NIH’s Expanding Definition of a Clinical Trial

2023 Update

History and Overview

In October 2014, NIH issued a Notice (NOT-OD-15-015) to the research community that it has revised its definition of a clinical trial. The Notice stated: “The revision is designed to make the distinction between clinical trials and clinical research studies clearer and to enhance the precision of the information NIH collects, tracks, and reports on clinical trials.” The Notice also stated that the revision “is not intended to expand the scope of the category of clinical trials.” Since September 2016, NIH issued other notices related to the expanded definition and developed a set of case studies intended to define what was and was not a clinical trial.

In apparent contradiction of the Notice, the definition of clinical trial and original case studies massively expanded the scope of clinical trials, sweeping in a broad section of basic behavioral and brain science research. The basic science community had originally paid little attention to this issue, not thinking that it applied to their research. However, as basic scientists have become aware of the breadth of the definition and policies, thousands of scientists – as well as the scientific societies and universities that represent them – have called on the NIH to modify and/or pause implementation of the policies until they receive adequate input from the affected communities.

To be clear, we support the NIH’s goal of increased transparency in federally-funded research, including the registering and reporting of research. We also agree that we have ethical obligations to human participants who give freely of their time to advance science and improve the human condition. However, we remain very concerned about the current efforts to sweep basic science into policies defined for clinical trials.

The basic science community is eager to work with NIH to accomplish the goals of enhanced transparency and good stewardship of taxpayer dollars. We recommend that NIH:

Pause implementation of the clinical trial policies as they affect basic scientists;
Seek input from the affected community of basic scientists and university administrations; and,
Work with the basic science community to create a registration and reporting framework for basic research that will ensure good stewardship of taxpayer dollars.

In response to concerns from the scientific community, in July of 2018, NIH issued a Request for Information (RFI; NOT-OD-18-217) seeking input regarding the regulation and implementation of clinical trial policies for Basic Experimental Studies involving Humans (BESH). NIH asked for examples of BESH that conflicted with the format and requirements of clinicaltrials.gov, as well as potential modifications for the site to be better suited for BESH.

Outreach efforts led to NIH announcing in July 2019 (NOT-OD-19-126) that more time was needed to assess and address these issues, and that enforcement of registering and reporting results of BESH on clinicaltrials.gov would be delayed through September 24, 2021. While FABBS and the greater basic scientific community considers this a victory, we will continue to monitor any developments and advocate for the needs of our members affected by these potential policy changes.

Below, we provide links to the basic NIH documents and a subset of the responses from the basic science community.

NIH Communications

Notice of Proposed Rulemaking: Clinical Trials Registration and Results Submission (Nov. 21, 2014)
Final Rule: Clinical Trials Registration and Results Submission (Sept. 21, 2016)

NIH Policies

Extension of Certain Flexibilities for Prospective Basic Experimental Studies With Human Participants (NOT-OD-19-126)
NIH Plans for Clinical Trial Specific Parent R01 and Parent R21 Funding Opportunity Announcements (NOT-OD-18-010)
The NIH Announces New Review Criteria for Career Development Award Applications Involving Clinical Trials (NOT-OD-17-121)
The NIH Announces New Review Criteria for Research Project Applications Involving Clinical Trials (NOT-OD-17-118)
NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information (NOT-OD-16-149)
Policy on Good Clinical Practice Training for NIH Awardees Involved in NIH-funded Clinical Trials (NOT-OD-16-148)
Policy on Funding Opportunity Announcements (FOA) for Clinical Trials (NOT-OD-16-147)
Notice of Revised NIH Definition of “Clinical Trial” (NOT-OD-15-015)

NIH “Open Mike” Blog (Center for Scientific Review Director Mike Lauer’s Blog)

Continuing to Work with the Community on Registration and Results Reporting for Basic Experimental Studies involving Humans (July 24, 2019)
Further Refining Case Studies and FAQs about the NIH Definition of a Clinical Trial in Response to Your Questions (January 4, 2018)
Implementing a New Human Subject and Clinical Trial Information Form (October 11, 2017)
4 Questions For Researchers and Institutions Involved In Human Subjects Research (August 11, 2017)
Building Better Clinical Trials through Stewardship and Transparency (September 16, 2016)
Improving Visibility of NIH-supported Clinical Trial Activities and Results (September 16, 2016)

Other NIH Info

Requirements for Grants and Contracts

History and Resources

Impact on Training Awards

New Application Forms (NIGMS news)

Protocol Registration Info

Dr. Lauer’s presentation at the NIH Council of Councils Advisory Committee Session: “Implementation of NIH Clinical Trials and
Transparency Reforms” Video (begins at 5:08:30), Slides (pdf)

GAO Report (one motivation for the new policies)

Case studies

Clinical Trials Decision Tree