FDA Signals Tougher Stance on Required ClinicalTrials.Gov Postings

Kerry Dooley Young

May 20, 2021

The US Food and Drug Administration (FDA) signaled it may soon enforce a federal requirement that sponsors of certain trials provide data to the public via the ClinicalTrials.gov database.

The agency on April 27 warned Acceleron Pharma that it might face penalties of $10,000 per day if it did not meet a 30-day deadline to submit information from a 2017 study to the ClinicalTrials.Gov website. It is the first such enforcement threat from the FDA, which to this point has sought voluntary compliance.

The agency issued a statement on April 28 from acting FDA Commissioner Janet Woodcock, MD, about stepped-up enforcement. Woodcock also drew attention to the issue on social media.

"The FDA takes its role in enforcing the http://ClinicalTrials.gov registration and results information submission requirements extremely seriously," she said in a tweet through her @DrWoodcockFDA handle. "We will continue to encourage voluntary compliance with these requirements and take appropriate actions when necessary."

Advocates who promote greater transparency of study results welcomed the FDA's action. But they also said they will be watching to see what the agency does beyond its announcement in its enforcement letter to Acceleron.

"This did seem designed to get headlines that say, 'We're doing something,' and if in fact this is the beginning of a program of enforcement, then that will be great," Deborah A. Zarin, MD, who served as director of ClinicalTrials.gov from 2005 to 2018, told Medscape Medical News in an interview. (Zarin also has consulted for ClinicalTrials.gov.)

But the FDA's choice of a target for a first possible enforcement action puzzled Zarin and others who follow the issue of federal enforcement of data disclosure requirements.

The FDA selected a study of a drug that never reached the market and for which trial results have already been made public.

Acceleron released the topline negative results involving the drug candidate dalantercept in a 2017 press release, in which the company also said it would discontinue development of dalantercept. Further, in 2019, the full results of the study were published in the journal Cancer. There is a link to the Cancer article on the ClinicalTrials.gov webpage, but this does not fulfill the disclosure requirement.

Acceleron had received a gentler FDA warning in 2020 about its failure to post the data from this trial on ClinicalTrials.gov. Receipt of the more recent letter, which added the prospect of a financial penalty, may have triggered the desired response.

ClinicalTrials.gov, which is run by the National Institutes of Health, shows that results for the Acceleron study in question were submitted on April 28 and that an initial quality control review of those results was completed on May 6. Acceleron has since resubmitted the results. As of Wednesday morning, the FDA still needed to complete quality review, according to the ClinicalTrials.gov website.

In response to Medscape's inquiry about whether Acceleron will face penalties, the FDA's press office said in an email: "NIH conducts a limited quality control review of the clinical trial results information that Acceleron submitted. FDA also will assess the submitted results information to determine whether the noncompliance has been remedied."

However, the FDA did not provide Medscape with the requested details about why the agency selected Acceleron's unsuccessful dalantercept trial as the target of the first serious enforcement action.

Missing Results Not Uncommon

Acceleron's case is far from the only instance of missing study results. In April, the FDA said it had sent more than 40 of its gentler warnings, the pre-notices of noncompliance, regarding cases involving missing data.

Yet the number of studies listed on ClinicalTrials.gov for which data are missing appears to be much higher. The Evidence Based Medicine DataLab at the University of Oxford built a website for tracking these cases using methods the team explained in a January 2020 article in The Lancet.

This website is called the FDAAA Trials Tracker, named after the FDA Amendments Act 2007 (FDAAA) that mandated posting of studies of products likely to fall under the agency's jurisdiction, such as drugs and medical devices. As of Monday evening, FDAAA Trials Tracker's dashboard indicated that the disclosure mandate had been completed for only 7348 of 10,101 trials for which disclosures are required.

"Unclear Why This One Was Chosen"

Acceleron is not an obvious case for the FDA's choice of an initial enforcement action, said Zarin, who now is the program director for the Multi-Regional Clinical Trials Center of Brigham and Women's Hospital and Harvard University, Boston, Massachusetts.

"If you're going to pick one out of the thousands of out-of-compliance trials, it is unclear why this one was chosen," Zarin said. "I would like to see a more systematic, transparent approach to enforcement that would actually put all trial sponsors on notice that they need to comply."

The FDAAA Trials Tracker identified instances in which the ClinicalTrials.gov site says data are missing for studies involving products that received FDA approval and that are on the market or are undergoing testing.

"Continued Prompting From Outside Organizations"

Advocates who promote greater transparency of study results welcomed the FDA's April 28 announcement of plans for tougher enforcement. But they also said it has taken significant prodding to get the agency to police the ClinicalTrials.gov website.

The nonprofit Universities Allied for Essential Medicines (UAEM) North America said it has long been using the Freedom of Information Act (FOIA) to try to compel the FDA to provide information about its enforcement of disclosure rules. In March, the Technology Law and Policy Clinic of New York University filed an FOIA request on behalf of UAEM.

In a statement, UAEM called the FDA's April 27 notice to Acceleron "a hopeful sign that the agency will now take its responsibility to enforce these requirements for trial sponsors seriously ― and without continued prompting from outside organizations."

Concerns about hidden study results date to at least the 1980s, note Nicholas DeVito, MPH, and colleagues in a 2020 article published in The Lancet. DeVito and colleagues are at Oxford and work on the FDAAA Trials Tracker.

They note that it wasn't until 2017 that the US Department of Health and Human Services put into effect the regulations needed to carry out the 2007 mandate that allows the FDA to enforce reporting compliance. In their article in The Lancet, DeVito and colleagues write that it was "disappointing" that the disclosure legislation had been "passed and then largely ignored."

Kerry Dooley Young is a freelance journalist based in Washington, D.C. She earlier covered health policy and the federal budget for Congressional Quarterly/CQ Roll Call and the pharmaceutical industry and the Food and Drug Administration for Bloomberg. Follow her on Twitter at @kdooleyyoung.

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