As discussed in a previous client alert (here), the Department of Health and Human Services (HHS) recently issued a final rule governing the requirements for public registration of trials and posting of data to the ClinicalTrials.gov database. In a significant expansion over the previous requirements, effective January 18, 2017, responsible parties will have to publicly report the results of more clinical trials, including some for investigational drug products and devices that may never reach the marketplace.
A critical component of the final rule is Subpart C, which fundamentally alters the scope of trials subject to reporting obligations to include clinical trials involving unapproved, uncleared, or unlicensed products, regardless of whether marketing authorization is being sought for the products. HHS determined that submission of results of applicable clinical trials for investigational medical products that are not commercially available furthers the statutory purpose of the database “to provide more complete results information and to enhance patient access to and understanding of the results of clinical trials.” 81 Fed. Reg. 64982, 64989 (Sept. 21, 2016).
Responsible parties will have 90 calendar days after the effective date to come into compliance with the requirements of the final rule, or April 18, 2017. Drug and device companies and other institutions conducting and planning to conduct clinical trials should take action to evaluate and ensure that all of their applicable procedures, policies, and research grant agreements appropriately consider these substantive changes to the clinical trial results reporting requirements under the final rule.
The following discussion provides a brief overview of the new results posting requirements and the transition rules in place for studies completed before and after the effective date of the regulation.
1. Results Posting for Studies of Unapproved Products Completed Before January 18, 2017:
For studies that are completed before the effective date of the regulation – January 18, 2017 – the current requirements under the Public Health Service Act (PHSA) apply, which has been interpreted to require results information only from clinical trials of products that are approved, licensed, or cleared. In other words, studies of unapproved drugs that are completed before January 18, 2017 will not need to have their results posted unless and until the drugs are approved.
2. Results Posting for Studies of Unapproved Products Completed After January 18, 2017:
For applicable clinical trials for which the product is not approved, licensed, or cleared by FDA, the results information must be submitted in accordance with 42 CFR 11.48 if the primary completion date is on or after the effective date of the rule. 42 CFR 11.42(b). Note that the “primary completion date” refers to the date that the final subject was examined or received an intervention for the purposes of final collection of data for the primary outcome. 42 CFR 11.10.
The general categories of data required for submission under 42 CFR 11.48 include: (1) participant flow, (2) demographic and baseline characteristics, (3) outcomes and statistical analyses, (4) adverse event information, (5) protocol and statistical analysis plan, (6) administrative information, and (7) additional results information for applicable device clinical trials of unapproved or uncleared devices.
Thus, if a study of an unapproved drug product is completed after January 18, 2017, then the study results would need to be submitted no later than one year after the primary completion date unless the submission deadline is delayed or waived, as discussed below.
3. Results Posting Rules for Approved Products:
For applicable clinical trials for which the product is approved, licensed, or cleared by FDA, the following rules apply (42 CFR 11.42(a)):
- If the primary completion date is before the effective date, the results information must be submitted in accordance with section 402(j) of the PHSA. Under 42 USC 282(j)(3)(C), the basic results information includes demographic and baseline characteristics of patient sample, primary and secondary outcomes, point of contact, and certain agreements. Under 42 USC 282(j)(3)(I), the adverse information includes serious adverse events and frequent adverse events. All of this information must be posted no later than one year after the primary completion date of the clinical trial, unless the submission deadline is delayed or waived, as discussed below.
- If the primary completion date for such trial is on or after the effective date, the results information must be submitted in accordance with 42 CFR 11.48 (as discussed in section 2 above). Once again, this information must be posted no later than one year after the primary completion date of the clinical trial, unless the submission deadline is delayed or waived, as discussed below.
4. Requests for Delayed Results Submission
As noted above, the standard submission deadline for reporting clinical trial results data for all applicable clinical trials is one year after the primary completion date of the clinical trial. But, there are several methods for seeking a deferral of the submission of results beyond the standard submission deadline. 42 CFR 11.44.
- For applicable clinical trials investigating new uses of already marketed products, a responsible party may submit a certification that an applicable clinical trial involves a product that has been approved, licensed, or cleared, for which the manufacturer is the sponsor of the study and an application, licensure, or clearance of the use has been filed or will be filed within one year. In such case, the delay would be until 30 calendar days after the product obtains marketing authorization for the use investigated in the study or other triggering events.
- The delayed submission also extends to applicable clinical trials for unapproved products for which initial approval, licensure, or clearance is sought. A responsible party may submit a certification that an applicable clinical trial involves a product that has not been approved, licensed, or cleared by FDA, and that the sponsor intends to continue with product development and is either seeking, or may at a future date seek, FDA approval, licensure, or clearance of the drug product. In such case, the delay would be until 30 calendar days after the product obtains marketing authorization for the use investigated in the study or the marketing application or premarket notification is withdrawn for an extended period of time.
- Notwithstanding the delayed submission provision, a responsible party must submit results information for studies involving approved or unapproved drugs within two years after the date of certification.
- A responsible party may also request an extension to the submission deadline for “good cause.” Written requests for good cause extensions must be submitted prior to the date on which results information is due and must include an explanation of why an extension is necessary and the estimated date that the information will be submitted. HHS has not defined “good cause,” but states in the final rule that it will issue guidance on what might be considered good cause under particular circumstances as soon as practicable.
- In addition, the final rule provides a pathway to request a waiver of the results submission requirement if HHS determines that extraordinary circumstances justify the waiver and that providing the waiver is consistent with the protection of public health or national security interests. 42 CFR 11.54. All certifications for delay, requests for extensions, and requests for waivers must be made prior to the applicable deadline to submit the results information.