Q1. What is a “mechanistic clinical trial”?
A1. The 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. (NOT-OD-15-015)
A mechanistic clinical trial is designed to understand a biological or behavioral process, the pathophysiology of a disease, or the mechanism of action of an intervention. (NOT-HL-17-546)
Q2. How is NHLBI soliciting applications for mechanistic clinical trials?
A2. Applications for mechanistic clinical trials may be submitted to the parent NIH R01 (Clinical Trial Required) Funding Opportunity Announcement (PAR-18-345). Per a companion notice (NOT-HL-17-546) that NHLBI published in conjunction with this FOA, NHLBI will only accept under this FOA applications that propose at least one mechanistic clinical trial among their aims; other types of clinical trials may not be supported under PAR-18-345. Applications for funding other types of clinical trials must be submitted in response to an NHLBI-published FOA designed specifically for other types of trials (such as Early Phase, Single-site in Phase II and beyond, and Multi-site in Phase II and beyond – please reference our page on the Clinical Trial Development Continuum).
Q3. What is a “parent” funding opportunity announcement (such as the “parent” NIH R01) referenced above?
A3. Parent announcements are broad funding opportunity announcements issued centrally by NIH allowing applicants to submit investigator-initiated applications for specific activity codes. They are open for up to 3 years and use standard due dates. In contrast, individual ICs may issue their own FOAs when they are soliciting applications for particular types of research or for research that has special requirements.
Q4. I am submitting an application for research that includes both a clinical trial and a number of basic research aims. Under what circumstances would this type of project with mixed clinical and basic science research aims be appropriate for one of the NHLBI FOAs for clinical trials as opposed to the NIH Parent R01 (clinical trial required)?
A4. If the clinical trial that you are proposing is aimed at testing the safety and effectiveness of a clinical product, and is in Phase II or above, either the NHLBI FOA for multi-site clinical trials or the FOA for single-site clinical trials may be appropriate. Associated research questions closely related to the aims of the clinical trial, such as understanding the intervention’s effects or the varied response of the participants to the intervention, are permitted as secondary aims under these FOAs.
However, if the study includes a clinical trial (1) as a method to explore fundamental mechanisms of normal biology or pathobiology, or (2) as a major precursor to, or iterative element of, a clinical study (whose design or conduct is predicated at least in part on the basic science study), then it may be more appropriate to apply for funding under the NIH parent R01 or the NHLBI P01.
You are encouraged to discuss your application with your program officer for further guidance.
Q5. Does the review process differ for applications submitted in response to the NIH Parent R01 FOA as compared to those submitted in response to an NHLBI clinical trial FOA?
A5. Yes. Applications submitted to the NIH Parent R01 FOA will be reviewed by a study section assembled by the NIH Center for Scientific Review. Applications submitted in response to an NHLBI FOA will be reviewed by a primary (scientific) review group that NHLBI organizes.
Q6. Is there a limitation on the budget or project period when mechanistic trials are funded through the Parent R01?
A6. No. As is true of all R01 awards, application budgets are not limited but need to reflect the actual needs of the proposed project. In addition, the scope of the proposed project should determine the project period. The maximum project period is 5 years.