On April 27, 2021, the U.S. Food and Drug Administration (FDA) issued its first Notice of Noncompliance to a company for failing to submit required clinical trial summary results information to ClinicalTrials.gov. In particular, FDA said Acceleron Pharma, Inc. violated the Public Health Service Act and the Federal Food, Drug, and Cosmetic Act by failing to submit clinical trial results for its study of Dalantercept and Axitinib, even after the information had been previously requested by the agency. This violation notice portends greater FDA scrutiny of the requirements for clinical trial transparency and disclosure, in accordance with the agency's stated goal of more aggressively enforcing these requirements for disclosure through ClinicalTrials.gov.
Federal law requires that responsible parties (typically clinical trial sponsors) register their studies on ClinicalTrials.gov within 21 days after the first human subject is enrolled, and submit certain summary results information for those trials, generally no later than one year after the study’s completion date, unless a deadline extension is obtained. However, historically, FDA enforcement of this rule has been limited. To the best of our knowledge, FDA’s Notice of Noncompliance to Acceleron is the first time the federal government has taken any form of public action against a party for failing to comply with the ClinicalTrials.gov requirements.
FDA is authorized to seek civil money penalties for violations of the ClinicalTrials.gov disclosure rule, including $10,000 for each day that a company fails to submit the required information. In a final guidance document published last August, FDA outlined its approach to identifying whether responsible parties have failed to submit required registration and/or summary results information to the ClinicalTrials.gov data bank for applicable clinical trials studying drug products, biological products, and medical devices. FDA said that it has sent more than 40 Pre-Notices of Noncompliance – none of which have been publicly released by FDA – to encourage voluntary compliance with the ClinicalTrials.gov requirements. However, the letter to Acceleron is the first Notice of Noncompliance issued for such a violation.
FDA noted it had contacted Acceleron in July 2020 seeking the clinical trial results, but those results have still not been posted to ClinicalTrials.gov. At least for now, it appears the agency will be focusing its enforcement on companies that were formally notified about potential non-compliance, but then failed to take the necessary corrective action. Yesterday’s Notice of Noncompliance gave Acceleron 30 days to submit the required summary results information prior to the imposition of penalties.
Acceleron’s clinical trial in question evaluated the safety and effectiveness of the drug Dalantercept in combination with Axitinib in patients with advanced renal cell carcinoma. This trial was apparently not successful and, after its completion, Acceleron appears to have discontinued further development of Dalantercept. Notably, the ClinicalTrials.gov implementing regulations still require the submission of results information for studies that failed and/or were stopped prematurely.
FDA has set up a website to list companies that have received Notices of Noncompliance from FDA and the amount of civil money penalties assessed. This strongly suggests that the agency anticipates future enforcement action in this arena. We previously wrote that increased FDA scrutiny of ClinicalTrials.gov compliance was likely, noting the possibility of additional criminal referrals for egregious cases, in addition to the potential imposition of civil money penalties.
Indeed, in a statement announcing the Notice of Noncompliance, FDA Acting Commissioner Janet Woodcock, M.D., said “FDA takes its role in enforcing the ClinicalTrials.gov registration and results information submission requirements extremely seriously and we will continue to encourage voluntary compliance with these requirements.”
The National Institutes of Health (NIH) will also continue to update the ClinicalTrials.gov records for applicable clinical trials that are the subject of a Notice of Noncompliance with information regarding whether the noncompliance has been corrected and the amount of civil money penalties assessed, if any. In addition, the ClinicalTrials.gov record for the Acceleron study now includes a new “FDAAA 801 Violations” tab, creating another way for the government to call out companies that fail to submit required clinical trial summary results information.
Finally, we note that all New Drug Applications, Biologics License Applications, and medical device marketing applications must contain a certification from the sponsor that it has complied with ClinicalTrials.gov requirements. The certification form explicitly states that a willful and knowing false statement in the certification is a criminal offense.