Part 1. Overview Information

Key Dates

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

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

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

Supporting fundamental research by funding individual projects has a number of consequences that could reduce the efficiency and effectiveness of the biomedical research enterprise in the U.S. To address these issues and increase the efficiency and efficacy of grant funding, the NIGMS Maximizing Investigators' Research Award (MIRA) is a single grant to provide support for the NIGMS-relevant program of research in an investigator's laboratory. For this FOA, eligibility to apply is limited to PD/PIs who are NIH-defined Early Stage Investigators (ESIs) at the time of submission and the "program of research" is defined as a collection of projects in the PD/PI’s lab that are within the mission of NIGMS. Applicants who receive R01, SC1, DP1, DP2, or any other type of disqualifying award prior to issuance of the ESI-MIRA become ineligible to receive the award.

In comparison to R01 funding of NIGMS ESI investigators, Maximizing Investigators Research Award for Early Stage Investigators (ESI MIRA) benefits include:

• No requirement or expectation for preliminary data, which will
  • Enable investigators to apply earlier in their independent research career, allowing them to secure grant funding that will launch and sustain a successful research career, and
  • Enhance investigators ability to move into research areas that are distinct from those of their postdoctoral mentors, which could increases chances for new scientific discoveries;
• Increased stability of funding for NIGMS-supported ESIs, improved success rates, and more graduated, rather than all-or-none, funding decisions for MIRA renewals;
• Larger award amount than the current average NIGMS R01 award to ESIs, while the project period will be similar;
• More flexibility to pursue new ideas and opportunities as they arise during the course of research because the award is not tied to specific aims;
• A reduction in administrative burden associated with managing multiple grants; and
• A reduction in required application writing.

In developing MIRA, NIGMS is committed to maintaining support for at least the current total number of NIGMS-funded early stage investigators and their associated programs of research. The Institute will also work to ensure that it maintains a broad and diverse research portfolio in terms of scientific areas, approaches, regions, institutions, and individuals. Such diversity will optimize returns on the Institute's investments by maximizing the ideas explored and the chances for important breakthroughs.

The NIGMS MIRA differs from other NIH institutes' R35 awards in that MIRA is not a grant designed to support a small number of "outstanding" investigators; instead it could potentially support most meritorious NIGMS investigators.

Overview of the ESI MIRA

An NIGMS ESI MIRA is intended to provide support for research within the NIGMS mission in the laboratory of an early stage investigator (ESI). NIGMS supports research on basic biological processes as well as translational and clinical research in certain areas. In addition to research designed to answer scientific questions and generate new ideas and hypotheses, the development of technology and computational approaches are supported. Within the scope of the MIRA, investigators will have the freedom to explore new avenues of inquiry that arise during the course of their research, as long as they remain within the mission of NIGMS. Work involving the addition of human subjects, clinical trials, vertebrate animals, stem cells, select agents, or a new foreign component would require prior approval by NIGMS staff according to existing policies and procedures.

The ESI MIRA program encourages eligible applicants to submit an ESI MIRA application early in their independent research careers and to move into research areas that are distinct from those of their postdoctoral mentors. Applicants who have not yet received independent research funding are encouraged to apply, as are those who have not had sufficient time and/or resources to generate independent senior author publications. Preliminary data are neither required nor expected, but if provided will be evaluated during the review process.

Research involving human subjects is permitted in the MIRA program. Clinical research must be completely within the context of the NIGMS clinical areas (anesthesiology, clinical pharmacology, sepsis, injury, and critical illness). Mechanistic clinical trials are permitted in MIRA when the mechanistic study is an essential part of the research program. Clinical research that involves recruitment of human subjects at more than one site, or the substantial financial support of multiple collaborators and subcontractors, is not allowed, because these fixed commitments are not consistent with the highly flexible nature of the MIRA program. Clinical trials that are designed to test safety and efficacy of interventions (Phase I, Phase II, Phase III) for the purpose of future clinical treatment and/or regulatory approval are not permitted in MIRA. Potential applicants are encouraged to confer with the program director managing awards in their specific research area, and if there are further questions, with the NIGMS Scientific/Research staff (in Section VII. Agency Contacts of this FOA) before submitting an ESI MIRA application that includes clinical research. NIGMS does not intend to fund applications that contain clinical research within the missions of other Institutes and Centers at NIH or other federal agencies.

MIRA may not be the best mechanism to support all kinds of research, even though the research may be within the NIGMS mission. Because the MIRA is expected to provide support for the research program of an independent investigator’s laboratory, PDs/PIs may find other grant programs better suited to research requiring financial support of collaborators and subcontractors.

Because the MIRA is intended to support a significant and ambitious program of research, the PD/PI is required to devote at least 51% of his/her total research effort to this award. See Section III.1 Eligible Individuals for more information about this requirement.

Investigators receiving a MIRA will be required to relinquish other NIGMS research grants, except for award mechanisms mentioned below. Investigators who receive support from NIGMS research grants of other investigators as collaborators and subcontractors on R01s will no longer be permitted to receive funds from those sources. Investigators who receive funds as project leaders on NIGMS multi-component grants (i.e., P01, P50 or RM1) will have their MIRA award level adjusted to remove any overlap between their MIRA and their multi-component grant. The MIRA Principal Investigator will be required to relinquish funding from the multi-component grant at the end of its competitive segment. NIGMS continues to encourage collaborative and interdisciplinary research when it is appropriate, and individual MIRA grantees are free to collaborate with one another or with other investigators using funds from their individual MIRA to support their contributions to the team's research. Investigators with K awards from another NIH institute may receive an NIGMS MIRA but will be required to adjust their person-months effort on those awards to be smaller than the person-months effort committed to MIRA.

A researcher funded by a MIRA will not subsequently be awarded any other sources of NIGMS funding, with the following exceptions:

• Grants supporting resources for the research community (e.g., P30, R24);
• Biomedical Technology Development and Dissemination program RM1 grants;
• Contracts;
• Grants supporting training, workforce development, or diversity building;
• Funding for clinical trials;
• INBRE (P20), COBRE (P20/P30), or IDeA-CTRs (U54);
• SBIR/STTR grants;
• Conference grants.

NIGMS will not accept applications from MIRA grantees for awards not on the above list that would begin prior to the end date of the MIRA.

Supplements to MIRAs: MIRAs will be eligible for Research Supplements to Promote Diversity in Health-Related Research, for Research Supplement to Promote Re-Entry into Biomedical and Behavioral Research Careers, and for Administrative Supplements for Equipment Purchases. Other supplements offered by NIGMS may also be made available to MIRA grantees, depending on the intention and constraints of the particular supplement program.

Renewals: ESI MIRA awardees will be eligible to renew their MIRAs through MIRA FOAs not limited to ESIs, e.g., through reissuances of PAR-19-367, which also provides NIGMS-funded investigators the opportunity to apply to the MIRA mechanism.

Resubmissions: Investigators who applied in response to RFA-GM-16-003, RFA-GM-17-004, or PAR-17-190 are welcome to apply provided they are still eligible (retain their ESI status), but the application must be written as a New submission without reference to the previous application or review or an Introduction to Application.

Prior Consultation with IC staff

NIGMS strongly encourages potential applicants to contact Scientific/Research Staff at least 6 weeks prior to submission for advice on the suitability of the proposed research for NIGMS. Applications that are determined to be outside of the NIGMS mission will not be accepted for review.

Section II. Award Information

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• U.S. Territory or Possession

• 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

Non-domestic (non-U.S.) Entities (Foreign Institutions) 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.

Applicant organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) 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. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• 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.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons.Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Subject to the eligibility criteria below, 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 his/her organization to develop an application for support. Women, individuals from underrepresented racial and ethnic groups, from disadvantaged backgrounds, or with disabilities are always encouraged to apply for NIH support.

Eligibility to apply for this FOA is limited to NIH defined Early Stage Investigators. ESI eligibility is determined at the time the application is submitted. Applications from investigators who are not eligible to receive the award will be administratively withdrawn without review. Note that ESI status can be extended beyond the normal 10-year window after completion of the terminal research degree or medical residency for certain life or career events, as described in NOT-OD-19-125 and on the NIH website. Applicants who receive R01, SC1, DP1, DP2, or any other type of disqualifying award prior to issuance of the ESI-MIRA, are ineligible to receive the award..

The PD/PI is required to devote at least 51% of his/her total research effort to this award. The total research effort should include his/her combined research effort at all institutions where the PD/PI holds an appointment and should be expressed in person-months. The total research effort should include the PD's/PI’s combined research effort at all institutions where the PD/PI holds an appointment, should be expressed in person-months, and should not include time expended toward teaching, administration not directly related to the PD's/PI's research, and/or clinical duties.

Only single PD/PI applications are allowed. Applications with multiple PD(s)/PI(s) will not be accepted.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications

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

It is anticipated that the MIRA review will be highly competitive; therefore, a PD/PI may submit an R01 application and a MIRA application in parallel. Should both applications be selected for funding, the PD/PI will be required to relinquish one of the awards.

PD/PIs who submitted a MIRA application in previous years and are still eligible for this FOA (i.e., retain their ESI status) are welcome to apply, but must submit a New application because Resubmission applications are not allowed.

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 FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

Project Summary/Abstract: Use the abstract to provide an overview of research in the laboratory, the goals for the next five years, and an overall vision of the research program. Do not include specific aims or use any similar designation in the abstract. This document should serve both the needs of the public and the needs of the reviewers for an introduction to the research plan.

Biographical Sketches: A biosketch should only be provided for the PD/PI and, in rare cases, for collaborator(s) receiving financial support from the MIRA

Personal Statement: Use the Personal Statement to address MIRA-specific elements of the Investigator Review Criterion. Include descriptions of any significant service or contributions to the research community.

Contributions to Science: This section of the biosketch should emphasize contributions over the past five years.

Include a link to your My Bibliography complete list of publications and be sure the data are complete and up to date.

Research Support: List ongoing and completed research projects with funding sources from the past three years, and briefly indicate the overall goals of the projects and your responsibilities. Do not include the number of person months or direct costs.

Do not present or include figures or preliminary data.

All instructions in the SF424 (R&R) Application Guide must be followed.

Itemized budget information is not required and will not be accepted. Instead, a total requested direct cost amount for each budget period, including requests for equipment purchase, is required. Other than years when equipment is requested, it is expected that the annual direct costs will remain constant in all years.

All instructions in the SF424 (R&R) Application Guide must be followed except as detailed below. While a 10-year R&R Detailed Budget form is provided in the application package, applicants may not request more than 5 years of support.

In order to allow submission of a budget request without filling out detailed yearly budgets, some basic information must be completed for NIH to successfully process the budget form. For each budget period:

1. Select the appropriate Budget Type.

2. Provide the Budget Period Start Date and End Date.

3. Section A: Senior/Key Persons provide an entry for the PD/PI, including the appropriate level of effort, and enter $0 for Requested Salary and $0 for Fringe Benefits. Entering $0 does not imply that the PD/PI will not receive any salary or fringe benefit support from the grant.

4. In Section C: Enter budget request for equipment. Provide complete justification using the Budget Justification.

5. In Section F: Other Direct Costs add a line item titled Requested Direct Costs and provide the total request for that budget period (up to $250,000). If equipment is requested in Section C, do not add the equipment budget in Section F. If consortium/subaward costs are requested, the consortium/subaward direct costs (not including consortium F&A) should be included in the "Requested Direct Costs."

Budget Justification: The following budget categories must be justified, where applicable: equipment and consortium/subaward costs.

Use the Budget Justification to provide the additional information requested in each budget category identified above only. Equipment quote(s) may be included here.

Consortium Justification: Consortium/Contractual Arrangements are not anticipated in most cases and must be extremely well justified. A letter from the subcontract PD/PI should be included making it clear why he/she cannot participate in collaborative research with the PD/PI without support from the MIRA. NIGMS will accept MIRA applications with foreign collaborations but will only provide funding for a foreign consortium arrangement when the collaboration is essential to the PD's/PI's research program and represents a unique scientific opportunity that cannot be supported by the collaborator without MIRA funds. List the individuals/organizations with whom consortium or contractual arrangements have been made and indicate whether the collaborating institution is foreign or domestic. Provide the total consortium/subaward costs for each budget period listing the total direct costs and indirect (F&A) costs separately.

F&A base: Also use the Budget Justification to explain any exclusions applied to the F&A base calculation.

Do not complete the R&R Subaward form. All budget information should be provided on the R&R Budget form.

Specific Aims: Do not submit a Specific Aims page, or identify specific aims, or use any similar designation in the Research Strategy.

Research Strategy: MIRA applications should not use the typical Research Strategy headings of Significance, Innovation, and Approach. This section should contain the following information: 1) Background on the area(s) of research and key gaps in our understanding or important challenges to be addressed; 2) Recent Progress by the PD/PI, focusing on the past five years, to give context for the overview of future research. This may include development of technical expertise and administrative skills such as mentoring. Do not repeat material adequately covered in the Biosketch. 3) Overview of Future Research Plans. This should be a description of the key questions or challenges the PD/PI plans to address and the general strategies that might be used to approach them. The focus should be on the importance of the questions or challenges. A detailed experimental plan should not be provided.

Note that preliminary data are neither expected nor required, and PD/PIs may wish to indicate this prominently in the Research Strategy. In lieu of preliminary data from the PI's independent lab, feasibility of the program may be demonstrated through literature citation, data from other sources, or data generated by the applicant as a graduate student or postdoctoral fellow. Although the proposed direction of the PD/PI's scientific program will be considered in review, if new opportunities or directions arise during the course of the research, the PD/PI will have the flexibility to change course and pursue them.

Given that the MIRA is meant to provide support for a research program within the NIGMS mission in a PD s/PI’s laboratory, and may include multiple projects on disparate topics, there is no obligation for the PD/PI to present a single unifying theme. Applicants should directly address the rationale, underlying the balance of effort and the resources dedicated to each activity, and how the activities are distinct or complementary.

The research strategy should address the requirements of the NIH policy on rigor in research as detailed in NOT-OD-18-228. This section should also address requirements related to sex as a biological variable as detailed in NOT-OD-15-102.

Letters of Support: A letter of support should be included from the department chair, dean, or other academic unit leader that describes institutional commitment to the development of the investigator and any other pertinent information. This information could include start-up packages and other institutional research support, space available to the PD/PI, salary support commitment for the PD/PI, skills and career development opportunities for the PD/PI, mentoring during the promotion and tenure process, and career advancement prospects for non-tenure track applicants. Letters from former mentors are not required, nor encouraged, except in the case of continuing collaborations.

Letters of support from collaborators must be limited to 2 pages, must not include attached Biographical Sketches, and should not circumvent page limitations by includingfigures and data.

Applications involving a consortium/contractual arrangement are expected to be rare. If a consortium/contractual arrangement must be included, the application must also include a letter of support from the subcontract PD/PI indicating why they cannot participate in collaborative research with the PD/PI without support from the MIRA.

The following modifications also apply:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

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

All instructions in the SF424 (R&R) Application Guide must be followed.

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 SF424 (R&R) Application Guide must be followed.

For this FOA, do not suggest a Scientific Review Group because applications will be reviewed by Special Emphasis Panels.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. 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. Overview Information 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 Policy on Late Application Submission.

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 SF424 (R&R) 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.

For this FOA:

• The MIRA will replace all current NIGMS funding of the laboratory. Institutions will be required to relinquish their interests in current NIGMS-funded research grants and withdraw pending applications where the applicant is listed as the PD/PI or multi-PD/PI.
• Transfer of a MIRA to a foreign institution will not be allowed. Addition of a foreign component, including a significant new foreign collaboration, requires NIGMS' prior approval; however, MIRA funds may be used to support a subcontract at a foreign institution, but only if the collaboration is essential to the PD's/PI's research program, represents a unique scientific opportunity, and cannot be supported by the collaborator without MIRA funds.
• A permanent change of PD/PI will not be allowed under the MIRA. A temporary change may be allowed with prior approval under circumstances such as sabbatical leave, medical conditions, disability, or personal or family situations. In case of changes in employment of the PD/PI (e.g., accepting an appointment at another institution, whether or not an appointment is retained at the institution which received the MIRA award), the PD/PI is required to maintain his/her commitment to the MIRA as originally reviewed and approved. The situation will be evaluated on a case by case basis and the MIRA could be terminated if continued support is not warranted.
• The PD/PI of a MIRA cannot receive funds from other NIGMS grants (e.g., as a sub-project leader or as the recipient of a sub-contract), excepting those listed in Section I.
• NIGMS will not consider funding future individual PD/PI or multiple PD/PI research grants from a MIRA investigator during the MIRA funded project period, except for applications included under the list of exempted awards in Section I. Thus, NIGMS will not accept applications for grants not on the list of exempted awards from MIRA PD(s)/PI(s) unless the earliest start date of the grant is after the end date of the MIRA grant?.
• Because most institutions expect some commitment from investigators to administrative, teaching, and/or clinical duties, any salary support for the PD/PI charged to the grant should generally be less than 51% of the PD/PI's annual salary and should in no case be more than the actual research effort the PD/PI will devote to the grant.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) 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 Component of the SF424(R&R) Application Package. 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 FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) 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 the National Institute of General Medical Sciences. Applications that are incomplete or non-compliant, or that do not fall within the NIGMS mission, will not be reviewed.

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 designs, methods, and interventions 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.

For this particular announcement, note the following:

The goal of this MIRA program is to provide support for an ESI’s laboratory's research program that is within the NIGMS mission, to offer an opportunity for these ESIs to receive support as early as possible in their careers, to give them relative freedom in pursuing their research goals, and encourage them to move into research areas that are distinct from those of their postdoctoral mentors. Applicants are expected to provide an overview of the research program/scientific questions they currently plan to address and a general description of possible strategies; experimental details are not expected. Given that the MIRA is meant to provide support for a research program within the NIGMS mission in a PD s/PI’s laboratory, and may include multiple projects on disparate topics, there is no obligation for the PD/PI to present a single unifying theme.

Reviewers should evaluate the likelihood the proposed research will launch and sustain a successful independent research program. Preliminary dataare not required and justification for the proposed work may be provided through literature citations, data from other sources, or data generated by the applicant as a graduate student or postdoctoral fellow. Similarly, early career stage applicants may not have yet published independently as senior or corresponding authors, and the absence of these publications should not be viewed as a weakness.

Reviewers will consider each of the review criteria below in the determination of scientific merit, however, individual review criterion scores will not be assigned. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a program that by its nature is not innovative may be essential to advance a field.

Significance

Does the research program 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 goals of the research are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the research change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

For this FOA: Are the theme and/or topics of the research program substantive and appropriate for long-term pursuit? Is the proposed research program appropriate in scope and ambition to address the scientific questions posed? Will the proposed research program permit the investigator to establish a uniquely independent place in the field of research?

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 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)

Is the PD/PI, collaborators, and other researchers well suited to the program? Do they have appropriate experience and training?

For this FOA: Does the PD/PI have a consistent record of productivity and scientific impact commensurate with the applicant's current career stage? Is s/he clearly the intellectual driver of the proposed research program? Has the PD/PI shown evidence of being creative and adaptable, able to recognize new opportunities and to explore new areas of scientific inquiry, and openness to the use of new systems and strategies, as appropriate for the proposed research program? Does the PD/PI have a strong potential to establish and sustain a successful independent program of research in his/her own laboratory? Does the PD/PI show promise as a mentor of undergraduate and graduate students, and postdoctoral associates, and the potential to establish a record of professional service?

In addition, for applications involving clinical trials: With regard to the proposed leadership for the project, do the PD/PI 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?

For this FOA: Will creative strategies be employed as needed and appropriate to address the research questions posed?

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

Is the overall strategy well-reasoned and appropriate to accomplish the overall goals of the research program? Has the investigator included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Has the PD/PI presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success adequately presented? If the program is in the early stages of development, will the strategy establish feasibility, and will particularly risky aspects be managed? Has the PD/PI presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the program 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 children, justified in terms of the scientific goals and research strategy proposed?

For this FOA: Is the logic of the approach compelling? Where preliminary data are not included, are the relevant concepts and methods sufficiently established by the prior literature? Is there a logical plan for sustained progress across a research program for the five-year award period? Is there evidence that the research program will evolve appropriately as the work is performed?

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, gender, 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/gender 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 approaches 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

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?

For this FOA: Is the environment conducive for the PD/PI to develop as an independent researcher? Are there appropriate facilities and institutional support to facilitate the advancement of the PD/PI as an established investigator whose laboratory will have a sustained impact on biomedical science?

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?

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 thecategories 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

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

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 following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

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 Center for Scientific Review, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

• 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.
• Will receive a written critique.

Applications will be assigned to NIGMS. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the National Advisory General Medical Sciences Council.

The following will be considered in making funding decisions

• Scientific and technical merit of the proposed research program as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed research to NIGMS priorities.
• Contributions to portfolio breadth and diversity as outlined in the NIGMS Strategic Plan.
• Other funding support to the PD/PI.

3. Anticipated Announcement and Award Dates

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

Additionally, a signed letter from the institution's Authorized Organizational Representative (AOR) stipulating to the following points will be required as just-in-time information after review for applications being considering for funding: The PD/PI will devote at least 51% of his/her total research effort to this award, inclusive of his/her combined research effort at all institutions where he/she holds an appointment (including foreign institutions). The total research effort should be determined in person-months and should not include time expended toward teaching, administration not directly related to the PD's/PI's research, and/or clinical duties. The institution and PD/PI are aware of and accept that other NIGMS research awards, except as allowed in Section I, must be relinquished, and pending NIGMS research applications withdrawn, as a condition of receiving a MIRA.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

2. Administrative and National Policy Requirements

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.htmlhttps://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.htmlor call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

3. Reporting

For this FOA, the instructions are hereby modified as follows:

a) Under Section B.1 What are the major goals of the research? Note that the goals of the program of research supported by the MIRA are broader than the specific aims of a single project and should be appropriately described. If the goals of the MIRA have changed, complete section B.1.a. Provide a rationale for the changes in the context of the originally proposed research program and explain how the research continues to fit within NIGMS mission interests.

b) Under Section B.4, Opportunities for Training and Professional Development, indicate if individual development plans have been used for any graduate students and/or post-doctoral fellows supported by this award.

c) Under section D.2.c. Changes in Other Support, indicate if there have been changes in Other Support. In addition to the revised Other Support page, include an explanation of how changes in other support relate to the activities supported by the MIRA.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

4. Evaluation

In carrying out its stewardship NIGMS will evaluate the MIRA programs, employing the measures identified below. In assessing the effectiveness of its research investments, NIH may request information from databases, PD/PIs, and from participants themselves. NIGMS will assess the program's overall outcomes and gauge its effectiveness in increasing the efficiency and efficacy of NIGMS funding. Upon the completion of a program evaluation, NIGMS will determine whether to (a) continue the program as currently configured, (b) continue the program with modifications, or (c) discontinue the program.

Evaluation Measures: The overall evaluation of the program will be based on metrics that will include, but are not limited to, the following:

• Number of ESI PD/PIs who apply for MIRA instead of R01s
• Publication rate of NIGMS MIRA grantees vs. traditional NIGMS grantees.
• Citation rate of NIGMS MIRA grantees vs. traditional NIGMS grantees.
• Level of interest of other NIGMS grantees and applicants in obtaining NIGMS MIRAs.
• Changes in NIGMS funding distribution and number of investigators supported by the Institute.
• Changes in the distribution over time of research topics studied by NIGMS MIRA vs. traditional grantees.
• Rate at which NIGMS MIRA grantees elect to apply to renew their awards vs. re-enter the traditional system.

Section VII. Agency Contacts

Finding Help Online:http://grants.nih.gov/support/(preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email:GrantsInfo@nih.gov(preferred method of contact)
Telephone: 301-637-3015

Grants.gov Customer Support(Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email:support@grants.gov

Sailaja Koduri, Ph.D.
National Institute of General Medical Sciences (NIGMS)
Email: sailaja.koduri@nih.gov

Maqsood Wani, Ph.D.
Center for Scientific Review (CSR)
Email: wanimaqs@csr.nih.gov

Lisa Moeller
National Institute of General Medical Sciences (NIGMS)
Email: moellerl@mail.nih.gov

Section VIII. Other Information