NCCIH Clinical Trial Funding Opportunity Announcements—Applicant FAQs
1. Why does NCCIH offer separate clinical trial funding opportunity announcements (FOAs) for mechanistic studies and clinical outcome studies?
NCCIH recognizes a difference between clinical trials that are designed to answer specific questions about the clinical effect(s) of interventions and mechanistic studies that have the primary goal of understanding how an intervention works.
- A clinical outcome study is defined as one with the objective of determining the clinical safety, tolerability, feasibility, efficacy, and/or effectiveness of pharmacologic, nonpharmacologic, behavioral, biologic, surgical, or device (invasive or noninvasive) interventions.
- A mechanistic study is defined as one designed to understand the mechanism of action of an intervention, a biological or behavioral process, or the pathophysiology of a disease.
- NCCIH has created a suite of separate clinical trial FOAs to support mechanistic research focused on understanding how a mind and body or natural product intervention works, and to support clinical research to develop and test the feasibility, efficacy, and effectiveness of mind and body or natural product interventions for particular conditions. We encourage investigators to choose which research question they wish to focus on first: “How Does This Intervention Work?” or “Does This Intervention Work for a Given Condition?" Investigators can then select an appropriate FOA.
2. What types of research do the NCCIH clinical trial FOAs support?
3. What kinds of human subjects research will NCCIH still accept through the Parent R01?
The National Institutes of Health (NIH) now offers three options for the Parent R01 (see comparison of FOA types by clinical trial allowability):
- Parent R01 Clinical Trial Not Allowed (PA-20-185): NCCIH will continue to accept applications to this FOA for observational studies such as survey studies, cohort studies, or case-control studies, as well as secondary analyses of existing data sets or banked samples.
- Parent R01 Clinical Trial Required (PA-20-183): NCCIH will only accept applications that propose human mechanistic trials/studies (see NOT-AT-20-001); no applications will be accepted that include any specific aims that propose to assess efficacy or effectiveness of any intervention, unless otherwise noted in a Notice of Special Interest.
- Parent R01 Basic Experimental Studies With Humans Required (PA-20-184): NCCIH will accept applications that propose basic science experimental studies involving humans, referred to in NOT-OD-18-212 as “prospective basic science studies involving human participants.” These studies assess biomedical or behavioral outcomes in humans for the purpose of understanding the fundamental aspects of phenomena without specific application toward processes or products in mind.
4. I want to apply for funding to further analyze an existing clinical trial database to address questions that are beyond those addressed in the planned primary analyses of the trial. Could I use a Parent R01 FOA? Which one?
Yes. Because you do not plan to enroll new participants and will not be recontacting study participants, you could use the Parent R01 Clinical Trial Not Allowed FOA (PA-20-185).
5. I want to apply for funding to conduct a prospective observational study of patients being treated in real-life practice settings. Could I use a Parent R01 FOA? Which one?
Yes. Because the participants are not assigned to a treatment as part of this observational study, you could use the Parent R01 Clinical Trial Not Allowed FOA (PA-20-185).
6. What will happen to my application if I submit a clinical trial focused on clinical outcomes to the Parent R01 (Clinical Trial Required) and ask for it to be assigned to NCCIH?
NCCIH won’t accept your application (see NOT-AT-20-001). The Center for Scientific Review (CSR) might be able to find another Institute or Center (IC) at NIH to accept it, but if other ICs won’t accept it because it doesn't align with their research priorities, the application will be withdrawn without review. To avoid this possibility, it is recommended that applicants contact NCCIH program directors for advice prior to submission and use the NCCIH clinical trial–specific FOAs when appropriate.
7. What’s different about the NCCIH-issued clinical trial FOAs?
The NCCIH FOAs are specifically designed for investigator-initiated clinical trials on complementary and integrative approaches.
- Applicants using the FOAs must provide details about their proposed clinical studies in a standardized way via the “PHS Human Subjects and Clinical Trials Information” form in the application package. (PHS stands for Public Health Service.)
- The NCCIH clinical trial FOAs also require additional attachments depending on each FOA. These attachments may include a Clinical Trial Experience Table, a Milestone Plan, and/or a Project Management Plan. Please check for “Related Notices” in the FOAs detailing any changes to required elements.
- NCCIH special review panels will use the information in the PHS Human Subjects and Clinical Trials Information form and the additional attachments to assess key elements of the clinical study, investigator experience, and how regulatory issues will be addressed.
8. How do I decide if NCCIH is the best fit for my proposal vs. other NIH ICs?
9. How do I decide which FOA to apply for?
10. Who will review applications submitted in response to NCCIH clinical trial FOAs?
Applications submitted to the Notice of Special Interest in Fundamental Science Research on Complementary and Integrative Health Approaches, including natural products or mind and body interventions, via the Parent R01 and R21 FOAs (NOT-AT-21-006), are reviewed by standing study sections in the NIH Center of Scientific Review. Most applications to other NCCIH clinical trial FOAs will be reviewed by NCCIH special review panels with expertise in both clinical trials and complementary health approaches. The panels will include experts familiar with the unique challenges faced by this research community. Panel members also provide valuable advice to NCCIH and constructive feedback to investigators.
11. What is the difference between an RFA (Request for Applications - Grants) and PA/PAR/PAS (Program Announcement/Program Announcement Reviewed by a Specific Institute)?
12. Are there additional review criteria that will affect my proposal's scores and prospects for funding?
Yes. Applicants are strongly encouraged to pay close attention to the review criteria in the FOA. Investigators must include all requested information and address the specific review criteria listed in the FOA. Review criteria will impact the scoring of the application.
13. I’ve heard that applications may be returned without review if they don't contain the required elements or aren't compliant with the FOA instructions. Is this true, and how can I be sure that my application is complete and compliant?
14. What materials can be included in an appendix of an NCCIH clinical trial application?
15. Are multisite trials allowed?
16. Are multisite trials expected to have a single Institutional Review Board (IRB)? Who will organize a single IRB?
NIH issued a policy in 2016 that establishes the expectation that a single IRB of record will be used for multisite research. You can find an introduction to this policy on NCCIH’s Research Blog and the full policy on NIH’s website. Information on special exceptions to the single IRB rule in studies involving U.S. Department of Veterans Affairs and U.S. Department of Defense sites can also be found here.
17. Will NCCIH be taking a more active role as a collaborator in my research?
19. Is data sharing encouraged?
Yes. In some cases, data sharing is required as part of the FOA or by NIH policies (like the NIH Genomic Data Sharing Policy). Please contact an NCCIH program director for details.
20. Is a recruitment plan required? Will NCCIH monitor progress of the trial? Are there consequences for failing to meet the recruitment milestones?
Yes, yes, and yes. Please consult NCCIH’s policy on Study Accrual and Retention for Human Subject Research for details. This policy provides transparency on how NCCIH carries out oversight of study accrual and retention. Corrective actions, up to and including cessation of recruitment for a study, are outlined in this policy.
21. What is a Data Safety and Monitoring Plan?
A complete description can be found on the NCCIH website: Data and Safety Monitoring of NCCIH-Funded Clinical Research. The website includes sample templates that applicants may use.
22. How does an applicant decide what the appropriate level of data and safety oversight is?
23. I received a good score on my clinical trial application at another IC, but they aren’t going to fund it. My research includes a complementary health intervention. Can my application be transferred to NCCIH?
In some cases, NIH applications can be transferred from one IC to another. NCCIH must be a participating component on the FOA for which the application was submitted for NCCIH to accept transfer. Additionally, the NIH IC that accepted your application must be willing to allow transfer of the application to NCCIH. Applicants are encouraged to begin this conversation with the program official assigned to the application before contacting NCCIH.
24. How many Clinical Trial Experience Tables am I required to include? Can I submit a table for each key personnel?
One table must be provided that includes all key personnel, and it must not exceed three pages. If your application includes more than one clinical trial (i.e., more than one study record), you may submit one table per study record with a unique filename for each study record as an attachment (e.g., “Clinical Trial Experience1.pdf”, “Clinical Trial Experience 2.pdf”). For two or more study records, it will be helpful to include more than one Clinical Trial Experience Table if key personnel for each trial (i.e., study record) includes different individuals.
25. Should I only include those clinical trials in the table where all the key personnel have collaborated in the past?
The Clinical Trial Experience Table does not have to be collaborative (i.e., you could list trials that a single key person worked on and others were not involved in), but you are only allowed one table to summarize the experience of all key personnel involved.
26. How many years of experience should I report in the Clinical Trial Experience Table?
The Clinical Trial Experience Table should demonstrate experience of key personnel in clinical trial conduct/coordination in the last 5 years.
27. What information should be included in the Milestones plan? Is there a template for the Milestone Plan that I could follow?
The Milestone Plan should describe the key milestones that you need to be meet throughout the lifecycle of the clinical trial to ensure its success. The processes that will be used to reach the milestones and a timetable identifying when each of these key milestones will be met need to be included in the plan. Some samples for milestones can be found in the NCCIH Clinical Trials Toolbox.