Clinical Trial

In its policy, effective January 25, 2018, the NIH defines “clinical trial” as a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.

If any of the proposed studies or experiments meet the definition of an NIH clinical trial, you must submit to a FOA that allows for clinical trials (“clinical trial optional” or “clinical trial required”), even if your work will also include clinical studies that are not clinical trials.

Prospectively Assigned

The term “prospectively assigned” refers to a pre-defined process (e.g., randomization) specified in an approved protocol that stipulates the assignment of research subjects (individually or in clusters) to one or more arms (e.g., intervention, placebo or other control) of a clinical trial. 

Intervention

An intervention is defined as a manipulation of the subject or subject’s environment for the purpose of modifying one or more health-related biomedical or behavioral processes and/or endpoints.

Examples of interventions include the following:

• drugs, small molecules or compounds
• biologics
• devices
• procedures (e.g., surgical techniques)
• delivery systems (e.g., telemedicine, face-to-face interviews)
• strategies to change health-related behavior (e.g., diet, cognitive therapy, exercise, development of new habits)
• treatment strategies
• prevention strategies
• diagnostic strategies

Health-Related Biomedical or Behavioral Outcome

“Health-related biomedical or behavioral outcome” is defined as the pre-specified goal(s) or condition(s) that reflect the effect of one or more interventions on human subjects’ biomedical or behavioral status or quality of life.

Examples of outcomes include the following:

• positive or negative changes to physiological or biological parameters (e.g., improvement of lung capacity, gene expression)
• positive or negative changes to psychological or neurodevelopmental parameters (e.g., mood management intervention for smokers, reading comprehension and /or information retention)
• positive or negative changes to disease processes
• positive or negative changes to health-related behaviors
• positive or negative changes to quality of life

The NIH has identified four questions that should be used to determine the difference between a clinical study and a clinical trial:

• Does the study involve human participants?
• Are the participants prospectively assigned to an intervention?
• Is the study designed to evaluate the effect of the intervention on the participants?
• Is the effect being evaluated a health-related biomedical or behavioral outcome?

If the answer to all four questions is “yes,” then the study meets the NIH definition of a clinical trial, even if the following statements are also true:

• You are studying healthy participants.
• Your study does not have a comparison group (e.g., placebo or control).
• Your study is only designed to assess the pharmacokinetics, safety and/or maximum tolerated dose of an investigational drug.
• Your study is utilizing a behavioral intervention.

Exclusions

Exclusions to this definition of clinical trial include the following:

• Studies intended solely to refine measures are not considered clinical trials.
• Studies that solely involve secondary research with biological specimens or health information are not clinical trials.

The Brown HRPP team encourages you to work with them on an individual basis to determine if your study meets the NIH clinical trial definition. It is recommended you contact them as far in advance of your grant application deadline as possible, as the determination that is made will dictate whether you can apply to a “clinical trial required” or “clinical trial not allowed” FOA/RFA.

The goal is to align your proposed work with a particular NIH frequently asked question (FAQ) and/or case study and reach a consensus regarding whether “Brown” (the HRPP team and the investigator) believes the proposed research is an NIH clinical trial.

If you would like an in-person educational session for a department, center, group of research teams or group of administrators, please contact the Institutional Review Board (IRB) manager on the HRPP team to discuss your needs and to schedule a training.

Human Subjects Research at Brown

Contact Your Program Officer

You are also strongly advised to confirm with your program officer your own independent clinical trial determination, or that which you’ve established with the HRPP team. If you work with the HRPP team to make a determination, they will provide a template email for you to use when contacting your program officer. 

Please copy Brown’s Quality Assurance/Quality Improvement administrator on any written correspondence with your program officer and NIH’s subsequent response. This will facilitate team efforts to build a library of responses to help guide future application of the clinical trial definition.

How to Address a Series of Studies 

The NIH encourages “lumping” together several aims or hypotheses into a single study record, to the extent that it makes sense for your research. Put another way, NIH has advised that the investigator describe a series of experiments as a set of variants of a single study design. Subsequently, this will enable one Clinicaltrials.gov registration to cover the entire study.

Complete GCP Training as Needed

Good Clinical Practice (GCP) training must be completed by any individuals who are responsible for study coordination, data collection and data management. These individuals may also seek informed consent from prospective participants, and collect and record information from research participants. If anyone on your study team meets this definition (most will), they must complete GCP training.

Human Subjects Research Education and Training