Regardless of whether you’re interested in proposing a clinical trial in your next application, you need to understand NIH’s definition of a clinical trial so that you can choose an appropriate notice of funding opportunity (NOFO). Our NOFOs designate whether they can or cannot accept clinical trials, and if you choose incorrectly, we may consider your application nonresponsive and reject it.
Since 2018, NIH has required all applications involving one or more clinical trials be submitted through a NOFO specifically designed for clinical trials. The purpose of this policy is to improve our ability to identify proposed clinical trials, ensure that key pieces of trial-specific information are submitted with each application, and uniformly apply trial-specific peer review criteria.
NIH defines a 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. Refer to Does Your Human Subjects Research Study Meet the NIH Definition of a Clinical Trial? for help applying the definition to your specific circumstance.
The implications of this policy include the following:
- You cannot include any research considered a clinical trial—no matter the scope—in any application you submit to a NOFO labeled “Clinical Trials Not Allowed.” Even if you don’t think of your proposed research as including a clinical trial, it’s the NIH definition of a clinical trial that matters and could lead to us rejecting your application.
- If you submit a clinical trial to a NOFO that allows clinical trials, you must also provide all necessary clinical-trial related documentation. NIH may reject applications lacking this information.
- For an ongoing grant award, you need NIAID’s prior approval before changing any aspects of research involving human subjects. Further, you cannot change an award’s scope from "No Clinical Trial" to "Includes a Clinical Trial" as a post-award action. Requests for such a change must be submitted through a clinical trial NOFO as a competitive revision (Type 3) application.
Skim NOFOs for Key Information on Clinical Trials
Again, NOFOs specify the allowability of clinical trials in both the Funding Opportunity Title and Section II. Award Information with the following designations:
| Clinical Trials Not Allowed | Only accepts applications that do not propose a clinical trial |
| Clinical Trial Required | Only accepts applications that propose a clinical trial |
| Clinical Trial Optional | Accepts applications that propose or do not propose a clinical trial |
Applications that are submitted to the incorrect clinical trial NOFO designation will be administratively withdrawn. If you are submitting a clinical trial, then follow the instructions in your chosen NOFO and NIH’s guidance on Human Subjects and Clinical Trials Information Form, the Clinical Trials Protocol Template, and other key documents described at NIH’s Clinical Trial Requirements for Grants and Contracts.
You may see other NIH Institutes use the designation “Basic Experimental Studies with Humans,” but NIAID does not participate in any such NOFOs.
Investigator-Initiated Clinical Trials
If you are planning to propose an investigator-initiated clinical trial (IICT), we strongly encourage you to take advantage of NIAID’s Investigator-Initiated Clinical Trial Resources. Our IICT guidance and processes are meant to steer investigators to a NOFO that best matches a planned project’s needs.
Choosing an appropriate IICT NOFO comes down to your readiness, project scope, and an assessment of risk. Refer to “How do I determine level of risk and choose an award type for my application?” on Investigator-Initiated Clinical Trial (IICT) Awards-General Questions and Answers.
A “high-risk” clinical trial is defined by NIAID as having one or more of the following:
- Provision of a non-routine intervention, that is, an intervention or non-routine use of an intervention that would not otherwise be provided for the condition under study in the local facility where the study is being conducted.
- Administration of an unlicensed product.
- Administration of a licensed product for an unapproved indication.
Again, we encourage prior consultations with NIAID program staff listed in our IICT NOFOs, ideally at least 12 weeks before you plan to submit an application.