Fewer than half of US clinical trials comply with law on reporting results

Man standing at flipboard with graphs and charts on it to show Fewer than half of US clinical trials comply with law on reporting results

Research into reporting of US clinical trial results finds that less than half (41%) are reported promptly onto the US trial registry, and one in three trials remain unreported. This is according to the first comprehensive study of compliance since new US regulations came into effect in January 2017.

The findings, published in The Lancet, indicate that trials with non-industry sponsors (such as universities, hospitals, and governments) are far more likely to breach the rules than trials sponsored by industry – with US Government sponsored trials least likely to post results on time at the world’s largest clinical trial registry, ClinicalTrials.gov.

It has been known for several decades that the results of clinical trials are often not fully reported. To improve public disclosure, and limit selective publishing of results, the US Food and Drug Administration Amendment Act (FDAAA) of 2007 requires sponsors of most US-regulated clinical trials to register and report results on ClinicalTrials.gov within 12 months of primary completion, irrespective of whether the results are positive or negative.

A subsequent ‘Final Rule’ to the Act took effect in January 2017. This introduced clearer reporting requirements including fines of up to US$10,000 a day for non-compliance (now US$12,103 inflation adjusted). National Institute of Health (NIH) leaders said that the Final Rule would result in “rapid increases” in the percentage of trials registered and shared on the US registry.

The authors say that the high rates of non-compliance found in the new study likely reflect the lack of enforcement by regulators, and they call for trial sponsors to be held to account by the FDA.

“Patients and clinicians cannot make informed choices about which treatments work best when trial results are routinely withheld. Clinical trials are not abstract research projects: they are large, expensive, practical evaluations that directly impact on patient care by informing treatment guidelines and evidence reviews.” says Dr Ben Goldacre from Oxford University, UK, who led the research.

He continues: “Sponsors are breaching their legal obligations, but also their ethical obligations to the patients who generously participate in clinical trials. Our study has identified over 2400 trials breaching the rules, but to our knowledge the FDA has never levied a single fine or other enforcement action, despite all the levers available to them. Compliance will only improve when action is taken.”

Non-reporting of clinical trial results has been well-documented since the 1980s, especially those trials finding no evidence of effectiveness for the treatment being tested. However, failing to disclose trial results threatens the integrity of the evidence base of all clinical medicine, breaches participants’ trust, and wastes valuable research resources.

The first trials covered by the Final Rule were due to report in January 2018. To investigate the extent of compliance with these new reporting requirements, the researchers examined all 4209 trials registered on ClinicalTrials.gov that were legally required to report results between March 2018 and September 2019. They also assessed trends in compliance, factors associated with compliance, and ranked individual sponsors according to their level of compliance.

Of the completed trials included in the study, around half (52%; 2178) had non-industry sponsors, most involved a drug intervention (71%; 2968), and most were solely conducted in the USA (71%; 3000).

Analyses found that only 41% (1722/4209) of completed clinical trials reported results within the one year legal deadline, whilst 36% (1523/4209) still had not been reported by 16 September 2019. Moreover, progress has stalled – the proportion of compliant trials has remained stable since July 2018. The median delay from completion to submitting results was 424 days – 59 days higher than the legal reporting requirement of one year.

Trials with an industry sponsor were much more likely to comply with the law than those with a non-industry or US Government sponsor (50% vs 34% vs 31% trials submitted in time). Better performance was also seen among sponsors with more experience of running large numbers of trials, when compared with those who have only ever run a very small number of projects (66% vs 21% trials submitted in time). Encouragingly, the authors say, this suggests that “research experience and robust internal governance processes can contribute to improved performance.”

Further analyses estimate that had the law been strictly enforced, over US$4 billion in fines could have been collected up to the end of September 2019.

The authors note that they only examine the availability of results on ClinicalTrials.gov as required by the law, and not the quality of the results or their availability elsewhere.

In September 2018, the UK Commons Select Committee called for clinical trials transparency expressing concern that nearly half of clinical trials fail to publish their results.