1. Why is NCCIH issuing new clinical trial funding opportunity announcements (FOAs) and no longer accepting most clinical trial applications via the Parent R01 FOA after May 8, 2017?
Clinical trials are recognized by all as a critically important and high-impact part of the NIH portfolio. Across NIH there is a concerted effort to strengthen the clinical trial portfolio. To achieve this goal, NIH has launched a multifaceted effort to improve the quality and efficiency of clinical trials by enhancing the application and award process and by improving the oversight of clinical trials.
Clinical trials are particularly important to NCCIH. Our mission involves studying health interventions widely used by the American public—interventions often used with scarce evidence of efficacy. We see substantial promise in many of these interventions, but we recognize that the evidence supporting their use is very incomplete. These clinical trial FOAs are part of the pathway to address gaps in current research and build a strong evidence base.
2. What types of research will the new FOAs fund?
They will fund investigator-initiated natural product studies and mind and body intervention studies, targeting support of all phases of clinical intervention development and testing.
We will support investigators working to establish “building blocks” that bridge the gap from basic research to high-impact clinical trials on complementary and integrative health interventions. Examples of building blocks include feasibility testing, assessment of outcome measures, and intervention fidelity testing. Since it is often difficult for investigators to find research funding to establish these building blocks, we’ve developed new mechanisms for these foundational components.
3. What kinds of human subjects research will NCCIH still accept through the Parent R01?
Applicants seeking funding for studies with human participants when the primary outcome/endpoint is explicitly mechanistic, rather than a clinical outcome, may continue to use the Parent R01, as may applicants proposing observational human studies or secondary data analysis. Also, animal and cell based studies will still be accepted through the Parent R01. (See NIH Guide Notice NOT-AT-17-006.)
If you aren’t sure which funding mechanism to use, please contact the appropriate NCCIH program director to discuss your proposed research.
4. What will happen to my application if I submit a clinical trial focused on clinical outcomes to the Parent R01 and ask for it to be assigned to NCCIH?
NCCIH won’t accept your application. 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 mission, the application will be withdrawn without review. To avoid this possibility, contact NCCIH program directors for advice and use the new NCCIH clinical trial–specific FOAs when appropriate.
5. What’s different about the new NCCIH-issued clinical trial FOAs?
The new FOAs are specifically designed for investigator-initiated clinical trials on complementary and integrative approaches.
- Applicants using the new FOAs must provide details about their proposed clinical studies in a standardized way via additional required attachments.
- NCCIH special review panels will use the additional information to assess key elements of the clinical study, investigator experience, and how regulatory issues will be addressed.
6. How do I decide if NCCIH is the best fit for my proposal vs. other NIH ICs?
We strongly encourage you to review the NCCIH Strategic Plan, including the top scientific priority areas listed in the plan, to see if your research interests might be in line with the Center’s. You may also review the Center’s active funding announcements and read any FOAs of interest. If NCCIH is one of several NIH components that has signed on to an FOA, pay attention to statements about our Center’s research interests. Also, look for NIH Guide notices listed in the FOA itself.
We encourage you to contact the appropriate NCCIH program director to discuss your potential application. It may facilitate the conversation if you send a short summary of the specific aims of your study.
7. Do the new clinical trial FOAs indicate that NCCIH will be focusing more on funding clinical research than basic and mechanistic research?
NCCIH is interested in funding a continuum of research. We remain interested in funding basic and mechanistic research, as well as clinical research.
The new clinical trial FOAs focus on helping projects move from basic and translational stages to clinical research and, where possible, toward the development of treatments. For example, we may look for reliable assessment of certain biological signatures of a natural product before funding an efficacy clinical trial on the product.
8. How do I decide which FOA to apply for?
NCCIH has developed separate series of independent clinical trial FOAs for (1) natural product studies and (2) mind and body interventions, so be sure you’re looking at the series best suited for your area of research.
Then, within that series, choose the FOA that most closely matches the stage of research that your project represents. Each series includes FOAs for early phase trials, intermediate trials, and full-scale efficacy, effectiveness, or pragmatic trials. Each FOA describes what type of preliminary data is needed for the stage of research that the FOA supports.
If you’re not sure which FOA is most suitable for your research, please contact the appropriate NCCIH program director.
9. Who will review applications submitted in response to these clinical trial FOAs?
The applications will be reviewed by NCCIH special review panels with expertise in both clinical trials and complementary health approaches. The panels will be assembled with a focus on including experts familiar with the challenges faced by this research community. They should be able to provide valuable advice to NCCIH and constructive feedback to investigators.
Natural product trial applications will go to a special review panel with expertise in clinical trials and natural products. Mind and body intervention trial applications will go to a different special review panel with expertise in clinical trials and mind and body interventions.
10. Are there new review criteria that will affect my proposal’s scores and prospects for funding?
Yes. Applicants need 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 FOAs. Review criteria will impact the scoring of the application.
11. I have heard that applications may be returned without review if they do not contain the required elements or are not compliant with the FOA instructions. Is this true, and how can I be sure that my application is complete and compliant?
Yes. It is standard procedure at NIH to review applications for completeness. The NCCIH clinical trial FOAs describe attachments and information that must be included for your application to be considered responsive and complete. If your application does not include these required elements, it will be returned to the submitting institution.
In addition, the FOAs indicate what stage of research will be supported by each FOA. If your proposed trial is not appropriate for the FOA (for example, if you submit an application for an efficacy trial to an early phase clinical research FOA), your application will be reviewed, but NCCIH will not fund it.
12. Are multisite trials allowed?
Yes, the UG3/UH3 FOAs encourage the submission of multisite trials to assess efficacy and effectiveness of complementary health approaches, and the U01 FOAs also allow multisite studies, but please discuss your proposed trial with the appropriate NCCIH program director before submitting your application.
All UG3/UH3 clinical trial proposals require the submission of a companion data coordinating center application (U24).
13. 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 Web site.
14. Do the mechanism changes reflect a de facto shift toward NCCIH soliciting research vs. investigator-initiated research?
Investigator-initiated proposals have always been the “bread and butter” of NIH and we continue to welcome these proposals. All of the new clinical trial FOAs provide a framework for investigator-initiated applications.
15. Will NCCIH be taking a more active role as a collaborator in my research?
For the cooperative agreement mechanisms (i.e., U awards), an NCCIH staff member will be assigned as a program scientist and participate in the steering committee for your award. This person is meant to serve as a resource to the study team.
NCCIH staff have knowledge of the challenges presented by complementary and integrative health research and are available to help grantees address these challenges. The NCCIH Clinical Research Toolbox is an example of one resource that we have developed to assist investigators.
16. Is it necessary to register all clinical trials with clinicaltrials.gov?
Yes. For more details, review the NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information.
17. Is data sharing encouraged?
Yes. Please contact an NCCIH program director for details.
18. 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 will carry out its oversight responsibilities.
19. 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. Should I use the parent R01 FOA?
Yes. Because you do not plan to enroll new participants and will not be recontacting study participants, you should use the parent R01 FOA.
20. I want to apply for funding to conduct a prospective observational study of patients being treated in real-life practice settings. Should I use the parent R01 FOA?
Yes. Because the participants are not assigned to a treatment as part of this observational study, you should use the parent R01 FOA.
21. I currently have a human subjects R01 from NCCIH. How do I submit a competitive renewal for my R01 (type 2)?
After May 8, 2017 (NOT-AT-17-006), NCCIH will no longer accept most clinical trial applications via the Parent R01 (PA-16-160). If your R01 was funded under the Parent R01 FOA, NCCIH will not accept your renewal application via this FOA. The CSR might be able to find another IC at NIH to accept it, but if other ICs won’t accept it because it doesn’t align with their missions, the application will be withdrawn without review.
To avoid this possibility, contact NCCIH program directors for advice and use the new NCCIH clinical trial-specific FOAs when appropriate.
22. I submitted an application with human subjects to NCCIH via the Parent R01 last year. Can I use the Parent R01 to resubmit my application to NCCIH now?
After May 8, 2017 (NOT-AT-17-006), NCCIH will no longer accept most clinical trial applications via the Parent R01 (PA-16-160). NCCIH will not accept new or resubmission applications via the Parent R01 FOA. The CSR might be able to find another IC at NIH to accept it, but if other ICs won’t accept it because it doesn’t align with their missions, the application will be withdrawn without review.
To avoid this possibility, contact NCCIH program directors for advice and use the new NCCIH clinical trial–specific FOAs when appropriate.
23. What is a Data Safety and Monitoring Plan?
A complete description can be found on the NCCIH Web site: Data and Safety Monitoring of NCCIH-Funded Clinical Research. The Web site includes sample templates that applicants may use.
24. How does an applicant decide whether a Data and Safety Monitoring Board (DSMB) is required?
NCCIH requires independent monitoring of all human subjects research. A DSMB is required for all Phase III trials and should be considered for other clinical trials with associated safety risks.
You can learn more from the documents in NCCIH’s Clinical Research Toolbox and from NCCIH’s policy on Data and Safety Monitoring of NCCIH-Funded Clinical Research.
25.What materials can be included in an appendix of an NCCIH clinical trial application?
Nearly all of NCCIH’s clinical trial FOAs require additional attachments including a protocol synopsis of up to 12 pages in a standardized format, an additional 3 pages for a table of all study investigators’ experience conducting clinical trials, and an additional 3 pages to describe how regulatory issues will be addressed by the study team. Additional items are required for multisite trials. Please see the instruction section of the FOA you plan to use for further details.
Per NIH policy, unless the FOA provides other instructions, applicants may use the appendix to include:
- Clinical trial protocols
- Investigator’s brochure from an Investigational New Drug application, as appropriate for the goals of the proposed research
- Blank informed consent/assent forms
- Blank surveys, questionnaires, and/or data collection instruments
- Other items only if they are specified in the FOA as allowable.
26. What is the difference between an RFA (Request for Applications – Grants) vs. PA/PAR/PAS (Program Announcement/Program Announcement Reviewed in an Institute)?
A PA/PAR/PAS is an ongoing solicitation, usually with multiple receipt dates. A PAR is a PA with special receipt, referral, and/or review considerations. A PAS is a PA that includes specific set-aside funds. RFAs are solicitations in a well-defined scientific area to accomplish specific program objectives. RFAs usually have a single receipt date, are reviewed by a review group convened only for that RFA, and have set-aside funds for awarding grants.
Please contact the appropriate NCCIH program director to ensure your proposed study is within NCCIH priorities before preparing an application.