You have an idea for a full-scale clinical trial that you would like to eventually fund with an R01. How do you go from concept to R01 funding for the full-scale trial?
NIH has several funding mechanisms that can help you lay the groundwork for a future R01-funded trial. Here, we outline some of the more common planning mechanisms and the features of each. Note that this is not an exhaustive list– your IC may have other mechanisms (e.g., U01) to help you plan for a future R01-funded trial. You can search for active NOFOs here. Always discuss your NOFO options with a program officer before applying.
R34 Planning Grant (17 Active NOFOs)
When I have an applicant looking to write a clinical trial planning grant, this is always the first mechanism we consider because it is ideally suited for this purpose and because there are many active NOFOs across ICs.
The R34 Planning Grant supports the planning and development of a clinical trial or research project. R34 funding covers activities such as:
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establishing the research team
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developing data management and research oversight tools
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refining the trial or research design
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collecting feasibility data
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developing procedure manuals
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refining recruitment, retention, and data collection procedures
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adapting study interventions for specific populations or settings.
There are R34 NOFOs that require clinical trials. In such cases, the planning grant is meant to allow for the early peer review of the rationale and concept for the proposed clinical trial. It will also support the development of clinical trial elements, and will lead to an application for support of a full-scale trial based on the elements developed during the planning period.
The parent R34 was phased out a few years ago, but many Institutes & Centers (ICs) offer their own R34. Awards can vary, but a typical amount is $450,000 total direct costs over 3 years. At time of writing, there were 17 active R34 NOFOs at NIH funded by a variety of ICs.
R21 Exploratory/Developmental Grants
The R21 is used for the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) There is a parent NOFO and many IC-sponsored mechanisms, but they are not typically designed specifically as clinical trial planning grants. Therefore, you must make certain that your specific NOFO allows the type of project you plan to propose. These NOFOs typically offer $275,000 total direct costs over two years, but time and budget may vary across NOFOs.
R61 Phase 1 Exploratory/Developmental Grant (3 active standalone NOFOs)
As part of a bi-phasic approach to funding exploratory and/or developmental research, the R61 provides support for the first phase of the award. However, at time of writing, there are 3 active standalone exploratory R61s: PAR-24-279, RFA-CA-25-003, and RFA-CA-25-001.
Some R61 NOFOs do not allow clinical trials. If paired with the R33, the clinical trial is required. R61 award amounts can vary tremendously by NOFO, but typical awards are $450K- $600K total direct costs and have project periods of up to 3 years. Be sure to check the NOFO. Choose the R61 (either standalone or paired with the R33 in a biphasic mechanism) if your exploratory project specifically fits the topic of an active NOFO and is sponsored by your target IC, and you need a larger budget than might be available on an R21 or R34.
Some researchers may use the R61as a way to de-risk an idea before moving forward with an R01 clinical trial. While it’s common to follow an R61 with an R33 (see below), if the NOFO doesn’t mandate it, you have the option to complete the R61 and move directly to an R01. Be sure to check your R61 NOFO for any conditions regarding the progression.
R33 Exploratory/Developmental Grants Phase II (11 active standalone NOFOs)
The R33 is typically combined in a phased mechanism, as the second phase with either R21 or R61 as the first phase. However, at time of writing, there are 11 standalone R33 NOFOs. Awards vary quite a bit by NOFO. Awards might be 2-5 years (3 years is typical). Many NOFOs don’t specify an annual cap on directs, while others state the annual cap should be $300-$350K per year or higher.
NIH’s definition of the R33 activity code says that only recipients of an R21 are eligible to apply for R33 support. However, certain program initiatives and NOFOs will establish criteria that allow applications to be received from awardees of other mechanisms, such as an R61. Also, applicants can apply for an R33 without having an active R61 or R21 as long as the proposed project aligns with the R33’s goals for that phase and the NOFO allows it.
Phased mechanisms. Phased mechanisms of any kind at NIH require you to meet certain milestones in the first phase in order to qualify for the second phase. These milestones should be carefully spelled out in the application so that program officers can determine during the project period whether you have met the milestones when you reach the “go/no go” point in the award cycle.
R21/R33: (2 active NOFOs) Some NOFOs are issued for biphasic R21 and R33 mechanisms. In these cases, the application should include components for both phases. The R21 provides support for the first phase of the award (up to two years) and the R33 provides funding for the second phase (up to 3 years).
R61/R33: (19 active NOFOs) This activity code is used in lieu of the R21/R33 activity code when larger budgets and/or project periods are required to establish feasibility for the project.
