On April 27, 2021, the United States Food and Drug Administration (FDA) issued its very first Notice of Noncompliance for failure to submit required results clinical trial data to ClinicalTrials.gov. The Notice, sent to Acceleron Pharma, Inc., relates to the company’s study, “A Phase 2 Randomized, Double-Blind Study of Dalantercept and Axitinib Compared to Placebo and Axitinib in Patients with Advanced Renal Cell Carcinoma,” which was completed in June 2017. As of the date of the citation Acceleron had still not submitted the final results data that were due one year after the primary completion date.
The April 2021 Notice follows a July 20, 2020, letter, in which the FDA requested Acceleron review its records for the clinical trial in question and “submit all required results information promptly.” That letter also indicated that the Agency would follow up on the July 2020 letter, “beginning 30 calendar days after you received our July 20, 2020, letter, and that we might take regulatory action if we determined that your company was not in compliance at that time.”
The Notice then goes on to note that Acceleron has still not submitted results information for the clinical trial as required and that the Agency was allowing Acceleron the opportunity to remedy the noncompliance by submitting the required clinical trial results information within 30 calendar days.
Additionally, the FDA may initiate an administrative action seeking a civil monetary penalty against the company of not more than $10,000, and if the company continues to ignore the FDA requests for information, the Agency may seek additional civil monetary penalties of not more than $10,000 per day until the violation is corrected.
The reporting requirements can be found in the Food and Drug Administration Amendments Act of 2007 (FDAAA) and are codified at Section 402(j) of the Public Health Services Act. The requirements mandate that the “responsible party” for a clinical trial register the trial and submit results data to ClinicalTrials.gov. While responsible parties are typically the sponsors of the clinical trial, the principal investigator can also be considered a responsible party if so designated by the sponsor. In order for principal investigators to be a responsible party, they must be responsible for conducting the trial, have access to and control over the data from the trial, and meet all requirements of submission of the trial information.
The requirement for sponsors and certain principal investigators to submit clinical trial registration and results data to ClinicalTrials.gov dates back to 2007 and is the result of concerns of lack of transparency in clinical trial results. Studies have suggested a significant lack of compliance with the reporting requirements, likely because of the lack of enforcement by the FDA. However, this initial citation should be seen as a cautionary tale to other sponsors and sponsors should take steps to ensure compliance with reporting requirements going forward. Sponsors should also audit the principal investigators’ reporting compliance and ensure they have proper contracts and agreements in place that protect them if the principal investigators fail to report.
Institutions, for their part, should also conduct a review to ensure compliance, including reviewing clinical trial agreements to determine whether sponsors are required to comply with the reporting requirements. Institutions may also consider reviewing clinical trial agreements to clarify that the reporting obligations belong to the sponsor, not the principal investigator.
In addition to sponsors and institutions, physician practices that conduct clinical research should also review their clinical trial agreements to determine if they require sponsors to comply with the reporting requirements. Physicians who act as sponsors for any investigator-initiated research need to ensure compliance with all registration and clinical trial reporting requirements.