Clinical Trial Applicants—Determine Level of Risk

Once you’ve confirmed your planned investigator-initiated research project meets NIH’s Definition of a Clinical Trial, you aren’t done double-checking definitions.

You next need to decide whether NIAID will consider your research to be high-risk. As explained in our recent Notice of Information: Submission of NIAID Investigator-Initiated Clinical Trials to Appropriate FOAs, knowing whether your study is high-risk or not will help determine the funding opportunity announcement (FOA) through which you should apply.

Level of Risk

NIAID defines a “high-risk" clinical trial as having one or more of the following attributes:

• Providing a non-routine intervention, i.e., 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
• Administrating an unlicensed product
• Administrating a licensed product for an unapproved indication

NIH uses the term “high-risk” differently in other contexts—most notably, you may see the phrase “high-risk, high-reward” when an initiative aims to fund innovative research or projects without strong preliminary data. But for clinical trials, the term implies the attributes listed above.

Play It Safe

If you are planning a clinical trial, contact NIAID program staff to request a prior consultation, ideally at least 10 weeks before the application due date. As described at Requesting Prior Consultation—Clinical Trial Applications and Planning Grants, a program officer can help you verify the proposed study’s level of risk.

Why the Distinction Matters

NIAID does not support high-risk clinical trial applications through the following FOAs:

• NIH Research Project Grant (Parent R01, Clinical Trial Required) 
• NIH Exploratory/Developmental Research Grant Program (Parent R21, Clinical Trial Required)

These FOAs are suitable to clinical trials that are not high-risk. However, our investigator-initiated clinical trial FOAs are the appropriate vehicles for proposing a high-risk clinical trial, e.g., NIAID Clinical Trial Implementation Cooperative Agreement (U01, Clinical Trial Required).

Learn more at Investigator-Initiated Clinical Trial Resources.