In alignment with NIH efforts to enhance stewardship over clinical trials, NIDCD has redefined the scope of R01 and U01 clinical trials applications to address risks in terms of safety, complexity, fiscal investment, and direct scientific/public health impact. The cooperative agreement U01 mechanism continues to be most appropriate for higher-risk clinical trials, which will benefit from the substantial scientific and programmatic involvement of an NIDCD Project Scientist. The Project Scientist will provide scientific/technical expertise and, in partnership with the Principal Investigator (PI), will be involved in protocol development; study implementation; and ensuring timely progress, protocol adherence, data quality, and participant safety.
For low-risk clinical trials, NIDCD participates in the following NIH Parent R01 funding opportunities:
- NIH Research Project Grant (Parent R01 Clinical Trial Required) PA-25-305
- NIH Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required) PA-25-303
For high-risk clinical trials, NIDCD has the following primary U01 funding opportunity:
Stand-alone independent clinical trials cannot be proposed as part of the research plan in a fellowship (F) application. See NIDCD Fellowships: Frequently Asked Questions for details.
The risk criteria for applying to the R01 or U01 mechanism are below:
| Award Type | R01 (if ALL of the criteria below are met) | U01 (if ANY of the criteria below are met) |
|---|---|---|
| FDA oversight of the intervention | Does not require FDA oversight, e.g., does not require an investigational new drug (IND) or investigational device exemption (IDE) application. Example: clinical trials involving use of a licensed product/device for an approved dose, population, and indication. In certain cases, may also include a clinical trial under an IND or IDE but is otherwise determined to be low-risk. | Requires FDA oversight, e.g., for investigational new drug (IND) or investigational device exemption (IDE) applications. |
| Anticipated risks to participants | Potential of the intervention to have safety risks to participants is low. Example: risks that are no greater than those encountered in routine medical care or procedures. | Has the potential to have higher safety risks to participants, for example:
|
| Study goals | Intends to gather scientific data/evidence to inform subsequent studies but is not aimed or sufficiently powered to directly change health policy or standard of care and is not an NIH-defined Phase III clinical trial. | Pivotal clinical trial such as an NIH-defined Phase III clinical trial: An NIH-defined Phase III clinical trial is a broadly-based, prospective Phase III clinical investigation, usually involving several hundred or more human subjects, for the purpose of evaluating an experimental intervention in comparison with a standard or controlled intervention or comparing two or more existing treatments. Often the aim of such investigation is to provide evidence leading to a scientific basis for consideration of a change in health policy or standard of care. The definition includes pharmacologic, non-pharmacologic, and behavioral interventions given for disease prevention, prophylaxis, diagnosis, or therapy. Community trials and other population-based intervention trials are also included. |
| Annual direct costs | Application budgets are generally less than $500,000 in direct costs in any year. | Applications exceeding the annual direct costs of $700,000 or more, in certain cases, may also be a criterion. |