Not Reporting Results of a Clinical Trial Is Academic Misconduct

Failure to report the results of clinical trials threatens the public's trust in research and the integrity of the medical literature, and should be considered academic misconduct at the individual and institutional levels. According to the ethical principles for research outlined in the Declaration of Helsinki, researchers have a duty to make publicly available the results of their research on human subjects and are accountable for the completeness and accuracy of their reports (1). When participants volunteer to take part in clinical trials, and expose themselves to interventions with unknown safety and efficacy profiles, they have a tacit assumption, based on trust, that the evidence generated will inform clinical science (2). Health care providers and medical societies, who are responsible for evaluating and synthesizing evidence and filling the gap between research and practice, need for investigators to fully report their results in a timely manner. The utility of the diligent search for truth in the medical literature depends on its completeness. However, when research findings are not consistently disseminated, the literature provides a skewed view of the science, which may bias reviews of the evidence. During the past 2 decades, efforts have been increasing to promote the reporting of clinical trial results. After the creation of ClinicalTrials.gov, a public registration database, the United States moved to establish consequences of not reporting clinical trial results. In particular, the U.S. Food and Drug Administration Amendments Act (FDAAA) of 2007 created legal requirements for certain intervention studies of FDA-regulated products to report results to the public within 12 months of study completion or 30 days of FDA approval, and established penalties, including fines and potential withholding of grant funding, for investigators or sponsors who do not report results (3). Although the FDA has the authority to issue fines of up to $10000 per day against clinical trial sponsors not posting results, no such fines have been levied. Since 18 January 2017, the Final Rule, the goal of which is to improve compliance and clarify uncertainties about the types of clinical trials subject to results reporting requirements, has been in effect (3). However, previous violations are forgiven under the rule. As of this writing, according to FDAAA TrialsTracker (http://fdaaa.trialstracker.net), a live tool that tracks FDAAA compliance and promotes trial transparency, the U.S. government could already have imposed more than $2.8 billion in fines for trials due after January 2018. In 2016, the National Institutes of Health (NIH) issued a complementary policy requiring that investigators report clinical trial results, although it has not yet announced the penalties. Overall, the effectiveness of these policies is unclear, and they do not cover all trials. Studies provide consistent evidence of inadequate reporting and publication of clinical trials. For instance, before the FDAAA, fewer than half of registered and completed trials were published (4). Even among NIH-funded trials registered at ClinicalTrials.gov and completed before 31 December 2008, fewer than half were published within 30 months of completion (5). Similar delays exist across trials supported by all funding types (6), and evidence suggests that substantial variation exists among academic centers, with results reporting on ClinicalTrials.gov (as of 27 September 2013) or publication (before July 2014) ranging from 16% to 55% within 24 months of study completion for trials completed between October 2007 and September 2010 (7). A look at large trials also reveals a disturbing reporting rate. Jones and colleagues (8) evaluated how often trials completed before 2009 with at least 500 participants were published or had results reported on ClinicalTrials.gov. They found that approximately one fourth did not post results and were not published a median of 60 months after trial completion. However, evidence suggests that progress has been made since the FDAAA was implemented: The vast majority of trials (90%) supporting FDA approval of new drugs for cardiovascular disease and diabetes have reported their results (9). The new study by Tatsioni and colleagues (10), which focuses on the reporting characteristics of large, registered, randomized controlled trials with long-unreported or unpublished results, builds upon the findings of Jones and colleagues and underscores growing concerns that reporting of clinical trial results does not meet legal and ethical standards. The authors identified the 500 largest clinical trials without reported results or publications registered on ClinicalTrials.gov. They found that these trials, which were unreported for 4 or more years after completion and had enrollments ranging from 511 to 11000 participants, were unlikely ever to be published or to report results on ClinicalTrials.gov. Several potential approaches may be taken to ensure that clinical trial results become publicly available. First and foremost, nonreporting should be considered academic misconduct. Institutions should suspend investigators who do not report results within a year of finishing a trial, unless extenuating circumstances exist that impede reporting. These institutions also should consider lack of reporting in the academic promotion process. Funding agencies, such as the NIH, should withhold support from researchers who do not report results. Investigators who have completed clinical trials without reported results should be prohibited from applying for additional grants and current grants should be suspended. An even stronger incentive would be to hold institutions accountable for reporting results. Lastly, the public must be made aware of the ongoing gaps in the reporting of clinical trial results by dissemination of a list of completed clinical trials without reported results. Together, these efforts may ensure that all stakeholders in clinical research fulfill their ethical obligations to trial participants. The conduct of research in humans comes with inviolable responsibilities, including the commitment to share what has been learned. No reason exists for the topline results of a clinical trial not to be made public. Failure to report is detrimental to the scientific process. When trial results are not publicly available for years after study completion, patients, institutional review boards, clinicians, researchers, and the public must rely on incomplete evidence, which may lead to misconceptions about the efficacy and safety of interventions. The time has arrived to address this threat to trust and science.