Measuring clinical trial transparency: an empirical analysis of newly approved drugs and large pharmaceutical companies

Abstract

ObjectivesTo define a series of clinical trial transparency measures and apply them to large pharmaceutical and biotechnology companies and their 2014 FDA-approved drugs.DesignCross-sectional descriptive analysis of all clinical trials supporting 2014 Food and Drugs Administration (FDA)-approved new drug applications (NDAs) for novel drugs sponsored by large companies.Data sourcesData from over 45 sources, including Drugs@FDA.gov, ClinicalTrials.gov, corporate and international registries; PubMed, Google Scholar, EMBASE, corporate press releases, Securities and Exchange Commission (SEC) filings and personal communications with drug manufacturers.Outcome measuresTrial registration, results reporting, clinical study report (CSR) synopsis sharing, biomedical journal publication, and FDA Amendments Acts (FDAAA) compliance, analysed on the drug level.ResultsThe FDA approved 19 novel new drugs, sponsored by 11 large companies, involving 553 trials, in 2014. We analysed 505 relevant trials. Per drug, a median of 100% (IQR 86%–100%) of trials in patients were registered, 71% (IQR 57%–100%) reported results or shared a CSR synopsis, 80% (70%–100%) were published and 96% (80%–100%) were publicly available in some form by 13 months after FDA approval. Disclosure rates were lower at FDA approval (65%) and improved significantly by 6 months post FDA approval. Per drug, a median of 100% (IQR 75%–100%) of FDAAA-applicable trials were compliant. Half of reviewed drugs had publicly disclosed results for all trials in patients in our sample. One trial was uniquely registered in a corporate registry, and not ClinicalTrials.gov; 0 trials were uniquely registered in international registries.ConclusionsAmong large pharmaceutical companies and new drugs, clinical trial transparency is high based on several standards, although opportunities for improvement remain. Transparency is markedly higher for trials in patients than among all trials supporting drug approval, including trials in healthy volunteers. Ongoing efforts to publicly track companies’ transparency records and recognise exemplary companies may encourage further progress.

Postmarket studies required by the US Food and Drug Administration for new drugs and biologics approved between 2009 and 2012: cross sectional analysis

“…Our study also found that about three quarters of postmarket clinical trials were registered on ClinicalTrials.gov, which is less than previously reported registration rates for clinical trials supporting New Drug Applications 2226. Our finding that about three quarters of the postmarket clinical trials had either reported results or were published is consistent with a recent study by the FDA, which showed that nearly two thirds of postmarket drug interventional clinical trials and other trials designated as “fulfilled” were published in either the scientific literature or on the ClinicalTrials.gov website 16.…”

“…Our findings suggest that clearer and more consistent regulatory standards and FDA oversight might be necessary to ensure universal registration and result reporting on ClinicalTrials.gov for applicable postmarket studies 2226. In particular, the FDA might need to provide additional clarity to sponsors about which trials need to be registered and when results need to be reported.…”

“…Similar reporting standards could be adopted for drug and biologic postmarketing requirements. These, and other suggestions to promote transparency and improve the oversight of postmarketing requirements,91322 may be key to ensuring the successful translation of results from postmarket studies into clinical practice.…”

“…Lastly, our sample of clinical trials could contain studies that were not “applicable clinical trials” according to the FDAAA. The FDAAA states that a trial must have a drug manufacturer in the USA for export or be conducted in the USA to be covered 14152122. We could not verify these characteristics because this information is difficult to determine on the basis of public information on postmarketing requirements.…”

“…One requirement for FDAAA coverage requires manufacturing data. In particular, the FDAAA states that a trial must have a drug manufacturer in the USA for export or be conducted in the USA in order to be covered 14152122. This information is difficult to determine with public sources.…”