Conclusions Compliance with the European Commission requirement for all trials to post results on to the EUCTR within 12 months of completion has been poor, with half of all trials non-compliant. EU registry data commonly contain inconsistencies that might prevent even regulators assessing compliance. Accessible and timely information on the compliance status of each individual trial and sponsor may help to improve reporting rates.

Results Of 7274 trials where results were due, 49.5% (95% confidence interval 48.4% to 50.7%) reported results. Trials with a commercial sponsor were substantially more likely to post results than those with a non-commercial sponsor (68.1% v 11.0%, adjusted odds ratio 23.2, 95% confidence interval 19.2 to 28.2); as were trials by a sponsor who conducted a large number of trials (77.9% v 18.4%, adjusted odds ratio 18.4, 15.3 to 22.1). More recent trials were more likely to report results (per year odds ratio 1.05, 95% confidence interval 1.03 to 1.07). Extensive evidence was found of errors, omissions, and contradictory entries in EUCTR data that prevented ascertainment of compliance for some trials.

Introduction

The results of clinical trials are used by clinicians, patients, and policy makers to make informed choices about the benefits and safety of interventions. Sharing the methods and results of all trials has therefore long been recognised as an ethical and scientific imperative.123 More recently, institutions such as the World Health Organization, European Commission, and US Food and Drug Administration have called for the disclosure of results.456 However, there is extensive and longstanding evidence that the methods and results of completed clinical trials are commonly left unreported. A 2014 systematic review identified 22 cohorts of studies included in trial registries: half were not published in a journal (54.2%, 95% confidence interval 42.0% to 65.9%), 17 that were following up cohorts of trials approved by ethics committees yielded similar rates of unpublished results, and studies with statistically significant results were more likely to be published (odds ratio 2.8, 95% confidence interval 2.2 to 3.5).7 These findings are consistent with a previous review.8

In the US, the FDA Amendments Act 2007 (FDAAA) requires sponsors to post results on to ClinicalTrials.gov itself, rather than be published in a journal, within 12 months of completion for certain categories of trial.6 The two cohort studies published to date on this topic report compliance rates of only one trial in five.910 FDAAA, however, has complexities and limitations. Importantly, not all trials on ClinicalTrials.gov are covered by the requirement to report results on to the register—only those meeting certain criteria; and there is no data field on ClinicalTrials.gov to easily identify the subset of trials required to report results. Furthermore, although a list of trials with certificates of exemption from reporting can be obtained and used as a proxy to help identify those trials not covered by the requirement to report results, in practice many sponsors have only requested these certificates when seeking prospective clarity from the regulator on individual trials where exemption may be contentious; therefore, many exempt trials have no such certification. In addition, the “final rule” that gives further detail on which trials are covered and sets out the process for addressing breaches, was not published until 2016; and the first few trials to be legally covered by this rule have only recently become due to report results.11 In addition, the final rule changed the number of trials covered by the act: trials on unapproved products completing before January 2017 are no longer required to post results after the product is approved.

In comparison, the European Commission is moving towards more straightforward transparency rules. Any trial of any medicinal product conducted since 2004 in an EU country has already been required to register on the European Union Clinical Trials Register (EUCTR), which is administered by the European Medicines Agency (EMA). Following the 2012 EC guideline 2012/c302/03, sponsors must ensure that all trials registered on EUCTR since 2004 disclose their results to the EMA within 12 months of trial completion; phase I trials are exempt unless they are denoted as being part of a paediatric investigation plan.12 These trial reports are posted publicly on to the EUCTR within 15 working days of receipt by the EMA and are required to include salient features such as results for all prespecified trial outcomes and statistical analyses, details of “serious” and “non-serious” adverse events, participants’ baseline characteristics, and protocol deviations, as well as discussion of design limitations and caveats.13 Following various delays in the EMA implementing the software platform for results posting, the final date for sponsors’ compliance was 21 December 2016.1415

We assessed compliance with the EU requirement to post results on to EUCTR for all trials on the registry, explored factors associated with non-compliance, identified the individual trial sponsors that are best at complying, and created a live online service, driven by regular updates of the EUCTR data, to give ongoing and regularly updated performance statistics for compliance.