Clinical Trial Transparency and the Public Release of Study Data
Recent changes to U.S. and E.U. regulations will increase the research industry’s obligations related to publishing clinical trial data.
Last month, the U.S. Department of Health and Human Services (HHS) issued a new rule clarifying and expanding the regulatory requirements for submitting clinical trial registration and summary results information to ClinicalTrials.gov, a publicly available database operated by the National Library of Medicine. The National Institutes of Health (NIH) simultaneously issued a complementary policy requiring all NIH-funded trials to register and submit summary results to ClinicalTrials.gov. E.U. regulations also increase study data publication requirements.
Of note, investigators and sponsors conducting research in the E.U. will soon be required to make layperson summaries of study results publicly available.
These changes represent a regulatory step towards the goal of clinical trial transparency. Similar to the trend towards for providing research participants with individual study results, the research community is increasingly advocating for returning general study results to research participants and publicly releasing study data.
This movement recognizes that providing a summary of study results acknowledges participants’ critical role in the research enterprise; shows participants what their contribution means; and maintains engagement in the research.1 Additionally, making study data publicly available helps individuals find research studies they might be eligible for and fosters public trust.2
The new HHS rule encourages submission of study data to the ClinicalTrials.gov database by:
- Clarifying which clinical trials of FDA-regulated drug products (including biological products) and device products must register with ClinicalTrials.gov.3
- Aiding sponsors and investigators in determining which studies are “applicable clinical trials” through the development of HHS guidance, including examples, case studies, and a checklist-based tool.4
- Specifying that clinical trial sponsors will be accountable for submitting information to ClinicalTrials.gov, unless the sponsor designates a qualified principles investigator as the responsible party.5
Access and Transparency
Going forward, clear timelines will enhance public access to clinical trial information. The new rules require study registration on ClinicalTrials.gov no later than 21 days after enrollment of the first participant and summary result information submission no later than 12 months after the clinical trial completion date.6 A two year extension will be possible, however, for some trials of unapproved products or products for which FDA marketing approval or clearance is being sought.7
The new HHS rule also improves transparency by:
- Significantly expanding the scope of protocols that require study summary results to include trials involving FDA-regulated products that have not yet been approved, licensed, or cleared.8
- Requiring additional registration and summary results information, including participant flow; demographic and baseline characteristics (including race and ethnicity, if collected); primary and secondary outcomes; adverse event information (including all-cause mortality); and the full protocol and statistical analysis plan.9
- Establishing the consequence of noncompliance, including identifying a clinical trial record as non-compliant in ClinicalTrials.gov; withholding grants for federally funded studies; and imposing civil monetary penalties.10
Unlike the E.U., U.S. regulations do not require layperson summaries of study results. Instead, the new HHS rule requires that study summaries submitted to ClinicalTrials.gov take an objective “tabular format.”11
In its discussion of the public comments related to whether “narrative summaries” should be required, HHS noted that many commentators expressed concern over the ability of study sponsors to write accurate, non-promotional, and non-misleading summaries.12 Some commentators suggested that if results summaries were required, guidelines and templates should be developed to help ensure consistency and appropriateness of content and format.13 Several commentators also encouraged HHS to consider implementing a peer review process or requiring preparation of summaries by independent medical writers.14
After considering the commentators’ concerns, HHS ultimately determined that there is a lack of evidence that narrative summaries would always meet the statutory prohibition on misleading or promotional language.15 HHS thus deferred the decision until further research is conducted to determine whether, and how, narrative summaries can be reliably and consistently produced without unlawfully promoting a medical product.16
The expanded ClinicalTrials.gov requirements are an important step towards acknowledging research participants’ contribution to and improving public trust in the research community. Providing layperson summaries of study results is the next step forward towards achieving clinical trial transparency. HHS should therefore make good on its intention to review current approaches for sharing trial results such U.S. Food and Drug Administration (FDA) Drug Trials Snapshots and Patient-Centered Outcomes Research Institute (PCORI) public release of research findings.17
HHS should also include members of the IRB community in the discussion. As a body that regularly reviews informed consent forms and recruitment advertisements for accuracy and understandability, IRBs should be considered a resource in the effort to develop processes around the review of narrative summaries.
1 See, e.g., SACHRP Letter to the HHS Secretary, Attachment D: Recommendations Regarding Return of General Research Results (April 24, 2015), http://www.hhs.gov/ohrp/sachrp-committee/recommendations/2015-april-24-attachment-d ; Patient-Centered Outcomes Research Institute (PCORI) Process for Peer Review of Primary Research and Public Release of Research Findings (February 24, 2015) http://www.pcori.org/sites/default/files/PCORI-Peer-Review-and-Release-of-Findings-Process.pdf ; Pfizer, Returning Clinical Data to Patients, http://www.pfizer.com/research/clinical_trials/trial_data_and_results/data_to_patients (last visited October 4, 2016).
3 42 C.F.R. § 11.10.
4 Clinical Trials Registration and Results Information Submission, 81 Fed. Reg. 64,981, 64,991 (Sept. 21, 2016) (codified at 42 C.F.R. § 11).
5 42 C.F.R. § 11.4.
6 42 C.F.R. § 11.24.
7 42 C.F.R. § 11.44.
8 42 C.F.R. § 11.40.
9 42 C.F.R. § 11.48.
10 42 C.F.R. § 11.66.
11 Clinical Trials Registration and Results Information Submission, at 65,006, supra note 3.
12 Clinical Trials Registration and Results Information Submission, at 64,998-64,999, supra note 3.