NIH Clinical Trials
Effective January 25, 2018, NIH requires that all applications involving one or more “clinical trials” be submitted through a Funding Opportunity Announcement (FOA) or request for proposal (RFP) specifically designed for clinical trials. This information is designed to assist investigators with applying the NIH’s definition of a clinical trial and to highlight resources available at Brown and provided by the NIH that will inform which types of FOAs / RFPs you can apply to if you are, or are not, proposing to conduct an NIH clinical trial. Information related to the NIH single IRB (sIRB) mandate, which may apply when you are proposing a multi-site clinical trial, can be found here.
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.
Key Terms for understanding & applying the NIH definition
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: 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.
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: 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.
Responsive to feedback, NIH revised its compilation of case studies it created to serve as examples of the types of studies that would or would not be considered a clinical trial under its revised definition. These Case Studies are continuing to evolve over time.
The NIH home page for the definition of Clinical Trial contains many helpful resources for investigators, including FAQs, a decision tree, general Case Studies, and Institute/Center specific case studies.
There is also a very helpful Q&A with Mike Lauer, the NIH deputy director for extramural research.
The NIH indicates that the following four questions that should be used to determine the difference between a clinical study and a clinical trial:
1. Does the study involve human participants?
2. Are the participants prospectively assigned to an intervention?
3. Is the study designed to evaluate the effect of the intervention on the participants?
4. Is the effect being evaluated a health-related biomedical or behavioral outcome?
The NIH indicates that if the answer to all four questions above is “yes,” then the 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)
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
Studies intended solely to refine measures are not considered clinical trials; and
Studies that solely involve secondary research with biological specimens or health information are not clinical trials.
The Brown HRPP encourages you to work with us on an individual basis to determine if your study meets the NIH Clinical Trial definition. We encourage you to contact us 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.
If you’d like an in-person educational session for a department, center, group of research teams, or group of administrators, please contact Alana Chetlen to discuss your needs and to schedule a training.
Who should I contact in the Brown HRPP with questions?
The primary contact for answering questions about the determination of whether a study meets the definition of an NIH clinical trial is Alana Chetlen. Your IRB Manager is also available to answer your questions.
The HRPP will work with you to evaluate whether your proposed research meets the NIH clinical trial definition. Our goal is to align your proposed work with a particular NIH FAQ and/or case study and reach a consensus regarding whether “Brown” (the HRPP and the investigator) believes the proposed research is an NIH clinical trial.
Should I also ask my Program Officer?
Yes! We (and the NIH) strongly advise you to confirm with your Program Officer your own independent clinical trial determination, or that which you’ve established with the Brown HRPP. NIH’s deputy director for extramural research has said:
“[Y]ou should ask your program officer [to clarify if your research meets the NIH clinical trial definition]…you should always have a low threshold to ask your program officer questions about anything. If you follow your program officer’s opinion, your grant proposal will not be disqualified for being on the wrong side of the clinical trial definition.” (source)
We also encourage you to copy Christiana Provencal on your written correspondence with your Program Officer and NIH’s subsequent response. This will facilitate the HRPP’s efforts to build a library of responses to help guidance future application of the clinical trial definition.
Can the Brown HRPP help with contacting my Program Officer?
The Brown HRPP will not contact your Program Officer directly; however, if you work with us to make a determination regarding whether your proposed research meets the NIH clinical trial definition, we will provide a template email for you to use when contacting your Program Officer. As we learn more about Program Officers’ determinations, we will be building a library of responses to help guide future application of the clinical trial definition.
The following FAQs are adapted, in large part, from this Q&A with NIH’s deputy director for extramural research. More FAQs will be added based on questions received from investigators and as we receive feedback from NIH Program Officers.
What happens if my proposal includes both clinical trials and studies that are not clinical trials? For example, study 1 is a methodological study and study 2 is a clinical trial. What type of FOA / RFA may I use for submission?
If any of the proposed studies/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.”)
The new FORMS-E grant proposal asks for a separate study record for each protocol. Basic behavioral and brain science studies usually involve a series of experiments. Does that mean I have to fill out dozens of pages of forms, one for each experiment?
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.
Is there additional training required of the researcher team if my study meets the definition of an NIH clinical trial?
Yes, 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 (and we anticipate that most will), they must complete GCP training. Detailed information about options to satisfy GCP training can be found here under the guidance titled Training Requirements & CITI Instructions.