NIH's Definition of a Clinical Trial

This page provides information, tools, and resources about the definition of a clinical trial. Correctly identifying whether a study is considered by NIH to be a clinical trial is crucial to how you will:

Select the right NIH funding opportunity for your research study
Write the research strategy and human subjects sections of your grant application and contract proposal
Comply with appropriate policies and regulations, including registration and reporting in ClinicalTrials.gov

Note: Misclassified clinical trial applications may be withdrawn.

Background

In 2016, NIH launched a multi-faceted effort to enhance its stewardship over clinical trials. The goal of this effort is to encourage advances in the design, conduct, and oversight of clinical trials while elevating the entire biomedical research enterprise to a new level of transparency and accountability. The NIH definition of a clinical trial was revised in 2014 in anticipation of these stewardship reforms to ensure a clear and responsive definition of a clinical trial. Learn more about why NIH has made changes to improve clinical trial stewardship.

NIH Definition of a Clinical Trial

A research study in which one or more human subjects are prospectively assigned prospectively assignedThe 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. to one or more interventions interventionsAn "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 include: drugs/small molecules/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; and, diagnostic strategies. (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes. health-related biomedical or behavioral outcomes.A "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 include: 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; and, positive or negative changes to quality of life.

DECISION TOOL

Your human subjects study may meet
the NIH definition of a clinical trial.

FIND OUT HERE

Use the following four questions 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?

Note that if the answers to the 4 questions are yes, your study meets the NIH definition of a clinical trial, even if…

You are studying healthy participants
Your study does not have a comparison group (e.g., placebo or control), or has a single arm
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, or measuring intent to change behavior
Only one aim or sub-aim of your study meets the clinical trial definition
Your study is no more than minimal risk

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.

Resources to Clarify the Definition

Case Studies

These simplified case studies illustrate the differences between clinical trials and clinical studies.

Decision Tree

Print this decision tree for an easy reference for the four questions that identify a clinical trial.

Related Guide Notice

NOT-OD-15-015 Notice of Revised NIH Definition of “Clinical Trial”