FDA threatens second company with fines over missing clinical trial results

The U.S. Food and Drug Administration has just fired a warning shot across the bow of a second drug company over its failure to make a clinical trial result public as required by law.

On 26 July, the FDA sent a “Notice of Noncompliance” to pharma company Accuitis, warning that it could be fined $10,000 per day if it does not make the missing trial result public within the next 30 days.

According to the FDA’s notice letter addressed to the company:

“If your company does not submit the required clinical trial results information… within 30 calendar days after receiving this Notice, FDA may also seek additional civil monetary penalties against your company…”

“In addition to civil monetary penalties, violations… could result in other regulatory action, such as injunction and/or criminal prosecution.”

STAT News reports that the letter seems to have had its intended effect:

"Rick Coulon, the chief executive officer of Accuitis, told us the company 'will be in full compliance with the FDA by the deadline stated,' but declined to answer other questions."

FDA IS FINALLY ENFORCING THE LAW

This is only the second “Notice of Noncompliance” issued by the FDA based on a law that requires trial sponsors – both companies and universities – to make the results of some (but by far not all) clinical trials public within 12 months of trial completion. The FDA issued its first notice in April 2021.

The FDA Amendments Act (FDAAA) was passed with overwhelming bipartisan support in 2007 to prevent companies from hiding unflattering trial results. Transparency advocates have long warned that the FDA’s lack of comprehensive enforcement of this law endangers patient safety and undermines public health.

According to a tracking tool developed by the University of Oxford, at least 2,811 clinical trials are currently missing results in violation of the law.

If the FDA fully enforced the law, it could by now have collected nearly $22 billion in fines. (Both of these figures are severe undercounts because the tracker only includes trials that came due after January 2018, while the law applies to trials stretching back to 2007.)

Image source: FDAAA Trials Tracker (updated daily)

SPEED AND SCOPE OF FDA ENFORCEMENT DISAPPOINTS

It is unclear why the FDA is not enforcing the law more broadly, especially as Joe Biden has promised to crack down on law-breaking trial sponsors.

Till Bruckner, founder of TranspariMED, said:

“While it is positive that the FDA is no longer completely turning a blind eye to violations of the law, the pace at which it is putting companies and universities on notice is disappointing. At the current speed, it will take the FDA literally over a thousand years to issue noncompliance notices for every missing trial result.”

“Some patients desperately waiting for these results may not even have one year left to live. The FDA should immediately contact all sponsors that are in violation of the law and give them 30 days to make all their missing trial results public, as stipulated by the law.”

"Both the letter of the law and Congressional intent are crystal clear: Clinical trial results must be made public, regardless of whether a company likes what the data show or not."

An industry disclosure expert who asked to remain anonymous told TranspariMED by email that:

"According to the FDA’s announced procedure, they would issue a pre-notice of noncompliance and give the sponsor 30 days to remedy the issue, after which the notice of noncompliance is issued if the problem remains."

"The Accuitis pre-notification was issued on October 26, 2020 – 9 months before the notice of noncompliance was finally issued. Similarly, Acceleron received a letter to correct their issue on July 20, 2020, but it also took about 9 months to issue the notice of noncompliance on April 27, 2021."

It seems likely that the FDA could be issuing many more notices of noncompliance if they issued them 9x faster as outlined in their own guidance.

"Bottom line: It’s a start, but time for the FDA to follow its procedures."

FDA CLAIMS TO USE 'RISK-BASED APPROACH' TO WARNING LETTERS

RAPS Regulatory Focus asked the FDA why Accuitis, in particular, had received a noncompliance letter, given the relatively small study size and relatively lower risk for patient harm in the rosacea study.

According to RAPS:

In response, the trade press office for FDA’s Center for Drug Evaluation and Research told RAPS that the agency “uses a risk-based approach to determine the situations in which Pre-Notices of Noncompliance will be issued, consistent with FDA’s public health mission and how the agency approaches its other compliance programs.”

The response continued, “The vast majority of recipients of pre-notices have taken voluntary action to address the issues of noncompliance. If recipients of pre-notices do not correct the issues of noncompliance, the agency will take appropriate action such as issuing a notice of noncompliance.”

Focus has asked FDA how many trialists have been notified of reporting deficiencies, and for a more precise characterization of the “vast majority” who have corrected reporting issues after receiving a pre-notice letter. This article will be updated with any information received in response.

DERMATOLOGICAL TRIAL VIOLATING THE LAW

The company that received the FDA warning, Accuitis, is a small privately funded pharma company developing potential dermatological treatments based on early stage discoveries made at Emory University.

The trial in question, NCT03064438, is a Phase 2 trial that tested the safety, efficacy and tolerability of a potential new treatment for acne rosacea on 36 patients.

The trial was scheduled to be completed in 2018, but the company failed both to provide the actual completion date and to upload the trial’s results.

The public registry ClinicalTrials.gov already publicly flags the Accuitis trial as violating the law. The trial’s results were recently made public in a medical journal, but journal publication does not satisfy FDA disclosure requirements, which require results to be uploaded onto the registry.

The legal focus on registry reporting, which is mirrored in Europe and endorsed by the World Health Organisation, is partially due to the fact that journal articles often ‘spin’ trial results to make them look more positive.

WHAT DOES THE FDA LETTER SAY?

Extracts from the FDA’s notice letter to Accuitis:

“The United States Food and Drug Administration (FDA) sent you a letter dated October 26, 2020, alerting you to potential noncompliance with the requirement to submit clinical trial results information to the ClinicalTrials.gov data bank.”

“[W]e requested that your company review its records for this clinical trial and submit all required results information promptly. We also stated that we… might take regulatory action if we determined that your company was not in compliance.”

“FDA has determined that your company failed to submit results information for the applicable clinical trial referenced above.”

“[FDA] is providing your company with the opportunity to remedy its noncompliance by submitting the required clinical trial results information within 30 calendar days after you receive this Notice of Noncompliance.”

“In addition, FDA has determined that your company failed to update the primary completion date for the referenced applicable clinical trial within 30 days after the trial reached its primary completion date.”

“If your company does not submit the required clinical trial results information… within 30 calendar days after receiving this Notice, FDA may also seek additional civil monetary penalties against your company… In addition to civil monetary penalties, violations… could result in other regulatory action, such as injunction and/or criminal prosecution.”

“We request that your company submit a written response to FDA within 30 calendar days after you receive this Notice, stating the actions your company has taken in response to this Notice.”

Some regulators in Europe have recently also signalled their intention to step up enforcement of trial reporting requirements. The Danish regulator has even threatened to impose prison sentences on those who keep trial results hidden.