences in either group. Significant differences were observed for both severity and erythema in the placebo and CHD-FA treated groups, and a significant difference was observed for scaling in the placebo-treated group. With regard to the investigator assessment of global response to treatment, a significant improvement was observed in the CHD-FA group when compared with the placebo group. A statistically significant decrease in visual analog scale score was observed in both groups, when comparing the baseline with the final results.Conclusion: CHD-FA was well tolerated, with no difference in reported side effects other than a short-lived burning sensation on application. CHD-FA significantly improved some aspects of eczema. Investigator assessment of global response to treatment with CHD-FA was significantly better than that with emollient therapy alone. The results of this small exploratory study suggest that CHD-FA warrants further investigation in the treatment of eczema.Keywords: fulvic acid, eczema, anti-inflammatory, efficacy, safety

Bioavailability and Safety of Vitamin D3 from Pizza Baked with Fortified Mozzarella Cheese: A Randomized Controlled Trial.

Science.gov (United States)

Al-Khalidi, Banaz; Chiu, Winnie; Rousseau, Dérick; Vieth, Reinhold

2015-09-01

To assess the bioavailability and safety of vitamin D3 from fortified mozzarella cheese baked on pizza. In a randomized, double-blind trial, 96 apparently healthy, ethnically diverse adults were randomized to consume 200 IU or 28 000 IU vitamin D3 fortified mozzarella cheese with pizza once weekly for a total of 8 weeks. Blood and urine samples were collected at baseline (week 1) and final (week 10) visits for serum 25-hydroxyvitamin D and other biochemical measures. The primary outcome compared serum 25-hydroxyvitamin D between groups at 10 weeks. The secondary outcome evaluated the safety of vitamin D dosing protocol as measured by serum and urine calcium, phosphate, creatinine, and serum parathyroid hormone (PTH). Serum 25-hydroxyvitamin D increased by 5.1 ± 11 nmol/L in the low-dose group (n = 47; P = 0.003), and by 73 ± 22 nmol/L in the high-dose group (n = 49; P pizza.

Safety and effects of two red blood cell transfusion strategies in pediatric cardiac surgery patients: a randomized controlled trial

NARCIS (Netherlands)

de Gast-Bakker, D. H.; de Wilde, R. B. P.; Hazekamp, M. G.; Sojak, V.; Zwaginga, J. J.; Wolterbeek, R.; de Jonge, E.; Gesink-van der Veer, B. J.

2013-01-01

To investigate the safety and effects of a restrictive red blood cell (RBC) transfusion strategy in pediatric cardiac surgery patients. Randomized controlled trial. Pediatric ICU in an academic tertiary care center, Leiden University Medical Center, Leiden, The Netherlands. One hundred seven

Computerized clinical decision support systems for therapeutic drug monitoring and dosing: A decision-maker-researcher partnership systematic review

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Weise-Kelly Lorraine

2011-08-01

Full Text Available Abstract Background Some drugs have a narrow therapeutic range and require monitoring and dose adjustments to optimize their efficacy and safety. Computerized clinical decision support systems (CCDSSs may improve the net benefit of these drugs. The objective of this review was to determine if CCDSSs improve processes of care or patient outcomes for therapeutic drug monitoring and dosing. Methods We conducted a decision-maker-researcher partnership systematic review. Studies from our previous review were included, and new studies were sought until January 2010 in MEDLINE, EMBASE, Evidence-Based Medicine Reviews, and Inspec databases. Randomized controlled trials assessing the effect of a CCDSS on process of care or patient outcomes were selected by pairs of independent reviewers. A study was considered to have a positive effect (i.e., CCDSS showed improvement if at least 50% of the relevant study outcomes were statistically significantly positive. Results Thirty-three randomized controlled trials were identified, assessing the effect of a CCDSS on management of vitamin K antagonists (14, insulin (6, theophylline/aminophylline (4, aminoglycosides (3, digoxin (2, lidocaine (1, or as part of a multifaceted approach (3. Cluster randomization was rarely used (18% and CCDSSs were usually stand-alone systems (76% primarily used by physicians (85%. Overall, 18 of 30 studies (60% showed an improvement in the process of care and 4 of 19 (21% an improvement in patient outcomes. All evaluable studies assessing insulin dosing for glycaemic control showed an improvement. In meta-analysis, CCDSSs for vitamin K antagonist dosing significantly improved time in therapeutic range. Conclusions CCDSSs have potential for improving process of care for therapeutic drug monitoring and dosing, specifically insulin and vitamin K antagonist dosing. However, studies were small and generally of modest quality, and effects on patient outcomes were uncertain, with no convincing

Visual presentations of efficacy data in direct-to-consumer prescription drug print and television advertisements: A randomized study.

Science.gov (United States)

Sullivan, Helen W; O'Donoghue, Amie C; Aikin, Kathryn J; Chowdhury, Dhuly; Moultrie, Rebecca R; Rupert, Douglas J

2016-05-01

To determine whether visual aids help people recall quantitative efficacy information in direct-to-consumer (DTC) prescription drug advertisements, and if so, which types of visual aids are most helpful. Individuals diagnosed with high cholesterol (n=2504) were randomized to view a fictional DTC print or television advertisement with no visual aid or one of four visual aids (pie chart, bar chart, table, or pictograph) depicting drug efficacy. We measured drug efficacy and risk recall, drug perceptions and attitudes, and behavioral intentions. For print advertisements, a bar chart or table, compared with no visual aid, elicited more accurate drug efficacy recall. The bar chart was better at this than the pictograph and the table was better than the pie chart. For television advertisements, any visual aid, compared with no visual aid, elicited more accurate drug efficacy recall. The bar chart was better at this than the pictograph or the table. Visual aids depicting quantitative efficacy information in DTC print and television advertisements increased drug efficacy recall, which may help people make informed decisions about prescription drugs. Adding visual aids to DTC advertising may increase the public's knowledge of how well prescription drugs work. Published by Elsevier Ireland Ltd.

Computed tomography of the brain, hepatotoxic drugs and high alcohol consumption in male alcoholic patients and a random sample from the general male population

Energy Technology Data Exchange (ETDEWEB)

Muetzell, S. (Univ. Hospital of Uppsala (Sweden). Dept. of Family Medicine)

1992-01-01

Computed tomography (CT) of the brain was performed in a random sample of a total of 195 men and 211 male alcoholic patients admitted for the first time during a period of two years from the same geographically limited area of Greater Stockholm as the sample. Laboratory tests were performed, including liver and pancreatic tests. Toxicological screening was performed and the consumption of hepatotoxic drugs was also investigated. The groups were then subdivided with respect to alcohol consumption and use of hepatotoxic drugs: group IA, men from the random sample with low or moderate alcohol consumption and no use of hepatotoxic drugs; IB, men from the random sample with low or moderate alcohol consumption with use of hepatotoxic drugs; IIA, alcoholic inpatients with use of alcohol and no drugs; and IIB, alcoholic inpatients with use of alcohol and drugs. Group IIB was found to have a higher incidence of cortical and subcortical changes than group IA. Group IB had a higher incidence of subcortical changes than group IA, and they differed only in drug use. Groups IIN and IIA only differed in drug use, and IIB had a higher incidence of brian damage except for anterior horn index and wide cerebellar sulci indicating vermian atrophy. Significantly higher serum levels of bilirubin, GGT, ASAT, ALAT, CK LD, and amylase were found in IIB. The results indicate that drug use influences the incidence of cortical and subcortical aberrations, except anterior horn index. It is concluded that the groups with alcohol abuse who used hepatotoxic drugs showed a picture of cortical changes (wide transport sulci and clear-cut of high-grade cortical changes) and also of subcortical aberrations, expressed as an increased widening on the third ventricle.

Computed tomography of the brain, hepatotoxic drugs and high alcohol consumption in male alcoholic patients and a random sample from the general male population

International Nuclear Information System (INIS)

Muetzell, S.

1992-01-01

Computed tomography (CT) of the brain was performed in a random sample of a total of 195 men and 211 male alcoholic patients admitted for the first time during a period of two years from the same geographically limited area of Greater Stockholm as the sample. Laboratory tests were performed, including liver and pancreatic tests. Toxicological screening was performed and the consumption of hepatotoxic drugs was also investigated. The groups were then subdivided with respect to alcohol consumption and use of hepatotoxic drugs: group IA, men from the random sample with low or moderate alcohol consumption and no use of hepatotoxic drugs; IB, men from the random sample with low or moderate alcohol consumption with use of hepatotoxic drugs; IIA, alcoholic inpatients with use of alcohol and no drugs; and IIB, alcoholic inpatients with use of alcohol and drugs. Group IIB was found to have a higher incidence of cortical and subcortical changes than group IA. Group IB had a higher incidence of subcortical changes than group IA, and they differed only in drug use. Groups IIN and IIA only differed in drug use, and IIB had a higher incidence of brian damage except for anterior horn index and wide cerebellar sulci indicating vermian atrophy. Significantly higher serum levels of bilirubin, GGT, ASAT, ALAT, CK LD, and amylase were found in IIB. The results indicate that drug use influences the incidence of cortical and subcortical aberrations, except anterior horn index. It is concluded that the groups with alcohol abuse who used hepatotoxic drugs showed a picture of cortical changes (wide transport sulci and clear-cut of high-grade cortical changes) and also of subcortical aberrations, expressed as an increased widening on the third ventricle

Nonsteroidal anti-inflammatory drug or glucosamine reduced pain and improved muscle strength with resistance training in a randomized controlled trial of knee osteoarthritis patients

DEFF Research Database (Denmark)

Petersen, Susanne G; Beyer, Nina; Hansen, Mette

2011-01-01

Petersen SG, Beyer N, Hansen M, Holm L, Aagaard P, Mackey AL, Kjaer M. Nonsteroidal anti-inflammatory drug or glucosamine reduced pain and improved muscle strength with resistance training in a randomized controlled trial of knee osteoarthritis patients.......Petersen SG, Beyer N, Hansen M, Holm L, Aagaard P, Mackey AL, Kjaer M. Nonsteroidal anti-inflammatory drug or glucosamine reduced pain and improved muscle strength with resistance training in a randomized controlled trial of knee osteoarthritis patients....

Efficacy and Safety of Drotaverine Hydrochloride in Children with Recurrent Abdominal Pain: A Randomized Placebo Controlled Trial.

Science.gov (United States)

Narang, Manish; Shah, Dheeraj; Akhtar, Hina

2015-10-01

To evaluate the efficacy and safety of Drotaverine hydrochroride in children with recurrent abdominal pain. Double blind, randomized placebo-controlled trial. Pediatric Gastroenterology clinic of a teaching hospital. 132 children (age 4-12 y) with recurrent abdominal pain (Apley Criteria) randomized to receivedrotaverine (n=66) or placebo (n=66) orally. Children between 4-6 years of age received 10 mL syrup orally (20 mg drotaverine hydrochloride or placebo) thrice daily for 4 weeks while children >6 years of age received one tablet orally (40 mg drotaverine hydrochloride or placebo) thrice daily for 4 weeks. Primary: Number of episodes of pain during 4 weeks of use of drug/placebo and number of pain-free days. Secondary: Number of school days missed during the study period, parental satisfaction (on a Likert scale), and occurrence of solicited adverse effects. Reduction in number of episodes of abdominal pain [mean (SD) number of episodes 10.3 (14) vs 21.6 (32.4); P=0.01] and lesser school absence [mean (SD) number of school days missed 0.25 (0.85) vs 0.71 (1.59); P=0.05] was noticed in children receiving drotaverine in comparison to those who received placebo. The number of pain-free days, were comparable in two groups [17.4 (8.2) vs 15.6 (8.7); P=0.23]. Significant improvement in parental satisfaction score was noticed on Likert scale by estimation of mood, activity, alertness, comfort and fluid intake. Frequency of adverse events during follow-up period was comparable between children receiving drotaverine or placebo (46.9% vs 46.7%; P=0.98). Drotaverine hydrochloride is an effective and safe pharmaceutical agent in the management of recurrent abdominal pain in children.

Rationale and design of the VISION study: a randomized, open-label study to evaluate the long-term safety of vonoprazan as maintenance treatment in patients with erosive esophagitis

Directory of Open Access Journals (Sweden)

Uemura N

2018-01-01

Full Text Available Naomi Uemura,1 Yoshikazu Kinoshita,2 Ken Haruma,3 Takashi Yao,4 Ryoji Kushima,5 Tatsuhiro Kanoo6 1Department of Gastroenterology and Hepatology, National Center for Global Health and Medicine, Kohnodai Hospital, Chiba, Japan; 2Department of Gastroenterology and Hepatology, Faculty of Medicine, Shimane University, Shimane, Japan; 3Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan; 4Department of Human Pathology, Juntendo University Graduate School of Medicine, Tokyo, Japan; 5Department of Clinical Laboratory Medicine, Shiga University of Medical Science Hospital, Shiga, Japan; 6Takeda Pharmaceutical Co., Ltd, Osaka, Japan Abstract: Erosive esophagitis (EE occurs when the epithelial mucosa is damaged due to gastric acid reflux, and the incidence of this disease is increasing in Japan due to changes in diet and lifestyle. The condition can be treated using proton pump inhibitors (PPIs that act by irreversibly blocking the H+,K+-ATPase responsible for acid secretion. Vonoprazan is a K+ competitive channel inhibitor, which reversibly and potently inhibits gastric acid secretion. However, long-term data on vonoprazan use are limited. The aim of the VISION trial is to investigate the long-term efficacy and safety of vonoprazan in comparison with the PPI lansoprazole. This randomized, multicenter, 5-year, open-label study has a planned recruitment of 195 participants (2:1 allocation vonoprazan:lansoprazole from 33 sites in Japan. The study comprises an 8-week “healing” phase (vonoprazan 20 mg or lansoprazole 30 mg p.o. and a 260-week “maintenance” phase (vonoprazan 10 mg or lansoprazole 15 mg. Safety populations in both phases are defined as participants who receive at least one dose of the study or control drug in the healing and maintenance phases, respectively. The full analysis set in both phases is defined as participants who are randomized and receive at least one dose of the study or

Nonclinical safety biomarkers of drug-induced vascular injury: current status and blueprint for the future.

Science.gov (United States)

Mikaelian, Igor; Cameron, Mark; Dalmas, Deidre A; Enerson, Bradley E; Gonzalez, Raymond J; Guionaud, Silvia; Hoffmann, Peter K; King, Nicholas M P; Lawton, Michael P; Scicchitano, Marshall S; Smith, Holly W; Thomas, Roberta A; Weaver, James L; Zabka, Tanja S

2014-06-01

Better biomarkers are needed to identify, characterize, and/or monitor drug-induced vascular injury (DIVI) in nonclinical species and patients. The Predictive Safety Testing Consortium (PSTC), a precompetitive collaboration of pharmaceutical companies and the U.S. Food and Drug Administration (FDA), formed the Vascular Injury Working Group (VIWG) to develop and qualify translatable biomarkers of DIVI. The VIWG focused its research on acute DIVI because early detection for clinical and nonclinical safety monitoring is desirable. The VIWG developed a strategy based on the premise that biomarkers of DIVI in rat would be translatable to humans due to the morphologic similarity of vascular injury between species regardless of mechanism. The histomorphologic lexicon for DIVI in rat defines degenerative and adaptive findings of the vascular endothelium and smooth muscles, and characterizes inflammatory components. We describe the mechanisms of these changes and their associations with candidate biomarkers for which advanced analytical method validation was completed. Further development is recommended for circulating microRNAs, endothelial microparticles, and imaging techniques. Recommendations for sample collection and processing, analytical methods, and confirmation of target localization using immunohistochemistry and in situ hybridization are described. The methods described are anticipated to aid in the identification and qualification of translational biomarkers for DIVI. © 2014 by The Author(s).

Maternal Efficacy and Safety Outcomes in a Randomized, Controlled Trial Comparing Insulin Detemir With NPH Insulin in 310 Pregnant Women With Type 1 Diabetes

DEFF Research Database (Denmark)

Mathiesen, Elisabeth R; Hod, Moshe; Ivanisevic, Marina

2012-01-01

OBJECTIVE This randomized, controlled noninferiority trial aimed to compare the efficacy and safety of insulin detemir (IDet) versus neutral protamine Hagedorn (NPH) (both with prandial insulin aspart) in pregnant women with type 1 diabetes. RESEARCH DESIGN AND METHODS Patients were randomized an...

Chemical dependency and drug testing in the workplace.

Science.gov (United States)

Osterloh, J D; Becker, C E

1990-05-01

Urine testing for drug use in the workplace is now widespread, with the prevalence of positive drug tests in the work force being 0% to 15%. The prevalence of marijuana use is highest, and this can be reliably tested. Though it is prudent to rid the workplace of drug use, there is little scientific study on the relationship of drug use and workplace outcomes, such as productivity and safety. Probable-cause testing and preemployment testing are the most common applications. Random testing has been less accepted owing to its higher costs, unresolved legal issues, and predictably poor test reliability. Legal issues have focused on the right to policy, discrimination, and the lack of due process. The legal cornerstone of a good program is a policy that is planned and agreed on by both labor and management, which serves both as a contract and as a procedure in which expectations and consequences are known. The National Institute on Drug Abuse is certifying laboratories doing employee drug testing. Testing methods when done correctly are less prone to error than in the past, but screening tests can be defeated by adulterants. Although the incidence of false-positive results is low, such tests are less reliable when the prevalence of drug abuse is also low.

Safety and feasibility of transcranial direct current stimulation in pediatric hemiparesis: randomized controlled preliminary study.

Science.gov (United States)

Gillick, Bernadette T; Feyma, Tim; Menk, Jeremiah; Usset, Michelle; Vaith, Amy; Wood, Teddi Jean; Worthington, Rebecca; Krach, Linda E

2015-03-01

Transcranial direct current stimulation (tDCS) is a form of noninvasive brain stimulation that has shown improved adult stroke outcomes. Applying tDCS in children with congenital hemiparesis has not yet been explored. The primary objective of this study was to explore the safety and feasibility of single-session tDCS through an adverse events profile and symptom assessment within a double-blind, randomized placebo-controlled preliminary study in children with congenital hemiparesis. A secondary objective was to assess the stability of hand and cognitive function. A double-blind, randomized placebo-controlled pretest/posttest/follow-up study was conducted. The study was conducted in a university pediatric research laboratory. Thirteen children, ages 7 to 18 years, with congenital hemiparesis participated. Adverse events/safety assessment and hand function were measured. Participants were randomly assigned to either an intervention group or a control group, with safety and functional assessments at pretest, at posttest on the same day, and at a 1-week follow-up session. An intervention of 10 minutes of 0.7 mA tDCS was applied to bilateral primary motor cortices. The tDCS intervention was considered safe if there was no individual decline of 25% or group decline of 2 standard deviations for motor evoked potentials (MEPs) and behavioral data and no report of adverse events. No major adverse events were found, including no seizures. Two participants did not complete the study due to lack of MEP and discomfort. For the 11 participants who completed the study, group differences in MEPs and behavioral data did not exceed 2 standard deviations in those who received the tDCS (n=5) and those in the control group (n=6). The study was completed without the need for stopping per medical monitor and biostatisticial analysis. A limitation of the study was the small sample size, with data available for 11 participants. Based on the results of this study, tDCS appears to be safe

Adverse events analysis as an educational tool to improve patient safety culture in primary care: a randomized trial.

Science.gov (United States)

González-Formoso, Clara; Martín-Miguel, María Victoria; Fernández-Domínguez, Ma José; Rial, Antonio; Lago-Deibe, Fernando Isidro; Ramil-Hermida, Luis; Pérez-García, Margarita; Clavería, Ana

2011-06-14

Patient safety is a leading item on the policy agenda of both major international health organizations and advanced countries generally. The quantitative description of the phenomena has given rise to intense concern with the issue in institutions and organizations, leading to a number of initiatives and research projects and the promotion of patient safety culture, with training becoming a priority both in Spain and internationally. To date, most studies have been conducted in a hospital setting, even though primary care is the type most commonly used by the public, in our experience. Our study aims to achieve the following:--Assess the registry of adverse events as an education tool to improve patient safety culture in the Family and Community Teaching Units of Galicia.--Find and analyze educational tools to improve patient safety culture in primary care.--Evaluate the applicability of the Hospital Survey on Patient Safety Culture by the Agency for Healthcare Research and Quality, Spanish version, in the context of primary health care. Experimental unifactorial study of two groups, control and intervention. Tutors and residents in Family and Community Medicine in last year of studies in Galicia, Spain. From the population universe through voluntary participation. Twenty-seven tutor-resident units in each group required, randomly assigned. Residents and their respective tutor (tutor-resident pair) in teaching units on Family and Community Medicine from throughout Galicia will be invited to participate. Tutor-resident pair that agrees to participate will be sent the Hospital Survey on Patient Safety Culture. Then, tutor-resident pair will be assigned to each group--either intervention or control--through simple random sampling. The intervention group will receive specific training to record the adverse effects found in patients under their care, with subsequent feedback, after receiving instruction on the process. No action will be taken in the control group. After

The discovery and development of proteomic safety biomarkers for the detection of drug-induced liver toxicity

International Nuclear Information System (INIS)

Amacher, David E.

2010-01-01

Biomarkers are biometric measurements that provide critical quantitative information about the biological condition of the animal or individual being tested. In drug safety studies, established toxicity biomarkers are used along with other conventional study data to determine dose-limiting organ toxicity, and to define species sensitivity for new chemical entities intended for possible use as human medicines. A continuing goal of drug safety scientists in the pharmaceutical industry is to discover and develop better trans-species biomarkers that can be used to determine target organ toxicities for preclinical species in short-term studies at dose levels that are some multiple of the intended human dose and again later in full development for monitoring clinical trials at lower therapeutic doses. Of particular value are early, predictive, noninvasive biomarkers that have in vitro, in vivo, and clinical transferability. Such translational biomarkers bridge animal testing used in preclinical science and human studies that are part of subsequent clinical testing. Although suitable for in vivo preclinical regulatory studies, conventional hepatic safety biomarkers are basically confirmatory markers because they signal organ toxicity after some pathological damage has occurred, and are therefore not well-suited for short-term, predictive screening assays early in the discovery-to-development progression of new chemical entities (NCEs) available in limited quantities. Efforts between regulatory agencies and the pharmaceutical industry are underway for the coordinated discovery, qualification, verification and validation of early predictive toxicity biomarkers. Early predictive safety biomarkers are those that are detectable and quantifiable prior to the onset of irreversible tissue injury and which are associated with a mechanism of action relevant to a specific type of potential hepatic injury. Potential drug toxicity biomarkers are typically endogenous macromolecules in

The efficacy and safety of the targeted drug combined with adriamycin liposome solution for HER-2-positive breast cancer

Directory of Open Access Journals (Sweden)

Zi-Ping Zhou

2017-05-01

Full Text Available Objective: To study the efficacy and safety of the targeted drug trastuzumab combined with adriamycin liposome solution for HER-2-positive breast cancer. Methods: A total of 112 patients with breast cancer who received chemotherapy in Department of Cardiothoracic Breast Surgery, Guangdong TongJiang Hospital between May 2014 and April 2016 were selected as the research subjects and divided into two groups by random number table, liposome group received trastuzumab + adriamycin liposome chemotherapy, and the control group received trastuzumab + adriamycin chemotherapy. Before chemotherapy as well as 4 weeks and 8 weeks after chemotherapy, serum levels of tumor markers, cytokines and myocardial injury indexes were detected, the electrocardiography was conducted and the degree of myocardial injury was determined. Results: 4 weeks and 8 weeks after chemotherapy, serum CEA, CA15-3, TPS, CTGF, TGF-β, TSGF, VEGF and MK levels of both groups were significantly lower than those before chemotherapy, serum CK-MB and cTnI levels were significantly higher than those before chemotherapy, limb leads QRS amplitudes and chest leads QRS amplitudes were significantly lower than those before chemotherapy, serum CEA, CA15-3, TPS, CTGF, TGF-β, TSGF, VEGF, MK, CK-MB and cTnI levels of liposome group were significantly lower than those of control group, and the limb leads QRS amplitudes and chest lead QRS amplitudes were significantly higher than those of control group. Conclusion: Targeted drug combined with adriamycin liposome therapy for HER-2-positive breast cancer can improve the curative effect and reduce the cardiotoxicity.

Evaluation of Vaginal Drug Levels and Safety of a Locally Administered Glycerol Monolaurate Cream in Rhesus Macaques.

Science.gov (United States)

Kirtane, Ameya R; Rothenberger, Meghan K; Frieberg, Abby; Nephew, Karla; Schultz-Darken, Nancy; Schmidt, Thomas; Reimann, Thomas; Haase, Ashley T; Panyam, Jayanth

2017-07-01

The human immunodeficiency virus epidemic affects millions of people worldwide. As women are more vulnerable to infection, female-controlled interventions can help control the spread of the disease significantly. Glycerol monolaurate (GML), an inexpensive and safe compound, has been shown to protect against simian immunodeficiency virus infection when applied vaginally. However, on account of its low aqueous solubility, fabrication of high-dose formulations of GML has proven difficult. We describe the development of a vaginal cream that could be loaded with up to 35% GML. Vaginal drug levels and safety of 3 formulations containing increasing concentrations of GML (5%w/w, 15%w/w, and 35%w/w) were tested in rhesus macaques after vaginal administration. GML concentration in the vaginal tissue increased as the drug concentration in the cream increased, with 35% GML cream resulting in tissue concentration of ∼0.5 mg/g, albeit with high interindividual variability. Compared with the vehicle control, none of the GML creams had any significant effect on the vaginal flora and cytokine (macrophage inflammatory protein 3α and interleukin 8) levels, suggesting that high-dose GML formulations do not induce local adverse effects. In summary, we describe the development of a highly loaded vaginal cream of GML, and vaginal drug levels and safety after local administration in macaques. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Efficacy and safety of amphotericin B emulsion versus liposomal formulation in Indian patients with visceral leishmaniasis: a randomized, open-label study.

Directory of Open Access Journals (Sweden)

Shyam Sundar

2014-09-01

Full Text Available India is home to 60% of the total global visceral leishmaniasis (VL population. Use of long-term oral (e.g. miltefosine and parenteral drugs, considered the mainstay for treatment of VL, is now faced with increased resistance, decreased efficacy, low compliance and safety issues. The authors evaluated the efficacy and safety of an alternate treatment option, i.e. single infusion of preformed amphotericin B (AmB lipid emulsion (ABLE in comparison with that of liposomal formulation (LAmB.In this multicentric, open-label study, 500 patients with VL were randomly assigned in a 3:1 ratio to receive 15 mg/kg single infusion of either ABLE (N = 376 or LAmB (N = 124. Initial cure (Day 30/45, clinical improvement (Day 30 and long term definitive cure (Day 180 were assessed.A total of 326 (86.7% patients in the ABLE group and 122 (98.4% patients in the LAmB group completed the study. Initial cure was achieved by 95.9% of patients in the ABLE group compared to 100% in the LAmB group (p = 0.028; 95% CI: -0.0663, -0.0150. Clinical improvement was comparable between treatments (ABLE: 98.9% vs. LAmB: 98.4%. Definitive cure was achieved in 85.9% with ABLE compared to 98.4% with LAmB. Infusion-related pyrexia (37.2% vs. 32.3% and chills (18.4% vs. 18.5% were comparable between ABLE and LAmB, respectively. Treatment-related serious adverse events were fewer in ABLE (0.3% compared to LAmB (1.6%. Two deaths occurred in the ABLE group, of which one was probably related to the study drug. Nephrotoxicity and hepatotoxicity was not observed in either group.ABLE 15 mg/kg single infusion had favorable efficacy and was well tolerated. Considering the demographic profile of the population in this region, a single dose treatment offers advantages in terms of compliance, cost and applicability.www.clinicaltrials.gov NCT00876824.

The efficacy and safety of irsogladine maleate in nonsteroidal anti-inflammatory drug or aspirin-induced peptic ulcer and gastritis.

Science.gov (United States)

Shim, Ki-Nam; Kim, Jin Il; Kim, Nayoung; Kim, Sang Gyun; Jo, Yun Ju; Hong, Su Jin; Shin, Jeong Eun; Kim, Gwang Ha; Park, Kyung Sik; Choi, Suck Chei; Kwon, Joong Goo; Kim, Jie-Hyun; Kim, Hyun Jin; Kim, Ji Won

2018-06-01

Irsogladine maleate, an enhancer of gastric mucosal protective factors, has demonstrated its efficacy for various gastric mucosal injuries. The aim of this study was to evaluate the efficacy and safety of irsogladine for prevention of nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin-induced peptic ulcer and gastritis. In this multicenter, randomized, double-blind, exploratory clinical trial, 100 patients over 50 years of age who needed continuous NSAIDs or aspirin for more than 8 weeks were randomly assigned to either test group (irsogladine maleate 2 mg, twice daily, 39 patients for full analysis) or placebo group (37 patients for full analysis). Primary outcomes were incidence of peptic ulcer and ratio of modified Lanza score (MLS) 2 to 4. Secondary outcome was the number of acute erosions confirmed by endoscopy at 8 weeks. Adverse effects were also compared. There were no significant differences in gastric protective effects between test and placebo groups. However, two cases of peptic ulcer in the placebo group but none in the test group were observed. These two cases of peptic ulcer were Helicobacter pylori-negative. In addition, H. pylori-negative group showed significant changes in MLS score (p = 0.0247) and edema score (p = 0.0154) after the treatment compared to those before treatment in the test group. There was no significant difference in adverse events between the two groups. The efficacy of irsogladine maleate was found in H. pylori-negative group, suggesting its potential as a protective agent against NSAIDs or aspirin-induced peptic ulcer and gastritis.

Effectiveness and short-term safety of modified sodium hyaluronic acid-carboxymethylcellulose at cesarean delivery: a randomized trial.

Science.gov (United States)

Kiefer, Daniel G; Muscat, Jolene C; Santorelli, Jarrett; Chavez, Martin R; Ananth, Cande V; Smulian, John C; Vintzileos, Anthony M

2016-03-01

The rising cesarean birth rate has drawn attention to risks associated with repeat cesarean birth. Prevention of adhesions with adhesion barriers has been promoted as a way to decrease operative difficulty. However, robust data demonstrating effectiveness of such interventions are lacking. We report data from a multicenter trial designed to evaluate the short-term safety and effectiveness of a modified sodium hyaluronic acid (HA)-carboxymethylcellulose (CMC) absorbable adhesion barrier for reduction of adhesions following cesarean delivery. Patients who underwent primary or repeat cesarean delivery were included in this multicenter, single-blinded (patient), randomized controlled trial. Patients were randomized into either HA-CMC (N = 380) or no treatment (N = 373). No other modifications to their treatment were part of the protocol. Short-term safety data were collected following randomization. The location and density of adhesions (primary outcome) were assessed at their subsequent delivery using a validated tool, which can also be used to derive an adhesion score that ranges from 0-12. No differences in baseline characteristics, postoperative course, or incidence of complications between the groups following randomization were noted. Eighty patients from the HA-CMC group and 92 controls returned for subsequent deliveries. Adhesions in any location were reported in 75.6% of the HA-CMC group and 75.9% of the controls (P = .99). There was no significant difference in the median adhesion score; 2 (range 0-10) for the HA-CMC group vs 2 (range 0-8) for the control group (P = .65). One third of the HA-CMC patients met the definition for severe adhesions (adhesion score >4) compared to 15.5% in the control group (P = .052). There were no significant differences in the time from incision to delivery (P = .56). Uterine dehiscence in the next pregnancy was reported in 2 patients in HA-CMC group vs 1 in the control group (P = .60). Although we did not identify any short

The efficacy and safety of S-flurbiprofen plaster in the treatment of knee osteoarthritis: a phase II, randomized, double-blind, placebo-controlled, dose-finding study

Directory of Open Access Journals (Sweden)

Yataba I

2017-04-01

Full Text Available Ikuko Yataba,1 Noboru Otsuka,1 Isao Matsushita,1 Hideo Matsumoto,2 Yuichi Hoshino3 1Taisho Pharmaceutical Co, Ltd, 2Institute for Integrated Sports Medicine, School of Medicine, Keio University, Tokyo, 3Department of Orthopedics Surgery, School of Medicine, Jichi Medical University, Tochigi, Japan Background: Nonsteroidal anti-inflammatory drug (NSAID patches are convenient for use and show much less gastrointestinal side effects than oral NSAIDs, whereas its percutaneous absorption is not sufficient for the expression of clinical efficacy at satisfactory level. S-flurbiprofen plaster (SFPP has shown dramatic improvement in percutaneous absorption results from animal and clinical studies. In this study, the efficacy and safety of SFPP were compared with placebo in patients with knee osteoarthritis (OA to determine its optimal dose. This was a multicenter, randomized, double-blind, parallel-group comparative study. Patients and methods: Enrolled 509 knee OA patients were treated with placebo or SFPP at 10, 20, or 40 mg applied on the affected site once daily for 2 weeks. The primary endpoint for efficacy was improvement in knee pain on rising from the chair assessed by visual analog scale (VAS. The other endpoints were clinical symptoms, pain on walking, and global assessment by both investigator and patient. Safety was evaluated by observing adverse events (AEs. Results: VAS change in knee pain from baseline to trial end was dose-dependent, least squares mean was 29.5, 31.5, 32.0, and 35.6 mm in placebo and SFPP 10, 20, and 40 mg, respectively. A significant difference was observed between placebo and SFPP 40 mg (P=0.001. In contrast, the effect of SFPP at a dose ≤20 mg was not significantly different from that of placebo. The proportion of the patients who achieved 50% pain relief was 72.4% in 40 mg and 51.2% in placebo (P<0.001. In all other endpoints, SFPP 40 mg showed significant improvement compared with placebo. The incidence of AEs was

'BeSAFE', effect-evaluation of internet-based, tailored safety information combined with personal counselling on parents' child safety behaviours: study design of a randomized controlled trial

Directory of Open Access Journals (Sweden)

van Beeck Eduard F

2010-08-01

Full Text Available Abstract Background Injuries in or around the home are the most important cause of death among children aged 0-4 years old. It is also a major source of morbidity and loss of quality of life. In order to reduce the number of injuries, the Consumer Safety Institute introduced the use of Safety Information Leaflets in the Netherlands to provide safety education to parents of children aged 0-4 years. Despite current safety education, necessary safety behaviours are still not taken by a large number of parents, causing unnecessary risk of injury among young children. In an earlier study an E-health module with internet-based, tailored safety information was developed and applied. It concerns an advice for parents on safety behaviours in their homes regarding their child. The aim of this study is to evaluate the effect of this safety information combined with personal counselling on parents' child safety behaviours. Methods/Design Parents who are eligible for the regular well-child visit with their child at child age 5-8 months are invited to participate in this study. Participating parents are randomized into one of two groups: 1 internet-based, tailored safety information combined with personal counselling (intervention group, or 2 personal counselling using the Safety Information Leaflets of the Consumer Safety Institute in the Netherlands for children aged 12 to 24 months (control group. All parents receive safety information on safety topics regarding the prevention of falling, poisoning, drowning and burning. Parents of the intervention group will access the internet-based, tailored safety information module when their child is approximately 10 months old. After completion of the assessment questions, the program compiles a tailored safety advice. The parents are asked to devise and inscribe a personal implementation intention. During the next well-child visit, the Child Health Clinic professional will discuss this tailored safety information

Using resources for scientific-driven pharmacovigilance: from many product safety documents to one product safety master file.

Science.gov (United States)

Furlan, Giovanni

2012-08-01

Current regulations require a description of the overall safety profile or the specific risks of a drug in multiple documents such as the Periodic and Development Safety Update Reports, Risk Management Plans (RMPs) and Signal Detection Reports. In a resource-constrained world, the need for preparing multiple documents reporting the same information results in shifting the focus from a thorough scientific and medical evaluation of the available data to maintaining compliance with regulatory timelines. Since the aim of drug safety is to understand and characterize product issues to take adequate risk minimization measures rather than to comply with bureaucratic requirements, there is the need to avoid redundancy. In order to identify core drug safety activities that need to be undertaken to protect patient safety and reduce the number of documents reporting the results of these activities, the author has reviewed the main topics included in the drug safety guidelines and templates. The topics and sources that need to be taken into account in the main regulatory documents have been found to greatly overlap and, in the future, as a result of the new Periodic Safety Update Report structure and requirements, in the author's opinion this overlap is likely to further increase. Many of the identified inter-document differences seemed to be substantially formal. The Development Safety Update Report, for example, requires separate presentation of the safety issues emerging from different sources followed by an overall evaluation of each safety issue. The RMP, instead, requires a detailed description of the safety issues without separate presentation of the evidence derived from each source. To some extent, however, the individual documents require an in-depth analysis of different aspects; the RMP, for example, requires an epidemiological description of the indication for which the drug is used and its risks. At the time of writing this article, this is not specifically

Combination of Deep Recurrent Neural Networks and Conditional Random Fields for Extracting Adverse Drug Reactions from User Reviews.

Science.gov (United States)

Tutubalina, Elena; Nikolenko, Sergey

2017-01-01

Adverse drug reactions (ADRs) are an essential part of the analysis of drug use, measuring drug use benefits, and making policy decisions. Traditional channels for identifying ADRs are reliable but very slow and only produce a small amount of data. Text reviews, either on specialized web sites or in general-purpose social networks, may lead to a data source of unprecedented size, but identifying ADRs in free-form text is a challenging natural language processing problem. In this work, we propose a novel model for this problem, uniting recurrent neural architectures and conditional random fields. We evaluate our model with a comprehensive experimental study, showing improvements over state-of-the-art methods of ADR extraction.

Combination of Deep Recurrent Neural Networks and Conditional Random Fields for Extracting Adverse Drug Reactions from User Reviews

Directory of Open Access Journals (Sweden)

Elena Tutubalina

2017-01-01

Full Text Available Adverse drug reactions (ADRs are an essential part of the analysis of drug use, measuring drug use benefits, and making policy decisions. Traditional channels for identifying ADRs are reliable but very slow and only produce a small amount of data. Text reviews, either on specialized web sites or in general-purpose social networks, may lead to a data source of unprecedented size, but identifying ADRs in free-form text is a challenging natural language processing problem. In this work, we propose a novel model for this problem, uniting recurrent neural architectures and conditional random fields. We evaluate our model with a comprehensive experimental study, showing improvements over state-of-the-art methods of ADR extraction.

Efficacy and safety of extended-release oxcarbazepine (Oxtellar XR™) as adjunctive therapy in patients with refractory partial-onset seizures: a randomized controlled trial

Science.gov (United States)

French, JA; Baroldi, P; Brittain, ST; Johnson, JK

2014-01-01

Objective To evaluate the efficacy, tolerability, and safety of once-daily 1200 mg and 2400 mg SPN-804 (Oxtellar XR™, Supernus Pharmaceuticals), an extended-release tablet formulation of oxcarbazepine (OXC), added to 1-3 concomitant antiepileptic drugs (AEDs) in adults with refractory partial-onset seizures, with or without secondary generalization. Methods The Prospective, Randomized Study of OXC XR in Subjects with Partial Epilepsy Refractory (PROSPER) study was a multinational, randomized, double-blind, parallel-group Phase 3 study. The primary efficacy endpoint was median percent reduction from baseline in monthly (28-day) seizure frequency for the 16-week double-blind treatment period in the intent-to-treat (ITT) population with analyzable seizure data. Other efficacy analyses included proportion of patients with ≥ 50% seizure reduction, proportion of patients seizure free, and the relationship between clinical response and plasma concentration. Results Median percent reduction was -28.7% for placebo, −38.2% (P = 0.08 vs placebo) for once-daily SPN-804 1200 mg, and −42.9% (P = 0.003) for SPN-804 2400 mg. Responder rates were 28.1%, 36.1% (P = 0.08), and 40.7% (P = 0.02); 16-week seizure-free rates in a pragmatic ITT analysis were 3.3%, 4.9% (P = 0.59), and 11.4% (P = 0.008), respectively. When data were analyzed separately for study site clusters, a post hoc analysis demonstrated that both SPN-804 dosages were significantly superior to placebo in median percent seizure reduction (placebo: −13.3%; 1200 mg: −34.5%, P = 0.02; 2400 mg: −52.7%, P = 0.006) in the North American study site cluster. A concentration–response analysis also supported a clinically meaningful effect for 1200 mg. Adverse event types reflected the drug's established profile. Adverse event frequency was consistent with a pharmacokinetic profile in which SPN-804 produces lower peak plasma concentrations vs immediate-release OXC. Once-daily dosing was not

Meta-analysis comparing efficacy and safety of first generation drug-eluting stents to bare-metal stents in patients with diabetes mellitus undergoing primary percutaneous coronary intervention

DEFF Research Database (Denmark)

De Luca, Giuseppe; Dirksen, Maurits T; Spaulding, Christian

2013-01-01

revascularization (hazard ratio 0.42, 95% confidence interval 0.29 to 0.59, p 1 year) with DES. In conclusion, this meta-analysis, based on individual patients' data from 11 randomized trials, showed that among patients with diabetes with STEMIs who undergo primary percutaneous coronary intervention, sirolimus...... with high rates of target vessel revascularization after bare-metal stent (BMS) implantation but also higher rates of ST after DES implantation. Therefore, the aim of this study was to perform a meta-analysis of individual patients' data to evaluate the long-term safety and effectiveness of DES compared......Several concerns have emerged regarding the higher risk for stent thrombosis (ST) after drug-eluting stent (DES) implantation, especially in the setting of ST-segment elevation myocardial infarction (STEMI). Few data have been reported so far in patients with diabetes mellitus, which is associated...

Ayurvedic medicine offers a good alternative to glucosamine and celecoxib in the treatment of symptomatic knee osteoarthritis: a randomized, double-blind, controlled equivalence drug trial.

Science.gov (United States)

Chopra, Arvind; Saluja, Manjit; Tillu, Girish; Sarmukkaddam, Sanjeev; Venugopalan, Anuradha; Narsimulu, Gumdal; Handa, Rohini; Sumantran, Venil; Raut, Ashwinikumar; Bichile, Lata; Joshi, Kalpana; Patwardhan, Bhushan

2013-08-01

To demonstrate clinical equivalence between two standardized Ayurveda (India) formulations (SGCG and SGC), glucosamine and celecoxib (NSAID). Ayurvedic formulations (extracts of Tinospora cordifolia, Zingiber officinale, Emblica officinalis, Boswellia serrata), glucosamine sulphate (2 g daily) and celecoxib (200 mg daily) were evaluated in a randomized, double-blind, parallel-efficacy, four-arm, multicentre equivalence drug trial of 24 weeks duration. A total of 440 eligible patients suffering from symptomatic knee OA were enrolled and monitored as per protocol. Primary efficacy variables were active body weight-bearing pain (visual analogue scale) and modified WOMAC pain and functional difficulty Likert score (for knee and hip); the corresponding a priori equivalence ranges were ±1.5 cm, ±2.5 and ±8.5. Differences between the intervention arms for mean changes in primary efficacy variables were within the equivalence range by intent-to-treat and per protocol analysis. Twenty-six patients showed asymptomatic increased serum glutamic pyruvic transaminase (SGPT) with otherwise normal liver function; seven patients (Ayurvedic intervention) were withdrawn and SGPT normalized after stopping the drug. Other adverse events were mild and did not differ by intervention. Overall, 28% of patients withdrew from the study. In this 6-month controlled study of knee OA, Ayurvedic formulations (especially SGCG) significantly reduced knee pain and improved knee function and were equivalent to glucosamine and celecoxib. The unexpected SGPT rise requires further safety assessment. Clinical Drug Trial Registry-India, www.ctri.nic.in, CTRI/2008/091/000063.

Oligonucleic Acid Drug List: monrd0015 [Oligonucleic Acid Drug Database[Archive

Lifescience Database Archive (English)

Full Text Available double-masked, controlled trial to establish the safety and efficacy of intravitr... controlled trial to establish the safety and efficacy of intravitreous administr...on ・a phase III randomized, double-masked, controlled trial in order to establish the safety

Efficacy and safety of lipegfilgrastim versus pegfilgrastim: a randomized, multicenter, active-control phase 3 trial in patients with breast cancer receiving doxorubicin/docetaxel chemotherapy

International Nuclear Information System (INIS)

Bondarenko, Igor; Gladkov, Oleg A; Elsaesser, Reiner; Buchner, Anton; Bias, Peter

2013-01-01

Lipegfilgrastim is a novel glyco-pegylated granulocyte-colony stimulating factor in development for neutropenia prophylaxis in cancer patients receiving chemotherapy. This phase III, double-blind, randomized, active-controlled, noninferiority trial compared the efficacy and safety of lipegfilgrastim versus pegfilgrastim in chemotherapy-naïve breast cancer patients receiving doxorubicin/docetaxel chemotherapy. Patients with high-risk stage II, III, or IV breast cancer and an absolute neutrophil count ≥1.5 × 10 9 cells/L were randomized to a single 6-mg subcutaneous injection of lipegfilgrastim (n = 101) or pegfilgrastim (n = 101) on day 2 of each 21-day chemotherapy cycle (4 cycles maximum). The primary efficacy endpoint was the duration of severe neutropenia during cycle 1. Cycle 1: The mean duration of severe neutropenia for the lipegfilgrastim and pegfilgrastim groups was 0.7 and 0.8 days, respectively (λ = −0.218 [95% confidence interval: –0.498%, 0.062%], p = 0.126), and no severe neutropenia was observed in 56% and 49% of patients in the lipegfilgrastim and pegfilgrastim groups, respectively. All cycles: In the efficacy population, febrile neutropenia occurred in three pegfilgrastim-treated patients (all in cycle 1) and zero lipegfilgrastim-treated patients. Drug-related adverse events in the safety population were reported in 28% and 26% of patients i006E the lipegfilgrastim and pegfilgrastim groups, respectively. This study demonstrates that lipegfilgrastim 6 mg is as effective as pegfilgrastim in reducing neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy. Eudra https://www.clinicaltrialsregister.eu/ctr-search/search?query The study protocol, two global amendments (Nos. 1 and 2), informed consent documents, and other appropriate study-related documents were reviewed and approved by the Ministry of Health of Ukraine Central Ethics Committee and local independent ethics committees (IECs)

Advancing Drug Safety Through Prospective Pharmacovigilance.

Science.gov (United States)

Pitts, Peter J; Le Louet, Hervé

2018-01-01

Much has changed in a relatively short period of time. There is a raging debate over the level of evidence expected to first introduce a treatment to patients based on smaller, more adaptive data sets. Some argue for less data followed by postapproval follow-up, others for more adaptive clinical trial designs and end-point modification driven by patient-focused drug development and use of real-world evidence. The transition in both the review and postmarketing regulatory framework is happening in front of our eyes in real time. To improve the ability of patients to receive high-quality, safe, effective, and timely care, better information via pharmacovigilance must be a priority as the world's many regulatory systems build the capacity to harness electronic health information to improve health, care quality, and safety. Globally, the widely variable ability of nations to build reliable regulatory systems (from precise review to robust pharmacovigilance) is a dangerous source of health care inequality. Developing validated tools and techniques for "predictive pharmacovigilance" will assist all health systems in better understanding the risks and benefits of the medicines they regulate by understanding what should be happening once a new medicine moves from risk-benefit regulatory efficacy to real-world risk-effectiveness. This will be of particular utility for smaller regulatory agencies with fewer resources. By comparing preapproval predictive pharmacovigilance data, developing regulatory authorities will be able to better understand the potential gap between what was predicted and what was actually measured (via more traditional pharmacovigilance methodologies). Predictive pharmacovigilance recognizes the value of understanding the imperfect reporting of real-world clinical use and that the absence of reporting is, in itself, an important postmarketing signal.

A randomized trial of telemedicine efficacy and safety for nonacute headaches.

Science.gov (United States)

Müller, Kai I; Alstadhaug, Karl B; Bekkelund, Svein I

2017-07-11

To evaluate long-term treatment efficacy and safety of one-time telemedicine consultations for nonacute headaches. We randomized, allocated, and consulted nonacute headache patients via telemedicine (n = 200) or in a traditional manner (n = 202) in a noninferiority trial. Efficacy endpoints, assessed by questionnaires at 3 and 12 months, included change from baseline in Headache Impact Test-6 (HIT-6) (primary endpoint) and pain intensity (visual analogue scale [VAS]) (secondary endpoint). The primary safety endpoint, assessed via patient records, was presence of secondary headache within 12 months after consultation. We found no differences between telemedicine and traditional consultations in HIT-6 ( p = 0.84) or VAS ( p = 0.64) over 3 periods. The absolute difference in HIT-6 from baseline was 0.3 (95% confidence interval [CI] -1.26 to 1.82, p = 0.72) at 3 months and 0.2 (95% CI -1.98 to 1.58, p = 0.83) at 12 months. The absolute change in VAS was 0.4 (95% CI -0.93 to 0.22, p = 0.23) after 3 months and 0.3 (95% CI -0.94 to 0.29, p = 0.30) at 12 months. We found one secondary headache in each group at 12 months. The estimated number of consultations needed to miss one secondary headache with the use of telemedicine was 20,200. Telemedicine consultation for nonacute headache is as efficient and safe as a traditional consultation. NCT02270177. This study provides Class III evidence that a one-time telemedicine consultation for nonacute headache is noninferior to a one-time traditional consultation regarding long-term treatment outcome and safety. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Patterns of use and impact of standardised MedDRA query analyses on the safety evaluation and review of new drug and biologics license applications.

Directory of Open Access Journals (Sweden)

Lin-Chau Chang

Full Text Available Standardised MedDRA Queries (SMQs have been developed since the early 2000's and used by academia, industry, public health, and government sectors for detecting safety signals in adverse event safety databases. The purpose of the present study is to characterize how SMQs are used and the impact in safety analyses for New Drug Application (NDA and Biologics License Application (BLA submissions to the United States Food and Drug Administration (USFDA.We used the PharmaPendium database to capture SMQ use in Summary Basis of Approvals (SBoAs of drugs and biologics approved by the USFDA. Characteristics of the drugs and the SMQ use were employed to evaluate the role of SMQ safety analyses in regulatory decisions and the veracity of signals they revealed.A comprehensive search of the SBoAs yielded 184 regulatory submissions approved from 2006 to 2015. Search strategies more frequently utilized restrictive searches with "narrow terms" to enhance specificity over strategies using "broad terms" to increase sensitivity, while some involved modification of search terms. A majority (59% of 1290 searches used descriptive statistics, however inferential statistics were utilized in 35% of them. Commentary from reviewers and supervisory staff suggested that a small, yet notable percentage (18% of 1290 searches supported regulatory decisions. The searches with regulatory impact were found in 73 submissions (40% of the submissions investigated. Most searches (75% of 227 searches with regulatory implications described how the searches were confirmed, indicating prudence in the decision-making process.SMQs have an increasing role in the presentation and review of safety analysis for NDAs/BLAs and their regulatory reviews. This study suggests that SMQs are best used for screening process, with descriptive statistics, description of SMQ modifications, and systematic verification of cases which is crucial for drawing regulatory conclusions.

Patterns of use and impact of standardised MedDRA query analyses on the safety evaluation and review of new drug and biologics license applications.

Science.gov (United States)

Chang, Lin-Chau; Mahmood, Riaz; Qureshi, Samina; Breder, Christopher D

2017-01-01

Standardised MedDRA Queries (SMQs) have been developed since the early 2000's and used by academia, industry, public health, and government sectors for detecting safety signals in adverse event safety databases. The purpose of the present study is to characterize how SMQs are used and the impact in safety analyses for New Drug Application (NDA) and Biologics License Application (BLA) submissions to the United States Food and Drug Administration (USFDA). We used the PharmaPendium database to capture SMQ use in Summary Basis of Approvals (SBoAs) of drugs and biologics approved by the USFDA. Characteristics of the drugs and the SMQ use were employed to evaluate the role of SMQ safety analyses in regulatory decisions and the veracity of signals they revealed. A comprehensive search of the SBoAs yielded 184 regulatory submissions approved from 2006 to 2015. Search strategies more frequently utilized restrictive searches with "narrow terms" to enhance specificity over strategies using "broad terms" to increase sensitivity, while some involved modification of search terms. A majority (59%) of 1290 searches used descriptive statistics, however inferential statistics were utilized in 35% of them. Commentary from reviewers and supervisory staff suggested that a small, yet notable percentage (18%) of 1290 searches supported regulatory decisions. The searches with regulatory impact were found in 73 submissions (40% of the submissions investigated). Most searches (75% of 227 searches) with regulatory implications described how the searches were confirmed, indicating prudence in the decision-making process. SMQs have an increasing role in the presentation and review of safety analysis for NDAs/BLAs and their regulatory reviews. This study suggests that SMQs are best used for screening process, with descriptive statistics, description of SMQ modifications, and systematic verification of cases which is crucial for drawing regulatory conclusions.

A Proof-of-Concept Randomized Controlled Study of Gabapentin: Effects on Cannabis Use, Withdrawal and Executive Function Deficits in Cannabis-Dependent Adults

OpenAIRE

Mason, Barbara J; Crean, Rebecca; Goodell, Vivian; Light, John M; Quello, Susan; Shadan, Farhad; Buffkins, Kimberly; Kyle, Mark; Adusumalli, Murali; Begovic, Adnan; Rao, Santosh

2012-01-01

There are no FDA-approved pharmacotherapies for cannabis dependence. Cannabis is the most widely used illicit drug in the world, and patients seeking treatment for primary cannabis dependence represent 25% of all substance use admissions. We conducted a phase IIa proof-of-concept pilot study to examine the safety and efficacy of a calcium channel/GABA modulating drug, gabapentin, for the treatment of cannabis dependence. A 12-week, randomized, double-blind, placebo-controlled clinical trial w...

Efficacy and safety of statin therapy in children with familial hypercholesterolemia - A randomized, double-blind, placebo-controlled trial with simvastatin

NARCIS (Netherlands)

de Jongh, Saskia; Ose, Leiv; Szamosi, Tamás; Gagné, Claude; Lambert, M.; Scott, Russell; Perron, P.; Dobbelaere, Dries; Saborio, M.; Tuohy, Mary B.; Stepanavage, Michael; Sapre, Aditi; Gumbiner, Barry; Mercuri, Michele; van Trotsenburg, A. S. Paul; Bakker, Henk D.; Kastelein, John J. P.

2002-01-01

Background-A multicenter, randomized, double-blind, placebo-controlled study was conducted to evaluate LDL cholesterol-lowering efficacy, overall safety, and tolerability and the influence on growth and pubertal development of simvastatin in a large cohort of boys and girls with heterozygous

Animal Product Safety Information

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... Home Animal & Veterinary Safety & Health Product Safety Information Product Safety Information Share Tweet Linkedin Pin it More ... to report adverse experiences with veterinary drugs. Additional Product Information Questions and Answers: Evanger’s Dog and Cat ...

Effects of a lifestyle programme on ambulatory blood pressure and drug dosage in treated hypertensive patients: a randomized controlled trial.

Science.gov (United States)

Burke, Valerie; Beilin, Lawrie J; Cutt, Hayley E; Mansour, Jacqueline; Wilson, Amy; Mori, Trevor A

2005-06-01

To assess effects of multifactorial lifestyle modification on antihypertensive drug needs in treated hypertensive individuals. Randomized controlled trial. Research studies unit. Overweight hypertensive patients, receiving one or two antihypertensive drugs, were recruited by advertising, and allocated randomly to a usual care group (controls; n = 118) or a lifestyle modification group (programme group; n = 123). A 4-month programme of weight loss, a low-sodium 'Dietary Approaches to Stop Hypertension'-type diet with added fish, physical activity and moderation of alcohol intake. After 4 months, if mean 24-h ambulatory blood pressure (ABP) was less than 135/85 mmHg, antihypertensive drugs were withdrawn over 4 weeks and long-term home blood pressure monitoring was begun. Antihypertensive drug requirements, ABP, weight, waist girth at 4 months and 1-year follow-up. Ninety control group and 102 programme group participants completed the study. Mean 24-h ABP changed after 4 months by -1.0/-0.3 +/- 0.5/0.4 mmHg in controls and -4.1/-2.1 +/- 0.7/0.5 mmHg with the lifestyle programme (P lifestyle modification in patients with treated hypertension reduced blood pressure in the short-term. Decreased central obesity persisted 1 year later and could reduce overall cardiovascular risk.

[Significance of re-evaluation and development of Chinese herbal drugs].

Science.gov (United States)

Gao, Yue; Ma, Zengchun; Zhang, Boli

2012-01-01

The research of new herbal drugs involves in new herbal drugs development and renew the old drugs. It is necessary to research new herbal drugs based on the theory of traditional Chinese medicine (TCM). The current development of famous TCM focuses on the manufacture process, quality control standards, material basis and clinical research. But system management of security evaluation is deficient, the relevant system for the safety assessment TCM has not been established. The causes of security problems, security risks, target organ of toxicity, weak link of safety evaluation, and ideas of safety evaluation are discussed in this paper. The toxicology research of chinese herbal drugs is necessary based on standard of good laboratory practices (GLP), the characteristic of Chinese herbal drugs is necessary to be fully integrated into safety evaluation. The safety of new drug research is necessary to be integrated throughout the entire process. Famous Chinese medicine safety research must be paid more attention in the future.

Safety and Efficacy of Rocuronium With Sugammadex Reversal Versus Succinylcholine in Outpatient Surgery-A Multicenter, Randomized, Safety Assessor-Blinded Trial.

Science.gov (United States)

Soto, Roy; Jahr, Jonathan S; Pavlin, Janet; Sabo, Daniel; Philip, Beverly K; Egan, Talmage D; Rowe, Everton; de Bie, Joris; Woo, Tiffany

Complex surgical procedures are increasingly performed in an outpatient setting, with emphasis on rapid recovery and case turnover. In this study, the combination of rocuronium for neuromuscular blockade (NMB) reversed by single-dose sugammadex was compared with succinylcholine followed by spontaneous recovery in outpatient surgery. This multicenter, randomized, safety assessor-blinded study enrolled adults undergoing a short elective outpatient surgical procedure requiring NMB and tracheal intubation. Patients were randomized to NMB with either rocuronium 0.6 mg/kg for tracheal intubation with incremental doses of rocuronium 0.15 mg/kg and subsequent reversal with sugammadex 4.0 mg/kg at 1-2 posttetanic counts or succinylcholine 1.0 mg/kg for intubation with spontaneous recovery. The primary efficacy end point was the time from sugammadex administration to recovery of the train-of-four ratio to 0.9; for succinylcholine, time from administration to recovery of the first twitch (T1) to 90% was assessed. From 167 patients enrolled, 150 received treatment. The all-subjects-treated population comprised 70 patients in the rocuronium-sugammadex group and 80 in the succinylcholine group. Geometric mean (95% confidence interval) time from the start of sugammadex administration to recovery of the train-of-four ratio to 0.9 was 1.8 (1.6-2.0) minutes. Geometric mean (95% confidence interval) time from succinylcholine administration to recovery of T1 to 90% was 10.8 (10.1-11.5) minutes. Health outcome variables were similar between the groups. Adverse events were reported in 87.1% and 93.8% of patients for rocuronium-sugammadex and succinylcholine, respectively. In conclusion, rocuronium for intubation followed by sugammadex for reversal of NMB offers a viable treatment option in outpatient surgery without prolonging recovery duration or jeopardizing safety.

The US Food and Drug Administration’s drug safety recommendations and long-acting beta2-agonist dispensing pattern changes in adult asthma patients: 2003–2012

Directory of Open Access Journals (Sweden)

Zhou EH

2017-03-01

Full Text Available Esther H Zhou,1 Sally Seymour,2 Margie R Goulding,1 Elizabeth M Kang,1 Jacqueline M Major,1 Solomon Iyasu1 1Division of Epidemiology, Office of Surveillance and Epidemiology, 2Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA Background: Emerging safety issues associated with long-acting beta2-agonist (LABA have led to multiple regulatory activities by the US Food and Drug Administration (FDA since 2003, including Drug Safety Communications (DSCs in 2010. These DSCs had three specific recommendations for the safe use of LABA products in adult asthma treatment. Methods: We examined the initiation of LABA-containing products for adult asthma treatment using an intermittent time series approach in a claims database from 2003 to 2012. We assessed the alignment of dispensing patterns with the following 2010 FDA recommendations: 1 contraindicated use of single-ingredient (SI-LABA without an asthma controller medication (ACM; 2 a LABA should only be used when asthma is not adequately controlled on inhaled corticosteroids (ICSs or ACM; and 3 step-down asthma therapy (e.g., discontinue LABA when asthma control is achieved. Results: There were 477,922 adults (18–64 years old dispensed a new LABA during 2003–2012. Among LABA initiators, patients who initiated an SI-LABA and who did “not” have an ACM dispensed on the same date decreased from >9% in 2003 (the initial labeling change to <2% post 2010 DSCs (p-value <0.0001 in the segmented regression model. The proportion of asthma patients dispensed an ICS in 6 months prior to initiating LABA treatment did not increase. The proportion of patients with longer than 4 months of continuous treatment did not decrease over the study period. Conclusion: Although the decrease in SI-LABA initiation is consistent with FDA’s recommendations, low ICS dispensing before initiating a LABA and LABA continuation practices require further efforts

Patient safety incident reports related to traditional Japanese Kampo medicines: medication errors and adverse drug events in a university hospital for a ten-year period.

Science.gov (United States)

Shimada, Yutaka; Fujimoto, Makoto; Nogami, Tatsuya; Watari, Hidetoshi; Kitahara, Hideyuki; Misawa, Hiroki; Kimbara, Yoshiyuki

2017-12-21

Kampo medicine is traditional Japanese medicine, which originated in ancient traditional Chinese medicine, but was introduced and developed uniquely in Japan. Today, Kampo medicines are integrated into the Japanese national health care system. Incident reporting systems are currently being widely used to collect information about patient safety incidents that occur in hospitals. However, no investigations have been conducted regarding patient safety incident reports related to Kampo medicines. The aim of this study was to survey and analyse incident reports related to Kampo medicines in a Japanese university hospital to improve future patient safety. We selected incident reports related to Kampo medicines filed in Toyama University Hospital from May 2007 to April 2017, and investigated them in terms of medication errors and adverse drug events. Out of 21,324 total incident reports filed in the 10-year survey period, we discovered 108 Kampo medicine-related incident reports. However, five cases were redundantly reported; thus, the number of actual incidents was 103. Of those, 99 incidents were classified as medication errors (77 administration errors, 15 dispensing errors, and 7 prescribing errors), and four were adverse drug events, namely Kampo medicine-induced interstitial pneumonia. The Kampo medicine (crude drug) that was thought to induce interstitial pneumonia in all four cases was Scutellariae Radix, which is consistent with past reports. According to the incident severity classification system recommended by the National University Hospital Council of Japan, of the 99 medication errors, 10 incidents were classified as level 0 (an error occurred, but the patient was not affected) and 89 incidents were level 1 (an error occurred that affected the patient, but did not cause harm). Of the four adverse drug events, two incidents were classified as level 2 (patient was transiently harmed, but required no treatment), and two incidents were level 3b (patient was

Pediatric Drug Safety Signal Detection: A New Drug–Event Reference Set for Performance Testing of Data-Mining Methods and Systems

NARCIS (Netherlands)

O.U. Osokogu (Osemeke); F. Fregonese (Federica); C. Ferrajolo (Carmen); K.M.C. Verhamme (Katia); S. de Bie (Sandra); G. Jong (Geert’t); M. Catapano (Mariana); D. Weibel (Daniel); F. Kaguelidou (Florentia); W.M. Bramer (Wichor); Y. Hsia (Yingfen); I. Wong (Ian); M. Gazarian (Madlen); J. Bonhoeffer (Jan); M.C.J.M. Sturkenboom (Miriam)

2015-01-01

textabstractBackground: Better evidence regarding drug safety in the pediatric population might be generated from existing data sources such as spontaneous reporting systems and electronic healthcare records. The Global Research in Paediatrics (GRiP)–Network of Excellence aims to develop

Republic of Georgia estimates for prevalence of drug use: Randomized response techniques suggest under-estimation.

Science.gov (United States)

Kirtadze, Irma; Otiashvili, David; Tabatadze, Mzia; Vardanashvili, Irina; Sturua, Lela; Zabransky, Tomas; Anthony, James C

2018-06-01

Validity of responses in surveys is an important research concern, especially in emerging market economies where surveys in the general population are a novelty, and the level of social control is traditionally higher. The Randomized Response Technique (RRT) can be used as a check on response validity when the study aim is to estimate population prevalence of drug experiences and other socially sensitive and/or illegal behaviors. To apply RRT and to study potential under-reporting of drug use in a nation-scale, population-based general population survey of alcohol and other drug use. For this first-ever household survey on addictive substances for the Country of Georgia, we used the multi-stage probability sampling of 18-to-64-year-old household residents of 111 urban and 49 rural areas. During the interviewer-administered assessments, RRT involved pairing of sensitive and non-sensitive questions about drug experiences. Based upon the standard household self-report survey estimate, an estimated 17.3% [95% confidence interval, CI: 15.5%, 19.1%] of Georgian household residents have tried cannabis. The corresponding RRT estimate was 29.9% [95% CI: 24.9%, 34.9%]. The RRT estimates for other drugs such as heroin also were larger than the standard self-report estimates. We remain unsure about what is the "true" value for prevalence of using illegal psychotropic drugs in the Republic of Georgia study population. Our RRT results suggest that standard non-RRT approaches might produce 'under-estimates' or at best, highly conservative, lower-end estimates. Copyright © 2018 Elsevier B.V. All rights reserved.

Relationship between drug interactions and drug-related negative clinical outcomes in two community pharmacies

Directory of Open Access Journals (Sweden)

Gonzalo M

2009-03-01

Full Text Available Drug interactions may represent an iatrogenic risk that should be controlled in community pharmacies at the dispensing level. Aim: We analyzed the association between potential drug-drug interactions (DDIs and negative clinical outcomes.Methods: We used dispensing data from two community pharmacies: instances where drug dispensing was associated with a potential DDI and a comparison group of randomized dispensing operations with no potential DDI. In cases where potential DDIs were detected, we analyzed the underlying negative clinical outcomes. Age and gender data were included in the analysis.Results: During the study period, we registered 417 potential DDIs. The proportion of women and age were higher in the study group than in the comparison group. The average potential DDIs per patient was 1.31 (SD=0.72. The Consejo General de Colegios Oficiales de Farmacéuticos (CGCOF database did not produce an alert in 2.4% of the cases. Over-the-counter medication use was observed in 5% of the potential DDI cases. The drugs most frequently involved in potential DDIs were acenocoumarol, calcium salts, hydrochlorothiazide, and alendronic acid, whereas the most predominant potential DDIs were calcium salts and bisphosphonates, oral antidiabetics and thiazide diuretics, antidiabetics and glucose, and oral anticoagulant and paracetamol. The existence of a drug-related negative clinical outcome was observed only in 0.96% of the potential DDI cases (50% safety cases and 50% effectiveness cases. Conclusions: Only a small proportion of the detected potential DDIs lead to medication negative outcomes. Considering the drug-related negative clinical outcomes encountered, tighter control would be recommended in potential DDIs with NSAIDs or benzodiazepines.

Achieving Drug and Alcohol Abstinence Among Recently Incarcerated Homeless Women: A Randomized Controlled Trial Comparing Dialectical Behavioral Therapy-Case Management With a Health Promotion Program.

Science.gov (United States)

Nyamathi, Adeline M; Shin, Sanghyuk S; Smeltzer, Jolene; Salem, Benissa E; Yadav, Kartik; Ekstrand, Maria L; Turner, Susan F; Faucette, Mark

Homeless female ex-offenders (homeless female offenders) exiting jail and prison are at a critical juncture during reentry and transitioning into the community setting. The purpose of the study was to compare the effect of a dialectical behavioral therapy-case management (DBT-CM) program with a health promotion (HP) program on achieving drug and alcohol abstinence among female parolees/probationers residing in the community. We conducted a multicenter parallel randomized controlled trial with 130 female parolees/probationers (aged 19-64 years) residing in the community randomly assigned to either DBT-CM (n = 65) or HP (n = 65). The trial was conducted in four community-based partner sites in Los Angeles and Pomona, California, from February 2015 to November 2016. Treatment assignment was carried out using a computer-based urn randomization program. The primary outcome was drug and alcohol use abstinence at 6-month follow up. Analysis was based on data from 116 participants with complete outcome data. Multivariable logistic regression revealed that the DBT-CM program remained an independent positive predictor of decrease in drug use among the DBT-CM participants at 6 months (p = .01) as compared with the HP program participants. Being non-White (p < .05) and having higher depressive symptom scores (p < .05) were associated with lower odds of drug use abstinence (i.e., increased the odds of drug use) at 6 months. DBT-CM increased drug and alcohol abstinence at 6-month follow-up, compared to an HP program.

TOPICALITY OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS IN TREATMENT OF FEVER IN CHILDREN

Directory of Open Access Journals (Sweden)

O.A. Mubarakshina

2010-01-01

Full Text Available Nonsteroidal anti-inflammatory drugs are widely used in pediatric practice for the treatment of fever. The choice of the drug from this group must be based on high effectiveness of medication and the lowest risk of adverse events. Only paracetamol and ibuprofen completely fulfill these requirements at the present times. They are officially recommended by WHO for the use as an anti-fever pediatric medication. The article examines advantages of ibuprofen compared to paracetamol on the basis of results of randomized studies. Author describes a safety of ibuprofen and opportunities of combined treatment with ibuprofen and paracetamol.Key words: children, fever, ibuprofen, paracetamol, treatment.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2010;9(2:156-160

Drug reimbursement and GPs' prescribing decisions: a randomized case-vignette study about the pharmacotherapy of obesity associated with type 2 diabetes: how GPs react to drug reimbursement.

Science.gov (United States)

Verger, Pierre; Rolland, Sophie; Paraponaris, Alain; Bouvenot, Julien; Ventelou, Bruno

2010-08-01

This study sought to identify the effect of drug reimbursability--a decision made in France by the National Authority for Health--on physicians' prescribing practices for a diet drug such as rimonabant, approved for obese or overweight patients with type-2 diabetes. A cross-sectional survey of French general practitioners (GPs) presented a case-vignette about a patient for whom this drug is indicated in two alternative versions, differing only in its reimbursability, to two separate randomized subsamples of GPs in early 2007, before any decision was made about reimbursement. The results indicate that (i) more than 20% of GPs in private practice would be willing to prescribe a non-reimbursed diet drug for patients with obesity complicated by type 2 diabetes; (ii) the number of GPs willing to prescribe it would increase by 47.6% if the drug were reimbursed, and (iii) such a drug would be adopted at a higher rate by GPs who have regular contacts with pharmaceutical sales representatives. In France, unlike most other countries, drug reimbursement status is a signal of quality. However, our results suggest that a significant proportion of GPs would spontaneously adopt anti-obesity drugs even if they were not reimbursed. Decisions about reimbursement of pharmaceutical products should be made taking into account that reimbursement is likely to intensify prescription.

A RFID grouping proof protocol for medication safety of inpatient.

Science.gov (United States)

Huang, Hsieh-Hong; Ku, Cheng-Yuan

2009-12-01

In order to provide enhanced medication safety for inpatients, the medical mechanism which adopts the modified grouping proof protocol is proposed in this paper. By using the grouping proof protocol, the medical staffs could confirm the authentication and integrity of a group of Radio-Frequency Identification (RFID) tags which are embedded on inpatient bracelets and the containers of drugs. This mechanism is designed to be compatible with EPCglobal Class-1 Generation-2 standard which is the most popular specification of RFID tags. Due to the light-weight computational capacity of passive tags, only the pseudo-random number generator (PRNG) and cyclic redundancy code (CRC) are allowed to be used in the communication protocol. Furthermore, a practical scenario of using this proposed mechanism in hospital to examine the medication safety is also presented.

The potential of the European network of congenital anomaly registers (EUROCAT) for drug safety surveillance: a descriptive study.

Science.gov (United States)

Meijer, Willemijn M; Cornel, Martina C; Dolk, Helen; de Walle, Hermien E K; Armstrong, Nicola C; de Jong-van den Berg, Lolkje T W

2006-09-01

European Surveillance of Congenital Anomalies (EUROCAT) is a network of population-based congenital anomaly registries in Europe surveying more than 1 million births per year, or 25% of the births in the European Union. This paper describes the potential of the EUROCAT collaboration for pharmacoepidemiology and drug safety surveillance. The 34 full members and 6 associate members of the EUROCAT network were sent a questionnaire about their data sources on drug exposure and on drug coding. Available data on drug exposure during the first trimester available in the central EUROCAT database for the years 1996-2000 was summarised for 15 out of 25 responding full members. Of the 40 registries, 29 returned questionnaires (25 full and 4 associate members). Four of these registries do not collect data on maternal drug use. Of the full members, 15 registries use the EUROCAT drug code, 4 use the international ATC drug code, 3 registries use another coding system and 7 use a combination of these coding systems. Obstetric records are the most frequently used sources of drug information for the registries, followed by interviews with the mother. Only one registry uses pharmacy data. Percentages of cases with drug exposure (excluding vitamins/minerals) varied from 4.4% to 26.0% among different registries. The categories of drugs recorded varied widely between registries. Practices vary widely between registries regarding recording drug exposure information. EUROCAT has the potential to be an effective collaborative framework to contribute to post-marketing drug surveillance in relation to teratogenic effects, but work is needed to implement ATC drug coding more widely, and to diversify the sources of information used to determine drug exposure in each registry.

Value of preapproval safety data in predicting postapproval hepatic safety and assessing the legitimacy of class warning.

Science.gov (United States)

Lin, Yeong-Liang; Wu, Ya-Chi; Gau, Churn-Shiouh; Lin, Min-Shung

2012-02-01

The objective of this study was to systematically evaluate whether preapproval safety data for nonhepatotoxic drugs and hepatotoxic drugs can be compared to improve preapproval prediction of postapproval hepatic safety and to assess the legitimacy of applying class warnings. Drugs within a therapeutic class that included at least one drug that had been withdrawn from the market because of liver toxicity or had a warning of potential liver toxicity issued by major regulatory agencies, and at least one drug free from such regulatory action, were identified and divided into two groups: drugs with and drugs without regulatory action. Preapproval clinical data [including the elevation rates of alanine aminotransferse (ALT) and withdrawal due to liver toxicity, the number of patients with combined elevation of ALT and bilirubin, and liver failure] and nonclinical data (including chemical structures, metabolic pathways, and other significant findings in animal studies) were compared between the two groups. Six drug classes were assessed in this study: thiazolidinediones, cyclooxygenase-2 inhibitors, fluoroquinolones, catechol-O-methyltransferase (COMT) inhibitors, leukotriene receptor inhibitors, and endothelin receptor antagonists. In two classes (COMT inhibitors and endothelin receptor antagonists), drugs with regulatory action had significantly higher rates of ALT elevation of more than threefold and greater numbers of patients with combined elevation of ALT and bilirubin than drugs without regulatory action. Drugs with regulatory action also had chemical structures or metabolic pathways associated with the toxicity. The legitimacy of class warnings was refuted in all six classes of drugs. Preapproval safety data may help predict postapproval hepatic safety and can be used to assess the legitimacy of applying class warnings.

Risk patterns in drug safety study using relative times by accelerated failure time models when proportional hazards assumption is questionable : an illustrative case study of cancer risk of patients on glucose-lowering therapies

NARCIS (Netherlands)

Ng, Edmond S-W; Klungel, Olaf H; Groenwold, Rolf H H; van Staa, Tjeerd-Pieter

2015-01-01

Observational drug safety studies may be susceptible to confounding or protopathic bias. This bias may cause a spurious relationship between drug exposure and adverse side effect when none exists and may lead to unwarranted safety alerts. The spurious relationship may manifest itself through

Efficacy and safety of tofacitinib as monotherapy in Japanese patients with active rheumatoid arthritis: a 12-week, randomized, phase 2 study.

Science.gov (United States)

Tanaka, Yoshiya; Takeuchi, Tsutomu; Yamanaka, Hisashi; Nakamura, Hiroyuki; Toyoizumi, Shigeyuki; Zwillich, Samuel

2015-07-01

To evaluate oral tofacitinib versus placebo for treatment of active rheumatoid arthritis in Japanese patients with inadequate response to disease-modifying antirheumatic drugs. In this double-blind, placebo-controlled, randomized, parallel-group, 12-week, phase 2 study (clinicaltrials.gov NCT00687193), 317 patients received tofacitinib: 1, 3, 5, 10, or 15 mg as monotherapy or placebo twice daily (BID). response rate by American College of Rheumatology (ACR) ≥ 20% improvement criteria (ACR20) at week 12. ACR20 response rates: 37.7% (20/53), 67.9% (36/53), 73.1% (38/52), 84.9% (45/53), and 90.7% (49/54) with tofacitinib: 1, 3, 5, 10, and 15 mg BID, respectively, versus 15.4% (8/52) with placebo (p tofacitinib versus placebo occurred from week 2 onward (p tofacitinib versus placebo from week 4 (p tofacitinib patients experienced treatment-related serious adverse events (AEs). Most common treatment-emergent AEs: nasopharyngitis (10% vs 12%) and hyperlipidemia (5% vs 0%). Serum creatinine, hemoglobin, and total-, low-, and high-density lipoprotein-cholesterol levels increased with tofacitinib. Tofacitinib produced dose-dependent ACR20 responses and reduced disease activity. The safety profile was consistent with that reported from global monotherapy trials.

Toxicological study on the safety of DTPA as a drug, (1)

International Nuclear Information System (INIS)

Fukuda, Satoshi; Iida, Haruzo

1983-01-01

In order to clarify the safety of Ca-DTPA and Zn-DTPA recommended to use as drugs in the therapeutic removal of incorporated radionuclides from the human body, the teratological study on these two agents was carried out in rats as one of a series of the toxicological tests. The teratological effects of DTPA were observed because the fetus is highly susceptible to any drug. The pregnant females of Wistar rat were injected subcutaneously daily on days 9-13 of gestation with 1, 6, 12, 24 and 36 H.D. (H.D. = human dose, 1 H.D. = 30μmol/kg body weight) of Ca-DTPA or Zn-DTPA, respectively. In the dams, no toxic effects were observed. In the fetuses, the decrease of the survival rate was observed in only the group injected daily with 36 H.D. of Ca-DTPA. Some cases of gross defects of fetuses: the exencephaly, microphthalmia, anophthalmia and fusion of ribs were observed in the groups injected daily with 12, 24 and 36 H.D. of Ca-DTPA. The results obtained show that Ca-DTPA should not be given to a pregnant woman. However, no toxic effects of either Ca-DTPA or Zn-DTPA observed in the dams ana of Zn-DTPA even in the fetuses indicate that these agents can be used by a radiation worker who usually is an adult man. (author)

Bl-1020, a new γ-aminobutyric acid-enhanced antipsychotic: results of 6-week, randomized, double-blind, controlled, efficacy and safety study.

Science.gov (United States)

Geffen, Yona; Keefe, Richard; Rabinowitz, Jonathan; Anand, Ravi; Davidson, Michael

2012-09-01

BL-1020 is a γ-aminobutyric acid (GABA)-enhanced antipsychotic that combines dopamine antagonism with GABA agonist activity. On the basis of animal models, we tested the hypotheses that BL-1020 would be effective in ameliorating both psychotic symptoms and cognitive impairments, with a favorable safety profile in acutely ill schizophrenia patients. 363 hospital-based psychiatric patients in India, Romania, and United States aged 18 to 65 years and meeting criteria for DSM-IV-TR diagnosis of chronic schizophrenia were randomized double-blind to receive BL-1020 10 mg/d, BL-1020 20-30 mg/d, placebo, or risperidone (2-8 mg/d) for 6 weeks. The main outcome measures were the positive and negative syndrome scale (PANSS), brief assessment of cognition in schizophrenia, readiness for discharge questionnaire, clinical global impressions scale (CGI) , and extrapyramidal symptom rating scale. The study ran from July 2008 to June 2009. BL-1020 20-30 mg was significantly better than placebo on PANSS (P = .02) and CGI (P schizophrenia composite score when compared to placebo (effect size = 0.50, P = .009), risperidone (effect size = 0.43, P = .019), and BL-1020 10 mg (effect size = 0.42, P = .013) after 6 weeks. BL-1020 appears to be an effective antipsychotic with possible procognitive effects that will need to be further tested for short- and long-term effects. A further randomized controlled trial using the U.S. Food and Drug Administration-recommended Measurement and Treatment Research to Improve Cognition in Schizophrenia cognitive battery is ongoing. ClinicalTrials.gov identifier: NCT00567710. © Copyright 2012 Physicians Postgraduate Press, Inc.

Addressing conflicts of interest in nanotechnology oversight: lessons learned from drug and pesticide safety testing

International Nuclear Information System (INIS)

Elliott, Kevin C.; Volz, David C.

2012-01-01

Financial conflicts of interest raise significant challenges for those working to develop an effective, transparent, and trustworthy oversight system for assessing and managing the potential human health and ecological hazards of nanotechnology. A recent paper in this journal by Ramachandran et al., J Nanopart Res, 13:1345–1371 (2011) proposed a two-pronged approach for addressing conflicts of interest: (1) developing standardized protocols and procedures to guide safety testing; and (2) vetting safety data under a coordinating agency. Based on past experiences with standardized test guidelines developed by the international Organization for Economic Cooperation and Development (OECD) and implemented by national regulatory agencies such as the U.S. Environmental Protection Agency (EPA) and Food and Drug Administration (FDA), we argue that this approach still runs the risk of allowing conflicts of interest to influence toxicity tests, and it has the potential to commit regulatory agencies to outdated procedures. We suggest an alternative approach that further distances the design and interpretation of safety studies from those funding the research. In case the two-pronged approach is regarded as a more politically feasible solution, we also suggest three lessons for implementing this strategy in a more dynamic and effective manner.

Addressing conflicts of interest in nanotechnology oversight: lessons learned from drug and pesticide safety testing

Energy Technology Data Exchange (ETDEWEB)

Elliott, Kevin C., E-mail: ke@sc.edu [University of South Carolina, Department of Philosophy, USC NanoCenter (United States); Volz, David C. [University of South Carolina, Department of Environmental Health Sciences, Arnold School of Public Health (United States)

2012-01-15

Financial conflicts of interest raise significant challenges for those working to develop an effective, transparent, and trustworthy oversight system for assessing and managing the potential human health and ecological hazards of nanotechnology. A recent paper in this journal by Ramachandran et al., J Nanopart Res, 13:1345-1371 (2011) proposed a two-pronged approach for addressing conflicts of interest: (1) developing standardized protocols and procedures to guide safety testing; and (2) vetting safety data under a coordinating agency. Based on past experiences with standardized test guidelines developed by the international Organization for Economic Cooperation and Development (OECD) and implemented by national regulatory agencies such as the U.S. Environmental Protection Agency (EPA) and Food and Drug Administration (FDA), we argue that this approach still runs the risk of allowing conflicts of interest to influence toxicity tests, and it has the potential to commit regulatory agencies to outdated procedures. We suggest an alternative approach that further distances the design and interpretation of safety studies from those funding the research. In case the two-pronged approach is regarded as a more politically feasible solution, we also suggest three lessons for implementing this strategy in a more dynamic and effective manner.

Addressing conflicts of interest in nanotechnology oversight: lessons learned from drug and pesticide safety testing

Science.gov (United States)

Elliott, Kevin C.; Volz, David C.

2012-01-01

Financial conflicts of interest raise significant challenges for those working to develop an effective, transparent, and trustworthy oversight system for assessing and managing the potential human health and ecological hazards of nanotechnology. A recent paper in this journal by Ramachandran et al., J Nanopart Res, 13:1345-1371 (2011) proposed a two-pronged approach for addressing conflicts of interest: (1) developing standardized protocols and procedures to guide safety testing; and (2) vetting safety data under a coordinating agency. Based on past experiences with standardized test guidelines developed by the international Organization for Economic Cooperation and Development (OECD) and implemented by national regulatory agencies such as the U.S. Environmental Protection Agency (EPA) and Food and Drug Administration (FDA), we argue that this approach still runs the risk of allowing conflicts of interest to influence toxicity tests, and it has the potential to commit regulatory agencies to outdated procedures. We suggest an alternative approach that further distances the design and interpretation of safety studies from those funding the research. In case the two-pronged approach is regarded as a more politically feasible solution, we also suggest three lessons for implementing this strategy in a more dynamic and effective manner.

Development of novel, 384-well high-throughput assay panels for human drug transporters: drug interaction and safety assessment in support of discovery research.

Science.gov (United States)

Tang, Huaping; Shen, Ding Ren; Han, Yong-Hae; Kong, Yan; Balimane, Praveen; Marino, Anthony; Gao, Mian; Wu, Sophie; Xie, Dianlin; Soars, Matthew G; O'Connell, Jonathan C; Rodrigues, A David; Zhang, Litao; Cvijic, Mary Ellen

2013-10-01

Transporter proteins are known to play a critical role in affecting the overall absorption, distribution, metabolism, and excretion characteristics of drug candidates. In addition to efflux transporters (P-gp, BCRP, MRP2, etc.) that limit absorption, there has been a renewed interest in influx transporters at the renal (OATs, OCTs) and hepatic (OATPs, BSEP, NTCP, etc.) organ level that can cause significant clinical drug-drug interactions (DDIs). Several of these transporters are also critical for hepatobiliary disposition of bilirubin and bile acid/salts, and their inhibition is directly implicated in hepatic toxicities. Regulatory agencies took action to address transporter-mediated DDI with the goal of ensuring drug safety in the clinic and on the market. To meet regulatory requirements, advanced bioassay technology and automation solutions were implemented for high-throughput transporter screening to provide structure-activity relationship within lead optimization. To enhance capacity, several functional assay formats were miniaturized to 384-well throughput including novel fluorescence-based uptake and efflux inhibition assays using high-content image analysis as well as cell-based radioactive uptake and vesicle-based efflux inhibition assays. This high-throughput capability enabled a paradigm shift from studying transporter-related issues in the development space to identifying and dialing out these concerns early on in discovery for enhanced mechanism-based efficacy while circumventing DDIs and transporter toxicities.

Efficacy and safety of a new microneedle patch for skin brightening: A Randomized, split-face, single-blind study.

Science.gov (United States)

Park, Kui Young; Kwon, Hyun Jung; Lee, Changjin; Kim, Daegun; Yoon, Jun Jin; Kim, Myeong Nam; Kim, Beom Joon

2017-09-01

Although microneedles are one of the best transdermal drug delivery systems for active compounds, few clinical trials have examined the safety and efficacy of brightening microneedle patches. To determine the efficacy and safety of a newly developed whitening microneedle patch. A split-face study was designed for efficacy assessment with 34 Korean women applying the tested product (a whitening microneedle patch) on one cheek and a control whitening essence on the other. We objectively measured changes in melanin index values and skin brightness by mexameter and chromameter. Each participant also used global assessment to determine skin whitening. In addition, 55 participants were selected for primary skin irritation tests and repeated insult patch tests for safety assessments. Mean skin brightness and melanin indexes improved (Pmicroneedle patch was effective and safe for skin brightening and would be a promising functional cosmetic product. © 2017 Wiley Periodicals, Inc.

Pharmacokinetics and Safety of Amenamevir in Healthy Subjects: Analysis of Four Randomized Phase 1 Studies.

Science.gov (United States)

Kusawake, Tomohiro; Keirns, James J; Kowalski, Donna; den Adel, Martin; Groenendaal-van de Meent, Dorien; Takada, Akitsugu; Ohtsu, Yoshiaki; Katashima, Masataka

2017-12-01

Amenamevir (ASP2151) is a nonnucleoside antiherpesvirus compound available for the treatment of varicella-zoster virus infections. In this article we summarize the findings of four phase 1 studies in healthy participants. Four randomized phase 1 studies investigated the safety and pharmacokinetics of single and multiple doses of amenamevir, including the assessment of age group effect (nonelderly vs elderly), food effect, and the relative bioavailability of two formulations. Amenamevir was administered orally at various doses as a single dose (5-2400 mg) or daily (300 or 600 mg/day) for 7 days. Following single and multiple oral doses, amenamevir demonstrated a less than dose proportional increase in the pharmacokinetic parameters area under the plasma drug concentration versus time curve from time zero to infinity (AUC inf ) and C max . After single and multiple oral 300-mg doses of amenamevir, no apparent differences in pharmacokinetics were observed between nonelderly and elderly participants. In contrast, with the amenamevir 600-mg dose both the area under the plasma drug concentration versus time curve from time zero to 24 h and C max were slightly increased and renal clearance was decreased in elderly participants. The pharmacokinetics of amenamevir was affected by food, with AUC inf increased by about 90%. In the bioavailability study, AUC inf and C max were slightly lower following tablet versus capsule administration (decreased by 14 and 12%, respectively), with relative bioavailability of 86%. The different amenamevir doses and formulations were safe and well tolerated; no deaths or serious adverse events were reported. Amenamevir had less than dose proportional pharmacokinetic characteristics. Age may have an influence on amenamevir pharmacokinetics; however, the effect was considered minimal. The pharmacokinetics of amenamevir were affected by food, with AUC inf almost doubling when amenamevir was administered with food. The concentration versus

Drug development: from concept to marketing!

Science.gov (United States)

Tamimi, Nihad A M; Ellis, Peter

2009-01-01

Drug development is an expensive, long and high-risk business taking 10-15 years and is associated with a high attrition rate. It is driven by medical need, disease prevalence and the likelihood of success. Drug candidate selection is an iterative process between chemistry and biology, refining the molecular properties until a compound suitable for advancing to man is found. Typically, about one in a thousand synthesised compounds is ever selected for progression to the clinic. Prior to administration to humans, the pharmacology and biochemistry of the drug is established using an extensive range of in vitro and in vivo test procedures. It is also a regulatory requirement that the drug is administered to animals to assess its safety. Later-stage animal testing is also required to assess carcinogenicity and effects on the reproductive system. Clinical phases of drug development include phase I in healthy volunteers to assess primarily pharmacokinetics, safety and toleration, phase II in a cohort of patients with the target disease to establish efficacy and dose-response relationship and large-scale phase III studies to confirm safety and efficacy. Experience tells us that approximately only 1 in 10 drugs that start the clinical phase will make it to the market. Each drug must demonstrate safety and efficacy in the intended patient population and its benefits must outweigh its risks before it will be approved by the regulatory agencies. Strict regulatory standards govern the conduct of pre-clinical and clinical trials as well as the manufacturing of pharmaceutical products. The assessment of the new medicinal product's safety continues beyond the initial drug approval through post-marketing monitoring of adverse events. Copyright 2009 S. Karger AG, Basel.

Efficacy and safety of topical Trikatu preparation in, relieving mosquito bite reactions: a randomized controlled trial.

Science.gov (United States)

Maenthaisong, Ratree; Chaiyakunapruk, Nathorn; Tiyaboonchai, Waree; Tawatsin, Apiwat; Rojanawiwat, Archawin; Thavara, Usavadee

2014-02-01

Trikatu is composed of dried fruits of Piper nigrum L and Piper retrofractum Vahl, and dried rhizomes of Zingiber officinale R. Although this preparation has been used to relieve pruritis, pain, and inflammation for a long time, there is no clinical evidence to confirm its efficacy and safety. Therefore, we performed a double-blind, within person-randomized controlled study of 30 healthy volunteers to determine efficacy and safety of topical Trikatu on mosquito bite reactions. All subjects were bitten by Aedes aegypti laboratory mosquitoes on their forearms and they were randomly assigned arms to apply either Trikatu or reference product on the mosquito bite papule. The main outcome was the difference of papule size reduction at 30 min, measured by a caliper, between the Trikatu and reference arms. Pruritis, redness, pain, and patient satisfaction were assessed at 15, 30, 60, 180, and 360 min as secondary outcomes. There were no significant differences between treatment and reference arms on any outcome at any time of measurement. Trikatu did not show additional effects for relieving mosquito bite reaction as compared with the reference product containing camphor, menthol, and eucalyptus. For further study, it is very important to consider a proper selection of subjects, comparator product, and concentration of extract when Trikatu preparation is investigated. Copyright © 2013 Elsevier Ltd. All rights reserved.

Efficacy and Safety of Drug-Eluting Stents in the Real World: 8-Year Follow-Up

Energy Technology Data Exchange (ETDEWEB)

Pellegrini, Denise Oliveira, E-mail: dennizmo@yahoo.com.br; Gomes, Vitor Osório; Lasevitch, Ricardo; Smidt, Luis; Azeredo, Marco Aurélio; Ledur, Priscila; Bodanese, Rodrigo; Sinnott, Leonardo; Moriguchi, Emílio; Caramori, Paulo [Hospital São Lucas PUC, Porto Alegre, RS (Brazil)

2014-09-15

Drug-eluting stents have been used in daily practice since 2002, with the clear advantages of reducing the risk of target vessel revascularization and an impressive reduction in restenosis rate by 50%-70%. However, the occurrence of a late thrombosis can compromise long-term results, particularly if the risks of this event were sustained. In this context, a registry of clinical cases gains special value. To evaluate the efficacy and safety of drug-eluting stents in the real world. We report on the clinical findings and 8-year follow-up parameters of all patients that underwent percutaneous coronary intervention with a drug-eluting stent from January 2002 to April 2007. Drug-eluting stents were used in accordance with the clinical and interventional cardiologist decision and availability of the stent. A total of 611 patients were included, and clinical follow-up of up to 8 years was obtained for 96.2% of the patients. Total mortality was 8.7% and nonfatal infarctions occurred in 4.3% of the cases. Target vessel revascularization occurred in 12.4% of the cases, and target lesion revascularization occurred in 8% of the cases. The rate of stent thrombosis was 2.1%. There were no new episodes of stent thrombosis after the fifth year of follow-up. Comparative subanalysis showed no outcome differences between the different types of stents used, including Cypher®, Taxus®, and Endeavor®. These findings indicate that drug-eluting stents remain safe and effective at very long-term follow-up. Patients in the 'real world' may benefit from drug-eluting stenting with excellent, long-term results.

Innovations in Post-Marketing Safety Research

NARCIS (Netherlands)

Stefánsdóttir, G.

2012-01-01

Safety surveillance is important during the entire life cycle of a drug. Pre-marketing trials have been shown to be ineffective in establishing the full safety profile of the drug, mainly due to their relatively small sample size and characteristics of the patients, which are usually younger and

The impact of different strategies to handle missing data on both precision and bias in a drug safety study: a multidatabase multinational population-based cohort study

Science.gov (United States)

Martín-Merino, Elisa; Calderón-Larrañaga, Amaia; Hawley, Samuel; Poblador-Plou, Beatriz; Llorente-García, Ana; Petersen, Irene; Prieto-Alhambra, Daniel

2018-01-01

affect relative risk estimation in EMR-based drug safety studies, since missing data are not often completely at random. Little improvement was seen in these data in terms of power with the inclusion of longitudinal MI compared with cross-sectional MI. The strategy for handling missing data in drug safety studies can have a large impact on both risk estimates and precision.

Effects of Music Therapy on Drug Therapy of Adult Psychiatric Outpatients: A Pilot Randomized Controlled Study

Science.gov (United States)

Degli Stefani, Mario; Biasutti, Michele

2016-01-01

Objective: Framed in the patients’ engagement perspective, the current study aims to determine the effects of group music therapy in addition to drug care in comparison with drug care in addition to other non-expressive group activities in the treatment of psychiatric outpatients. Method: Participants (n = 27) with ICD-10 diagnoses of F20 (schizophrenia), F25 (schizoaffective disorders), F31 (bipolar affective disorder), F32 (depressive episode), and F60 (specific personality disorders) were randomized to receive group music therapy plus standard care (48 weekly sessions of 2 h) or standard care only. The clinical measures included dosages of neuroleptics, benzodiazepines, mood stabilizers, and antidepressants. Results: The participants who received group music therapy demonstrated greater improvement in drug dosage with respect to neuroleptics than those who did not receive group music therapy. Antidepressants had an increment for both groups that was significant only for the control group. Benzodiazepines and mood stabilizers did not show any significant change in either group. Conclusion: Group music therapy combined with standard drug care was effective for controlling neuroleptic drug dosages in adult psychiatric outpatients who received group music therapy. We discussed the likely applications of group music therapy in psychiatry and the possible contribution of music therapy in improving the psychopathological condition of adult outpatients. In addition, the implications for the patient-centered perspective were also discussed. PMID:27774073

Long-Term Safety of In Utero Exposure to Anti-TNFα Drugs for the Treatment of Inflammatory Bowel Disease

DEFF Research Database (Denmark)

Chaparro, M; Verreth, A; Lobaton, T

2018-01-01

OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNFα drugs...... in utero with that of children who were not exposed to the drugs. METHODS: Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNFα medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception. Non......-exposed cohort: children from mothers with IBD not treated with anti-TNFα agents or thiopurines at any time during pregnancy or the 3 months before conception. The cumulative incidence of severe infections after birth was estimated using Kaplan-Meier curves, which were compared using the log-rank test. Cox...

Efficacy and safety of ginger in osteoarthritis patients: a meta-analysis of randomized placebo-controlled trials.

Science.gov (United States)

Bartels, E M; Folmer, V N; Bliddal, H; Altman, R D; Juhl, C; Tarp, S; Zhang, W; Christensen, R

2015-01-01

The aim of this study was to assess the clinical efficacy and safety of oral ginger for symptomatic treatment of osteoarthritis (OA) by carrying out a systematic literature search followed by meta-analyses on selected studies. Inclusion criteria were randomized controlled trials (RCTs) comparing oral ginger treatment with placebo in OA patients aged >18 years. Outcomes were reduction in pain and reduction in disability. Harm was assessed as withdrawals due to adverse events. The efficacy effect size was estimated using Hedges' standardized mean difference (SMD), and safety by risk ratio (RR). Standard random-effects meta-analysis was used, and inconsistency was evaluated by the I-squared index (I(2)). Out of 122 retrieved references, 117 were discarded, leaving five trials (593 patients) for meta-analyses. The majority reported relevant randomization procedures and blinding, but an inadequate intention-to-treat (ITT) analysis. Following ginger intake, a statistically significant pain reduction SMD = -0.30 ([95% CI: [(-0.50, -0.09)], P = 0.005]) with a low degree of inconsistency among trials (I(2) = 27%), and a statistically significant reduction in disability SMD = -0.22 ([95% CI: ([-0.39, -0.04)]; P = 0.01; I(2) = 0%]) were seen, both in favor of ginger. Patients given ginger were more than twice as likely to discontinue treatment compared to placebo ([RR = 2.33; 95% CI: (1.04, 5.22)]; P = 0.04; I(2) = 0%]). Ginger was modestly efficacious and reasonably safe for treatment of OA. We judged the evidence to be of moderate quality, based on the small number of participants and inadequate ITT populations. Prospero: CRD42011001777. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Index to Drug-Specific Information

Science.gov (United States)

... Postmarket Drug Safety Information for Patients and Providers Index to Drug-Specific Information Share Tweet Linkedin Pin ... options Linkedin Pin it Email Print Note: This Index does not include all FDA approved drugs. It ...

Home closure as a weapon in the Dutch war on drugs: Does judicial review function as a safety net?

Science.gov (United States)

Bruijn, L Michelle; Vols, Michel; Brouwer, Jan G

2018-01-01

A widespread sense of a failing criminal justice system and increased feelings of insecurity changed the response to crime into a culture of control, which is characterized by policies that punish and exclude. In the Netherlands, these influences can be witnessed in the war on drugs where local authorities use their administrative power to close homes involved in drug-related crime. Citizens can invoke judicial review over these administrative interferences by claiming that such closure results in an unfair balance between purposes, means and consequences. This paper assesses whether judicial review functions as a safety net against losing one's home due to drug-related crime. We used doctrinal legal research methods to examine the "law in the books" and empirical legal research methods to analyse the "law in action". We used a survey to investigate how often the drug-related closure power was used in 2015, and we statistically analysed all published case law of Dutch lower courts between 2007 and 2016. The scope of the closure power broadened over the years and our data show that local authorities fiercely make use of this instrument. In 41.4% of the cases, citizens are successful in fighting the closure. While scholarly literature indicates that judicial courts function as safeguards by questioning the proportionality of administrative action, raising a proportionality defence does not necessarily result in a more favourable outcome for citizens. In fact, raising a proportionality defence makes it more likely to result in dismissal of the appeal. The stretched scope of the drug-related closure power together with the relatively low success rate of citizens who fight the loss of their home and a seemingly meaningless proportionality check show no sign of a safety net against the loss of one's home at the suit of a local authority. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Protocol of the impact of alternative social assistance disbursement on drug-related harm (TASA) study: a randomized controlled trial to evaluate changes to payment timing and frequency among people who use illicit drugs.

Science.gov (United States)

Richardson, Lindsey; Laing, Allison; Milloy, M-J; Maynard, Russ; Nosyk, Bohdan; Marshall, Brandon; Grafstein, Eric; Daly, Patricia; Wood, Evan; Montaner, Julio; Kerr, Thomas

2016-07-29

Government social assistance payments seek to alleviate poverty and address survival needs, but their monthly disbursement may cue increases in illicit drug use. This cue may be magnified when assistance is disbursed simultaneously across the population. Synchronized payments have been linked to escalations in drug use and unintended but severe drug-related harms, including overdose, as well as spikes in demand for health, social, financial and police services. The TASA study examines whether changing payment timing and frequency can mitigate drug-related harm associated with synchronized social assistance disbursement. The study is a parallel arm multi-group randomized controlled trial in which 273 participants are randomly allocated for six assistance cycles to a control or one of two intervention arms on a 1:1:1 basis. Intervention arm participants receive their payments: (1) monthly; or (2) semi-monthly, in each case on days that are not during the week when cheques are normally issued. The study partners with a community-based credit union that has developed a system to vary social assistance payment timing. The primary outcome is a 40 % increase in drug use during the 3 days beginning with cheque issue day compared to other days of the month. Bi-weekly follow-up interviews collect participant information on this and secondary outcomes of interest, including drug-related harm (e.g. non-fatal overdose), exposure to violence and health service utilization. Self-reported data will be supplemented with participant information from health, financial, police and government administrative databases. A longitudinal, nested, qualitative parallel process evaluation explores participant experiences, and a cost-effectiveness evaluation of different disbursement scenarios will be undertaken. Outcomes will be compared between control and intervention arms to identify the impacts of alternative disbursement schedules on drug-related harm resulting from synchronized income

Protocol of the impact of alternative social assistance disbursement on drug-related harm (TASA study: a randomized controlled trial to evaluate changes to payment timing and frequency among people who use illicit drugs

Directory of Open Access Journals (Sweden)

Lindsey Richardson

2016-07-01

Full Text Available Abstract Background Government social assistance payments seek to alleviate poverty and address survival needs, but their monthly disbursement may cue increases in illicit drug use. This cue may be magnified when assistance is disbursed simultaneously across the population. Synchronized payments have been linked to escalations in drug use and unintended but severe drug-related harms, including overdose, as well as spikes in demand for health, social, financial and police services. Methods/design The TASA study examines whether changing payment timing and frequency can mitigate drug-related harm associated with synchronized social assistance disbursement. The study is a parallel arm multi-group randomized controlled trial in which 273 participants are randomly allocated for six assistance cycles to a control or one of two intervention arms on a 1:1:1 basis. Intervention arm participants receive their payments: (1 monthly; or (2 semi-monthly, in each case on days that are not during the week when cheques are normally issued. The study partners with a community-based credit union that has developed a system to vary social assistance payment timing. The primary outcome is a 40 % increase in drug use during the 3 days beginning with cheque issue day compared to other days of the month. Bi-weekly follow-up interviews collect participant information on this and secondary outcomes of interest, including drug-related harm (e.g. non-fatal overdose, exposure to violence and health service utilization. Self-reported data will be supplemented with participant information from health, financial, police and government administrative databases. A longitudinal, nested, qualitative parallel process evaluation explores participant experiences, and a cost-effectiveness evaluation of different disbursement scenarios will be undertaken. Outcomes will be compared between control and intervention arms to identify the impacts of alternative disbursement schedules on

Di-22:6-bis(monoacylglycerol)phosphate: A clinical biomarker of drug-induced phospholipidosis for drug development and safety assessment

International Nuclear Information System (INIS)

Liu, Nanjun; Tengstrand, Elizabeth A.; Chourb, Lisa; Hsieh, Frank Y.

2014-01-01

The inability to routinely monitor drug-induced phospholipidosis (DIPL) presents a challenge in pharmaceutical drug development and in the clinic. Several nonclinical studies have shown di-docosahexaenoyl (22:6) bis(monoacylglycerol) phosphate (di-22:6-BMP) to be a reliable biomarker of tissue DIPL that can be monitored in the plasma/serum and urine. The aim of this study was to show the relevance of di-22:6-BMP as a DIPL biomarker for drug development and safety assessment in humans. DIPL shares many similarities with the inherited lysosomal storage disorder Niemann–Pick type C (NPC) disease. DIPL and NPC result in similar changes in lysosomal function and cholesterol status that lead to the accumulation of multi-lamellar bodies (myeloid bodies) in cells and tissues. To validate di-22:6-BMP as a biomarker of DIPL for clinical studies, NPC patients and healthy donors were classified by receiver operator curve analysis based on urinary di-22:6-BMP concentrations. By showing 96.7-specificity and 100-sensitivity to identify NPC disease, di-22:6-BMP can be used to assess DIPL in human studies. The mean concentration of di-22:6-BMP in the urine of NPC patients was 51.4-fold (p ≤ 0.05) above the healthy baseline range. Additionally, baseline levels of di-22:6-BMP were assessed in healthy non-medicated laboratory animals (rats, mice, dogs, and monkeys) and human subjects to define normal reference ranges for nonclinical/clinical studies. The baseline ranges of di-22:6-BMP in the plasma, serum, and urine of humans and laboratory animals were species dependent. The results of this study support the role of di-22:6-BMP as a biomarker of DIPL for pharmaceutical drug development and health care settings. - Highlights: • A reliable biomarker of drug-induced phospholipidosis (DIPL) is needed for humans. • Di-22:6-BMP is specific/sensitive for DIPL in animals as published in literatures. • The di-22:6-BMP biomarker can be validated for humans via NPC patients. • DIPL

Di-22:6-bis(monoacylglycerol)phosphate: A clinical biomarker of drug-induced phospholipidosis for drug development and safety assessment

Energy Technology Data Exchange (ETDEWEB)

Liu, Nanjun; Tengstrand, Elizabeth A.; Chourb, Lisa; Hsieh, Frank Y., E-mail: frank.hsieh@nextcea.com

2014-09-15

The inability to routinely monitor drug-induced phospholipidosis (DIPL) presents a challenge in pharmaceutical drug development and in the clinic. Several nonclinical studies have shown di-docosahexaenoyl (22:6) bis(monoacylglycerol) phosphate (di-22:6-BMP) to be a reliable biomarker of tissue DIPL that can be monitored in the plasma/serum and urine. The aim of this study was to show the relevance of di-22:6-BMP as a DIPL biomarker for drug development and safety assessment in humans. DIPL shares many similarities with the inherited lysosomal storage disorder Niemann–Pick type C (NPC) disease. DIPL and NPC result in similar changes in lysosomal function and cholesterol status that lead to the accumulation of multi-lamellar bodies (myeloid bodies) in cells and tissues. To validate di-22:6-BMP as a biomarker of DIPL for clinical studies, NPC patients and healthy donors were classified by receiver operator curve analysis based on urinary di-22:6-BMP concentrations. By showing 96.7-specificity and 100-sensitivity to identify NPC disease, di-22:6-BMP can be used to assess DIPL in human studies. The mean concentration of di-22:6-BMP in the urine of NPC patients was 51.4-fold (p ≤ 0.05) above the healthy baseline range. Additionally, baseline levels of di-22:6-BMP were assessed in healthy non-medicated laboratory animals (rats, mice, dogs, and monkeys) and human subjects to define normal reference ranges for nonclinical/clinical studies. The baseline ranges of di-22:6-BMP in the plasma, serum, and urine of humans and laboratory animals were species dependent. The results of this study support the role of di-22:6-BMP as a biomarker of DIPL for pharmaceutical drug development and health care settings. - Highlights: • A reliable biomarker of drug-induced phospholipidosis (DIPL) is needed for humans. • Di-22:6-BMP is specific/sensitive for DIPL in animals as published in literatures. • The di-22:6-BMP biomarker can be validated for humans via NPC patients. • DIPL

Comparative efficacy and safety of Crocus sativus L. for treating mild to moderate major depressive disorder in adults: a meta-analysis of randomized controlled trials

Directory of Open Access Journals (Sweden)

Yang XY

2018-05-01

Full Text Available Xiangying Yang,1 Xiaolu Chen,1 Yixiao Fu,2 Qinghua Luo,2 Lian Du,2 Haitang Qiu,2 Tian Qiu,2 Li Zhang,1 Huaqing Meng2 1The First Branch, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China Purpose: To investigate the efficacy and safety of saffron in the treatment of major depressive disorder (MDD in comparison to placebo and synthetic antidepressants. Patients and methods: We conducted a systematic search in several electronic databases as well as manual search in bibliographies of relevant studies. We included randomized controlled trials that investigated the efficacy and safety of saffron for treating MDD in adults in comparison to either placebo or synthetic antidepressants. Primary outcome was change in scores on depressive symptoms from baseline. Secondary outcomes included remission rate, response rate, and drop-out rate for all reasons. We chose a random-effects model in order to obtain more conservative results. Standardized mean differences (SMDs and odds ratios (ORs with 95% confidence intervals (CIs were estimated as the overall effect index by inverse variance models. Results: Seven studies were included in this meta-analysis. Overall quality of these included studies was moderate. As for the primary outcome, saffron showed more improvements in depression symptoms when compared with placebo, with an SMD of -1.22 (95% CI -1.94, -0.49, P=0.001. Meanwhile, saffron was as effective as synthetic antidepressants, with an SMD of 0.16 (95% CI -0.25, 0.57, P=0.44. Moderate heterogeneity existed in our analysis. Through subgroup analyses, we found that treatment dosage and duration, types of synthetic antidepressants administered in the comparison group, and outcome measures could explain most of the variance. No differences were found in remission rate, response

Feasibility, Safety, and Compliance in a Randomized Controlled Trial of Physical Therapy for Parkinson's Disease

Directory of Open Access Journals (Sweden)

Jennifer L. McGinley

2012-01-01

Full Text Available Both efficacy and clinical feasibility deserve consideration in translation of research outcomes. This study evaluated the feasibility of rehabilitation programs within the context of a large randomized controlled trial of physical therapy. Ambulant participants with Parkinson's disease (PD (n=210 were randomized into three groups: (1 progressive strength training (PST; (2 movement strategy training (MST; or (3 control (“life skills”. PST and MST included fall prevention education. Feasibility was evaluated in terms of safety, retention, adherence, and compliance measures. Time to first fall during the intervention phase did not differ across groups, and adverse effects were minimal. Retention was high; only eight participants withdrew during or after the intervention phase. Strong adherence (attendance >80% did not differ between groups (P=.435. Compliance in the therapy groups was high. All three programs proved feasible, suggesting they may be safely implemented for people with PD in community-based clinical practice.

Monitoring antimalarial safety and tolerability in clinical trials: A case study from Uganda

Directory of Open Access Journals (Sweden)

Mpimbaza Arthur

2008-06-01

Full Text Available Abstract Background New antimalarial regimens, including artemisinin-based combination therapies (ACTs, have been adopted widely as first-line treatment for uncomplicated malaria. Although these drugs appear to be safe and well-tolerated, experience with their use in Africa is limited and continued assessment of safety is a priority. However, no standardized guidelines for evaluating drug safety and tolerability in malaria studies exist. A system for monitoring adverse events in antimalarial trials conducted in Uganda was developed. Here the reporting system is described, and difficulties faced in analysing and interpreting the safety results are illustrated, using data from the trials. Case description Between 2002 and 2007, eleven randomized, controlled clinical trials were conducted to compare the efficacy, safety, and tolerability of different antimalarial regimens for treatment of uncomplicated malaria in Uganda. The approach to adverse event monitoring was similar in all studies. A total of 5,614 treatments were evaluated in 4,876 patients. Differences in baseline characteristics and patterns of adverse event reporting were noted between the sites, which limited the ability to pool and analyse data. Clinical failure following antimalarial treatment confounded associations between treatment and adverse events that were also common symptoms of malaria, particularly in areas of lower transmission intensity. Discussion and evaluation Despite prospectively evaluating for adverse events, limitations in the monitoring system were identified. New standardized guidelines for monitoring safety and tolerability in antimalarial trials are needed, which should address how to detect events of greatest importance, including serious events, those with a causal relationship to the treatment, those which impact on adherence, and events not previously reported. Conclusion Although the World Health Organization has supported the development of

Safety voice for ergonomics (SAVE project: protocol for a workplace cluster-randomized controlled trial to reduce musculoskeletal disorders in masonry apprentices

Directory of Open Access Journals (Sweden)

Laurel D. Kincl

2016-04-01

Full Text Available Abstract Background Masons have the highest rate of overexertion injuries among all construction trades and rank second for occupational back injuries in the United States. Identified ergonomic solutions are the primary method of reducing exposure to risk factors associated with musculoskeletal disorders. However, many construction workers lack knowledge about these solutions, as well as basic ergonomic principles. Construction apprentices, as they embark on their careers, are greatly in need of ergonomics training to minimize the cumulative exposure that leads to musculoskeletal disorders. Apprentices receive safety training; however, ergonomics training is often limited or non-existent. In addition, apprenticeship programs often lack “soft skills” training on how to appropriately respond to work environments and practices that are unsafe. The SAVE program – SAfety Voice for Ergonomics – strives to integrate evidence-based health and safety training strategies into masonry apprenticeship skills training to teach ergonomics, problem solving, and speaking up to communicate solutions that reduce musculoskeletal injury risk. The central hypothesis is that the combination of ergonomics training and safety voice promotion will be more effective than no training or either ergonomics training alone or safety voice training alone. Methods/design Following the development and pilot testing of the SAVE intervention, SAVE will be evaluated in a cluster-randomized controlled trial at 12 masonry training centers across the U.S. Clusters of apprentices within centers will be assigned at random to one of four intervention groups (n = 24 per group: (1 ergonomics training only, (2 safety voice training only, (3 combined ergonomics and safety voice training, or (4 control group with no additional training intervention. Outcomes assessed at baseline, at the conclusion of training, and then at six and 12 months post training will include

Safety voice for ergonomics (SAVE) project: protocol for a workplace cluster-randomized controlled trial to reduce musculoskeletal disorders in masonry apprentices.

Science.gov (United States)

Kincl, Laurel D; Anton, Dan; Hess, Jennifer A; Weeks, Douglas L

2016-04-27

Masons have the highest rate of overexertion injuries among all construction trades and rank second for occupational back injuries in the United States. Identified ergonomic solutions are the primary method of reducing exposure to risk factors associated with musculoskeletal disorders. However, many construction workers lack knowledge about these solutions, as well as basic ergonomic principles. Construction apprentices, as they embark on their careers, are greatly in need of ergonomics training to minimize the cumulative exposure that leads to musculoskeletal disorders. Apprentices receive safety training; however, ergonomics training is often limited or non-existent. In addition, apprenticeship programs often lack "soft skills" training on how to appropriately respond to work environments and practices that are unsafe. The SAVE program - SAfety Voice for Ergonomics - strives to integrate evidence-based health and safety training strategies into masonry apprenticeship skills training to teach ergonomics, problem solving, and speaking up to communicate solutions that reduce musculoskeletal injury risk. The central hypothesis is that the combination of ergonomics training and safety voice promotion will be more effective than no training or either ergonomics training alone or safety voice training alone. Following the development and pilot testing of the SAVE intervention, SAVE will be evaluated in a cluster-randomized controlled trial at 12 masonry training centers across the U.S. Clusters of apprentices within centers will be assigned at random to one of four intervention groups (n = 24 per group): (1) ergonomics training only, (2) safety voice training only, (3) combined ergonomics and safety voice training, or (4) control group with no additional training intervention. Outcomes assessed at baseline, at the conclusion of training, and then at six and 12 months post training will include: musculoskeletal symptoms, general health perceptions, knowledge of

Probing cardiac repolarization reserve in drug safety assessment

NARCIS (Netherlands)

Nalos, L.

2011-01-01

Excessive prolongation of cardiac repolarization, manifested as QT prolongation on ECG, is common unwanted side effect of many drugs and drug candidates. Prolongation of QT interval may lead to life threatening cardiac arrhythmia – Torsade de Point (TdP). Number of drugs was withdrawn from the

Efficacy and safety of diclofenac sodium 2% topical solution for osteoarthritis of the knee: a randomized, double-blind, vehicle-controlled, 4 week study.

Science.gov (United States)

Wadsworth, L Tyler; Kent, Jeffrey D; Holt, Robert J

2016-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are standard therapy for osteoarthritis (OA). Topically applied NSAIDs reduce systemic exposure compared with oral NSAIDS, and European guidelines recommend their use. The NSAID diclofenac is available in a range of topical formulations. Diclofenac 1% gel and 1.5% four times daily and 2% twice daily (BID) solutions are approved to reduce pain from OA of the knee(s). The objective of this study was to investigate the efficacy and safety of diclofenac sodium 2% topical solution BID versus vehicle control solution for treating pain associated with OA of the knee. A phase II, 4 week, randomized, double-blind, parallel-group, two-arm, vehicle-controlled study compared pain relief with diclofenac sodium 2% topical solution versus control (vehicle only) in patients aged 40 to 85 years with radiographically confirmed primary OA of the knee. ClinicalTrials.gov identifier NCT01119898. The primary efficacy outcome was change from baseline to the final visit in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. Secondary outcomes included additional WOMAC subscales and patient global assessment of OA. Treatment-emergent adverse events (TEAEs), skin irritation, and vital signs were assessed and collected throughout the study. Of 260 patients randomized, 259 received ≥1 dose of study drug. Significantly greater reductions in least-squares mean (standard error) WOMAC pain scores were observed for diclofenac-treated (-4.4 [0.4]) versus vehicle-treated patients (-3.4 [0.4]) at the final visit (p = 0.040). The most commonly reported TEAEs were administration site conditions. The vehicle-treated group experienced slightly more TEAEs than the active treatment group (38.8% vs. 31.5%). No serious adverse events were reported. Administration of diclofenac sodium 2% topical solution BID resulted in significantly greater improvement in pain reduction in patients with OA of the knee versus vehicle

Evaluation of the efficacy and safety of olanzapine as an adjunctive treatment for anorexia nervosa in adolescent females: a randomized, double-blind, placebo-controlled trial

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Moher David

2008-01-01

Full Text Available Abstract Background Anorexia Nervosa (AN is a serious, debilitating condition that causes significant physical, emotional, and functional impairment. The condition is characterized by destructive weight loss behaviours and a refusal to maintain body weight at or above a minimally normal weight for age and height. AN often develops in adolescence and is a predominantly female disorder. Treatment for AN typically involves medical, nutritional and psychological interventions. Pharmacotherapy is also often used; however, the literature on the effectiveness of these drugs in a pediatric population is very limited. Olanzapine, which is an 'atypical' antipsychotic, is becoming more widespread in the treatment of AN. Olanzapine is hypothesized to facilitate weight gain, while decreasing levels of agitation and decreasing resistance to treatment in young women with AN. This randomized, double-blind placebo-controlled trial seeks to examine the effectiveness and safety of olanzapine in female youth with AN. Methods/Design Adolescent females between the ages of 12 and 17 diagnosed with AN (either restricting or binge/purge type or Eating Disorder Not Otherwise Specified with a Body Mass Index of less than or equal to 17.5, will be offered inclusion in the study. Patients will be randomly assigned to receive either olanzapine or placebo. Patients assigned to receive olanzapine will start at a low dose of 1.25 mg/day for three days, followed by 2.5 mg/day for four days, 5 mg/day for one week, then 7.5 mg/day (the target dose chosen for 10 weeks. After 10 weeks at 7.5 mg the medication will be tapered and discontinued over a period of two weeks. The effectiveness of olanzapine versus placebo will be determined by investigating the change from baseline on measures of eating attitudes and behaviors, depression and anxiety, and change in Body Mass Index at week 12, and after a follow-up period at week 40. It is anticipated that 67 participants will be recruited

Application of Model Animals in the Study of Drug Toxicology

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Song, Yagang; Miao, Mingsan

2018-01-01

Drug safety is a key factor in drug research and development, Drug toxicology test is the main method to evaluate the safety of drugs, The body condition of an animal has important implications for the results of the study, Previous toxicological studies of drugs were carried out in normal animals in the past, There is a great deviation from the clinical practice.The purpose of this study is to investigate the necessity of model animals as a substitute for normal animals for toxicological studies, It is expected to provide exact guidance for future drug safety evaluation.

Random Assignment of Schools to Groups in the Drug Resistance Strategies Rural Project: Some New Methodological Twists

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Pettigrew, Jonathan; Miller-Day, Michelle; Krieger, Janice L.; Zhou, Jiangxiu; Hecht, Michael L.

2014-01-01

Random assignment to groups is the foundation for scientifically rigorous clinical trials. But assignment is challenging in group randomized trials when only a few units (schools) are assigned to each condition. In the DRSR project, we assigned 39 rural Pennsylvania and Ohio schools to three conditions (rural, classic, control). But even with 13 schools per condition, achieving pretest equivalence on important variables is not guaranteed. We collected data on six important school-level variables: rurality, number of grades in the school, enrollment per grade, percent white, percent receiving free/assisted lunch, and test scores. Key to our procedure was the inclusion of school-level drug use data, available for a subset of the schools. Also, key was that we handled the partial data with modern missing data techniques. We chose to create one composite stratifying variable based on the seven school-level variables available. Principal components analysis with the seven variables yielded two factors, which were averaged to form the composite inflate-suppress (CIS) score which was the basis of stratification. The CIS score was broken into three strata within each state; schools were assigned at random to the three program conditions from within each stratum, within each state. Results showed that program group membership was unrelated to the CIS score, the two factors making up the CIS score, and the seven items making up the factors. Program group membership was not significantly related to pretest measures of drug use (alcohol, cigarettes, marijuana, chewing tobacco; smallest p>.15), thus verifying that pretest equivalence was achieved. PMID:23722619

Drug Repositioning of Proton Pump Inhibitors for Enhanced Efficacy and Safety of Cancer Chemotherapy

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Kenji Ikemura

2017-12-01

Full Text Available Proton pump inhibitors (PPIs, H+/K+-ATPase inhibitors, are the most commonly prescribed drugs for the treatment of gastroesophageal reflux and peptic ulcer diseases; they are highly safe and tolerable. Since PPIs are frequently used in cancer patients, studies investigating interactions between PPIs and anticancer agents are of particular importance to achieving effective and safe cancer chemotherapy. Several studies have revealed that PPIs inhibit not only the H+/K+-ATPase in gastric parietal cells, but also the vacuolar H+-ATPase (V-ATPase overexpressed in tumor cells, as well as the renal basolateral organic cation transporter 2 (OCT2 associated with pharmacokinetics and/or renal accumulation of various drugs, including anticancer agents. In this mini-review, we summarize the current knowledge regarding the impact of PPIs on the efficacy and safety of cancer chemotherapeutics via inhibition of targets other than the H+/K+-ATPase. Co-administration of clinical doses of PPIs protected kidney function in patients receiving cisplatin and fluorouracil, presumably by decreasing accumulation of cisplatin in the kidney via OCT2 inhibition. In addition, co-administration or pretreatment with PPIs could inhibit H+ transport via the V-ATPase in tumor cells, resulting in lower extracellular acidification and intracellular acidic vesicles to enhance the sensitivity of the tumor cells to the anticancer agents. In the present mini-review, we suggest that PPIs enhance the efficacy and safety of anticancer agents via off-target inhibition (e.g., of OCT2 and V-ATPase, rather than on-target inhibition of the H+/K+-ATPase. The present findings should provide important information to establish novel supportive therapy with PPIs during cancer chemotherapy.

Chinese Herbal Medicine for Acute Mountain Sickness: A Systematic Review of Randomized Controlled Trials

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Jie Wang

2013-01-01

Full Text Available Objectives. We aimed to assess the current clinical evidence of Chinese herbal medicine for AMS. Methods. Seven electronic databases were searched until January 2013. We included randomized clinical trials testing Chinese herbal medicine against placebo, no drugs, Western drugs, or a combination of routine treatment drugs against routine treatment drugs. Study selection, data extraction, quality assessment, and data analyses were conducted according to Cochrane standards. Results. Nine randomized trials were included. The methodological quality of the included trials was evaluated as low. Two trials compared prescriptions of Chinese formula used alone with Western drugs. A meta-analysis showed a beneficial effect in decreasing the score of AMS (MD: −2.23 [−3.98, −0.49], P=0.01. Only one trial compared prescriptions of Chinese formula used alone with no drugs. A meta-analysis showed a significant beneficial effect in decreasing the score of AMS (MD: −6.00 [−6.45, −5.55], P<0.00001. Four trials compared Chinese formula used alone with placebo. A meta-analysis also showed a significant beneficial effect in decreasing the score of AMS (MD: −1.10 [−1.64, −0.55], P<0.0001. Two trials compared the combination of Chinese formula plus routine treatment drugs with routine treatment drugs. A meta-analysis showed a beneficial effect in decreasing the score of AMS (MD: −5.99 [−11.11, −0.86], P=0.02. Conclusions. No firm conclusion on the effectiveness and safety of Chinese herbal medicine for AMS can be made. More rigorous high-quality trials are required to generate a high level of evidence and to confirm the results.

Safety of Lifitegrast Ophthalmic Solution 5.0% in Patients With Dry Eye Disease: A 1-Year, Multicenter, Randomized, Placebo-Controlled Study.

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Donnenfeld, Eric D; Karpecki, Paul M; Majmudar, Parag A; Nichols, Kelly K; Raychaudhuri, Aparna; Roy, Monica; Semba, Charles P

2016-06-01

To evaluate the 1-year safety of lifitegrast ophthalmic solution 5.0% in patients with dry eye disease compared with placebo. SONATA (Safety Of a 5.0% coNcentrATion of lifitegrAst ophthalmic solution) was a multicenter, randomized, prospective, double-masked, placebo-controlled phase 3 study (NCT01636206). Adults (≥18 years) with dry eye disease (Schirmer test score ≥1 and ≤10 mm; corneal staining score ≥2.0) were randomized 2:1 to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 360 days. The primary objective was percentage and severity of treatment-emergent adverse events (TEAEs). Secondary objectives were ocular safety measures: corneal fluorescein staining, drop comfort, best-corrected visual acuity, slit-lamp biomicroscopy, and intraocular pressure over 7 visits. Exploratory objectives included concentration of lifitegrast in plasma. The safety population comprised 331 participants (220 lifitegrast; 111 placebo). There were no serious ocular TEAEs. Overall, 53.6% of participants receiving lifitegrast experienced ≥1 ocular TEAE versus 34.2% in the placebo group; most TEAEs were mild to moderate in severity. Rates of discontinuation because of TEAEs were 12.3% (lifitegrast) versus 9.0% (placebo). The most common (>5%) TEAEs occurring in either treatment group were instillation site irritation (burning), instillation site reaction, visual acuity reduced, dry eye, and dysgeusia (change in taste). Ocular safety parameters for lifitegrast were similar to placebo. The mean plasma lifitegrast concentration at 360 days (n = 43) was below the limit of detection. There was no indication of systemic toxicity or localized infectious complications secondary to chronic immunosuppression. Lifitegrast ophthalmic solution 5.0% seemed safe and well tolerated in this study, with no unexpected adverse events.

Projecting future drug expenditures--2009.

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Hoffman, James M; Shah, Nilay D; Vermeulen, Lee C; Doloresco, Fred; Martin, Patrick K; Blake, Sharon; Matusiak, Linda; Hunkler, Robert J; Schumock, Glen T

2009-02-01

Drug expenditure trends in 2007 and 2008, projected drug expenditures for 2009, and factors likely to influence drug expenditures are discussed. Various factors are likely to influence drug expenditures in 2009, including drugs in development, the diffusion of new drugs, drug safety concerns, generic drugs, Medicare Part D, and changes in the drug supply chain. The increasing availability of important generic drugs and drug safety concerns continue to moderate growth in drug expenditures. The drug supply chain remains dynamic and may influence drug expenditures, particularly in specialized therapeutic areas. Initial data suggest that the Medicare Part D benefit has influenced drug expenditures, but the ultimate impact of the benefit on drug expenditures remains unclear. From 2006 to 2007, total U.S. drug expenditures increased by 4.0%, with total spending rising from $276 billion to $287 billion. Drug expenditures in clinics continue to grow more rapidly than in other settings, with a 9.9% increase from 2006 to 2007. Hospital drug expenditures increased at a moderate rate of only 1.6% from 2006 to 2007; through the first nine months of 2008, hospital drug expenditures increased by only 2.8% compared with the same period in 2007. In 2009, we project a 0-2% increase in drug expenditures in outpatient settings, a 1-3% increase in expenditures for clinic-administered drugs, and a 1-3% increase in hospital drug expenditures.

The safety of treatment options available for gout.

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Schlesinger, Naomi

2017-04-01

Gout is the most common inflammatory arthritis in humans. Gout treatment includes rapid initiation of anti-inflammatory medications for acute attacks and chronically treating with urate lowering drugs as well as chronic anti-inflammatory prophylaxis. Areas covered: This review aims to provide an overview and discussion of the safety concerns of current treatment options available for gout. Expert opinion: Gout is a curable disease with appropriate treatment. The advent of new therapies provides encouraging opportunities to improve gout management. However, clinicians should be aware of some of the safety concerns of medications used to treat acute and chronic gout. When prescribing medications for gout one has to be mindful of the presence of comorbidities commonly affecting gout patients that may affect drug safety and efficacy, especially in the elderly and in patients treated with multiple drugs. The benefits of gout drugs, usually, outweigh their safety concerns. Studies are needed in gout patients with chronic kidney disease and/or cardiovascular disease, so that escalation of dosing /combination of anti-inflammatory drugs needed to suppress gouty inflammation as well as escalation of dosing/combination of urate lowering drugs needed to achieve target serum urate level will lead to better understanding of gout treatment safety issues.

48 CFR 923.7001 - Nuclear safety.

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2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Nuclear safety. 923.7001... ENVIRONMENT, CONSERVATION, OCCUPATIONAL SAFETY, AND DRUG-FREE WORKPLACE Environmental, Energy and Water Efficiency, Renewable Energy Technologies, and Occupational Safety Programs 923.7001 Nuclear safety. The DOE...

Z-drug for schizophrenia: A systematic review and meta-analysis.

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Kishi, Taro; Inada, Ken; Matsui, Yuki; Iwata, Nakao

2017-10-01

No systematic reviews and meta-analyses on the use of Z-drug for schizophrenia are available. Randomized, placebo-controlled, or non-pharmacological intervention-controlled trials published before 03/20/2017 were retrieved from major healthcare databases and clinical trial registries. A meta-analysis including only randomized, placebo-controlled trials was performed. Efficacy outcomes were measured as improvement in overall schizophrenia symptoms, total sleep time, and wake after sleep onset. Safety/acceptability outcomes were discontinuation rate and individual adverse events. Four trials [1 alpidem placebo-controlled study (n=66), 2 eszopiclone placebo-controlled studies (n=60), and 1 eszopiclone, shallow needling-controlled study (n=96)] were identified. The meta-analysis showed no significant differences in any outcome between pooled Z-drug and placebo treatment groups. For individual studies, alpidem was superior to placebo in improving the overall schizophrenia symptoms. One of the eszopiclone studies showed that eszopiclone was superior to placebo in improving the Insomnia Severity Index scores. Another eszopiclone study showed that eszopiclone did not differ from shallow needling therapy in improving both schizophrenia- and insomnia-related symptoms. Although this study failed to show significant benefits for the use of Z-drug in the treatment of schizophrenia, it showed that short-term use of eszopiclone is an acceptable method for treating persistent insomnia among these patients. Copyright © 2017 Elsevier B.V. All rights reserved.

German Center Subanalysis of the LEVANT 2 Global Randomized Study of the Lutonix Drug-Coated Balloon in the Treatment of Femoropopliteal Occlusive Disease.

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Scheinert, Dierk; Schmidt, Andrej; Zeller, Thomas; Müller-Hülsbeck, Stefan; Sixt, Sebastian; Schröder, Henrik; Weiss, Norbert; Ketelsen, Dominik; Ricke, Jens; Steiner, Sabine; Rosenfield, Kenneth

2016-06-01

To report a subanalysis of the German centers enrolling patients in the prospective, global, multicenter, randomized LEVANT 2 pivotal trial (ClinicalTrials.gov identifier NCT01412541) of the Lutonix drug-coated balloon (DCB) for the treatment of femoropopliteal occlusive disease. Among the 476 patients in LEVANT 2, 126 patients (mean age 67.1±9.6 years; 79 men) were enrolled at the 8 participating German sites between August 2011 and July 2012 and were randomized 2:1 to treatment with the Lutonix DCB (n=83) vs an uncoated balloon during percutaneous transluminal angioplasty (PTA, n=43). All patients had intermittent claudication or rest pain (Rutherford categories 2-4). Average lesion length was 58 mm and average treated length was 100 mm. Severe calcification was present in 11% of lesions, and 23% were total occlusions. The efficacy outcome was primary patency at 12 months, and the safety outcome was 12-month freedom from a composite of perioperative death, index limb-related death, amputation (below or above the ankle), and index limb revascularization. Secondary endpoints included target lesion revascularization (TLR), major adverse events, and functional outcomes. Demographic, clinical, and lesion characteristics were matched between Lutonix DCB and PTA groups, as were the final percent diameter stenosis (19%) and procedure success (91%). By Kaplan-Meier analysis, the 12-month primary patency rate was 80% vs 58% (p=0.015) and the composite safety endpoint rate was 94% vs 72% (p=0.001), respectively. Freedom from TLR was higher for DCBs (96%) vs PTA (82%, p=0.012). Major adverse events were similar for both groups. The benefit favoring DCB over PTA was observed in German men and women. Compared to the non-German LEVANT 2 cohort, there was a shorter time between insertion and inflation of treatment balloons (21.8 vs 39.5 seconds, pGerman cohort. Balloons were inflated to higher pressures (9.0 vs 7.7 atm, pGerman cohort had a higher baseline stenosis, final

A phase I trial to evaluate the safety and pharmacokinetics of low-dose methotrexate as an anti-malarial drug in Kenyan adult healthy volunteers

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Oyoo George O

2011-03-01

Full Text Available Abstract Background Previous investigations indicate that methotrexate, an old anticancer drug, could be used at low doses to treat malaria. A phase I evaluation was conducted to assess the safety and pharmacokinetic profile of this drug in healthy adult male Kenyan volunteers. Methods Twenty five healthy adult volunteers were recruited and admitted to receive a 5 mg dose of methotrexate/day/5 days. Pharmacokinetics blood sampling was carried out at 2, 4, 6, 12 and 24 hours following each dose. Nausea, vomiting, oral ulcers and other adverse events were solicited during follow up of 42 days. Results The mean age of participants was 23.9 ± 3.3 years. Adherence to protocol was 100%. No grade 3 solicited adverse events were observed. However, one case of transiently elevated liver enzymes, and one serious adverse event (not related to the product were reported. The maximum concentration (Cmax was 160-200 nM and after 6 hours, the effective concentration (Ceff was Conclusion Low-dose methotraxate had an acceptable safety profile. However, methotrexate blood levels did not reach the desirable Ceff of 250-400-nM required to clear malaria infection in vivo. Further dose finding and safety studies are necessary to confirm suitability of this drug as an anti-malarial agent.