By: Robert M. Califf, M.D., Commissioner of Food and Drugs
Biomedical and healthcare progress is dependent upon research that informs our decisions. The clinical trial is the most reliable method to determine the benefits and risks of interventions. The formation of ClinicalTrials.gov in February 2000 was a major step forward by providing a public record of trials. From a modest start, it has evolved significantly since its launch. The U.S. Food and Drug Administration monitors compliance with the ClinicalTrials.gov registration and results information submission requirements as a critical part of our mission to protect public health.
Transparency of clinical trial information, including through ClinicalTrials.gov, is essential to scientific advancement. Making clinical trial information publicly available fulfills the commitment to volunteer research participants and also enhances public trust. Simply put: if a human experimental study is done and the existence of the study and the results are not publicly available, it is difficult to assert that obligation of the researchers to contribute to generalizable knowledge has been met.
Another important benefit is the sharing of results that are unfavorable to the study sponsor or the investigators; prior to ClinicalTrials.gov many of these studies went unreported in the scientific literature, leading to a biased perspective on the benefits and risks of interventions. The FDA takes regulatory action when we identify potential or actual noncompliance with the registration and results information submission requirements specified by law for ClinicalTrials.gov.
ClinicalTrials.gov Background and Scope of FDA Oversight
ClinicalTrials.gov was designed with the initial goal of providing a consumer-friendly database that would enable patients and other stakeholders to find information about available clinical trials, particularly for trials testing the effectiveness of experimental drugs for patients with serious or life-threatening diseases or conditions. The Food and Drug Administration Amendments Act of 2007 fundamentally changed this scope because of concerns about transparency to require more types of trials to be registered, broader trial registration information, and the submission of summary results information for certain trials.
Today, ClinicalTrials.gov provides a rich source of data regarding the state of clinical research, including information about research results. Almost half a million clinical trials are registered with ClinicalTrials.gov; however, only a small portion, less than 15%, appear to be applicable clinical trials (ACTs) subject to FDA oversight of registration and results information submission requirements. Although the FDA is not tasked with enforcing the submission of results information for the more than 85% of registered trials that are not ACTs, there is an ethical obligation on the part of sponsors, trialists, and their associated institutions, to make results of trials available to the public, and this obligation can be met by submitting results information to the ClinicalTrials.gov database.
The FDA takes its oversight of clinical trials seriously and encourages voluntary compliance with the ClinicalTrials.gov requirements. Together with our National Institutes of Health partners, we communicate transparency expectations and obligations under the law. We use a risk-based approach to prioritize compliance and enforcement actions for the violations that pose the greatest risk to public health. The FDA issues a Preliminary Notice of Noncompliance (Pre-Notice) to encourage voluntary compliance. Failure to address potential violations after receiving a Pre-Notice may result in further FDA regulatory action, including a Notice of Noncompliance and/or civil money penalties.
Our Pre-Notices and Notices of Noncompliance are highly effective. For example, to date, more than 90% of the over 100 Pre-Notices issued resulted in responsible parties successfully addressing any potential noncompliance. None of the Notices of Noncompliance required further FDA regulatory action. The FDA issued response letters to all five recipients of Notices of Noncompliance, and all five cases have been resolved.
The FDA is committed to promoting clinical trial transparency and will continue to advance our compliance activities related to the ClinicalTrials.gov database. As the agency continues its compliance activities, we encourage sponsors, trialists, and the entire clinical research community to uphold their legal and ethical responsibilities to register and submit their clinical trial results information. The importance of ensuring that the conduct of clinical trials is publicly acknowledged and that the results are made available to ensure that research participants have contributed to generalizable knowledge cannot be overstated. The ClinicalTrials.gov database will continue to play a crucial role in our collective efforts to make sure that a complete record of interventional clinical trials is available.