Clinical Trial or Not? Know the Answer

Investigators, does your proposed study include a clinical trial (CT)? If you are unsure of the answer, this article should help.

To determine the answer, use NIH’s Decision Tree for Clinical Trial Definition and reference NIH’s Online Decision Tool. Do not use a scientific judgement call or use prior experience.

Four Key Questions Determine CT Designation

A research study is a CT if all the following four questions are answered “yes.” Answering “no” to any of these questions means, by the NIH definition, the study is not a CT. Be sure to click on the links for definitions of terms to ensure you reach the correct conclusion.

1. Does the study involve human participants?

Note: the designation does not apply to secondary studies using existing unidentifiable biological specimens, data collected without identifiers, or data that are publicly available.

2. Are the participants prospectively assigned to an intervention?

Note: Randomization is not a requirement for a study to be a CT as long as the assignment of the research subjects is predefined. A single-arm trial qualifies as a predefined assignment.

3. Is the study designed to evaluate the effect of the intervention on the participants?

Note: If the answer is yes, the study is a CT. If the study generates data that are not used to measure an effect on the participants but only to assign the participants to a group or category (e.g., disease severity), then the study is likely not a CT.

4. Is the effect being evaluated a health-related biomedical or behavioral outcome?

Note: This refers to the pre-specified goals or conditions that reflect the effect of one or more interventions on human subjects’ biomedical or behavioral status or quality of life.

Are You Proposing Basic Experimental Studies Involving Humans (BESH)?

BESH studies are those that meet both the definition of basic research and the NIH definition of a clinical trial, and are therefore subject to NIH clinical trials policies, such as registration and results reporting. While all BESH meet the NIH CT definition, not all CTs are BESH.

Go to Answering the 4 Clinical Trial Questions for BESH on the BESH website for explanations of the responses. To help you determine whether your study fits within a BESH funding opportunity announcement (FOA), go to Key Characteristics of BESH.

Completing the Application Forms

If your study qualifies as a CT, you need to apply to an appropriate FOA (that is, one that accepts CTs) and complete section G.500 - PHS Human Subjects and Clinical Trials Information as part of your application. Keep in mind, the peer reviewers who assess your application will reference NIH’s New Review Criteria for Research Project Applications Involving Clinical Trials.

If you have questions, touch base with the scientific/research contact listed in Section VII. Agency Contacts of the FOA to which you are applying.

Resources

• NIH Definition of Clinical Trial Case Studies
• Frequently Asked Questions (FAQ): NIH Clinical Trial Definition, for example:
  • Are studies that evaluate the effect of an intervention on research participants, but do not have a comparison group (e.g., placebo, control) considered to be clinical trials?
  • Do funding opportunity announcements (FOAs) for Career Development (K) awards allow clinical trials?
  • Am I proposing human subjects research if I obtain specimens/data from a repository or database?