How to Win BRAIN Initiative Cell Atlas Network (BICAN): Specialized Collaboratory on Human, Non-human Primate, and Mouse Brain Cell Atlases (R01 Clinical Trial Not Allowed) (RFA-MH-22-292)

Section V. Application Review Information 1. Criteria Only 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:Since this FOA specifically seeks applications to systematically generate brain cell census and atlas data and possibly related tools, the NIH expects that some applications may propose mature and well-established approaches to produce robust high quality datasets for broad use by the research community. 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 review criteria and additional review criteria (as applicable for the project proposed). Scored Review Criteria Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field. Significance 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? Specific to this FOA: How well do the proposed aims and scientific questions align with the overarching goals and the expected outcomes of the BICAN? To what extent do the efforts described in the Plan for Enhancing Diverse Perspectives further the significance of the project? Investigator(s) Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance, and organizational structure appropriate for the project? Specific to this FOA: Are the PD/PI and other key personnel devoting sufficient time/effort to achieve the goals? To what extent will the efforts described in the Plan for Enhancing Diverse Perspectives strengthen and enhance the expertise required for the project? 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? Specific to this FOA: How well does the application describe evidence that demonstrates the novelty of cell atlas and census data to be generated? To what extent will the novel data lead to transformative, paradigm-shifting advances of the field? To what extent will the efforts described in the Plan for Enhancing Diverse Perspectives meaningfully contribute to innovation? Approach Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects? If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed? Specific to this FOA: For projects involving the use of human brain tissue, how well does the application describe and discuss Human Brain Specimen Acquisition, Processing, and Characterization? Is the proposed plan likely to result in high quality brain specimens suitable for the proposed analyses? How well does the application describe and discuss the data quality and reproducibility, and data breadth and depth? Does the Assay Sampling Plan provide adequate details? Are potential pitfalls clearly discussed and minimized accordingly? How well does the application provide a rationale and supporting data on the adequacy of the cell sampling strategy? Will experimental designs result in high-resolution cell atlas and cell census data? How well does the application present preliminary data to support feasibility of the proposed scalable methods and adequate throughput? Are rate-limiting steps identified and appropriately addressed? How well does the application demonstrate an effective workflow? Does the adequately application describe workflow assessments and proposed improvements? Does the application demonstrate the capability to generate data at scale? Does the application provide sufficient evidence of how production goals are set and can be attained? How well does the application describe data management, modeling, analysis, visualization, and integration? Is the plan for data registration to a brain atlas and/or common brain coordinate system adequate? Does the application adequatelypropose and justify standards and formats of the data/metadata, data analysis methods? Are there appropriate data infrastructure(s) and pipeline(s) to support data sharing? How well does the Data Sharing Plan provide a summary of the shared data, a description of the data standards, a plan for the data archiving, and a timeline for data submission to the archive and sharing data with the research community? How well does the Resource Sharing Plan provide a summary of the shared resources, a plan for the resource dissemination via open repositories, and a timeline for sharing the resources with the research community? Are the timeline and milestones associated with the Plan for Enhancing Diverse Perspectives well-developed and feasible? Environment Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment, and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? To what extent will features of the environment described in the Plan for Enhancing Diverse Perspectives (e.g., collaborative arrangements, geographic diversity, institutional support) contribute to the success of the project? Additional Review Criteria As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items. Milestones Are the milestones and timelines sufficiently clear, quantitative, and actionable? Do the milestones provide proper criteria for evaluating the progress and direction of the proposed research? How thorough and appropriate are the plans for critically evaluating and revising milestones on a regular basis? How feasible are the timelines proposed for achieving the milestones? 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, the committee will 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, the committee will 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. Inclusion of Women, Minorities, and Individuals Across the Lifespan When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research. Vertebrate Animals The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment 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. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section. Biohazards Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed. Resubmissions For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project Renewals Not Applicable Revisions Not Applicable Additional Review Considerations Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review. 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. Applications from Foreign Organizations Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources. Select Agent Research Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s). Resource Sharing Plans Not Applicable Authentication of Key Biological and/or Chemical Resources: For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources. Budget and Period of Support Reviewers will consider 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 NIMH, 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. Appeals of initial peer review will not be accepted for applications submitted in response to this FOA. 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 FOA. 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. Programmatic balance. The purpose is to develop a network with complementary capabilities towards generating a comprehensive brain cell atlas. Therefore, decisions about awards will consider the mix of capabilities offered by the proposed centers and collaboratories. Relevance of the proposed project to program priorities including the PEDP. 3. Anticipated Announcement and Award Dates After 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.