PAR-27-003-Full-Announcement.html

Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of General Medical Sciences (NIGMS)

National Eye Institute (NEI)

National Human Genome Research Institute (NHGRI)

National Institute on Aging (NIA)

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

National Institute of Allergy and Infectious Diseases (NIAID)

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

National Institute on Deafness and Other Communication Disorders (NIDCD)

National Institute of Dental and Craniofacial Research (NIDCR)

National Institute on Drug Abuse (NIDA)

National Institute of Neurological Disorders and Stroke (NINDS)

National Library of Medicine (NLM)

National Center for Complementary and Integrative Health (NCCIH)

Funding Opportunity Title

Collaborative Program Grant for Interdisciplinary Teams (RM1 Clinical Trial Optional)

Activity Code

RM1 Research Project with Complex Structure

Announcement Type

New

Related Notices

Check for any recent Notices of NIH Policy Changes that may impact application requirements.

Funding Opportunity Number (FON)

PAR-27-003

Companion Funding Opportunity

None

Number of Applications

See Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s)

93.859, 93.121, 93.879, 93.846, 93.867, 93.855, 93.853, 93.866, 93.173, 93.273, 93.279, 93.172, 93.473

Funding Opportunity Purpose

This Notice of Funding Opportunity (NOFO) supports interdisciplinary research teams of three to six Program Directors/Principal Investigators (PDs/PIs) to address ambitious and challenging research questions. Collaborative program teams are expected to be integrated, working together to tackle a single focused scientific goal that requires considerable synergy and meaningful team interaction. Program goals should not be achievable through individual efforts or a collection of projects. Teams are encouraged to consider far-reaching objectives that will produce major advances in their fields.

Funding Opportunity Goal(s)

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.

Key Dates

Posted Date

October 14, 2026

Open Date (Earliest Submission Date)

October 17, 2026

November 17, 2026

November 17, 2026

Not Applicable

July 2027

January 26, 2027

January 26, 2027

Not Applicable

December 2027

May 26, 2027

May 26, 2027

Not Applicable

April 2028

September 27, 2027

September 27, 2027

Not Applicable

July 2028

January 26, 2028

January 26, 2028

Not Applicable

December 2028

May 26, 2028

May 26, 2028

Not Applicable

April 2029

September 26, 2028

September 26, 2028

Not Applicable

July 2029

January 26, 2029

January 26, 2029

Not Applicable

December 2029

May 29, 2029

May 29, 2029

Not Applicable

April 2030

September 26, 2029

September 26, 2029

Not Applicable

July 2030

All applications are due by 5:00 PM local time of applicant organization.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Expiration Date

September 27, 2029

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the How to Apply - Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the How to Apply - Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

Table of Contents

Part 1. Overview Information Key Dates Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description Section II. Award Information Section III. Eligibility Information Section IV. Application and Submission Information Section V. Application Review Information Section VI. Award Administration Information Section VII. Agency Contacts Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

C omplex and challenging research questions benefit from the integrated effort of multiple Program Directors/Principal Investigators (PDs/PIs) employing complementary approaches with different areas of expertise. These efforts can converge on high-impact discoveries, such as creating new disciplines, resolving longstanding questions, unraveling intractable problems, or defining new areas that challenge existing paradigms.

This NOFO invites Collaborative Program Grant (Team Science) applications from organizations that propose projects addressing complex and challenging scientific problems within the missions of participating NIH Institutes and Centers (ICs). The Team Science Grant is designed to support interdisciplinary research that offers significant advantages over supporting individual research grants or Program Project/Center grants, which often have separate aims or components. Interdisciplinary research teams must have a highly integrated approach to tackle a single, focused scientific problem and achieve anticipated outcomes. Team Science applications should demonstrate interdependent collaboration and synergy among all PD/PIs and show that the team's combined knowledge and expertise are essential to achieving program objectives and addressing unanticipated challenges.

Research involving human subjects is permitted. NIH-defined clinical trials are optional. Applicants are encouraged to identify a participating IC that supports their area of research. Applications that bridge the research interests of more than one area of science are also encouraged but must remain within the missions of participating ICs.

Features of successful applications include:

In addition, the following considerations may be useful in crafting an application combining multiple perspectives, experiences, and career stages:

Prior Consultation with IC staff A limited number of Team Science applications will be funded. Applicants are strongly encouraged to consult with relevant ICs' staff as early as possible prior to submission. Staff can advise on:

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

Applications Not Responsive to this NOFO The following types of applications are not responsive to this NOFO and will not be reviewed:

Applications that propose a clinical trial and only align with the mission of an IC that does not support clinical trials. ICs that do not support clinical trials under this NOFO include: National Institute of Dental and Craniofacial Research (NIDCR)

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

Funding Instrument

Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed

New

Renewal

Resubmission

Revision

The OER Glossary and the How to Apply - Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Clinical Trial?

Optional: Accepting applications that either propose or do not propose clinical trial(s).

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations and the receipt of a sufficient number of meritorious applications.

Award Budget

Applications may request budgets of up to $1.5 million in direct costs per year; however, most awards are expected to be between $500,000–$900,000 in direct costs annually.

Award Project Period

Applications may request up to five years of support. Teams wishing to continue their project beyond 5 years are strongly advised to consult with participating ICs prior to submitting a renewal application. Renewals beyond ten years of total support are not allowed.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Local Governments

Federal Governments

Eligible Agencies of the Federal Government

U.S. Territory or Possession

Other

Independent School Districts

Public Housing Authorities/Indian Housing Authorities

Native American Tribal Organizations (other than Federally recognized tribal governments)

Faith-based or Community-based Organizations

Regional Organizations

Foreign Organizations/Foreign Collaborations

Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

NIH will no longer issue awards (i.e., new, renewal, or non-competing continuation) to domestic or foreign entities that involve foreign subawards/subcontracts. All NIH-funded research involving foreign subawards/subcontracts must be submitted in response to a NOFO that is specifically designated for funded international collaborations. See NIH Grants Policy Statement 16.8 Collaborative International Research Awards.

Applications involving foreign subawards/subcontracts submitted in response to this NOFO will be deemed noncompliant and will not be considered for funding. This policy applies to all monetary international collaborations resulting in foreign subawards/subcontracts, however, it does not preclude unfunded international collaborations or foreign components, funding for foreign consultants, or procurement of unique equipment or supplies from foreign vendors.

Required Registrations

Applicant Organizations Applicant organizations must complete and maintain the following registrations as described in the How to Apply - Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code. Foreign organizations must obtain a NATO Commercial and Government Entity (NCAGE) Code (in lieu of a CAGE code) in order to register in SAM. Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.

Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. Obtaining an eRA Commons account can take up to 2 weeks.

All PD(s)/PI(s) must be registered with ORCID. The personal profile associated with the PD(s)/PI(s) eRA Commons account must be linked to a valid ORCID ID. For more information on linking an ORCID ID to an eRA Commons personal profile see the ORCID topic in our eRA Commons online help.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support.

Applications must be submitted as multiple PD/PI applications, with three to six PDs/PIs, all of whom must hold appointments at domestic institutions. Visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply - Application Guide.

Qualified scientists with the interest and ability to develop a team science program to address an important research question are encouraged to apply:

2. Cost Sharing This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

Section IV. Application and Submission Information

1. Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise (in this NOFO, in a policy notice, or other notice from NIH Guide for Grants and Contracts). Conformance to the requirements in the How to Apply - Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Page Limitations All page limitations described in the How to Apply – Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:

The Research Strategy is limited to 20 pages and must include the following three components: A) Program Description, B) Team Integration Plan, and C) Summary Table as specified in the Research Plan instructions. If the Research Strategy exceeds 20 pages, the submitted application will be withdrawn without review.

Instructions for Application Submission

The following section supplements the instructions found in the How to Apply – Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

SF424(R&R) Other Project Information

Project Summary/Abstract: The abstract should provide an overview of a single focused goal for the next five years, and the overall vision of a collaborative research program led by an integrative team.

Facilities and Other Resources: Describe aspects of the institutional environment and regional research resources that support team science, including how access to these resources will be ensured for team members and across institutional sites if appropriate.

SF424(R&R) Senior/Key Person Profile

R&R Budget

A single integrated application budget must cover research expenses, personnel, equipment, resource assignments, and other costs of the program (e.g., animal use, clinical research, Data Management and Sharing). If applicable, subcontracts may be requested. The requested budget should be consistent with the number of PDs/PIs and the scope, complexity, and resource requirements of the proposed program. Costs associated with team coordination, integration, and sharing of resources and data across team members may also be requested.

These programs are complex and require significant effort from all PDs/PIs involved. In general, a minimum effort of 2.4 calendar months is expected from each PD/PI. Please refer to IC profile web pages for the specific effort expectations for participating ICs. Participating ICs' staff will verify that the research effort requirements are met before issuing an award.

Do not request inflationary increases in the overall budget or in any individual budget category. Year-to-year budget changes should reflect shifts in research activities or expected ramp-up or ramp-down of the program, not cost-of-living adjustments. Equipment that duplicates institutional or regional shared facilities already available to investigators must be identified and justified.

R&R Subaward Budget

PHS 398 Cover Page Supplement

PHS 398 Research Plan All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Research Strategy: The Research Strategy must include three components: A) Program Description, B) Team Integration Plan, and C) Summary Table and be uploaded as a single attachment.

A) Program Description (Must be included within the 20-page Research Strategy limit) The proposed research must be presented as an integrated scientific program with a single, highly focused research goal or problem with sufficient scope, complexity and impact to justify significant resource investment towards a team-based approach. The single goal structure is designed to promote strong integration across interdependent or interrelated components at the conceptual, technical, and interpersonal level. The extent of integration expected for the Team Science Grant goes beyond the structure of a traditional R01 mechanism or Program Project/Center grant.

To provide a concise overview of the whole project, an optional graphical scheme illustrating the interconnections of the proposed research and collaborative team may be included.

The Program Description should address the following:

Rigor and Transparency: NIH requires researchers to follow its guidelines for rigorous and transparent research (see NIH guidance for rigor and transparency in grant applications). This means designing strong experiments, reducing bias, reporting results honestly, and interpreting findings carefully.

When writing your application, make sure to:

B) Team Integration Plan (Must be included within the 20-page Research Strategy limit) The Team Integration Plan should describe how all team members, including PDs/PIs, co-investigators, collaborators, and consultants, will work together effectively, sharing leadership so that no single person controls team priorities and credit. The plan must make a compelling case that the team's combined skills, integrated knowledge, and institutional context are both necessary and sufficient to achieve the project's goals and address unexpected challenges.

Important note: A separate Multiple PD/PI Leadership Plan is also required as its own attachment to describe governance, organizational structure, and operation among the leadership team and distribution of overall available resources. Follow the How to Apply - Application Guide instructions and do not repeat the same information. Team Integration and Multiple PD/PI Leadership Plan should complement each other to address team collaboration and team operation, respectively. Both plans will be evaluated together by the reviewers.

The Team Integration Plan should discuss the following:

C) Required Summary Table (Must be included within the 20-page Research Strategy limit) A Summary Table should illustrate the program's single focused goal, the set of research questions it addresses, the composition of the PD/PI team and how each member contributes to the integrated effort, and the anticipated milestones for project advancement. How the team will discuss and adjust plans in response to milestone achievement or unexpected challenges may be addressed elsewhere in the Research Strategy.

The Summary Table should discuss the following:

Letters of Support: Letters of support from each collaborator should be limited to one page, must not include Biographical Sketches, and must not include figures and data. Letters of support from foreign collaborators may be subject to NOT-OD-25-098 and require Foreign Justification.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

Other Plan(s):

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

A Data Management and Sharing Plan (DMS Plan) is required for any NIH-funded or conducted research that will generate scientific data. Applicants must submit the DMS Plan at the time of application using the NIH DMS Plan Format Page. The DMS Plan must address the elements in the structured format. Where the DMS Plan Format Page requires a "Yes or No" response, no additional narrative is allowed.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply - Application Guide.

No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply - Application Guide, with the following additional instructions:

If you answered "Yes" to the question "Are Human Subjects Involved?" on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

Delayed Onset Study Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the How to Apply - Application Guide must be followed.

PHS Assignment Request Form

3. Unique Entity Identifier and System for Award Management (SAM) See Part 2. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times Part I. contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH's electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the How to Apply – Application Guide.

5. Intergovernmental Review (E.O. 12372) This initiative is not subject to intergovernmental review.

6. Funding Restrictions All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.

7. Other Submission Requirements and Information Applications must be submitted electronically following the instructions described in the How to Apply - Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization's profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply - Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Mandatory Disclosure

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at grantdisclosures@oig.hhs.gov.

Post Submission Materials Applicants are required to follow the instructions for post-submission materials, as described in the policy

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.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

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?

In addition, for applications involving clinical trials Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

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?

In addition, for applications involving clinical trials With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

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?

In addition, for applications involving clinical trials Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

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, 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?

In addition, for applications involving clinical trials Does the application adequately address the following, if applicable Study Design Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, sex, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Specific to this NOFO:

Program Description:

Team Integration Plan and Multiple PD/PI Leadership Plan:

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?

In addition, for applications involving clinical trials If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

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.

Study Timeline

Specific to applications involving clinical trials Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

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 Human Subjects Policies

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for inclusion.