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Frequently Asked Questions
NIH Clinical Trial Definition
Initial Posting: August 10, 2017
Last Revised: September 8, 2017


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      A. QUESTIONS ABOUT THE CLINICAL TRIAL DEFINITION

    1. Why is the NIH definition of a clinical trial so broad?

      We are dealing with a serious problem. NIH-funded scientists are not publicizing nearly half of the trials they conduct and complete in a timely manner.  This is an unacceptable state of affairs.  Our purpose in defining clinical trials as we do is to improve dissemination and transparency. The bottom line: if public money is going to be spent to conduct experiments on people, you are expected to report the results.  It is not right to conduct experiments on people (at taxpayer expense) and keep the results secret. 

       

      In our policy notice on the Dissemination of NIH Funded Clinical Trial Information we stated, “We disagree with commenters who suggested that there is no need for coverage of certain types of trials, such as early exploratory trials, small trials, trials assessing only safety, or trials that terminate before reaching enrollment targets.  The benefits of transparency and the need to fulfill the ethical obligation to participants is as relevant to these types of trials as to any other type.”  

    2. What is the difference between clinical research and a clinical trial?

      Clinical trials are clinical research studies. 

      Clinical research includes all research involving human participants. It does not include secondary studies using existing biological specimens or data collected without identifiers or data that are publicly available. (https://humansubjects.nih.gov/glossary

      Clinical trials are clinical research studies involving human participants assigned to an intervention in which the study is designed to evaluate the effect(s) of the intervention on the participant and the effect being evaluated is a health-related biomedical or behavioral outcome.

    3. How can researchers determine whether a proposed study is a clinical trial?

      The following questions should be used to determine whether a study meets the NIH clinical trial definition:

      • 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 answers are all “yes,” the study is a clinical trial.

      If any answers are “no,” the study is not a clinical trial

    4. Does the primary outcome of a study need to be a health-related outcome in order for a study to be considered a clinical trial?

      If any outcome is health-related and the answers to the four questions are all yes, then the study meets the clinical trial definition. You should note, though, that all NIH-funded research investigating biomedical or behavioral outcomes is considered to be health-related.  Hence, if the outcome is biomedical or behavioral, the study may be a clinical trial (if the answers to the other three questions are “yes”).  Many clinical trials are “mechanistic” or “exploratory” falling outside the realm of efficacy or effectiveness trials. 

    5. Does assessing any behavioral outcome make a study a clinical trial?
      No. If the study is not designed to assess whether a prospectively assigned intervention modifies a behavioral outcome, the study is not a clinical trial.
    6. What is the difference between the clinical trial definition in the revised Common Rule and the NIH clinical trial definition?

      NIH considers the two definitions to have the same meaning. 

      Revised Common Rule §__.102(b): “Clinical trial means 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 the interventions on biomedical or behavioral health-related outcomes.”

      https://www.gpo.gov/fdsys/pkg/FR-2017-01-19/pdf/2017-01058.pdf

      NIH clinical trial definition: “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.” (Oct 23, 2014)

      https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-015.html

    7. Does risk to human participants factor into whether a study is considered to be a clinical trial?

      Risk is not part of the NIH clinical trial definition. NIH considers the study to be a clinical trial as long as all elements of the NIH clinical trial definition are met.

       

    8. What is the sub-definition of "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 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.

    9. Are measurements the same as interventions?

      No; measurements are used to collect data, while interventions are used to modify health-related endpoints. A manipulation or modification in one’s behavior or environment for the purpose of measurement alone is not considered a clinical trial. 

    10. What types of behavioral manipulations or tasks does NIH consider to be interventions?

      A manipulation or task is an intervention if it is used to modify a health-related biomedical or behavioral outcome. However, a manipulation or task used expressly for measurement, and not modification, would not be an intervention.  

    11. If all of my participants receive the same intervention/treatment, are these participants "prospectively assigned"?

      Yes, it is not a requirement to have multiple treatment groups to be considered prospectively assigned.  We do consider single-arm trials to be trials.

    12. What are some examples of outcomes that are not "health related biomedical or behavioral"?

      While the vast majority of NIH-funded studies are health related, a few are not. For example, a study that evaluates if enrollment in a summer internship program alters the student’s opinions on their educational pathway would not be assessing a health-related biomedical or behavioral outcome.

    13. Does the NIH clinical trial definition apply to foreign awards?

       Yes; the NIH clinical trial definition applies to all NIH-funded studies.

       

    14. Will the definition of clinical trial create inequities in peer review?

      Applications will continue to be assigned to study sections based on the topic of science.  We will take all needed steps to assure that every application is reviewed by peers with the appropriate expertise.

       

    15. Isn't it administratively burdensome to have a definition of clinical trial that requires so many studies involving human participants to report their results?
      Results reporting should not be considered a burden. Reporting results is an essential part of the scientific process; it is an integral component of the scientific method.
    16. How will NIH educate researchers?

      NIH will continue to update case studies, FAQs, tools, and resources to clarify guidance around the NIH clinical trial definition.  See resources at: https://grants.nih.gov/policy/clinical-trials.htm

       Additionally, NIH staff are prepared to help researchers determine whether their studies meet the NIH clinical trial definition.

       


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      B. SPECIFIC CASES

    1. If a proposed clinical study includes a plan for addressing incidental findings, is the study considered to be a clinical trial?

      No; having a plan for addressing incidental findings does not determine whether a study is considered to be a clinical trial.  To determine whether your study meets the NIH clinical trial definition, please refer to the four questions above that outline the criteria.

    2. Are studies that propose to evaluate a clinical intervention or to develop a diagnostic tool considered to be clinical trials?

      It depends; studies that involve prospective assignment of human participants to an intervention, which may be a clinical intervention or development of a diagnostic tool, and that are designed to evaluate an effect of the intervention on the participant, where the effect is a biomedical or behavioral health outcome, are clinical trials. (See Case Study https://grants.nih.gov/policy/clinical-trials/case-studies.htm#case7b). Studies designed only to validate the sensitivity or specificity of a tool are not clinical trials (See Case Study https://grants.nih.gov/policy/clinical-trials/case-studies.htm#case7a)

    3. Are studies that elicit the opinions or preferences from human participants considered to be clinical trials?

      It depends. Studies eliciting opinions or preferences in the absence of an intervention are not considered to be clinical trials. However, studies that gather opinions from participants after an experimental manipulation or intervention, may be clinical trials. 

    4. Are observational studies, which do not include an intervention, considered to be clinical trials?

      No; in order to meet the NIH clinical trial definition there must be an intervention.

    5. Are studies that involve only healthy participants considered to be clinical trials?

      Yes; studies involving healthy participants are considered clinical trials if all elements of the NIH clinical trial definition are met.

    6. Are studies that are not designed to impact diagnoses or treatment of patients considered to be clinical trials?

      It depends; studies that meet all elements of the NIH clinical trial definition are considered to be clinical trials.

    7. Are studies designed to compare the diagnostic performance of two approved diagnostic devices considered to be clinical trials?

      No; a study must be designed to evaluate the effect of the intervention on the human participant to meet the NIH clinical trial definition. In this example, the study is designed to compare the functionality of devices, and not the effect of the devices on the participant. (Case Studies https://grants.nih.gov/policy/clinical-trials/case-studies.htm#case8a). 

    8. Must a health-related outcome be permanent or lasting in order for a study to be a clinical trial?

      No; a transient health-related outcome is sufficient for a study to be considered a clinical trial, as long as all other elements of the NIH clinical trial definition are met.

       

    9. Are studies that coordinate with health-care providers where the outcome is measured in their patients considered to be clinical trials?

      Yes; in these studies, both the healthcare providers and patients are human participants, and the healthcare providers become part of the intervention.  The study is considered to be a clinical trial as long as all other elements of the NIH clinical trial definition are met. (See Case Study https://grants.nih.gov/policy/clinical-trials/case-studies.htm#case20)

    10. Are studies with just a few research participants considered to be clinical trials?

      Yes; the NIH clinical trial definition specifies that there must be one or more human participants involved in the study. Therefore, single case studies or N-of-1 trials are clinical trials. The study is considered to be a clinical trial if all elements of the NIH clinical trial definition are met.

    11. Are studies ancillary to clinical trials considered to be clinical trials as well?

      Yes; if the ancillary study adds an additional manipulation (prospectively assigned intervention) and all elements of the NIH clinical trial definition are met.

      No; if the ancillary study is only adding additional measures to an existing clinical trial.

    12. Are studies that use correlational designs considered to be clinical trials?

      No; studies using correlational designs to prospectively associate biomedical or behavioral parameters with other health-related measures, but do not involve an intervention, do not meet the NIH clinical trial definition.

      No; studies using correlational designs to prospectively associate biomedical or behavioral [MQ1] parameters with other health-related measures, but do not involve an intervention, do not meet the NIH clinical trial definition.


       [MQ1]Missing on web

    13. Are studies designed to understand a disease mechanism considered to be clinical trials?

      It depends. Studies that are mechanistic in nature but do rely on an intervention to modify a health-related outcome may be considered a clinical trial. However, studies that do not use an intervention, would not be a clinical trial.

    14. Are studies that compare two different methods of diagnosing a disease in patients to determine the reliability of a new method, but have no intention of using the results to inform the clinical care of the patients, considered to be clinical trials?

      No; studies that involve a comparison of methods and that do not evaluate the effect of the interventions on the participant do not meet the NIH clinical trial definition.

    15. 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?

      Studies need not include a comparison group to meet the NIH clinical trial definition.  As long as all of the elements of the NIH clinical trial definition are met, the study would be considered to be a clinical trial.


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