The results of many clinical trials must be made public according to U.S. law. However, the law in question remains unenforced, leaving over five billion dollars in potential fines uncollected. In this guest blog, three scholars explain efforts to force the Food and Drug Administration’s hand by taking it to court.
Clinical trial transparency—in the form of publicly accessible trial registration and complete, timely, and accurate results reporting—is essential for patients, physicians, researchers, and the public.
It helps patients find trials to enroll in and ensures that both patients and referring clinicians have sufficient knowledge to make informed decisions. Results reporting also reduces publication bias and helps researchers avoid duplicating studies, promoting public accountability and efficiency in federally funded research.
Over the last year, the Collaboration for Research Integrity and Transparency (CRIT) at Yale University has been working to improve the U.S. government’s monitoring and enforcement of compliance of clinical trials registration and results reporting on the American trial registry, ClinicalTrials.gov.
The centerpiece of this work is strategic litigation under the Administrative Procedure Act (APA) that seeks a court order compelling the Food and Drug Administration (FDA) and National Institutes of Health (NIH) to comply with the law governing ClinicalTrials.gov.
In the United States, administrative agencies such as the FDA and NIH have the power to interpret federal statutes and to create and enforce regulations. The APA is a tool that plaintiffs can use to sue such agencies and request that a federal court correct agencies when agencies create regulations that are contradictory to federal statute, when agencies fail to take certain actions that they are required to take, or when agencies otherwise fail to comply with federal statute.
CRIT has also submitted public comments on FDA’s draft guidance concerning proposed penalties for trial sponsors that fail to comply with ClinicalTrials.gov’s registration and reporting requirements.
This blog post describes CRIT’s work.
1. Litigation concerning ClinicalTrials.gov
The most important law governing ClinicalTrials.gov is the Food and Drug Administration Amendments Act (FDAAA).
FDAAA, a federal statute enacted in 2007, requires sponsors of certain clinical trials to post the “Basic Results” of their trials to ClinicalTrials.gov by a certain date.
Importantly, the statute specifies that Basic Results [or ‘summary results’] must be reported for all clinical trials of all FDA-approved drugs or medical devices, including those drugs or devices that were not approved by the study completion date, but have subsequently been approved.
Though FDAAA was enacted in 2007, the Department of Health and Human Services (HHS) and NIH waited until 2017, a decade later, to promulgate a regulation interpreting it: the FDAAA Final Rule.
Even worse, the FDAAA Final Rule purports to exempt clinical trial sponsors from the statutory requirement to report Basic Results for an applicable clinical trial of an approved product if the trial was completed (1) before the effective date of the Final Rule (January 2017) and (2) before the drug or device studied in the trial was approved by the FDA. (Such trials are referred to as “pre-Rule, pre-approval trials.”).
Thus, the Final Rule creates a loophole through which the results of a significant portion of clinical trials over the course of a decade can be withheld from the public.
In July 2018, CRIT filed a lawsuit against FDA, NIH, and HHS. That suit, since voluntarily dismissed, challenged these agencies to begin monitoring and enforcing clinical trial sponsors’ compliance with ClinicalTrials.gov reporting requirements.
The suit may have helped to prompt FDA to issue its draft guidance entitled “Civil Money Penalties Relating to the ClinicalTrials.gov Data Bank: Guidance for FDA Staff, Responsible Parties, and Submitters of Certain Applications and Submissions to FDA” in September 2018. (The draft guidance, and CRIT’s criticism of it, are discussed in more detail below.)
On December 7, 2018, attorneys at CRIT working with Yale Law School’s Media Freedom and Information Access Clinic (MFIA) filed their now-pending suit in federal court in Manhattan against the FDA, NIH, and HHS, again under the Administrative Procedure Act.
In essence, the lawsuit asks the court to right two wrongs.
First, the lawsuit asks the court to set aside the portions of the FDAAA Final Rule that purport to exempt the sponsors of pre-Rule, pre-approval clinical trials of FDA-approved products from their statutory obligation to disclose trial results on ClinicalTrials.gov. By purporting to exempt a decade of trials in this way, the Final Rule contradicts the plain language of FDAAA.
(In FDAAA, Congress expressly mandated disclosure of Basic Results when a drug or device in a clinical trial receives FDA approval subsequent to its study completion date. In addition, federal law generally requires the FDA to review the results of at least one, and typically at least two, randomized controlled clinical trials before approving a new drug or device, so it would be difficult to fathom that Congress did not intend to mandate results reporting for clinical trials completed before the product approval date.)
Second, the lawsuit asks the court to compel NIH to post public notices of noncompliance when clinical trial sponsors fail to comply with their statutory obligations to disclose clinical trial information on ClinicalTrials.gov. FDAAA explicitly requires NIH to monitor compliance with registration and results reporting requirements and mandates that NIH post public notices of noncompliance on ClinicalTrials.gov identifying those sponsors who have missed their deadlines or otherwise failed to comply. Yet, to date, the NIH has not posted any such public notices.
2. CRIT’s public comments on FDA’s draft guidance
In addition to supporting the lawsuit, CRIT has also submitted public comments to the FDA, explaining that the FDA can and must do more to monitor and enforce trial sponsors’ compliance with ClinicalTrials.gov registration and reporting requirements.
[Note: TranspariMED and dozens of patients, doctors and researchers also submitted comments. The only two comments opposing the imposition of sanctions came from the lobby groups PhRMA and ADVAMED. Full story here.]
CRIT noted that the FDA’s duty to monitor compliance with registration and results reporting requirements on ClinicalTrials.gov is mandatory under FDAAA, not discretionary, despite the draft guidance’s suggestion to the contrary.
Furthermore, CRIT observed that FDA’s proposal to monitor compliance through the Bioresearch Monitoring Program would be inadequate, as the Program incorporates the Final Rule’s improper loophole exempting pre-Rule, pre-approval trials from scrutiny.
Although nearly a year has elapsed since the FDA released its draft guidance on trial registration and results reporting to ClinicalTrials.gov, the FDA has not yet issued any final guidance, let alone announced any enforcement efforts.
This guest blog was written by Shweta Kumar (JD Candidate, University of Virginia School of Law), Christopher Morten (JD, PhD, New York University School of Law), and Joseph S. Ross (MD, MHS, Yale University School of Medicine). TranspariMED slightly edited the text they submitted to make it more accessible to a lay audience.