By James E. Valentine* & Anne Marie Murphy –
On November 19, 2014, the National Institutes of Health (“NIH”) announced the much anticipated Notice of Proposed Rulemaking on clinical trials registration and results submission (“NPRM”). While the Food and Drug Administration Amendments Act (“FDAAA”) Section 801 is self-implementing for certain of the law’s expanded requirements, it leaves several key aspects of implementation to this rulemaking. As we previously reported, since FDAAA was passed in 2007, there have been quite a few developments in the implementation of the ClinicalTrials.gov reporting requirements. Once final, this rulemaking will replace all previous guidance to date.
The NPRM would expand and clarify many aspects of the clinical trials registration and results submission requirements set out in FDAAA. The statute left several key areas of expansion of results reporting to be considered in the rulemaking process, including results reporting for unapproved drugs and submission of summary narratives and trial protocols. Because these items were set aside for rulemaking, they were among some of the most highly anticipated.
Results information for trials of products that are not approved
FDAAA Section 801 explicitly mandates the submission of results information for applicable clinical trials of drugs and devices that are approved or cleared. By contrast, whether or not to require results reporting for similar trials when products are not approved was left for NIH to determine through rulemaking. Pursuant to this authority, the NPRM proposes to require submission of results, regardless of whether approval of the product is sought or the product is ultimately approved. Notably, the NPRM retains the ability to delay results submission for these trials, but it is limited to a maximum three years after the completion date for products pursuing approval.
NIH set out four reasons in support of their proposal to require results information for trials of unapproved products. They argue that making this information publically available will:
- Mitigate the bias in information available to the public about studied medical products that stem from selective disclosure of clinical trial results;
- Help protect the safety of participants to who volunteer to be in clinical trials by reducing the likelihood that people will unknowingly design, approve, or participate in clinical trials that are unnecessary, or are potentially harmful;
- Broaden the evidence base for systematic reviewers and others involved in assessing the benefits and harms of classes of drugs and devices; and
- Fulfill the agreement made with human subjects who agree to participate in clinical trials that the knowledge obtained will be available for use in advancing biomedical science.
NIH does not appear to be deterred by concerns about commercial competitiveness resulting from disclosure of results information from trials for unapproved products. Specifically, the NPRM proposes to mitigate this concern by providing delayed results submission. The proposal would require results submission for applicable clinical trials for unapproved drugs not later than one year after the completion date of the clinical trial, unless a certification is submitted prior to that deadline indicating that initial approval is being sought or may be sought at a future date.
This delay in results submission would be limited to two years after the submission of the certification, and only one certification could be submitted per trial. Thus, the total delay in disclosure of results would be up to three years after the completion date. Although product development will frequently extend beyond this timeframe, NIH argues three years “would provide sponsors with significant lead time” in development over potential competitors.
Non-technical and technical summaries of clinical trials and results
FDAAA Section 801 requires rulemaking to consider expanding submissions to contain non-technical and/or technical written summaries of the clinical trial, if these summaries can be included without being misleading or promotional. In order to make this determination, NIH would like to evaluate the value to the public of such summaries. The Agency would also like to demonstrate that such narrative summaries can be consistently produced in a way that will not be objective and not misleading. Thus, the NPRM defers the decision about whether to require submission of narrative summaries, inviting public comment on methods that might help answer this question.
Full clinical trial protocols
Similarly, FDAAA Section 801 requires consideration during rulemaking of whether to submit the full clinical trial protocol or only “information on the protocol” that may be necessary to help evaluate the results of the trial. The NPRM outlined three ways this statutory requirement could be satisfied, by requiring submission of:
- Additional structured data elements derived from, or describing, the protocol;
- Portions of the final protocol or other narrative information about the conduct of the study that is associated with the protocol (e.g., a statistical analysis plan, if not part of the protocol); or
- The full protocol at the time of results submission (i.e., the final version of the protocol, including all amendments).
The NPRM does not propose to require any of these possibilities. Instead, it invites public comment on whether the information that is already proposed to be required in the NPRM meets the statutory requirement to provide “information on the protocol” or, alternatively, if any of these three proposed options for submitting additional information should be required.
The NPRM is scheduled to be published in the Federal Register on November 21, 2014. Once published, comments can be submitted to docket number NIH-2011-0003 at Regulations.gov. NIH also announced, in conjunction with the NPRM, a draft policy that would extend similar registration and reporting requirements to all clinical trials funded by NIH, regardless of whether they are subject to FDAAA.
*Not admitted to practice law. Working under the supervision of the Firm’s attorneys.