Dr. William Parks_Signficance Innovation.pptx

Dr. William Parks_How to Craft the "Significance” & "Innovation" Sections of a Grant Application.

1. Significance and Innovation William Parks, PhD Department of Medicine Cedars-Sinai Medical Center

2. Significance and Innovation Required R01 Grant Sections Face Page Table of Contents Performance Site Project Description: Abstract Project Narrative: 2 sentences References Cited Facilities and Other Resources Equipment Key Personnel Biosketches Budget (all years) Budget Justification Introduction (resubmission only) Specific Aims Research Strategy Significance Innovation Approach Protection of Human Subjects Women & Minorities Planned Enrollment Table Children Vertebrate Animals Select Agents Multiple PI Plan Letters of Support Data Management & Sharing Authentication of Key Biological and/or Chemical Resources PHS Assignment Form

3. Significance and Innovation Scored Review Criteria Investigator Initiated R-series Grants Significance Investigator Approach Innovation Environment Overall Impact

4. New ‘Simplified’ Review Framework January 2025 - https://grants.nih.gov/policy/peer/simplifying-review.htm For RPGs only (not K, F, others) Will not affect application materials Still vague; guide to reviewers not yet released " Should the proposed research project be conducted? ” Significance Approach

5. Innovation

6. Innovation Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? Current Instructions to Reviewers

7. Innovation Two flavors New concepts or challenges to existing paradigms or dogma New reagents, assays, technologies, practices, etc. Often not a major review criteria – but can be a big plus Not mentioned in instructions to reviewers for K or F applications

8. Innovation Keep it short 1-2 paragraphs Bulleted list No data, figures Do not be redundant Be realistic, be succinct We are exploring the novel concept that excess syndecan-1 promotes dysfunction of AT2-to-AT1 differentiation in age-related fibrosis. Our approaches include a variety of new, sophisticated quantitative tools, including a computational method to identify senescent cells and a dual-recombinase cell-specific genetic lineage mouse model.

9. Innovation Applicant’s Assessment of their Innovative Strengths Reviewers’ Assessment of the Innovative Strengths

10. Significance

11. Significance – Review Criterion Does the project address an important problem or a critical barrier to progress in the field ? Is the prior research that serves as the key support for the proposed project rigorous ? If the aims of the project are achieved , how will scientific knowledge, technical capability, and/or clinical practice be improved ?  How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Instructions to Reviewers

12. What is Significance and How is it Evaluated? Not related to the disease or cellular process you are studying After all, all diseases are significant Basic science research can have an impact Rather, if the aims are achieved , will scientific knowledge, technical capability, and/or clinical practice be improved? Hence, Research Approach impacts Significance A wet-lab proposal that is descriptive or derivative or will gather correlative information will not be significant - Epidemiology or clinical studies may seek associative findings Evaluation of and attention to rigor

13. Common Misconception Significance only means translational science, clinical importance, and/or disease related Not true : basic research can have a great an impact “ NIH’s mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability. ” An application does not need to show the potential for clinical impact You do not need to develop a new drug!

14. Describe the strengths and weaknesses/gaps in the rigor of the prior research (published and unpublished) that serves as the key support for the proposed project and plans to address weaknesses/gaps. Rigor : Strict application of the scientific method to ensure robust and unbiased experimental design, methodology, analysis, interpretation, and reporting of results. Research Plan: Must address relevant variables Sample size, sex, age, weight, health condition, etc. Must address sex (approach) Authentication of key biological and/or chemical resources (1 page) Rigor is addressed by reviewers under both Significance (previous) and Approach (planned) https://grants.nih.gov/grants/peer/guidelines_general/Reviewer_Guidance_on_Rigor_and_Transparency.pdf https://grants.nih.gov/grants/guide/notice-files/NOT-OD-18-228.html Significance – Rigor of Previous Work, Yours and Others

15. Discuss the rigor of the research and data – both yours and others – that form the foundation of your project. Discuss how will you address any weaknesses pointed out in #1. Include strategies that assure a lack of bias and an overall robust approach. Address relevant variables, especially sex. How to Address Rigor in the Research Strategy Significance Approach

16. Significance ( Background) 1-1.5 pages Critically review the literature and provide a clear premise No limit on number of citations Original, timely papers over reviews Rigor: Point out gaps and flaws; strengths, too Do not be afraid to say you disagree with something (but explain why and how you will correct this travesty) Be diplomatic Limit discussion to things (pathways, diseases, molecules, etc.) you will study Show (tempered) enthusiasm Know your audience Get the reviewers interested Pet Peeves Needlessly long Not focused Not timely nor scholarly Reliance on reviews Uses the word “ exciting ” more than once Poorly developed premise Does not address rigor

17. Overall Impact vs. Significance Overall Impact Likelihood of making a sustained, powerful influence on the field Integrates the 5 scored criteria Not the mean of the 5 criteria Significance Focus on relevance and likelihood of making a meaningful advance if the aims are achieved. Addresses an important problem or critical barrier to progress Topic ≠ Significance