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

The purpose of this Funding Opportunity Announcement (FOA) is to stimulate new research on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) that will identify etiologies, study pathophysiology and disease manifestations, develop new methods for diagnosis, and/or characterize the heterogeneity seen between individuals with ME/CFS.

ME/CFS is a poorly understood, complex, and chronic disease. People with ME/CFS experience a wide range of debilitating symptoms including post-exertional malaise, unrefreshing sleep, joint and muscle pain, and cognitive difficulties. Individuals with ME/CFS often do not return to pre-disease levels of activity.

The cause of ME/CFS is unknown. There are no diagnostic tests or FDA-approved treatments for the disease. ME/CFS affects individuals of all ages as well as all racial, ethnic, and socioeconomic groups. It is estimated that between 1 and 4 million Americans suffer from ME/CFS and women are four times more likely to be diagnosed than men. At least one quarter of people with ME/CFS will be house- or bed-bound at some point during the disease.

ME/CFS is co-morbid with other chronic conditions including Postural Orthostatic Tachycardia Syndrome (POTS), Ehler’s Danlos Syndrome (EDS) and chronic pain conditions such as temporomandibular joint disease, vulvodynia, endometriosis, fibromyalgia, interstitial cystitis/painful bladder syndrome, chronic prostatitis/chronic pelvic pain syndrome, and irritable bowel disease. The relationship to these other diseases remains to be further elucidated through epidemiological and basic research.

A 2015 report by the Institute of Medicine of the National Academy of Sciences concluded that ME/CFS is a serious, chronic, complex systemic disease that often can profoundly affect the lives of patients . Research on ME/CFS has described underlying biological abnormalities involve many organ systems in individuals with ME/CFS compared with healthy controls. Abnormalities in the neuroendocrine and autonomic nervous system as well as impaired cognition and abnormal imaging studies indicate that there is both central and peripheral nervous system involvement in ME/CFS. Metabolomic studies on ME/CFS indicate that cellular energy generation is impaired and numerous studies have identified immune system dysfunction.

There is significant need for expanded research on ME/CFS to identify biomarkers of disease that can be utilized for diagnosis and to measure progression of disease and response to treatment. Rigorous research is needed to identify the etiology of the disease and distinguish them from physiological abnormalities that are secondary consequences of the disease. Research on ME/CFS clearly demonstrates that it is a very heterogeneous disease, so the development of rigorous protocols to subtype individuals with various and different manifestations of ME/CFS and distinguish them from conditions exhibiting overlapping symptoms are needed. Current treatments for ME/CFS are aimed at symptom management, so a better understanding of the etiology and pathophysiology of ME/CFS will provide insight into appropriate treatments for this disease.

Innovative, rigorous, and well-designed studies are needed to provide a better understanding of ME/CFS, prevalence, pathogenesis, and pathophysiology, with the goal of developing improved diagnostic and intervention strategies. The heterogeneity of the ME/CFS population should be recognized in basic, translational and clinical research; for example, sex, age/developmental stage, racial and ethnic variations should be considered along with medical history, age of onset of disease, disease severity, as well as length of illness. This FOA encourages the integration of basic research with clinical observations in forming study hypotheses. The multisystem nature of the disease will benefit from a collaborative interdisciplinary (across scientific disciplines) team approach that may lead to the insights necessary to provide a foundation for understanding, diagnosing and treating ME/CFS.

Areas of interest where scientific opportunities exist to meet the objectives of this funding opportunity cut across many disciplines. Applicants are encouraged to review the Trans-NIH ME/CFS website (https://www.nih.gov/mecfs) for information about the NIH, resources and tools for grant writing, and other relevant information.

Among other issues, investigators are encouraged to consider the following in their applications:

1. Multidisciplinary approaches to the proposed research.
2. For clinical studies utilizing human subjects, the applicant should clearly state which case definition and the specific data collection instruments that will be used to obtain the data needed to apply that case definition for ME/CFS. In addition, sufficient clinical data should be obtained in order to categorize the study participants according to any of the primary case definitions in use for ME/CFS.
3. The health status of the control groups utilized in clinical studies should use valid data collection instruments.
4. Utilization of the common data elements (CDEs) developed for ME/CFS in clinical studies is highly encouraged.
5. Consideration of the physical activity levels of all study participants (individuals with ME/CFS and controls) using validated and standardized instruments is encouraged.
6. Information on confounding factors such as physical fitness level, co-morbid conditions, and presence of other diseases should be collected for all study participants.
7. Clinical characterization of study participants that inform the scope of ME/CFS and how the symptoms and severity of disease change over time is encouraged.
8. Research to identify and validate subtypes of ME/CFS is encouraged.
9. The use of telemedicine or other approaches to include individuals with ME/CFS who are home- or bed-bound are encouraged.
10. Studies of individuals with ME/CFS in the pediatric and adolescent age groups are encouraged.
11. If scientifically appropriate, the inclusion of disease comparison groups with other fatiguing illnesses (for example, multiple sclerosis, systemic lupus erythematosus, major depression, Sjogren’s Syndrome, etc.) is encouraged.
12. The use of validated wearable devices and/or apps for symptom tracking is encouraged.
13. If scientifically and ethically appropriate, provocation studies to help reveal the underlying cause(s) of ME/CFS are encouraged.

Proposed research projects should have relevance to the research priorities of the Institutes, Centers or Offices sponsoring this funding announcement. Specific considerations are listed below:

Specific Areas of Research Interest

Areas of interest where scientific opportunities exist to meet the objectives of this funding opportunity cut across many disciplines. Proposed research should have relevance to the research priorities of the Institutes, Centers or Offices sponsoring this funding announcement. Specific considerations are listed below:

National Center for Complementary and Integrative Health (NCCIH) - NCCIH will accept applications investigating the mechanisms by which complementary and integrative health approaches may improve ME/CFS treatment and/or ME/CFS comorbidity management. The proposed research may include basic and mechanistic studies in cellular systems or model organisms, as well as clinical mechanistic studies to develop improved complementary intervention strategies for ME/CFS and its associated comorbidities. Complementary and integrative approaches may include mind/brain-focused practices (i.e., meditation, hypnosis), body-based approaches (i.e., acupuncture, massage, spinal manipulation), meditative exercise (i.e., yoga, tai chi, qi gong), or natural products (i.e., botanicals, dietary supplements, probiotics), in isolation or in combination with conventional medical treatments. NCCIH will not fund applications examining clinical efficacy and/or effectiveness through this PAR.

National Heart, Lung and Blood Institute (NHLBI) - Some research areas of particular interest to NHLBI include, but are not limited to:

• Alterations in cardiopulmonary or hemodynamic status, including orthostatic intolerance and/or POTS (Postural Orthostatic Tachycardia Syndrome)
• Disturbances in sleep and circadian rhythm in individuals with ME/CFS
• Abnormalities in blood cell form, function, microcirculation, or oxygen delivery in individuals with ME/CFS

Some examples of potential research questions of interest to NHLBI include, but are not limited to:

• What are the underlying mechanisms and/or relationships between venous pooling, blood cell mass and volume, autonomic dysregulation, and cerebral perfusion that may contribute to symptomatic postural orthostatic tachycardia, neurally-mediated hypotension, and heart rate variability during head-up tilt testing?
• What role, if any, does the endothelium or vasculature in general play in inflammation an oxidative and nitrosative stress?
• What is the mechanistic basis of impaired oxygen delivery, lowered anerobic threshold, and hemodynamic alterations seen in ME/CFS with exercise?
• What is the etiology of the alterations in sleep patterns and accompanying symptoms and what are some potentially mitigating interventions?

National Institute on Alcohol Abuse and Alcoholism (NIAAA) -The mission of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) is to generate and disseminate fundamental knowledge about the effects of alcohol on health and well-being, and apply that knowledge to improve diagnosis, prevention, and treatment of alcohol-related problems, including alcohol use disorder, across the lifespan.

National Institute of Allergy and Infectious Disease (NIAID) - NIAID is interested in: 1) Studies on the etiology and pathogenesis in ME/CFS, including the elucidation of infectious etiology of ME/CFS and physiological and genetic host determinants involved in ME/CFS manifestations including, but not limited to microbiome-related studies; 2) Identification of potential triggers or modifiers of immune responses or immune cell metabolism that contribute to ME/CFS; 3) Application of current methodologies (e.g., immune phenotyping) or computational modeling to better characterize human immune responses triggered in ME/CFS; 4) Identification of immune/inflammatory biomarkers in cerebrospinal fluid, blood, urine, etc. that can identify physiologically relevant subgroups of ME/CFS; including but not limited to peripheral and immune tissue-based analyses

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) - The mission of the NIAMS is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases. Research areas include rheumatology, orthopaedics, dermatology, metabolic bone diseases, heritable disorders of bone and cartilage, inherited and inflammatory muscle diseases, and sports and rehabilitation medicine. Applicants are encouraged to discuss potential applications with the appropriate NIAMS program director

National Institute of Dental and Craniofacial Research (NIDCR) - NIDCR is interested in studies that investigate the comorbidity of ME/CFS with orofacial pain and/or Temporomandibular Joint Disorders (TMDs). Topics of interest include but are not limited to prevalence of overlap and shared underlying etiologies, pathophysiology, disease manifestations and mechanisms of disease as well as evolution of these overlaps. Secondary data analysis of well-phenotyped cohorts and/or analysis of banked biospecimens from well-phenotyped cohorts to determine common genetic, epigenetic, other omic , immune or endocrine factors linking these conditions are encouraged. Clinical trials designed to answer specific questions about the safety, tolerability, efficacy, effectiveness, clinical management, and/or implementation of pharmacologic, behavioral, biologic, surgical, or device interventions will only be supported by NIDCR if submitted to an NIDCR clinical trials-specific FOA https://www.nidcr.nih.gov/research/clinical-trials. Awardees will be required to comply with the NIDCR Clinical Terms of Award for activities that involve human subjects. Investigators are encouraged to contact NIDCR program staff to discuss potential research projects prior to application submission to determine alignment of the planned studies with priorities of the Institute mission and strategic plan.

National Institute of Environmental Health Sciences (NIEHS) - The mission of the National Institute of Environmental Health Sciences (NIEHS) is to discover how the environment affects people to promote healthier lives. The NIEHS is interested in supporting research projects that address or seek to understand how exposures to toxic environmental insults alter biologic processes and are linked to disease initiation, progression, or morbidity. In addition, NIEHS is interested in research that leads to the development of prevention and intervention strategies to reduce environmentally induced diseases. Examples of environmental exposures relevant to the mission of the NIEHS include, but are not limited to, industrial chemicals or manufacturing byproducts, e-waste, metals, pesticides, herbicides, and inhaled toxicants including indoor air pollutants from cooking and other sources, climate variability and the environmental impacts of natural and man-made disasters. NIEHS is interested in exposures throughout life and disease outcomes than manifest throughout the lifespan. Early life exposures and their biological consequences are of particular interest and include exposures before and during pregnancy and children’s environmental health outcomes that may arise from these exposures

National Institute of Mental Health (NIMH) - NIMH supports research to discover the causes of mental illness and to develop more effective and safer interventions. NIMH is interested in research on underlying mechanisms and/or relationships between ME/CFS and co-morbid psychiatric disorders across the life span. Studies that include as goals the determination of safety or clinical efficacy of interventions are outside of the scope of this FOA. Applicants interested in evaluating treatments for clinical efficacy should apply through one of the FOAs listed at the NIMH clinical trials website, which includes links to the NIMH CT FAQs. NIMH strongly encourages applicants to consult with NIMH Program Officials when developing plans for an application. This early contact will provide an opportunity to clarify NIMH policies and guidelines and identify whether the proposed project is consistent with NIMH program priorities, and to determine which available FOA would best support the proposed research. This is particularly important if there is doubt as to whether or not the submission is determined to be an NIH-defined clinical trial, and if found to be a clinical trial, whether it is a mechanistic study as described by NIMH.

National Institute of Neurological Disorders and Stroke (NINDS) - NINDS is interested in research on ME/CFS across the lifespan that includes, but is not limited to: 1) Studies on the etiology and pathogenesis of symptoms in ME/CFS impacting the central, autonomic and peripheral nervous systems; 2) Development of new model systems (both in vitro and in vivo) to study the pathophysiology of ME/CFS and its impact on the nervous system; and 3) Human neuroimaging studies to elucidate changes in the CNS in individuals with ME/CFS. Research on biomarker development or validation relevant to the NINDS mission should utilize the relevant NINDS FOAs:

• Discovery of Biomarkers and Biomarker Signatures for Neurological and Neuromuscular Disorders (R61/R33 Clinical Trial Optional)
• Analytical Validation of Candidate Biomarkers for Neurological Disease (U01 Clinical Trial Optional)
• Analytical Validation of a Candidate Biomarker for Neurological Disease (U44 - Clinical Trial Optional)
• Clinical Validation of Candidate Biomarkers for Neurological Diseases (U01 Clinical Trial Optional)
• Clinical Validation of a Candidate Biomarker for Neurological Disease (U44 - Clinical Trial Optional)

National Library of Medicine (NLM) - NLM is interested in novel computational and statistical approaches that support dynamic mapping of symptoms, deep phenotyping, real-time modeling of the disease across a patient’s history; synthetic models that can be fine-tuned to use in different population groups that reflect differences for minority groups and genders. AI to discover and to train tools to identify possible errors and gaps in existing data sets. Visualizations that help a clinician or patient understand the patient’s current state and propose treatment options. Intelligent tools that can rewrite relevant health text to suit patients whose reading or language skills are not well developed.

Office of Behavioral and Social Sciences Research (OBSSR) - OBSSR is interested in research aimed at understanding the psychosocial factors that impact individuals diagnosed with ME/CFS, especially those factors that may impact diagnosis, disease progression, and treatment.

Applications for studies that explore innovative ideas or investigative techniques and technologies applied to studying ME/CFS should provide a strong scientific rationale for the hypothesis-driven and rigorous studies proposed. Sex as a biological variable should be addressed as should all of the potential confounding factors described above.

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)
• Eligible Agencies of the Federal Government
• 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)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are 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.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101)

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

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

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.

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

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.

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

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

Section V. Application Review Information

1. Criteria

Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

Reviewers will consider how the proposed research addresses novel and innovative research that will break new ground or extend previous discoveries toward new directions.

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?

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?

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?

Approach

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

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

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?

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

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

For Revisions, 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.

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

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

• 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.

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

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

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.

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.

Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

3. Reporting

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 agreementsare 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.

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:[email protected](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:[email protected]

Vicky Whittemore, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1917
Email: [email protected]

Yisong Wang, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-480-9483
Email: [email protected]v

Cheryl McDonald, M.D.
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-693-5352
Email: [email protected]

Kathy Jung, Ph.D.
National Institute for Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-8744
Email: [email protected]v

Joseph Breen, Ph.D.
National Institute of Allergy and Infectious Disease (NIAID)
Telephone: 240-292-4123
Email: [email protected]v

Yan Wang, M.D., Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: (301) 594-5032
Email: [email protected]

Melissa Ghim, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-496-7853
Email: [email protected]

Jonathan Hollander, Ph.D.
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 984-287-3269
Email: [email protected]v

Michael Humble, Ph.D.
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 984-287-3272
Email: [email protected]v

Mi Hillefors, MD, PhD
National Institute of Mental Health (NIMH)
Telephone: 301-443-2738
Email: [email protected]

Hua-Chuan Sim, M.D.
National Library of Medicine (NLM)
Telephone: 301-594-4882
Email: [email protected]v?

Dana Schloesser, Ph.D.
Office of Behavioral and Social Sciences Research (OBSSR)
Telephone: 301-451-3975
Email: [email protected]

Alexei Kondratyev, Ph.D.
Center for Scientific Review (CSR)
Phone: 301-435-1785
Email: [email protected]?

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected]

Shelley Carow
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-3788
Email: [email protected]v

Judy Fox
National Institute for Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-4701
Email: [email protected]

Donna Sullivan
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2979
Email: [email protected]

Jamie M. Thompson
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-3614
Email: [email protected]

Diana Rutberg, M.B.A.
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-564-4798
Email: [email protected]

Barbara Gittleman, M.A.
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 984-287-3261
Email: [email protected]v

Rita Sisco
National Institute of Mental Health (NIMH)
Telephone: 301-443-2805
Email: [email protected]v

Tamara Kees
National Institute of Mental Health (NIMH)
Telephone:301-443-8811
Email: [email protected]

Samantha Tempchin
National Library of Medicine (NLM)
Telephone: 301-496-4222
Email: [email protected]

Section VIII. Other Information