By James E. Valentine* & David B. Clissold –
The pendulum has been swinging: the medical research community and public health advocates want access to clinical trials data used to support marketing applications of FDA-regulated medical products. In 2007 that pendulum picked up momentum, with the enactment of Section 801 of the FDA Amendments Act of 2007 (“FDAAA”), which amended the PHS Act § 402 to expand the clinical trial registry data bank created by Section 113 of the FDA Modernization Act of 1997 (“FDAMA”). Areas of expansion included the types of clinical trials that must be registered in ClinicalTrials.gov, the data elements that must be submitted, and the required submission of certain results data.
Requiring the registration and submission of summary results of clinical trials of medical products was seen as a way to, among other things, allow the use of research results to contribute to medical knowledge for the benefits of patients, the research community, and the general public.
As it turned out, FDAAA Section 801 was not the end-all-be-all solution, especially since the statute left a plethora of questions on how to comply with the requirements: including questions as to who is a “responsible party” and what is an “applicable clinical trial” that would be subject to results reporting (we covered these early developments in 2008 and 2009 here, here, here, here, here, and here; NIH has a webpage with current information on the FDAAA 801 requirements).
Although no refinements were made in the latest round of FDA-focused legislation, the FDA Safety and Innovation Act of 2012 (“FDASIA”), policymakers on both sides of the aisle, as well as FDA, have recently proposed additional ways to increase transparency and access to clinical trial data and results in hopes of spurring medical product innovation and improving public health.
Rep. Ed Markey (D-MA) reintroduces The Trial and Experimental Studies Transparency (“TEST”) Act
For over a year now, Rep. Markey, along with Rep. Waxman and other House democrats, have been discontent with the underreporting of clinical trial results as required by FDAAA Section 801 (we previously reported here). Rep. Markey first introduced the Trial and Experimental Studies Transparency (“TEST”) Act in August 2012 (see here), but it never made it out of the committee stage.
As it was introduced this session, on May 16, 2013, H.R. 2031 would increase results reporting by expanding the reporting requirements for ClinicalTrials.gov, closing what is describes as “loopholes” in the original 2007 scheme. The TEST Act would do so by:
- Expanding reporting requirements to include interventional studies conducted outside the United States.
- Expanding reporting requirements to postmarket surveillance of class II or class III devices that involve data collection from human subjects.
- Requiring the submission to ClinicalTrials.gov of supporting documents, including protocol documents and consent documents used to enroll trial subjects.
- Requiring all interventional studies to be registered with the database before the first participant is enrolled in the trial.
- Strengthening reporting requirements so that results from all covered trials are posted on ClinicalTrials.gov within one year of the completion of the trial, while also limiting the delayed submission of results to only trials on medical products that have never before been approved for any use and up to only two years after trial completion.
The TEST Act also attempts to increase compliance by:
- Requiring the NIH Director and FDA Commissioner to report to Congress on the number of clinical trials with information submitted and steps taken to enforce compliance.
Rep. Tom Reed (R-NY) reintroduces the renamed Clinical Trial Cancer Mission 2020 Act
Another advocate for increasing clinical trials results reporting to ClinicalTrails.gov is Rep. Reed, who sees clinical trial results availability not only as a way to improve medical knowledge and research, but as a way to “safeguard taxpayer dollars from funding redundant research” (see Reed’s press release here). His legislation, the Clinical Trial Cancer Mission 2020 Act (“CTCM 2020”) Act came just about a month after the introduction of the TEST Act, and takes a different approach to increasing clinical trial results reporting to ClinicalTrials.gov.
As it was introduced this session, on May 16, 2013, H.R. 2301 (no, this is not déjà vu, the bill number is just very similar to the TEST Act’s) addresses what he describes as a “lack of enforcement in reporting clinical trial results.”
The CTCM 2020 Act would do two primary things:
- Adds a provision to include a clinical trial whether or not it results in a positive or negative outcome, as well as subject Department of Defense-funded clinical trials to the requirements to certify information submission to the NIH.
- Adds an “enhanced enforcement” subsection that would make the penalty for failure to report required clinical trial information to ClinicalTrials.gov within a 30-day correction period ineligibility for grant funding from the United States government, as well as create a repayment obligation for any grant amount provided.
(For a more detailed overview of this legislation, see our previous post here from last session).
FDA announces “Availability of Masked and De-Identified Non-Summary Safety and Efficacy Data”
Going beyond the summaries of clinical trials data that FDAAA Section 801 requires to be reported to ClinicalTrials.gov, FDA is proposing to use its new mandates under FDASIA Section 1124, “Advancing regulatory science to promote public health innovation,” to make available de-identified (i.e., cannot identify individual study participants) and masked (i.e., cannot identify a specific product or application) data derived from medical product applications.
In a Federal Register notice (Docket No. FDA-2013-N-0271), FDA announced as part of its Regulatory Science Initiative, this effort which has goals similar to that of the results reporting to ClinicalTrials.gov:
- To improve efficiency and effectiveness of medical product development by making available this clinical and preclinical data derived from marketing applications, which would then facilitate innovation in the development of new products.
- To maximize the contribution of patients who participate in clinical trials to the benefit of society.
FDA expects that allowing other experts outside of the Agency to conduct analyses of the data will contribute to identification of potentially valid endpoints for clinical trials, understanding of the predictive value of preclinical models, clarification of how medical products work in different diseases, and information for development of novel clinical designs and endpoints. Additionally, FDA hopes that this information could be used by sponsors, e.g., being used as a model of disease progression in control arms for future studies of the same disease or indication even without the identification of a product or even product class, for the characterization of risk factors only involving control group data, and validating a biomarker as a surrogate clinical outcome or as a predictive classifier of potential treatment response using class-wide data to show consistency.
FDA is currently accepting comments on the availability of this data to aid the Agency in the difficult task of establishing methods to appropriately mask the clinical trial data to prevent someone from identifying the product or application.
* Law student