Dataset Information

FDAAA legislation is working, but methodological flaws undermine the reliability of clinical trials: a cross-sectional study.

ABSTRACT: The relationship between clinical research and the pharmaceutical industry has placed clinical trials in jeopardy. According to the medical literature, more than 70% of clinical trials are industry-funded. Many of these trials remain unpublished or have methodological flaws that distort their results. In 2007, it was signed into law the Food and Drug Administration Amendments Act (FDAAA), aiming to provide publicly access to a broad range of biomedical information to be made available on the platform ClinicalTrials (available at https://www.clinicaltrials.gov). We accessed ClinicalTrials.gov and evaluated the compliance of researchers and sponsors with the FDAAA. Our sample comprised 243 protocols of clinical trials of biological monoclonal antibodies (mAb) adalimumab, bevacizumab, infliximab, rituximab, and trastuzumab. We demonstrate that the new legislation has positively affected transparency patterns in clinical research, through a significant increase in publication and online reporting rates after the enactment of the law. Poorly designed trials, however, remain a challenge to be overcome, due to a high prevalence of methodological flaws. These flaws affect the quality of clinical information available, breaching ethical duties of sponsors and researchers, as well as the human right to health.

SUBMITTER: Marin Dos Santos DH

PROVIDER: S-EPMC4485238 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

FDAAA legislation is working, but methodological flaws undermine the reliability of clinical trials: a cross-sectional study.

Marin Dos Santos Douglas H DH Atallah Álvaro N ÁN

PeerJ 20150625

The relationship between clinical research and the pharmaceutical industry has placed clinical trials in jeopardy. According to the medical literature, more than 70% of clinical trials are industry-funded. Many of these trials remain unpublished or have methodological flaws that distort their results. In 2007, it was signed into law the Food and Drug Administration Amendments Act (FDAAA), aiming to provide publicly access to a broad range of biomedical information to be made available on the pla ...[more]

PMID: 26131374

Similar Datasets

Project description:IntroductionTreatment options and decisions are often based on the results of clinical trials. We have evaluated the public availability of results from completed, registered phase III clinical trials on diabetic nephropathy and current treatment options.MethodsThis was a cross-sectional analysis in which STrengthening the Reporting of OBservational studies in Epidemiology criteria were applied for design and analysis. In June 2017, 34 completed phase III clinical trials on diabetic nephropathy in the ClinicalTrials. gov registry were identified and matched to publications in the ClinicalTrials.gov registry and to those in the PubMed and Google Scholar databases. If no publication was identified, the principal investigator was contacted. The ratio of published and non-published studies was calculated. Various parameters, including study design, drugs, and comparators provided, were analyzed.ResultsDrugs/supplements belonged to 26 different categories of medications, with the main ones being angiotensin-converting enzyme inhibitors, angiotensin-II receptors blockers, and dipeptidyl-peptidase-4-inhibitors. Among the trials completed before 2016 (n = 32), 22 (69%) were published, and ten (31%) remained unpublished. Thus, data on 11 different interventions and more than 1000 patients remained undisclosed. Mean time to publication was 26.5 months, which is longer than the time constrictions imposed by the U.S. Food and Drug Administration Amendments Act. Most trials only showed weak effects on micro- and macroalbuminuria, with an absolute risk reduction of 1.0 and 0.3%, respectively, and the number needed to treat varied between 91 and 333, without any relevant effect on end-stage-renal disease by intensive glucose-lowering treatment. Comparison of the results, however, was difficult since study design, interventions, and the renal outcome parameters vary greatly between the studies.ConclusionDespite the financial and human resources involved and the relevance for therapeutic guidelines and clinical decisions, about one-third of phase III clinical trials on diabetic nephropathy remain unpublished. Interventions used in published trials showed a low efficacy on renal outcome.FundingDeutsche Forschungsgemeinschaft (DFG): SFB 1118.

Project description:ObjectiveTo identify the availability of results for trials registered on the European Union Clinical Trials Register (EUCTR) compared with other dissemination routes to understand its value as a results repository.DesignCross sectional audit study.SettingEUCTR protocols and results sections, data extracted 1-3 December 2020.PopulationRandom sample of 500 trials registered on EUCTR with a completion date of more than two years from the beginning of searches (ie, 1 December 2018).Main outcome measuresProportion of trials with results across the examined dissemination routes (EUCTR, ClinicalTrials.gov, ISRCTN registry, and journal publications), and for each dissemination route individually. Prespecified secondary outcomes were number and proportion of unique results, and the timing of results, for each dissemination route.ResultsIn the sample of 500 trials, availability of results on EUCTR (53.2%, 95% confidence interval 48.8% to 57.6%) was similar to the peer reviewed literature (58.6%, 54.3% to 62.9%) and exceeded the proportion of results available on other registries with matched records. Among the 383 trials with any results, 55 (14.4%, 10.9% to 17.9%) were only available on EUCTR. Also, after the launch of the EUCTR results database, median time to results was fastest on EUCTR (1142 days, 95% confidence interval 812 to 1492), comparable with journal publications (1226 days, 1074 to 1551), and exceeding ClinicalTrials.gov (3321 days, 1653 to undefined). For 117 trials (23.4%, 19.7% to 27.1%), however, results were published elsewhere but not submitted to the EUCTR registry, and no results were located in any dissemination route for 117 trials (23.4%, 19.7% to 27.1).ConclusionsEUCTR should be considered in results searches for systematic reviews and can help researchers and the public to access the results of clinical trials, unavailable elsewhere, in a timely way. Reporting requirements, such as the EU's, can help in avoiding research waste by ensuring results are reported. The registry's true value, however, is unrealised because of inadequate compliance with EU guidelines, and problems with data quality that complicate the routine use of the registry. As the EU transitions to a new registry, continuing to emphasise the importance of EUCTR and the provision of timely and complete data is critical. For the future, EUCTR will still hold important information from the past two decades of clinical research in Europe. With increased efforts from sponsors and regulators, the registry can continue to grow as a source of results of clinical trials, many of which might be unavailable from other dissemination routes.

Project description:BACKGROUND: Poor accrual is a significant barrier to the successful completion of oncology clinical trials; half of all phase 3 oncology trials close due to insufficient accrual. Timely access to accrual data fosters an understanding of successful trial design and can be used to inform the design of new clinical trials prospectively. Accrual statistics are available within research networks, such as the cancer cooperative groups, but comprehensive data reflecting the overall portfolio of cancer clinical trials are lacking. As a demonstration case, the purpose of this study was to quantify the public availability of accrual data across all recent renal cell carcinoma (RCC) trials. METHODS: The database for the Aggregate Analysis of ClinicalTrials.gov (AACT) summarizes all trials registered between October 2007 and September 2010. In total, 108 trials of pharmacologic therapy for RCC were included. Accrual data on these trials were gathered via ClinicalTrials.gov (CTG), a manual review of resulting publications, and online surveys sent to principle investigators or trial coordinators. RESULTS: In total, 26% (20 of 76) of trials listing a government, academic, or cooperative group (GAC) sponsor responded to the survey vs 0% (0 of 32) of those listing only industry sponsors. Across all methods, accrual data were available for only 40% (43 of 108) of trials, including 37% (28 of 76) of GAC trials and 47% (15 of 32) of industry trials. Moreover, 87% (66 of 76) of GAC trials were ongoing (open, actively recruiting, or of unknown status) vs 75% (24 of 32) of industry trials, while 9% (10 of 108) of trials were terminated or suspended. CONCLUSIONS: Despite extensive efforts (surveys, phone calls, CTG abstraction, publication searches), accurate accrual data remained inaccessible for 60% of the RCC trial cohort. While CTG reports trial results, ongoing accrual data are also critically needed. Poor access to accrual data will continue to limit attempts to develop a national summary of clinical trials metrics and to optimize the cancer clinical research portfolio.

Project description:ObjectiveTo assess risk of bias and to investigate methodological issues concerning the design, conduct and analysis of randomised controlled trials (RCTs) testing acupuncture for knee osteoarthritis (KOA).MethodsPubMed, EMBASE, Cochrane Central Register of Controlled Trials and four major Chinese databases were searched for RCTs that investigated the effect of acupuncture for KOA. The Cochrane tool was used to examine the risk of bias of eligible RCTs. Their methodological details were examined using a standardised and pilot-tested questionnaire of 48 items, together with the association between four predefined factors and important methodological quality indicators.ResultsA total of 248 RCTs were eligible, of which 39 (15.7%) used computer-generated randomisation sequence. Of the 31 (12.5%) trials that stated the allocation concealment, only one used central randomisation. Twenty-five (10.1%) trials mentioned that their acupuncture procedures were standardised, but only 18 (7.3%) specified how the standardisation was achieved. The great majority of trials (n=233, 94%) stated that blinding was in place, but 204 (87.6%) did not clarify who was blinded. Only 27 (10.9%) trials specified the primary outcome, for which 7 used intention-to-treat analysis. Only 17 (6.9%) trials included details on sample size calculation; none preplanned an interim analysis and associated stopping rule. In total, 46 (18.5%) trials explicitly stated that loss to follow-up occurred, but only 6 (2.4%) provided some information to deal with the issue. No trials prespecified, conducted or reported any subgroup or adjusted analysis for the primary outcome.ConclusionThe overall risk of bias was high among published RCTs testing acupuncture for KOA. Methodological limitations were present in many important aspects of design, conduct and analyses. These findings inform the development of evidence-based methodological guidance for future trials assessing the effect of acupuncture for KOA.

Project description:ObjectivesTo provide a detailed and current characterisation of funding of a representative sample clinical trials. We also aimed to develop guidance for standardised reporting of funding information.MethodsWe addressed the extent to which clinical trials published in 2015 in any of the 119 Core Clinical Journals included a statement on the funding source (eg, whether a not-for-profit organisation was supported by a private-for-profit organisation), type of funding, amount and role of funder. We used a stepwise approach to develop a guidance and an instrument for standardised reporting of funding information.ResultsOf 200 trials, 178 (89%) included a funding statement, of which 171 (96%) reported being funded. Funding statements in the 171 funded trials indicated the source in 100%, amount in 1% and roles of funders in 50%. The most frequent sources were governmental (58%) and private-for-profit (40%). Of 54 funding statements in which the source was a not-for-profit organisation, we found evidence of undisclosed support of those from private-for-profit organisation(s) in 26 (48%). The most frequently reported roles of funders in the 171 funded trials related to study design (42%) and data analysis, interpretation or management (41%). Of 139 randomised controlled trials (RCTs) addressing pharmacological or surgical interventions, 29 (21%) reported information on the supplier of the medication or device. The proposed guidance addresses both the funding information that RCTs should report and the reporting process. Attached to the guidance is a fillable PDF document for use as an instrument for standardised reporting of funding information.ConclusionAlthough the majority of RCTs report funding, there is considerable variability in the reporting of funding source, amount and roles of funders. A standardised approach to reporting of funding information would address these limitations. Future research should explore the implications of funding by not-for-profit organisations that are supported by for-profit organisations.

Dataset Information

FDAAA legislation is working, but methodological flaws undermine the reliability of clinical trials: a cross-sectional study.

Publications

FDAAA legislation is working, but methodological flaws undermine the reliability of clinical trials: a cross-sectional study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets