This month is the third anniversary of the implementation of the new U.S. regulations that require clinical trials to report results within one year of completion, dubbed the Final Rule of the FDA Amendments Act -- but compliance remains poor, and is not improving, with U.S. government-sponsored trials most likely to breach.
Fewer than half (41%) of clinical trial results are reported promptly onto the U.S. trial registry, and one in three trials remain unreported, according to the first comprehensive study of compliance since new 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 government-sponsored trials least likely to post results on time at the world's largest clinical trial registry, ClinicalTrials.gov.
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WHAT'S THE IMPACT
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 U.S. Food and Drug Administration Amendment Act of 2007 requires sponsors of most U.S.-regulated clinical trials to register and report results on ClinicalTrials.gov within 12 months of primary completion, regardless 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 $10,000 a day for non-compliance (now $12,103, adjusted for inflation). National Institute of Health leaders said that the Final Rule would result in "rapid increases" in the percentage of trials registered and shared on the U.S. registry.
The authors said 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.
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. But failing to disclose trial results threatens the integrity of the evidence base of all clinical medicine, breaches participants' trust, and wastes valuable research resources.
WHAT ELSE YOU SHOULD KNOW
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 4,209 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%) had non-industry sponsors, most involved a drug intervention (71%), and most were solely conducted in the U.S. (71%).
Analyses found that only 41% of completed clinical trials reported results within the one year legal deadline, while 36% still had not been reported by September 16, 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 government sponsor. Better performance was also seen among sponsors with more experience running large numbers of trials, when compared with those who have only ever run a very small number of projects.
Encouragingly, the authors said, 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, more than $4 billion in fines could have been collected up to the end of September 2019.
THE LARGER TREND
A substantial proportion of pharmaceutical industry payments to authors of oncology clinical trials published in major scientific journals are not disclosed, 2018 research showed. The publications focused on clinical trials that tested new cancer drugs.
Previous studies have investigated funding disclosures among the authors of clinical practice guidelines. But this was the first study to examine financial conflict of interest in the publication of clinical trials that underpin FDA approval of new oncology drugs.