A new study has found that 1,523 clinical trials of medicines and medical devices have failed to make their results public on the United States database due to the FDA’s failure to enforce a key medical transparency law.
There is overwhelming evidence that hidden clinical trial results harm patients and undermine public health.
Nonetheless, the team of researchers from the University of Oxford found that:
36% of trials subject to the law were missing results
23% had posted their results late
Only 41% of trials reported results on the government-run Clinicaltrials.gov registry within one year.
Among the largest trial sponsors, only two – AstraZeneca and Novartis – fully and consistently complied with the law. Overall, industry sponsors were significantly more likely to be compliant than universities and U.S. government agencies, and sponsors running large numbers of trials were significantly more likely to be compliant than smaller sponsors.
Alarmingly, the study team found that compliance with the law is not increasing over time. “Currently, there is no sign of improvement”, they wrote, “the proportion of compliant trials has plateaued at around 40% since July, 2018.”
The chart below shows the performance of the largest clinical trial sponsors in the United States, measured by the percentage of their trials with results available. (The chart does not take into account whether or not these results were posted on time.)
The authors of the study commented that:
“Patients and clinicians cannot make informed choices when the results of clinical trials are routinely withheld. The importance of addressing the bias from non-publication of clinical trials has been emphasised since at least the 1980s. It is therefore disappointing to note that 40 years later the community has only progressed to legislation being passed and then largely ignored… To our knowledge, there have been no fines imposed by the FDA to date.”
“In our view, compliance with both EU and US legislation on trial reporting will only improve when regulators routinely impose fines and other sanctions on sponsors who breach their ethical and legal obligation to report trial results appropriately.”
A separate investigation by Charles Piller published a few days previously found that:
"[O]f 184 sponsor organizations with at least five trials due as of 25 September 2019, 30 companies, universities, or medical centers never met a single deadline. As of that date, those habitual violators had failed to report any results for 67% of their trials and averaged 268 days late for those and all trials that missed their deadlines. They included such eminent institutions as the Harvard University–affiliated Boston Children’s Hospital, the University of Minnesota, and Baylor College of Medicine—all among the top 50 recipients of NIH grants in 2019."
"For example, in one long-overdue trial, researchers compared the efficacy of different chemotherapy regimens in 200 patients with advanced lymphoma; another—nearly 2 years late—tests immunotherapy against conventional chemotherapy in about 600 people with late-stage lung cancer."
"FDA now says it won’t brandish its big stick—penalties of up to $12,103 a day for failing to report a trial’s results—until after the agency issues further “guidance” on how it will exercise that power. It has not set a date. NIH said at a 2016 briefing on the final rule that it would cut off grants to those who ignore the trial reporting requirements, as authorized in the 2007 law, but so far has not done so."
"FDA could have collected more than $6 billion in ClinicalTrials.gov penalties so far. The agency has yet to demand a single dollar. And despite more than 2600 trials for which results are overdue or were filed late, NIH has yet to withhold a single grant as a result or post a single violation notice on ClinicalTrials.gov."
An ongoing lawsuit is seeking to force the Food and Drug Administration to finally impose fines.
U.S. government agencies had the lowest compliance rate of any type of sponsor. According to the Oxford study, over 68% of trials run by government agencies violated the law. “The fact that the US Government cannot [sic] comply with its own laws is especially concerning,” the authors of the study point out.
In contrast to the European Clinical Trial Regulation, which required only drug trials to report their results, the American FDA Amendments Act also covers many trials of medical devices. A quarter of the trials in the study cohort were device trials.
According to a 2018 World Health Organisation document:
“Legislation or supporting regulations… [should] require all clinical trials to be registered… prior to commencing the trial, public disclosure of results of any newly conducted clinical trial, public disclosure of unreported results for clinical trials conducted in the past, [and] sanctions if a clinical trial is not registered and / or results are not reported.”
The study by Nicholas DeVito et al. was published in the Lancet on 17 January 2020.