Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

NATIONAL INSTITUTES OF HEALTH (NIH)

National Eye Institute (NEI)

National Heart, Lung, and Blood Institute (NHLBI)

National Institute on Aging (NIA)

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

National Institute of Allergy and Infectious Diseases (NIAID)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

National Institute on Deafness and Other Communication Disorders (NIDCD)

National Institute of Dental and Craniofacial Research (NIDCR)

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

National Institute of Environmental Health Sciences (NIEHS)

National Institute of Mental Health (NIMH)

National Institute on Minority Health and Health Disparities (NIMHD)

National Library of Medicine (NLM)

National Center for Complementary and Integrative Health (NCCIH)

National Cancer Institute (NCI)

Funding Opportunity Title

Lasker Clinical Research Scholar's Program (Si2/R00 Clinical Trial Optional)

Activity Code

Si2/R00 Intramural Clinical Research Scholar Transition Award

Announcement Type

Reissue of

PAR-24-202

Related Notices

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

Funding Opportunity Number (FON)

PAR-27-076

Companion Funding Opportunity

None

Number of Applications

See Part 2, Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s)

93.310, 93.307, 93.173, 93.233, 93.837, 93.838, 93.839, 93.840, 93.853, 93.213, 93.398, 93.879, 93.855, 93.865, 93.866, 93.847, 93.113, 93.372, 93.242, 93.121, 93.273

Funding Opportunity Purpose

This NOFO encourages applications for the Lasker Clinical Research Scholars Program. The program supports the research activities of clinical researchers during the early stages of their independent careers as they work to improve human health.

The program offers the opportunity for a unique bridge between the NIH intramural and extramural research communities and contains two phases. In the first phase, Lasker Scholars will receive appointments for up to 5-7 years as tenure-track investigators within the NIH Intramural Research Program with independent research budgets. In the second phase, successful scholars will receive up to 3 years of NIH support for their research at an extramural research institute, or can remain as an investigator within the intramural program.

Funding Opportunity Goal(s)

This listing covers multiple offices in the NIH Office of the Director that offer assistance awards or supplements to assistance awards.

Key Dates

Posted Date

August 31, 2026

Open Date (Earliest Submission Date)

October 06, 2026

November 06, 2026

Not Applicable

Not Applicable

July 2027

July 09, 2027

Not Applicable

Not Applicable

April 2028

July 07, 2028

Not Applicable

Not Applicable

April 2029

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

July 08, 2028

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

This is a career development program to foster the development of early stage, independent clinical investigators. The NIH funds research and research training at extramural institutions, as well as within the NIH Intramural Research Program (IRP) to support the development of clinical treatments for disease and to improve human health. However, these efforts can be hindered by barriers to clinical and translational research. Such barriers include limited research time for clinical investigators, increases in the length of time to independent careers, and access to hospital facilities and patient enrollments.

To address those barriers, the NIH has created the Lasker Clinical Research Scholars (Lasker Scholars) program that will offer applicants the opportunity to compete for a unique combination of intramural and extramural resources for clinical research. The program will support a small number of clinical researchers in the early stages of their independent careers to promote their development as fully independent scientists.

The program honors the contributions of Mary and Albert Lasker to the NIH and to the overall biomedical community.

The Lasker Scholars program aims to support successful candidates in two phases. Applicants will respond to this Notice of Funding Opportunity (NOFO) for an initial period of support through a position in the NIH IRP. Selected scholars who successfully complete the initial phase and internal review, and who meet the criteria described below, will be able to either remain within the IRP or receive up to 3 years of extramural grant funding in the second phase.

First Phase: The first phase will support scholars in the IRP for up to 5 years, with the possibility of an extension for an additional 2 years. NIH may grant additional extensions, as needed, on a case by case basis. Successful applicants for the Lasker Scholars Program will be appointed as independent tenure-track investigators within an NIH Institute or Center, a process that includes being hired as a full-time employee at the NIH and completing the procedures required of new Federal government employees. As Federal employees, Lasker Scholars will be subject to certain regulations and policies that will govern their relationships with outside organizations. Nonetheless, in certain cases, Lasker Scholars may be able to maintain relationships with their previous institution. The IRP will provide space, research expenses, full salary, and Federal employee benefits. Scholars will develop independent research activities over the course of their stay in the IRP and will be formally reviewed by a panel of senior extramural investigators every 2-4 years to evaluate their research progress. More information about the IRP can be found at http://irp.nih.gov/ Second Phase: Upon successfully completing the initial IRP phase of the program, the Lasker Scholar will be eligible for two options in the second phase.

Option 1. Remain in the IRP with continued intramural funding and progression to tenured senior investigator status, if consistent with formal reviews and assessments. Retention in the IRP will be dependent on the development of a mutual agreement between the Scholar and the IRP. Tenure at the NIH requires evaluation and approval by the NIH Deputy Director for Intramural Research.

Option 2. Scholars who successfully complete at least five years in the first phase of the program will be considered for up to 3 years of support to continue their research as independent clinician scientists at an extramural institution. This support is contingent upon obtaining an appropriate full-time tenure-track or tenured extramural position at an eligible institution, and the successful NIH programmatic review of the scholar's progress during the intramural phase of the award. Scholars who choose to leave the Lasker program before completing 5 years of research in the IRP will not be eligible for the Lasker Scholars Grant but may be eligible to compete for other extramural NIH research grants as announced in the NIH Guide for Grants and Contracts.

RESEARCH AREAS OF INTEREST

Applicants are strongly encouraged to discuss their proposed research with the NIH prior to submission to ascertain that there is programmatic interest in their research area. See the Scientific/Research Contacts listed in Section VII, Agency Contacts.

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

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

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

It is anticipated that up to 5 awards will be made in each cycle of the program.

Award Budget

Award budgets are composed of salary and other program-related expenses, as described below:

Intramural Phase (SI2) Allowable Costs:

Scholars will be supported by intramural funds provided by the NIH Institute/Center in which they are conducting their research. Budget details for the intramural phase will be negotiated with the sponsoring Institute/Center. Salary will be consistent with that offered scientists in similar, intramural NIH positions.

Extramural Phase (R00) Allowable Costs:

For the extramural phase (R00) applicants can request direct costs of up to $499,000 per year. This amount includes salaries, fringe benefits, and research costs.

Indirect Costs:

Indirect costs will be reimbursed at the extramural sponsoring institution's indirect cost rate.

Award Project Period

The initial phase of research in the IRP is for 5 years with the possibility of a 2-year extension. Additional extensions, as needed, may be approved on a case by case basis. The extramural phase of the program is for up to 3 years.

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

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 not allowed.

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)

Eligible applicants include physicians, dentists and nurses (including MD, MD/PhD, DO, DDS, DMD, RN/PhD, or equivalent clinical doctoral degree from an accredited domestic or foreign institution) who have a professional license to practice clinically in the U.S. The program is intended for investigators at the early stages of their independent careers. Applicants will generally have completed or be completing a post-residency clinical fellowship, and will have demonstrated sufficient patient-oriented research experience to qualify for a tenure-track level appointment. Tenured applicants are not eligible. Applicants do not have to be U.S. citizens or permanent residents, although selected Scholars must qualify for and maintain appropriate visa/residency status throughout the program. An application can be submitted on behalf of the candidate by the candidate's current institution, even if that is not the institution where the candidate would be affiliated if selected as a Lasker Scholar. Individuals not affiliated with an organization, or who want to submit an application independently of their current organization, may 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.

To prevent a lapse in funding, an applicant can submit a Lasker Scholar application in which the research is similar to that in an NIH award already held by the applicant. Should the applicant be selected for and accept a Lasker Scholar award, the previous NIH award must be relinquished prior to accepting the Lasker appointment. Applicants can also submit an R01 application and a related Lasker Scholar application in parallel. Should both applications be selected for funding, the applicant will be permitted to accept only one of the awards.

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.

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

Facilities and Other Resources: Rather than indicate the resources available, describe the resources that the proposed research will need. Also indicate the specific resources and environmental features that will be needed for research in Phase 2 of the program, should that be conducted in an extramural institution, including subject populations, collaborative arrangements, and/or equipment.

SF424(R&R) Other Project Information

SF424(R&R) Senior/Key Person Profile

R&R Budget

Itemized budget information is not required at the time of application. The following instructions may be used to submit the R&R Budget.

For each budget period of the Si2 phase, usually project years 1-5:

For each budget period of the R00 phase, usually project years 6-8, a total requested amount up to $499,000 is allowed. Itemized budget information is not required at the time of application. If awarded, the R00 applicant institution (at the time of transition to the R00 phase) will submit a detailed budget for each budget period of the R00 project period that reflects the direct and indirect costs at the R00 applicant institution.

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:

Specific Aims: State concisely the goals of the proposed research and summarize the expected outcome(s), including the impact that the results of the proposed research will have on human health. List succinctly the specific objectives of the research proposed, e.g., to challenge an existing paradigm or clinical practice, create a novel design, solve a specific problem, test a stated hypothesis, address a critical barrier to progress in the field, or develop new technology.

Research Strategy:

(a) Significance – Explain the importance of the problem or critical barrier to progress in the field that the proposed project addresses. Explain how the proposed project will improve the field, as well as the effect on human health. Describe how the field will be changed if the proposed aims are achieved.

(b) Innovation – Explain how the application challenges and seeks to shift current clinical practice or research paradigms. Describe any novel theoretical concepts, approaches or methodologies, instrumentation or intervention(s) to be developed or used, and any advantage over existing methodologies, instrumentation, or intervention(s). Explain any refinements, improvements, or new applications of theoretical concepts, approaches or methodologies, instrumentation or interventions.

(c) Approach – Describe the overall strategy, methodology, and analyses to be used to accomplish the specific aims of the project. Include how the data will be collected, analyzed and interpreted. Discuss potential problems, alternative strategies, and benchmarks for success anticipated to achieve the aims. If the project is in the early stages of development, describe any strategy to establish feasibility, and address the management of any high risk aspects of the proposed work. Include preliminary data, if appropriate. Point out any procedures, situations, or materials that may be hazardous to personnel and precautions to be exercised. Include a prospective timeline for the project. For human subjects research, provide a brief explanation of human subjects protection and inclusion plans.

(d) Milestones - List specific "go/no-go" milestones that the applicant plans to achieve during the Phase I, intramural phase of the research. The milestones are not a reiteration of the Specific Aims, but are measurable, specific endpoints for the Phase I research that will allow NIH extramural staff to assess research progress and appropriateness for Phase 2 support. The milestones should include a timeline for achieving the goals, and may include alternative goals should the original approaches not succeed.

Vertebrate Animals: Successful scholars will submit their proposed research to review boards in the intramural research program upon being selected. Applicants need to follow the SF424 (R&R) Application Guide to complete this section for the extramural portion of the proposed work.

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 is not applicable for this NOFO.

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

Do not complete. Indicate that for the Si2 phase, successful scholars will submit their proposed research to review boards in the intramural research program upon being selected. Applicants proposing human subjects and or clinical trials for the extramural (R00) portion of the proposed work should create a delayed onset study record.

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.

Justification Attachment Applicants proposing human subjects or clinical trials for the extramural (R00) portion of the proposed work should indicate these will not begin until after 5 years of research, and the study information is not yet available. The information will be provided in the R00 application.

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, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Letters of Reference Letters of reference are an important component of the Lasker Clinical Research Scholar application. Applicants should arrange to have four letters of reference submitted on their behalf. Applications that are missing letters of reference will not be reviewed. Late letters will not be accepted. Applicants are responsible for monitoring the submission of letters to ensure that the letters have been submitted prior to the submission deadline. Applicants are encouraged to check the status of their letters in their eRA Commons accounts.

To submit a letter of reference, the referee will need the following information:

Notice of Funding Opportunity (NOFO) for this announcement: PAR-26-114.

The applicant's Commons Username (Note: Referees do not need to be registered in the Commons and do not need their own Commons Username – only the Commons Username of the applicant is required);

The applicant's first and last name (note – the name must match exactly the applicant's name in the Commons);

The URL to the letter submission page (https://public.era.nih.gov/commonsplus/public/reference/submitReferenceLetter.era);

The letter of reference submission dates – Deadline for receipt of letters is 5:00 p.m. (ET) on the application due date.

Letters of reference are confidential to the extent permitted by law. Email confirmations will be sent to both the applicant and the referee. Note: Since email can be unreliable, it is the applicant's responsibility to check the status of letters of reference periodically in the Commons.

Instructions for Referees:

Letters may be submitted to the Commons at (https://public.era.nih.gov/commonsplus/public/reference/submitReferenceLetter.era) beginning one month before the application due date, and must be submitted no later than 5:00 p.m. (ET) on the application due date.

Late letters will not be accepted and applications missing letters of reference may not be reviewed.

The applicant's name should be placed at the top of the letter. Although signatures are not required, the letter must include a signature block with the referee's full name, title, institution, and contact information:

In two pages or less, describe the applicant's qualities that support the applicant's claim to possess the scientific, leadership and management skills necessary to conduct successful, independent clinical research. When possible, give specific examples that illustrate these qualities.

Note: The letter submission page can be accessed without signing in to the Commons, and referees do not need to be registered in the Commons. Referees must provide the applicant's Commons User Name (User ID) and the other information below:

Referee Information (the individual providing the letter of reference):

Referee's First and Last Name (Required) Referee's Middle Initial (MI) (Not Required) Referee's Email Address (Required) Referee's Institution/Affiliation (Required) Referee's Department (Required)

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

Any instructions provided here are in addition to the instructions 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.

For this particular NOFO, note the following:

The goal of the Lasker Clinical Research Scholars Program is to support a small number of exceptional clinical researchers in the early stages of their independent careers, and to promote their development to fully independent scientists. Therefore, the review will emphasize the accomplishments and potential of the applicant, as well as the research project.

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, community behaviors or health care policy? 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?

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?

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?

Environment

Has the applicant identified the scientific environment, subject populations, or collaborative arrangements that will be needed to conduct the proposed Phase I research? Assuming successful completion of the proposed milestones, has the candidate identified appropriate and sufficient institutional resources, such as subject populations, collaborations, and equipment, that will be needed for the Phase 2 portion of the research?

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. 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 three points: (1) a complete description of all proposed procedures including the species, strains, ages, sex, and total numbers of animals to be used; (2) justifications that the species is appropriate for the proposed research and why the research goals cannot be accomplished using an alternative non-animal model; and (3) interventions including analgesia, anesthesia, sedation, palliative care, and humane endpoints that will be used to limit any unavoidable discomfort, distress, pain and injury in the conduct of scientifically valuable research. Methods of euthanasia and justification for selected methods, if NOT consistent with the American Veterinary Medical Association (AVMA) Guidelines for the Euthanasia of Animals, is also required but is found in a separate section of the application. For additional information on review of the Vertebrate Animals Section, please refer to the Worksheet for Review of the Vertebrate Animals 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 (as applicable), 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

For Renewals (as applicable), the committee will consider the progress made in the last funding period.

Revisions

For Revisions (as applicable), the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

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.

Applications from Foreign Organizations

Not applicable

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

Reviewers will comment on whether the Resource Sharing Plan(s) (e.g., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

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 CSR, in accordance with NIH peer review policies and…