Writing NIH Research Project Grants in the Era of Three-Factor Review

In January 2025, NIH adopted the "Simplified Review Framework" (SRF) for Research Project Grant (RPG) applications, shifting the emphasis in grant review. Some investigators may be wondering whether this new framework requires a change in how they write their applications. Below, we explain the goals of the SRF, share feedback from reviewers and NIH staff about it, and provide advice on how to effectively write these applications. 

 

Goals of the Simplified Review Framework (SRF)

The SRF applies to the following grants, which NIH defines as RPGs:

  • Research Grant series: R01, R03, R15, R16, R21, R33, R34, R36, R61, RC1, RC2, RC4, RF1, RL1, RL2, R21/R33 (phased), R61/R33 (phased)
  • Cooperative Agreement series: U01, U34, U3R, UA5, UC1, UC2, UC4, UF1, UG3, UH2, UH3, UH5, UH2/UH3 (phased), UG3/UH3 (phased)

The changes reframe the former scored review criteria (Significance, Investigator, Innovation, Approach, Environment) as three Factors, and this is intended to:

  1. Focus reviewers on three central questions
    • Factor 1: How important is the proposed research? >> Should it be done?
    • Factor 2: How rigorous and feasible are the methods? >> Can it be done?
    • Factor 3: Do the investigators and institution(s) have the expertise and resources necessary to carry out the project? >> Will it be done?
  2. Simplify and strengthen review
    • The SRF shifts away from extensive sets of complex questions and instead encourages reviewers to consider how concepts are integrated.
    • The changes also discourage “yes-no” thinking for Factors 1 and 2.
  3. Reduce reputational bias
    • Reviewers report the adequacy of investigator expertise and institutional resources as a binary choice vs. a numerical rating.
    • This is scored as “Appropriate” or “Additional Resources or Expertise Needed.”
  4. Emphasize rigor in clinical trial design
    • Inclusion criteria and coding, study timelines for clinical trial applications, and plans for valid design and analysis of Phase III clinical trials were removed from "Additional Review Criteria" and integrated into Factor 2 (Rigor and Feasibility).
  5. Reduce reviewer burden
    • Peer reviewers no longer evaluate three (of the original five) "Additional Review Considerations" (Applications from Foreign Organizations, Select Agents, Resource Sharing Plans) because they are not directly related to scientific merit.
    • Instead, NIH staff review these considerations prior to funding.

 

Scoring in the SRF

As in the past, reviewers provide an overall impact score, which reflects their assessment of the likelihood that the project will exert a sustained, powerful influence on the research field(s) involved. As described on the NIH web page Simplified Peer Review Framework (scroll about halfway down), the overall impact score takes into consideration the review criteria (framed as Factors 1, 2, and 3), as well as "Additional Review Criteria" (as applicable for the proposed project), but the project does not need to be strong in all categories to be judged likely to have major scientific impact. Below, we provide brief summaries of the aspects of the proposed research (i.e., termed "Considerations") that reviewers are asked to take into account in evaluating the criteria under Factors 1–3.

  • Factor 1: Importance of the Research (Should it be done?)
    This factor encompasses the criteria Significance and Innovation. It receives a score from 1–9.

    Considerations for Significance

    • Whether the proposed research does all of the following: addresses a key gap or critical problem; advances knowledge or technology; and is justified by background evidence and a rigorous scientific rationale

    Considerations for Innovation

    • Whether the overall impact of the project is enhanced because it either: applies novel concepts, methods, or technologies; or uses existing concepts, methods, technologies in novel ways
    • How extensively this innovation influences the importance of undertaking the proposed research

Think of Significance and Innovation as being complementary – a project may receive a good Factor 1 score if it is very significant but not especially innovative.

  • Factor 2: Approach (Can it be done?)
    This factor includes only the Approach criterion but focuses on two aspects of the scientific quality of the proposed work: rigor and feasibility. This factor receives a score from 1–9.

    Considerations for Rigor

    • Whether the proposed approach has the potential to produce data that are unbiased, reproducible, and robust because it incorporates appropriate controls, sample sizes, analyses, reporting, and plans to address relevant biological variables
    • For studies involving vertebrate animals and human subjects (including clinical trials), whether further relevant considerations for rigor are met

    Considerations for Feasibility

    • Whether the proposed approach is sound and achievable within the allotted timeframe; whether the approach includes plans to address problems or new challenges that emerge; and for proposals where feasibility is less certain, whether the potential for major advances is high
    • For studies involving human subjects (including clinical trials), whether further considerations for feasibility are met, particularly in relation to recruitment, retention, and milestones

  • Factor 3: Expertise and Resources (Will it be done?)
    This factor encompasses the Investigator and Environment criteria and it receives a score of either “Appropriate” or “Additional Expertise or Resources Needed.” When the latter score is given, reviewers must explain what the additional needs are.

    Considerations for Investigator(s)

    • Whether the investigator(s) have the appropriate background, training, and expertise to conduct the proposed work (reviewers take the investigator's career stage into account)
    • For Multiple Principal Investigator (MPI) applications, how likely it is that the leadership plan will facilitate coordination and collaboration

    Considerations for Environment

    • Whether the institutional resources are appropriate to ensure that the proposed work will be successfully executed

 

Impressions of the SRF from study section chairs

The Center for Scientific Review interviewed study section chairs about their impressions of peer review under the SRF and published four short video excerpts (see Learn What Reviewers Say About Implementing the Simplified Review Framework). Below we summarize the key takeaways from those videos:

  • Culture shift to focus more on Factor 1: Importance of the Research
    • The discussion in some study sections now centers on whether the proposed research will move the field forward and, if so, how.
    • Because of the increase in emphasis on whether the research should be done, Factor 1 now sets the ceiling for Overall Impact score.
  • Need for specificity in describing the importance of the proposed research
    • Previously, review was focused on the relevance of the research project to health outcomes (why study of disease x is important), but now review is focused on why this project needs to be done.
    • Therefore, it is no longer sufficient to mention the disease that the work is relevant to and/or the importance of that disease. It is critical to explain specifically how the proposed research will move the field forward.
  • Increased efficiency resulting in more time for discussion
    • Emphasis is now on the importance of the research vs. technical minutia.
    • Considering Significance and Innovation together (Factor 1) reduces the work.
    • Because the PI and institution are reviewed after the science, discussion is less focused on Factor 3.
    • Because primary reviewers have less to cover, more time is available for overall discussion.

 

NIH Instructions and SERCC advice for writing the Research Strategy

The NIH introduces the SRF as “the same research strategy, reviewed in a new way.” This highlights the fact that despite the changes to the review process the instructions for writing a research grant have not changed (see the SF424 Guide – Forms I). Therefore, our advice for the structures of the Specific Aims and Research Strategy documents has not changed (see SERCC Templates and Embedded Examples, NIH Research Grant (R) Application Template, and Strategies for addressing Scientific Premise and Rigor).

  • The key sections NIH requires are still “Significance,” “Innovation,” and “Approach.” We do not recommend renaming these or using the following as higher-level headers:
    • “Significance and Innovation” and “Approach”
    • “Importance of the Research” and “Rigor and Feasibility”
  • For the Significance section, we continue to recommend including the following subsections:
    • Importance of the problem
    • Scientific context and rigor of prior research
    • Significance of the expected research contribution
  • For the Innovation section, we continue to recommend presenting the one to three aspects of the proposed research that are most innovative, and for each explaining:
    • Current strategies and their limitations
    • Ways in which the proposed research differs from current strategies and overcomes past limitations
    • Advances that will be possible only because of the new approach or concept
  • For the Approach section, we continue to recommend including:
    1. A subsection about general aspects of rigor and reproducibility that apply to all the proposed aims
      • This may be further divided into subsections (with headings) on specific aspects of rigor, especially any that are typically highlighted in your field (e.g., power analysis, statistics).
    2. For each aim (and specific to that aim), a subsection that incorporates:
      • The title of that aim
      • Paragraphs about the rationale, justification and feasibility, research design (one paragraph per activity), and aspects of rigor and reproducibility
      • A paragraph about expected outcomes
      • A paragraph about potential problems and alternative strategies
    3. For all aims collectively, a description of your timeline and/or benchmarks for success
      • This information is most effectively presented in a table (space permitting).
    4. A subsection on future directions that would build on the collective outcomes
      • This is optional for many funding mechanisms but highly recommended for pilot or seed grants.

 

Best of luck as you prepare your next RPG for submission to the NIH! 
Chris Blaumueller and the SERCC Team

 

Resources:

  1. Simplified Peer Review Framework
  2. Learn What Reviewers Say About Implementing the Simplified Review Framework
  3. How to Apply – Application Guide
    • General (G) instructions are available in both HTML and PDF format. These can be used to complete the application forms following all standard instructions, and they include information for specific programs (e.g., research, training, multi-project, etc) as well.
    • Filtered instructions for each specific grant program (R, K, T, M, B) are also available as PDFs; these omit any information that is not relevant for that program.
  4. SERCC Templates and Embedded Examples for NIH Research Grant (R) Applications