How to Win Focused Technology Research and Development (R01 Clinical Trial Not Allowed) (PAR-25-203)

Section V. Application Review Information 1. CriteriaOnly the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system. For this particular announcement, note the following:The intent of this NOFO is to support high risk projects that are not ready for testing biological hypotheses. As such, the objectives may not address untested biological questions or gain new biological knowledge. Applications should be innovative, include measurable end-point objectives and intermediate milestones, and describe risk management. Preliminary data, theoretical evaluation, alternative approaches, and well-described criteria for success and failure can mitigate risk. The objectives should include development of a functioning prototype(s) that may not be as efficient, robust, or versatile as the final version, but should demonstrate utility to resolve significant biomedical problems. The research strategy should include validation of the technology against known standards such as synthetic models and characterized, gold-standard, biological systems. Projects that are at an intermediate stage, with incomplete preliminary data, but with substantial remaining risk, may request reduced budgets or a shorter project duration. Overall Impact Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following scored review criteria and additional review criteria (as applicable for the project proposed). An application does not need to be strong in all categories to be judged likely to have a major scientific impact. Scored Review Criteria Reviewers will consider Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate factor score. Factor 1. Importance of the Research (Significance and Innovation) SignificanceEvaluate the importance of the proposed research in the context of current scientific challenges and opportunities, either for advancing knowledge within the field, or more broadly. Assess whether the application addresses an important gap in knowledge in the field, would solve a critical problem, or create a valuable conceptual or technical advance.Evaluate the rationale for undertaking the study, the rigor of the scientific background for the work (e.g., prior literature and/or preliminary data) and whether the scientific background justifies the proposed study.InnovationEvaluate the extent to which innovation influences the importance of undertaking the proposed research. Note that while technical or conceptual innovation can influence the importance of the proposed research, a project that is not applying novel concepts or approaches may be of critical importance for the field.Evaluate whether the proposed work applies novel concepts, methods or technologies or uses existing concepts, methods, technologies in novel ways, to enhance the overall impact of the project. Specific to this NOFO:Assess whether the proposed technology development would impact a significant biomedical research community and be of practical utility. Factor 2. Rigor and Feasibility (Approach) ApproachEvaluate the scientific quality of the proposed work. Evaluate the likelihood that compelling, reproducible findings will result (rigor) and assess whether the proposed studies can be done well and within the timeframes proposed (feasibility).Rigor:Evaluate the potential to produce unbiased, reproducible, robust data.Evaluate the rigor of experimental design and whether appropriate controls are in place.Evaluate whether the sample size is sufficient and well-justified.Assess the quality of the plans for analysis, interpretation, and reporting of results.Evaluate whether the investigators presented adequate plans to address relevant biological variables, such as sex or age, in the design, analysis, and reporting.For applications involving human subjects or vertebrate animals, also evaluate:the rigor of the intervention or study manipulation (if applicable to the study design).whether outcome variables are justified.whether the results will be generalizable or, in the case of a rare disease/special group, relevant to the particular subgroup.whether the sample is appropriate and sufficiently robust to address the proposed question(s).For applications involving human subjects, including clinical trials, assess the adequacy of inclusion plans as appropriate for the scientific goals of the research. Considerations of appropriateness may include disease/condition/behavior incidence, prevalence, or population burden, population representation, and/or current state of the science.Feasibility:Evaluate whether the proposed approach is sound and achievable, including plans to address problems or new challenges that emerge in the work. For proposed studies in which feasibility may be less certain, evaluate whether the uncertainty is balanced by the potential for major advances.For applications involving human subjects, including clinical trials, evaluate the adequacy and feasibility of the plan to recruit and retain an appropriate and robust population of participants. Additionally, evaluate the likelihood of successfully achieving the proposed enrollment based on age, racial, ethnic, and sex categories.For clinical trial applications, evaluate whether the study timeline and milestones are feasible. Specific to this NOFO: Assess whether developed technologies will have substantially improved performance relative to currently available tools.Assess whether the project objectives will lead to a working prototype, or whether experimental results will provide an adequate foundation for the next phase of development efforts.Evaluate project intermediate and end point objectives or milestones and assess whether data collection and analysis process(es) will enable quantitative assessment of project outcomes and milestones. If project is at an intermediate stage with insufficient feasibility studies, evaluate the approach for rapidly evaluating the feasibility of the proposed technology. Factor 3. Expertise and Resources (Investigator(s) and Environment) Investigator(s) Evaluate whether the investigator(s) have demonstrated background, training, and expertise, as appropriate for their career stage, to conduct the proposed work. For Multiple Principal Investigator (MPI) applications, assess the quality of the leadership plan to facilitate coordination and collaboration. Environment Evaluate whether the institutional resources are appropriate to ensure the successful execution of the proposed work. Additional Review Criteria As applicable for the project proposed, reviewers will consider the following additional items while determining scientific and technical merit, but will not give criterion scores for these items, and should consider them in providing an overall impact score. Protections for Human Subjects For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects; 2) adequacy of protection against risks; 3) potential benefits to the subjects and others; 4) importance of the knowledge to be gained; and 5) data and safety monitoring for clinical trials.For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, evaluate: 1) the justification for the exemption; 2) human subjects involvement and characteristics; and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects. Vertebrate Animals When the proposed research includes Vertebrate Animals, evaluate the involvement of live vertebrate animals according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animals Section. Biohazards When the proposed research includes Biohazards, evaluate whether specific materials or procedures that will be used are significantly hazardous to research personnel and/or the environment, and whether adequate protection is proposed. Resubmissions Not Applicable Renewals As applicable, evaluate the progress made in the last funding period. Revisions Not Applicable Additional Review Considerations As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score. Authentication of Key Biological and/or Chemical Resources For projects involving key biological and/or chemical resources, evaluate the brief plans proposed for identifying and ensuring the validity of those resources. Budget and Period of Support Evaluate whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research. 2. Review and Selection Process Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons. As part of the scientific peer review, all applications will receive a written critique. Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score. Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions: Scientific and technical merit of the proposed project as determined by scientific peer review. Availability of funds. Relevance of the proposed project to program priorities. Breadth of the Institute’s research portfolio, approaches, and investigators. Total amount of funding available to the investigator. Early-stage investigator status. At-risk investigator status. If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov. NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships. 3. Anticipated Announcement and Award DatesAfter the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.