The US Food and Drug Administration (FDA) recently released a draft guidance on the enforcement of US regulations on clinical trial disclosure and certification regulations.
The guidance addresses civil money penalties for “responsible parties and/or submitters of certain applications and submissions to FDA regarding drug products, biological products, or device products.”
According to the guidance, violations of the Federal Food, Drug, and Cosmetic Act (FD&C Act) requirements relating to the ClinicalTrials.gov databank will “generally” be identified through evidence collected during inspections conducted as part of FDA’s Bioresearch Monitoring Program (BIMO).
Thomas Wicks, chief strategy officer at TrialScope noted that the initial response to this guidance has been muted.
“While the FDA is still gathering comments, sponsors we have spoken with seem to consider the proposal a fairly pragmatic approach overall,” he told us.
However, Wicks said transparency advocates critical of current disclosure practices are disappointed with the perceived lack of comprehensive enforcement.
In the European Union (EU), all clinical trials on the EU Clinical Trials Register (EUCTR) must report their results in the registery within a year of completion by law.
The BMJ recently issued a report that found “extensive evidence” of “errors, omissions, and contradictory entries in EUCTR data that prevented ascertainment of compliance for some trials.”
The researchers from the University of Oxford also have launched a tracker, which shows that more than 50% of clinical trials in the EU are not registering their results within a year of completion.
Earlier this year, the researchers also launched a similar tracker for the US, which shows a slightly higher disclosure rate at 59.5%.
According to the tracker, the US Government could have imposed fines of at least $757,133,205 as of October 5, 2018.
“Aside from the financial penalties, which incidentally continue to increase with inflation, a public notice of non-compliance may added to the record on ClinicalTrials.gov,” Wicks explained.
“Additionally, when submitting a subsequent marketing application to the FDA, the representative of sponsor must attest in Form 3674 that the organization has complied with the disclosure regulations, making the sponsor representative personally liable,” he added.
$10,000 per day, per study
TrialScope VP of Global Transparency, Francine Lane, said the penalties speak to the gravity of non-compliance, as a $10,000 fine could potentially be levied for the first adjudication, with a $10,000 fine issued per day, per study until compliance is achieved.
Lane noted that with taking inflation into account, these numbers could reach $11,500 per day, per study. “While this guidance is welcome, some may argue that tying penalties to a formal inspection falls short of public expectations of enforcement for clinical trial data that should be in the public domain,” she said.
According to the guidance, several factors will be considered in determining the amount of civil money penalty under the relevant statutory limits. These include: “the nature, circumstances, extent, and gravity of the violation(s) and, with respect to the violator, ability to pay, effect on ability to continue to do business, any history of prior such violations, the degree of culpability and such other matters as justice may require.”
As Lane explained, the FDA’s risk-based approach of prioritizing high-risk clinical trials, or those deemed of great public importance, “may provide the perception that many sponsors struggling with non-compliance could continue their current course without penalties.”
The FDA is accepting comments on the draft guidance until November 20, 2018.