Frequently Asked Questions for PAR-21-079 - NHLBI Clinical Trial Pilot Studies (R34 Clinical Trial Optional)
Frequently Asked Questions:
Program Officials listed in the FOA can address any questions not listed here.
Q1: Are first in human studies, early safety studies, phase I, other early development intervention studies or other feasibility studies responsive to this Funding Opportunity Announcement (FOA)?
A1: Probably not. If your intent is an early safety study or Phase I study, you should look at Funding Opportunity Announcement PAR-18-683 or PAR-18-684, NHLBI Early Phase Clinical Trials for Therapeutics and/or Diagnostics. The intent of this NHLBI R34 FOA is to provide support to collect information needed to finish the design of a clinical trial with public health importance. A review consideration specific to this FOA is “Is acquisition of pilot study data critical to address the objectives of a full-scale trial?” In general, first in human studies, early safety studies, studies to define dose-response or other Phase I or I-II type studies will not meet the criterion of both “necessary and sufficient” to design the planned full-scale trial with large public health impact.
Q2: What should be included in the “Future Clinical Trial Description” if the design of full-scale trial is not final?
A2: The purpose of this attachment is to provide context for the goals of the R34 award. The reviewers will use this information to evaluate how the pilot study contributes to the full scale trial’s goals and how the results of the pilot study will inform its design. Specifically, the application should contain enough information for the reviewers to evaluate: 1) the hypothesis of the trial; 2) the public health impact of the trial; 3) whether the planned design of the trial will address the hypothesis; 4) how the information gathered through an R34 grant will contribute to the design of the trial; and 5) whether the information gathered with the R34 is both necessary and sufficient for you to make the final decisions about the trial design.
Q3: I have developed a clinical trial and need support to identify clinical sites, finalize the protocol and write the manual of procedures. Is the NHLBI R34 mechanism appropriate?
A3: No, it is not. Some R34 FOAs sponsored by other NIH institutes permit this, but the NHLBI PAR-21-XXX is specifically tailored to support research addressing gaps in knowledge necessary to complete the design of a trial with large public health impact.
Q4: If I am an Early Stage Investigator (ESI) and am awarded an R34, will I lose the ESI status?
A4: No, an R34 does not count against the ESI status. However, other factors could. Please see the NHLBI Funding and Operating Guidelines, subheading on Early Stage Investigators.
Q5: If I qualify as an Early Stage Investigator (ESI), will I be given special funding consideration?
A5: No, the R34 is not eligible for ESI special funding consideration.
Q6: Where is my R34 application reviewed?
A6: The R34 applications are reviewed by a committee that is convened by the NHLBI Office of Scientific Review and reviews all the R34 applications. You can expect these reviewers to review the R34s looking for many of the same things as a regular clinical trial. You will need a strong justification of the public health impact and the importance of the follow-up trial. In general, the review group expects clinically important outcomes in the follow-up trial or evidence that intervention on the surrogates correlates strongly with the clinical outcome. You will also need clear data management and analysis plans. It should be very clear how you will use the information from the R34 to inform the follow-up trial. They will want to know, for example, what your decision criteria are and how will you decide that a full-scale trial is justified based on the information you gathered in the R34 or how you will use the information to modify your plan. And, as usual, the reviewers will evaluate your ability as investigators.
Q7: My R34 application will include a multi-site clinical trial. Is this permitted?
A7: Yes, a multi-site clinical trial is permitted in the R34 application if it is scientifically justified to obtain the “necessary and sufficient” information needed to design the subsequent trial.
Q8: Can I submit two R34s for the same planned follow-up trial?
A8: No. If you need two R34s, neither one will meet the criterion of “both necessary and sufficient” to design the follow-up trial.
Q9: If I submitted an application for a clinical trial to NHLBI previously and the reviewers said that I needed more data to justify or show feasibility of one aspect, may I apply for an R34 for that trial?
A9: Yes, if the questions you are asking meet the criteria of PAR-21-NNN, you may apply, even if you have already applied unsuccessfully for the same trial. The R34 will be a new application; however, following completion of the R34, the follow-up application will be considered a resubmission (A1).
Q10: How do I decide whether to submit an R34 or UG3/UH3 for a small multi-site intervention trial?
A10: If you have all the information that you need to design the trial, you should apply directly to PAR-19-329 and PAR-19-330. The NHLBI R34 mechanism is specifically designed to allow investigators to collect information needed to enhance the quality of the trial design and the likelihood of successful launch and completion.
Q11: Are studies involving vertebrate animals appropriate to be conducted under this FOA?
A11: Although not specifically prohibited by the PAR, it is very unlikely that studies involving vertebrate animals will contribute to the completion of aims that are necessary and sufficient to commence a definitive trial of public health impact and is discouraged.
Q12: I serve on study section and am eligible for continuous submission. May I submit my application late?
A12: Yes, see the NIH Continuous Submission page for full details including how to check your eligibility, and the associated Frequently Asked Questions. If you have further questions about this, please contact the Scientific Review Officer, listed in the FOA.
Q13: Are there any additional instructions for the application?
A13: Follow the instructions in the SF424 Application Guide as modified by the instructions in the FOA. Note that the FOA requires additional attachments, such as the “Future Clinical Trial Description”, any contracts, memorandums of understanding or agreements, and any FDA approval. Detailed information is contained in Section IV.2. Applications may not be reviewed if they do not contain the required information. Please read the entire FOA for all the requirements, many of which have changed from previous issuances of this PAR.
Q14: Are appendices permitted?
A14: Only limited appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide. NIH issued a series of notices, the most recent on January 12, 2018, NOT-OD-18-126, Updated Appendix Policy Eliminates Clinical Trial-Related Materials. The required file, “Future Clinical Trial Description.pdf” should be included as an attachment. It should be included under the “Other Project Information” section of the application, should be bookmarked for easy access by reviewers, and may not exceed 3 pages. It should provide a description to the extent known of the future clinical trial to provide context for information sought in the R34 award.
Q15: Should the required future clinical trial description file be submitted as an appendix?
A15: No, see the related question Q.14. The R-34 required file, “Future Clinical Trial Description.pdf”, should be included under “Other Project Information” section of the application, should be bookmarked for easy access by reviewers, and may not exceed 3 pages.
Q16: May I include the description of the subsequent clinical trial in the main body of the application?
A16: No, the “Future Clinical Trial Description.pdf” file is required and should be included as an attachment. The summary should not describe any pilot trial(s) that may be conducted during the R34 period of award.
Q17: May I conduct focus groups during the R34?
A17: Data collection from focus groups or other sources may be appropriate for this FOA when adequately justified, and supportable as both necessary and sufficient for the finalization of the study design for the subsequent full-scale trial. Just as with the collection of information from other sources, the reviewers will evaluate the methods and plans for how the information will be analyzed and used.
Q18: Is this mechanism appropriate for an implementation research study to develop an app or other electronic interface to be used as part of the implementation strategy to be tested?
A18: If development of the app or other electronic interface is both necessary and sufficient to design and carry out a phase II or above implementation clinical trial, then this funding mechanism could be appropriate. However, if the purpose of the proposal is to develop a de novo implementation strategy, this FOA is likely not appropriate because this study will likely not meet the criterion of both “necessary and sufficient” to design the planned full-scale trial with large public health impact.
Q19: Since applications are reviewed by the NHLBI Office of Scientific Review-convened committee, does the panel have specific expertise in implementation science and behavioral science?
A19: Applications are reviewed within an NHLBI-convened study section, which includes scientists with expertise appropriate to the submitted applications for each specific review rounds.
Q20: I wish to conduct an implementation trial using an implementation framework to guide my design and outcomes. Is this mechanism appropriate for evaluating the most appropriate implementation framework to use for the larger-scale trial?
A20: Yes, if this information is necessary and sufficient for designing the planned full-scale trial with large public health impact.
Q21: I am working with some fellow investigators developing a clinical trial and am wondering which mechanism is the best fit.
A21: If you are considering a clinical trial, we recommend reviewing the criteria in all the NHLBI Funding Opportunity Announcements (The Catalyzing Clinical Trial Design FOAs are no longer active.) Further embedded within the FOAs is the link to the NHLBI Notice that contains, among other information, the information that Phase II and beyond trial applications must be submitted to an NHLBI specific FOA and multi-site trials must have a separate CCC and DCC application. If you anticipate that the combined cost will be more than $500,000 in direct costs in any year, see Applications with Direct Costs of $500,000 or More in Any One Year. If you still have questions, please call the contact program staff in your subject area.
Q22: I am planning on submitting an application for a clinical trial, but am trying to understand the difference between the first phases of the UG3/UH3 and R61/R33 and an R34.
A22: The NHLBI Clinical Trial Pilot Studies-R34 FOA specifically states that the studies in the R34 must be both necessary and sufficient to finalize the design of the subsequent full scale trial. The first phases of the UG3/UH3 and R61/R33 are to support development of the protocol, manual of operations, and other resources necessary to the performance of the trial; further development of study partnerships; finalization and Institutional Review Board/Data and Safety Monitoring Board approval of the trial protocol and informed consent(s)/assent(s); and activation of clinical sites. In general, the expectation is to enroll the first subject before the UG3 or R61 year.
Q23: I want to perform a non-traditional clinical trial or an adaptive trial and need support for developing the appropriate statistical plan, including simulations, in collaboration with biostatisticians with unique expertise or novel trial design experience. Is this permitted?
A23: Yes. Appropriate collaborations in studies to develop non-traditional trial design or novel statistical approach are appropriate, as long as they are necessary AND sufficient to design the subsequent trial.
Last Updated: March 10th, 2020