Quality of Reporting of Bioequivalence Trials Comparing Generic to Brand Name Drugs: A Methodological Systematic Review

BACKGROUND: Generic drugs are used by millions of patients for economic reasons, so their evaluation must be highly transparent. OBJECTIVE: To assess the quality of reporting of bioequivalence trials comparing generic to brand-name drugs. METHODOLOGY/PRINCIPAL FINDINGS: PubMed was searched for reports of bioequivalence trials comparing generic to brand-name drugs between January 2005 and December 2008. Articles were included if the aim of the study was to assess the bioequivalency of generic and brand-name drugs. We excluded case studies, pharmaco-economic evaluations, and validation dosage assays of drugs. We evaluated whether important information about funding, methodology, location of trials, and participants were reported. We also assessed whether the criteria required by the Food and Drug Administration (FDA) and the European Medicine Agency (EMA) to conclude bioequivalence were reported and that the conclusions were in agreement with the results. We identified 134 potentially relevant articles but eliminated 55 because the brand-name or generic drug status of the reference drug was unknown. Thus, we evaluated 79 articles. The funding source and location of the trial were reported in 41% and 56% of articles, respectively. The type of statistical analysis was reported in 94% of articles, but the methods to generate the randomization sequence and to conceal allocation were reported in only 15% and 5%, respectively. In total, 65 articles of single-dose trials (89%) concluded bioequivalence. Of these, 20 (31%) did not report the 3 criteria within the limits required by the FDA and 11 (17%) did not report the 2 criteria within the limits required by the EMA. CONCLUSIONS/SIGNIFICANCE: Important information to judge the validity and relevance of results are frequently missing in published reports of trials assessing generic drugs. The quality of reporting of such trials is in need of improvement

Applicability and generalisability of the results of systematic reviews to public health practice and policy: a systematic review

<p>Abstract</p> <p>Background</p> <p>The purpose of the study was to evaluate systematic reviews of research into two public health priorities, tobacco consumption and HIV infection, in terms of the reporting of data related to the applicability of trial results (i.e., whether the results of a trial can be reasonably applied or generalized to a definable group of patients in a particular setting in routine practice, also called external validity or generalisability).</p> <p>Methods</p> <p>All systematic reviews of interventions aimed at reducing or stopping tobacco use and treating or preventing HIV infection published in the Cochrane database of systematic reviews and in journals indexed in MEDLINE between January 1997 and December 2007 were selected. We used a standardized data abstraction form to extract data related to applicability in terms of the context of the trial, (country, centres, settings), participants (recruitment, inclusion and exclusion criteria, baseline characteristics of participants such as age, sex, ethnicity, coexisting diseases or co-morbidities, and socioeconomic status), treatment (duration, intensity/dose of treatment, timing and delivery format), and the outcomes assessment from selected reviews.</p> <p>Results</p> <p>A total of 98 systematic reviews were selected (57 Cochrane reviews and 41 non-Cochrane reviews); 49 evaluated interventions aimed at reducing or stopping tobacco use and 49 treating or preventing HIV infection. The setting of the individual studies was reported in 45 (46%) of the systematic reviews, the number of centres in 21 (21%), and the country where the trial took place in 62 (63%). Inclusion and exclusion criteria of the included studies were reported in 16 (16%) and 13 (13%) of the reviews, respectively. Baseline characteristics of participants in the included studies were described in 59 (60%) of the reviews. These characteristics concerned age in about half of the reviews, sex in 46 (47%), and ethnicity in 9 (9%).</p> <p>Applicability of results was discussed in 13 (13%) of the systematic reviews. The reporting was better in systematic reviews by the Cochrane Collaboration than by non-Cochrane groups.</p> <p>Conclusions</p> <p>Our study highlighted the lack of consideration of applicability of results in systematic reviews of research into 2 public health priorities: tobacco consumption and HIV infection.</p

Dechartres_Comparison_of_Estimates_between

This excel file includes all relevant trial-level variables to replicate the meta-epidemiological analysis for the article " Comparison of Estimates between Cohort and Case-control studies in Meta-analyses of Therapeutic Interventions: A Meta-epidemiological Study"   Variable coding nMA = meta-analysis ID studyID = number of study ID author = first author last name date = year of publication design = [0] prospective nonrandomized study (all subjects are recruited and evaluated prospectively, but the control arm is not created through randomization) [1] retrospective cohort study (subjects are evaluated retrospectively and study arms are concurrent [without matching]) [2] historical control study (uses retrospective, nonconcurrent controls) [3] case-control study (compared groups are defined on the basis of the outcome and/or matching is used) [4] other or not specified design funding = [0] public, [1] private, [2] both, [3] unreported, [4] unclear center = [0] single center, [1]  multicenter, [2] unreported propens = propensity score analysis conducted [0] with matching, [1] with adjustment, [2] with weighting, [3] unreported adjust = confounding variables were adjusted for in analysis [0] yes, [1] no, [2] unreported ana_exp = number of participants analyzed in experimental group  ana_ctl = number of participants analyzed in control group  ana_both = number of participants analyzed in both groups out_exp = number of participants with outcome in experimental group out_ctl = number of participants with outcome in control group out_both = number of participants with outcome in both groups result = were the results reported as [OR], [RR], [HR], or unreported [.] unad_CI = unadjusted 95% confidence interval for results adj_CI = adjusted 95% confidence interval for results unad_val = unadjusted value for results adj_val = adjusted value for results logestcrude=log estimate for the crude analysis selogestcrude=standard error of the log estimate for the crude analysis logestadj= log estimate for the adjusted analysis selogestadj=standard error of the log estimate for the adjusted analysis logest=log estimate (adjusted if adjusted analyses, crude if no adjusted analysis) selogest= corresponding standard error casecontrol= 1=case control study; 0=cohort study pharmaco= 1=pharmacological intervention, 0=non-pharmacological intervention      </p

Evaluation des caractéristiques des essais associées à l'effet traitement dans les méta-analyses

Les méta-analyses sont devenues des outils indispensables pour synthétiser l'ensemble des connaissances disponibles. Néanmoins, si les résultats des études sont biaises, la méta-analyse risque d'être biaisée. Les études méta-épidémiologiques permettent de comparer l'effet traitement entre les essais avec et sans une caractéristique d'intérêt dans des échantillons de méta-analyses. Elles ont permis d'étudier l'influence sur l'effet traitement de caractéristiques associées à la validité interne. En utilisant une approche méta-épidémiologique, nous avons évalué l'influence d'autres caractéristiques des essais sur l'effet traitement dans les méta-analyses. Nous avons montré que l'effet traitement était plus important dans les essais monocentriques que dans les essais multicentriques. Puis, nous avons évalué l'influence de l'effectif de l'essai sur l'effet traitement au sein des méta-analyses. Nous avons trouvé que non seulement les petits essais mais également les essais de taille modérée montraient un effet traitement plus important que les essais les plus grands dans une méta-analyse. Ces travaux nous ont amenés à réfléchir à la meilleure estimation de l'effet traitement dans une méta-analyse. Nous avons comparé l'influence de plusieurs stratégie^ d'analyse sur l'effet traitement : la méta-analyse de tous les essais, la méta-analyse restreinte aux essais à faible risque de biais, la méta-analyse restreinte aux essais les plus larges, l'essai le plus précis. Les conclusions d'un quart des méta-analyses montrant un effet bénéfique du traitement expérimental quand tous les essais étaient inclus étaient contradictoires avec le résultat de l'une des stratégies alternatives d'analyse.PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Incapacités des porteurs de prothèses de hanche ou de genou (résultats de l'enquête nationale "Handicap, incapacités, dépendance")

Décrire les incapacités des porteurs de prothèse de hanche et de genou. L échantillon (16945 personnes) interrogé en 1999 et en 2001 comprenait 527 personnes avec une prothèse de hanche et 202 avec une prothèse de genou. Les personnes avec une prothèse de hanche rapportaient plus de difficultés que la population générale pour se pencher (OR=4.5, 95% CI : 3.1, 6.6), monter les escaliers (OR=2.2, 95% CI : 1.5, 3.1), marcher plus de 300 mètres (OR=1.6, 95% CI : 1.03, 2.6), s habiller (OR=2.9, 95% CI : 2.1, 4.2). Les porteurs de prothèse de genou rapportaient plus de difficultés que la population générale pour les activités liées à la mobilité. Pour les 2 types de prothèses, l évolution des incapacités était similaire à la population générale. Ces résultats pourraient permettre d adapter la prise en charge post-opératoire et de mieux informer les patients.ST QUENTIN EN YVELINES-BU (782972101) / SudocSudocFranceF

Re: Cardiotoxicity of immune checkpoint inhibitors: A systematic review and meta-analysis of randomised clinical trials

International audienc