The National Institutes of Health (NIH) on Friday issued a final rule that its leaders said is expected to result in “rapid increases” in the percentage of trials registered and shared via ClinicalTrials.gov, though it remains to be seen if the $10,000 per day penalties that can be assessed by the US Food and Drug Administration (FDA) will be strictly enforced.
Writing in a JAMA Viewpoint on Friday, NIH Director Francis Collins and other senior leaders said: “Investigators and sponsors who fail to comply with the regulation may be subject to civil monetary penalties assessed by FDA. In addition, NIH will withhold clinical trial funding to grantee institutions if the agency is unable to verify adequate registration and results reporting from all trials funded at that institution. The availability of results will promote innovations in clinical trial design and avoid duplication of unsuccessful strategies, thereby avoiding unnecessary risks to research participants.”
A special report in the New England Journal of Medicine, also published Friday, says the US trials registry currently has more than 224,000 study records, but only 23,000 display results.
“Compliance with the results-reporting requirements, however, has been low across many sectors of the clinical research enterprise,” the NIH authors write. “We believe this low compliance to be due, in part, to the ambiguity of some statutory requirements. The details provided in the final rule should help increase accountability within the clinical research enterprise: going forward, investigators, sponsors, and the general public will be better able to evaluate what information is required to be submitted and, in general, whether compliance has been achieved.”
Clinical trials from public and private sector sponsors that will need to meet the requirements of the new rule include those for drugs and biologics that are controlled, clinical investigations (other than Phase 1 trials), of a product subject to FDA regulation; and prospective clinical studies of health outcomes comparing an intervention with a device product against a control in humans (other than small feasibility studies) or any pediatric post-market surveillance studies required by FDA.
Trials will need to be registered on the ClinicalTrials.gov site no later than 21 days after the first participant is enrolled.
And results need to be submitted to the website no later than a year after a trial’s “primary completion date,” with a “possible delay of up to an additional 2 years for trials of unapproved products or of products for which initial FDA marketing approval or clearance is being sought, or approval or clearance of a new use is being sought.”
In terms of non-compliance, the final rule, which NIH notes “does not dictate how clinical trials should be designed or conducted, or what data must be collected,” mandates that non-compliant trials will be called out on ClinicalTrials.gov. For federally funded trials, grant funding can be withheld if required reporting cannot be verified.
FDA will still have the ability to assess civil monetary penalties of up to $10,000 per day (amount to be adjusted going forward) though the agency has yet to assess such penalties. For trials receiving NIH funds, non-compliance may lead to suspension or termination of grant or contract funding.
The ClinicalTrials.gov data-entry system, known as the Protocol Registration and Results System (PRS), is expected to be ready to support all regulatory submission requirements by the rule’s effective date on 18 January 2017.
Sponsors will have until 18 April 2017 to comply with the final rule. NIH says it will be providing educational materials to the regulated community at https://prsinfo.clinicaltrials.gov.
“When people participate in clinical trials, they are volunteering to create generalizable knowledge to help others in the future and we want their participation honored by ensuring that the existence of trials and their results are available to all patients and their healthcare providers, as well as researchers,” said FDA Commissioner Robert M. Califf in a statement. “The FDA will help ensure compliance with these new requirements so that patients and providers can have confidence in and access to significantly more clinical trial information, and researchers can improve clinical trial focus and design.”
Informed by nearly 900 comments, the final rule also:
- Provides a checklist for evaluating which clinical trials are subject to the regulations and who is responsible for submitting required information
- Expands the scope of trials for which summary results information must be submitted to include trials involving FDA-regulated products that have not yet been approved, licensed or cleared by FDA
- Requires additional registration and summary results data elements to be submitted to ClinicalTrials.gov, including the race and ethnicity of trial participants, if collected, and the full protocol
- Requires additional types of adverse event information.
Clinical Trials Registration and Results Information Submission Final Rule
Summary of HHS/NIH Initiatives to Enhance Availability of Clinical Trial Information
Summary Table of HHS/NIH Initiatives to Enhance Availability of Clinical Trial Information