FDA and NIH Don’t Always Enforce Clinical Trial Transparency Regulations

Recently, Science magazine reviewed more than 4,700 clinical trials whose results should have been posted on the National Institutes of Health (NIH) website under a 2017 rule enacted by the NIH and the Food and Drug Administration (FDA). The 2017 rule enacted a “final rule” to clarify expectations and penalties for failing to disclose trial results in a 2007 law that made posting mandatory for many trials in a federal database. According to Science, despite the rule taking effect two years ago, on January 18, 2018, many trial sponsors ignore the requirement and federal officials do little to nothing to enforce the law.

According to the study, reporting rates by most large pharmaceutical companies and universities has improved, but performance by other trial sponsors – including the NIH! – was flat. Those sponsors are required to input results and other data within one year of completing a trial. However, Science found that of 184 sponsor organizations with at least five trials due as of September 25, 2019, 30 companies/universities/medical centers never met any deadlines. In fact, those “habitual violators” failed to report any results for 67% of their trials and averaged a 268-day delay for those and all trials that missed their deadlines.

Notably, the violations can be found in trials in most fields of medicine and can lead to patients not having access to vital information. Science notes that, 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.

Science notes that none of the institutions disputed the findings of this investigation when contacted for comment. In the nearly 5000 trials Science reviewed, sponsors ran afoul of the reporting law more than 55% of the time. And that doesn’t include the hundreds of cases where the sponsors got credit for reporting trial results, but the results have yet to be publicly posted because of quality lapses flagged by ClinicalTrials.gov staff.

While many scientists who conduct the clinical trials, as well as the trial sponsors/funders, have downplayed concerns about late and missing results in ClinicalTrials.gov, the missing information has the potential to help patients suffering as each month there are doctors, researchers, and potential trial participants who rely on the site for healthcare.

Deborah Zarin, a physician at Brigham and Women’s Hospital and Harvard and former head of ClinicalTrials.gov, says the Science findings show failures of the research culture, FDA, and NIH. “If this was a priority for the leadership of NIH, then they could ensure that high-quality, timely reporting happened all of the time,” says Zarin, an NIH-paid research consultant for the database. “You can set up processes so trial reporting is an expectation. You can’t pass ‘go’ and collect $200 until this is done.”

However, based on comments reported by Science, this is not a priority for either agency.

Lyric Jorgenson, NIH deputy director for science policy, says her agency has been “trying to change the culture of how clinical trial results are reported and disseminated; not so much on the ‘aha, we caught you,’ as much as getting people to understand the value, and making it as easy as possible to share and disseminate results.”

Patrick McNeilly, an official at the FDA who handles trial enforcement matters, recently told an industry conference session on ClinicalTrials.gov that “FDA has limited resources, and we encourage voluntary compliance.” He said the agency also reviews reporting of information on ClinicalTrials.gov as part of inspections of trial sites, or when it receives complaints.

It also doesn’t help that the law has been around since 2007, and has never really been enforced, nor have there ever really been any severe punishments for not conforming. According to Science, “until 2015, even the most active investigators at clinical research institutions treated the law more as a suggestion.” Then, in 2016, NIH and FDA rolled out the final rule with FDA Commissioner Robert Califf saying it would be “pretty hard to hide that you are doing a clinical trial or hide the result” and that the FDA would finally begin to enforce the $10,000 daily penalty for noncompliance permitted under the law (recently, that amount rose to $12,000). NIH Director Francis Collins agreed that enforcement would begin, promising that NIH would publicly flag reporting violations directly on the website.

However, as noted by Science, three years later, TrialsTracker estimates that FDA could have collected more than $6 billion in ClinicalTrials.gov penalties so far. The agency did not demand any money in fines. 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.

This is unlikely to become a priority for either agency in the near future. However, should it become a louder issue, it is likely that the FDA and NIH may finally begin to crack down.