The US Food and Drug Administration finally seems poised to begin cracking down on drug companies and medical research institutions that violate the legal requirement to post the results of clinical trials onto Clinicaltrials.gov, the world's largest clinical trial registry.
In a guidance document published today, the FDA announced that:
"Civil money penalties may be assessed for failing to submit required clinical trial registration and/or results information to the ClinicalTrials.gov data bank..."
However, the new guidance falls significantly short of the long-standing demand by transparency campaigners, including TranspariMED, Transparency International, and Cochrane, as well as the AllTrials campaign, that the FDA impose penalties for every single clinical trial that fails to report results.
Instead, the FDA only intends to enforce the law selectively, and apparently only in a minority of cases:
The FDA guidance states that:
"[T]he Centers intend to identify potential violations of the FD&C Act’s requirements relating to the ClinicalTrials.gov data bank in part through evidence collected during inspections conducted as part of FDA’s BIMO program. Generally, FDA’s BIMO activities are associated with the submission of a research or marketing application or as a part of the Agency’s investigation of a complaint. When evaluating potential violations identified during these activities, FDA intends to utilize a risk-based approach to determine the situations in which Pre-Notice Letters will be issued consistent with FDA’s public health mission and how the Agency approaches its other compliance programs. In applying this risk-based approach to applicable clinical trials, the Centers intend to focus their enforcement and regulatory attention in the following areas:
Responsible parties who have failed to submit required clinical trial registration and/or results information under section 402(j) of the PHS Act, including its implementing regulations in 42 CFR part 11, for higher risk applicable clinical trials or applicable clinical trials of public health importance.
Responsible parties or submitters for which there is a pattern of previous noncompliance with the requirements to submit clinical trial information and/or certifications under section 402(j) of the PHS Act, including its implementing regulations in 42 CFR part 11.
Applicable clinical trials for which noncompliance with the requirements under section 402(j) of the PHS Act, including its implementing regulations in 42 CFR part 11, exists in conjunction with potential noncompliance with other statutory and/or regulatory requirements pertaining to the conduct of the trial."
An online tracking tool developed by EBM Data Lab at Oxford University shows that the FDA could collect over $673 million in fines if it fully enforced the law.
Since the 2007 FDA Amendments Act's Final Rule came into force in February 2018, over 500 clinical trials have already fallen foul of the law.
However, the new FDA guidance only envisions the imposition of the maximum fine under certain circumstances.
The guidance states that:
"The statutory maximum penalties under the FD&C Act for committing these prohibited acts are not more than $10,000 for all violations adjudicated in a single proceeding... and, if a violation is not corrected within 30 days following notification of such violation, not more than $10,000 for each day that the violation continues after such period until the violation is corrected...
In determining the amount of civil money penalty under the relevant statutory limits, the following factors are considered: 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."
Expert observers welcomed the move but sounded a cautious note.
Despite its serious limitations, the FDA's new guidance seems to mark a step in the right direction.
Founder of TranspariMED, Till Bruckner said:
"The FDA has finally taken a small, tentative step in the right direction. The results of tens of thousands of clinical trials remain unknown, so patients, doctors and health insurers cannot accurately assess the effectiveness and cost-effectiveness of medicines already on the market. Failure to report clinical trial results is not a victimless crime. It harms patients, slows down the development of new treatments and cures, and drives up health care costs. Patients, doctors and taxpayers must keep up the pressure to ensure that the FDA fully enforces this law, so that we can access the results of all clinical trials."
Several months ago, TranspariMED filed a Freedom of Information request with the FDA asking how many 'warning letters' it had already sent out to sponsors who had broken the trial reporting law. To date, the FDA has not provided that information.
The 2007 Food and Drug Administration Act (FDAAA) only covers some clinical trials. Many other clinical trials fall outside the scope of the Act, including many trials conducted by US researchers on US patients within the United States.
Data shows that US universities in particular often violate the law. However, in recent years, some of them have significantly improved their performance.
The failure of the FDA to enforce clinical trial transparency rules is mirrored in Europe.
A new trials tracker released last week revealed that thousands of clinical trials were missing results on the European trial registry, in violation of European Union guidelines.
Neither the European Medicines Agency (EMA) nor national governments have so far moved to enforce those rules, prompting Transparency International to call on the EMA and governments to finally put into place effective monitoring systems and sanctions.
The FDA's new guidance document can be found here.