In 2007, Congress passed the “Food and Drug Administration Amendments Act of 2007,” the purpose of which was, in part, to update the FDA’s rules surrounding clinical trials. The FDA took nearly a decade to review the law, seek public comment, and then daft a final Rule implementing its requirements. The “Final Rule for Clinical Trials Registration and Results Information Submission” was final on Sept. 21, 2016. This final Rule is intended to make it clear to industry members, investigators, and the public which trials must be reported to the federal government, how they are to be reported, when they must be reported and whether compliance with requirements has been achieved. The Rule will go into effect on Jan. 18, 2018 and will then be published in the Federal Register at 42 C.F.R. § 11.
ClinicalTrials.gov and historic practices
Since ClinicalTrials.gov was created, the U.S. Department of Health and Human Services has operated ClinicalTrials.gov as a single location to accomplish many tasks surrounding clinical trials. ClinicalTrials.gov is a vehicle by which patients can identify a study that they wish to participate in, as well as serving the purpose of openly tracking study progress and outcomes. This site:
- Promotes research integrity by allowing simpler and more open changes to protocols and enabling greater research transparency;
- Promoting evidence-based medicine, enhancing the ability for investigators to track and report outcomes and makes research easier to locate and evaluate;
- Promotes more efficient allocation of resources by investigators because of its flexibility in creating and managing new trials.
By creating this site, the hope was that clinical trials were more open to the public both in terms of results, as well as identifying the studies that the FDA has indicated could move forward.
Rule changes to reporting
However, even with the creation of ClinicalTrials.gov, follow-through by sponsors and investigators was not consistent. Often trial outcomes and registration of trials was not always performed, and utilization was not as high as the agency sought initially. As a result, the new Rule provides a legally enforced timeline for registration and results reporting, and study sponsors will be held responsible for compliance. Generally, the new Rule has several main provisions. The following is a simple summary of the Rule’s requirements:
1. Requires registration and results submission for applicable clinical trials (also known as “ACTs”).
a. ACTs are those trials that are:
i. Initiated on or after January 18, 2017 for studying an FDA-regulated drug or device;
ii. Is for the purposes of performing studies which support an IND or IDE;
iii. The facility is in the U.S., the product has been assigned an IND or IDE number, and even if the product will be manufactured in the US for export.
iv. Does not apply to Phase 1 clinical trials (for drugs or biologics) or trials for which the primary purpose is for device feasibility studies.
2. Clarifies and expands information required upon registration.
a. Registration information must be submitted no later than 21 calendar days after the first human subject is enrolled (known as the Study Start Date).
i. Information describing, in depth, the purpose and scope of the trial;
ii. Recruitment information, describing who will be considered for participation;
iii. Location information for the study; and
iv. Administrative data about the facility, the sponsor and other identifying information such as the Unique Protocol Identifier.
c. Is submitted by the “Responsible Party” who is the sponsor as a default, and then is generally the principle investigator once one is designated.
3. Expands the scope of results reporting, including trials of unapproved products
a. Results reporting portal will be opened for testing around Oct. 22, 2017.
b. Final release of the online Protocol Registration and Results System (“PRS”) will be in November 2017.
c. Results filing deadlines will be based on the trial’s completion date. The new Rule applies to studies whose Primary Completion Date (date on which the final subject was examined or received an intervention for the purposes of final data collection) is on or after Jan. 18, 2017. Results reporting due one year after the primary completion date.
i. There are opportunities for extension, but no more than two years.
d. Results for studies involving products, whether or not they are approved, licensed or cleared by the FDA, must be reported if the trials were required to be registered.
4. Clarifies and expands the kinds of data that must be reported with results. Includes the following:
a. Participant “flow”
b. Demographic and baseline data
c. Outcomes and statistical analysis
d. Adverse event information
e. Protocol and statistical analysis plan
f. Administrative information like that provided during initial registration
5. Revises the Quality Control and ClinicalTrials.gov posting process.
These changes are potentially significant for investigators, sponsors or Contract Research Organizations (CROs) which have been in the clinical trial business for a significant period of time. These new requirements impose more structure on what was a poorly used system, which resulted in inconsistent use and follow-through. It is intended that under this new Rule, there will be a significant increase in the amount of data being provided to the FDA and potentially to the public. The new Rule is intended to expand the data that is accessible related to study outcomes. This expansion of data reporting and accessibility may pose some problems for companies in terms of protecting proprietary information for products not yet approved but are in the trial process. It will be critical that companies monitor their intellectual property protections and ensure that these protections are in place when reporting under the Rule.