The Food and Drug Administration (FDA) and the National Institutes of Health (NIH) have the authority to regulate clinical trial reporting requirements. Despite this authority, FDA and NIH have scantly enforced this area since the requirements were created by Congress in 2007, hindering the clinical trial transparency promised to the public. However, there may be a shift in the lackadaisical enforcement over such reporting. On April 28, 2021, Acting FDA Commissioner Janet Woodcock, M.D., announced that that the agency had sent more than 40 pre-notices to sponsors of clinical trials for failing to submit required clinical trial results to ClinicalTrials.gov. Notably, a Notice of Noncompliance was issued for the first time.
Under the Food and Drug Administration Amendments Act of 2007 (FDAAA), sponsors of clinical trials are required to submit registration and summary results information to the clinical trial data bank, ClinicalTrials.gov, managed by NIH’s National Library of Medicine. A sponsor, also known as a “responsible party,” of a clinical trial may be one of a variety of organizations, including academic institutions, hospitals, private companies, and government research organizations. Federal law requires that responsible parties, such as the trial sponsors, register applicable clinical trials on ClinicalTrial.gov within 21 days after the first human subject is enrolled. They also must subsequently submit certain summary results information for those trials no later than one year after the study’s completion date, unless the deadline is extended. NIH finalized regulations implementing those requirements in 2017.
FDA’s role in implementing and enforcing the relevant clinical trial reporting requirements under the FDAAA is three-fold. First, a responsible party must certify its compliance with ClinicalTrials.gov requirements when submitting certain human drug, biological product, and device applications. Second, a responsible party must include a statement in the informed consent documents for applicable clinical trials (i.e., those that will be entered into the ClinicalTrials.gov databank as required by FDAAA). Third, FDA may take compliance and enforcement activities related to failure to submit the required clinical trial information to the databank.
The statutory and regulatory requirements are intended to provide greater transparency regarding clinical trials. Submitting such clinical trial information enhances public trust by creating a transparent and robust public record of clinical trials and information about their results. Making the results of the clinical trial studies publicly available enables these studies to inform treatment guidelines and recommendation statements. As noted above, FDA has the authority to take enforcement action when these legal requirements are not met, but it had not done so until April 2021. An FDA guidance document issued in 2020, however, may have foreshadowed these recent agency actions.
In August 2020, FDA finalized guidance on the topic of clinical trial data requirements and enforcement (as we previously blogged about). As a brief refresher, according to the guidance, enforcement will focus on responsible parties who have submitted false or misleading information to the databank or who have failed to submit a certification (or who knowingly submitted a false certification) to FDA regarding the submitter’s compliance with the requirements set out in the law. If the FDA believes a responsible party has failed to comply with its registration, results submission, or certification obligations, the agency will send a Preliminary Notice of Noncompliance (Pre-Notice) Letter to that party. The Pre-Notice Letter will give the recipient 30 days to voluntarily correct the potential violation. After the 30-day period, FDA will conduct a follow-up review and assessment to determine if the potential violation has indeed been remedied. If it remains unaddressed, FDA may proceed to issue a Notice of Noncompliance, levy civil monetary penalties, issue an injunction, or even pursue criminal prosecution.
At the time of this blog post, the agency reported that it has sent more than 40 Pre-Notices of Noncompliance to sponsors in order to encourage compliance with the ClinicalTrials.gov requirements. In addition, on April 28, 2021, FDA issued its first Notice of Noncompliance to a clinical trial sponsor for failing to submit the required summary results information to ClinicalTrials.gov. The responsible party acknowledged receipt of the Notice and intends to comply with the Agency’s request.
Besides being publicly posted on the FDA website, NIH also will update the ClinicalTrials.gov records for applicable clinical trials that are subject to a Notice of Noncompliance with information regarding whether the noncompliance has been corrected and the amount of civil money penalties assessed, if any. In its recent statement, FDA did not elaborate on whether the other recipients of the Pre-Notices of Noncompliance have taken action to comply with the requirements. Time will tell if additional enforcement actions follow.
The Pre-Notices of Noncompliance and the sole Notice of Noncompliance may signal a shift in the agency’s priorities. Specifically, the Notice of Noncompliance may be the beginning of stricter enforcement for clinical trial reporting requirements. In the strongly worded statement from Dr. Woodcock, FDA declared that it “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. When necessary, the FDA will take appropriate actions to help ensure that required information is available on ClinicalTrials.gov as required by law and for the benefit of clinical trial participants and public health.”
Keep an eye-out; this may be only the beginning of FDA’s exercise of enforcement over clinical trial requirements. Clinical trial sponsors and principal investigators should check their registrations and ensure that all relevant clinical trial results are reported on a timely manner. It is also advisable to alert responsible party employees of the reporting requirements and the mandatory 30-day updates to the records in order to avoid receiving either a Pre-Notice or a Notice of Noncompliance.
We will continue to keep our readers updated on any additional activities in this area.