Part 1. Overview Information

Key Dates

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

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

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts).

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

More than 25 million Americans suffer from daily chronic pain, a highly debilitating medical condition that is complex and difficult to manage. In recent decades, there has been an overreliance on the prescription of opioids for chronic pain despite their poor ability to improve function and high addiction liability. This contributed to a significant and alarming epidemic of opioid overdose deaths and addictions. Innovative scientific solutions to develop alternative pain treatment options are thus critically needed.

Through targeted research efforts, the NIH’s Helping to End Addiction Long-term (HEAL) Initiative aims to support the development of safe and effective therapeutics and devices to treat pain with little or no addiction liability. This funding opportunity announcement (FOA) is designed to support integrated efforts of three or more (up to six) PDs/PIs to pursue bold, impactful, and challenging research in basic and clinical pain domains to understand the biology of specific human pain conditions as well as pain associated with various diseases/disorders and pain across the lifespan, including mechanistic underpinning of heterogeneity and stratification of patients with specific pain conditions and co-morbidities. The research approach should be interdisciplinary in nature, and the research teams are expected to establish a common goal that requires collaboration, synergy, and managed team interactions. Proposed research should support a cohesive, single, well-integrated research plan with a singular focus, one set of aims, and a budget without subprojects. Proposed research should not represent a collection of individual efforts or parallel projects. Teams must leverage appropriate multi-disciplinary expertise to develop new principles and methods for experimentation, analysis, and interpretation. Teams are encouraged to consider transformative objectives with defined 5-year outcomes that will produce major advances in the understanding of human pain conditions and are likely to improve strategies for effective management of human pain.

Background

The NIH HEAL Initiative:

This funding announcement is part of the NIH HEAL Initiative to speed scientific solutions to the national opioid public health crisis. The NIH HEAL Initiative bolsters research across NIH to (1) improve treatment for opioid misuse and addiction and (2) enhance pain management. More information and periodic updates about the HEAL Initiative is available at: https://heal.nih.gov/.

The NIH HEAL Initiative aims to identify new, safer treatment options for pain management to improve quality of life and reduce the number of people exposed to the risks of opioids. Human pain conditions, including those associated with a wide array of diseases, and the underlying mechanisms are difficult to study and understand with the currently utilized approaches that largely use separate and individually focused clinical and preclinical research studies. This represents a significant knowledge gap as well as creates challenges in the discovery, biological understanding and therapeutic developments, and management strategies targeted at specific human pain conditions, including patient stratification of pain, and co-morbidities. Furthermore, there is a continued need for models that better reflect human pathological and/or disease-associated pain conditions, outcome measures and endpoints, including patient stratification of pain, which could be effectively achieved with integrated clinical and basic/preclinical research. The NIH HEAL Initiative recognizes the need to support emerging research opportunities of broad scope and complexity in pain that require innovative team science approaches. This concept, as part of a suite of NIH HEAL Initiative programs and funding opportunities, has the mission of enhancing pain management. RM1 is a team science approach to achieve a single shared goal that requires multiple research groups and laboratories working together.

Achieving the goals of the NIH HEAL Initiative will require a high level of coordination and sharing between investigators. It is expected that NIH HEAL Initiative grant award recipients will cooperate and coordinate their activities after awards are made by participating in Program Director/Principal Investigator (PD/PI) meetings, including an annual HEAL Investigators Meeting, as well as other activities.

Program Objectives and Scope

A team science approach expands our capacity to pursue challenging problems in the understanding of human pain conditions and the underlying biology in a comprehensive, interdisciplinary, rigorous, and mechanistic manner. This funding opportunity announcement (FOA) encourages an integrated interdisciplinary team efforts to pursue bold, impactful, and challenging research in basic and clinical pain domains to understand the biology of specific human pain conditions as well as pain associated with diverse diseases/disorders, including mechanistic underpinning of heterogeneity and stratification of patients with specific pain conditions and co-morbidities. Furthermore, it will expand our capacity to pursue challenging problems in basic biological understanding, therapeutics development and effective management of human pain conditions.

This FOA is designed to support team-based cross-cutting research approaches that combine clinical and basic research across technical and conceptual boundaries to achieve a common goal of enhancing our understanding on the pain processing under normophysiological and pathological conditions in humans. The research program should comprise of a synergistic, cohesive, well-defined, and sufficiently focused approaches to reach its goal, so that meaningful outcomes can be achieved within 5 years. Examples of outcomes for individual projects include, but not limited to, establishing a basis for future clinical pain management approaches, establishing new domains for basic research that has been informed by clinical data/experience, and establishing knowledgebase and/or platforms for the discovery and development of condition & evidence-based therapeutics and/or devices for the treatment of pain in humans. This FOA encourages a team of investigators with expertise in multiple disciplines to pursue coordinated research that could integrate diverse areas of expertise under one umbrella, including (but not limited to):

• Clinical pain management
• Clinical pain research
• Preclinical/basic pain biology and modeling
• Human psychology
• Specific disease and/or pathological conditions (both human and preclinical models)
• Animal behavior,
• Artificial Intelligence
• Data science

The research teams are expected to establish a common goal that requires collaboration, synergy, and managed team interactions. Proposed research should not represent a collection of individual efforts or parallel projects. Teams are encouraged to consider transformative objectives with defined 5-year outcomes. This approach would provide an effective roadmap for employing reverse translational approaches to establish more clinically relevant models for individual human pain conditions, including heterogeneity and patient stratification in pain and co-morbidities. Also, it would provide powerful tools, models and approaches for the development and translation of pain condition-specific efficacious therapeutics, and next-generation clinical management of pain. An integrated understanding of human pain biology at basic/preclinical and clinical domains, looking at specific pathological or disease conditions, including patient stratification of pain and co-morbidities, would be tremendously informative towards precision medicine in pain in the future.

Applications will be expected to include multidisciplinary and rigorous research approach, and clear projections on expected outcomes on integrated understanding on human pain biology at basic/preclinical and clinical domains, looking at specific pathological or disease conditions, including patient stratification of pain and co-morbidities, by the end of the grant award duration.

Projects should be focused on a specific pain condition, including but not limited to acute pain, chronic pain, painful neuropathy, musculoskeletal pain, headache, osteoarthritis, diabetic neuropathy, chemotherapy-induced neuropathy, eye pain, sickle-cell pain, post-surgical pain, cancer pain, visceral pain, obstetric pain, gynecologic pain, post stroke pain, myofascial pain, painful disorders of the orofacial region, pain co-occurring with substance use disorders, pain conditions across the lifespan including in the context of aging, and other conditions will be considered. Applications focused on conditions that are commonly treated with opioids and/or other substances with high misuse potential and/or with high addiction potential are a high program priority for the NIH HEAL Initiative .

Applicants are strongly encouraged to consult with NIH HEAL Initiative program staff as plans for an application are being developed.

Applications that propose extrapolations of a single line of research or propose parallel but independent advancement of different areas in pain are not appropriate for this FOA.

The list below includes representative, but not exhaustive, examples of interdisciplinary opportunities:

• Basic, translational, and/or clinical collaborations with a goal of reaching a significantly higher mechanistic understanding of specific human pain conditions, pain associated with diverse diseases/disorders, mechanistic underpinning of heterogeneity and stratification of patients with specific pain conditions and co-morbidities.
• Scientific efforts requiring integration of previously siloed and/or disparate areas of scientific or technical expertise to understand specific human pain conditions, heterogeneity and stratification of patients with specific pain conditions and co-morbidities.
• A scientific question that requires the leverage of an innovative combination of tools and approaches to understand specific human pain conditions, heterogeneity and stratification of patients with specific pain conditions and co-morbidities.

For applications proposing a clinical trial, note the following definitions and restrictions for this funding announcement:

• Clinical trials are research studies in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes. For this funding announcement, only the following types of clinical trials will be supported:
  • Mechanistic trials, defined as studies designed to understand a biological or behavioral process, the pathophysiology of a disease, or the mechanism of action of an intervention (i.e., how an intervention works, but not if it works or is safe).
  • Basic Experimental Studies with Humans (BESH), defined as basic research studies involving humans that seek to understand the fundamental aspects of phenomena.
• Clinical trials designed primarily to determine the safety, tolerability, and/or clinical efficacy of an intervention will not be supported under this FOA.
• For further clarification on how NIH defines the different types of clinical trials, please refer to the following resources:
  • NOT-OD-15-015: Notice of Revised NIH Definition of Clinical Trial
  • NIH's Definition of a Clinical Trial
  • Decision Tree for NIH Clinical Trial Definition
  • Guidance for Basic Experimental Studies with Humans (BESH) Funding Opportunities
  • NIH Definition of Clinical Trial Case Studies

For applications proposing translational projects, applicants are encouraged to consider several programs and FOAs listed on the NIH HEAL website at https://heal.nih.gov/funding/open.

Program Organization

This program is distinct from several program project mechanisms available in multiple NIH ICs in that it will support a cohesive, single, well-integrated research plan with a singular focus, one set of aims, and a budget without subprojects that enable interdisciplinary research teams to accomplish goals that could not be achieved individually. This program also requires a Multiple PD/PI (MPI) structure with a minimum of three PD/PIs (up to six) who will each bring a distinct scientific viewpoint or expertise necessary to pursue the interdisciplinary approach. Applicants are expected to describe a cohesive program with a single set of specific aims sufficient to accomplish program objectives that can be achieved within a maximum of 5 years. Program objectives that are unlikely to be achieved within 5 years are not appropriate for this FOA. Applications for smaller projects with one or two PD/PIs should consider submitting a multi-PD/PI application to the "NIH Research Project Grant (Parent R01)" FOA (see the Parent Announcement website for the current issuance of this FOA).

The NIH HEAL Initiative recognizes that the success of team science hinges on well-managed team interactions, clear timelines and benchmarks for success, and a commitment to promoting diverse perspectives. Therefore, the following three components are required as "Other Project Information" as an attachment (see Section IV). Applications that fail to include these attachments will be considered incomplete and will be withdrawn.

1. Team Management Plan

Studies of team science have highlighted the need for effective management structures to achieve program goals. These structures grow in importance as the team size increases. Many resources exist to aid in developing effective team-based programs (see e.g., the NCI Collaboration and Team Science Field Guide). Note that a "Multiple PD/PI Leadership Plan" is also required as a separate attachment, and the information in that plan should not be duplicated here. Whereas the Multiple PD/PI Leadership Plan focuses on leadership by and interactions across the PD/PIs, the Team Management Plan focuses on management of the whole team/key personnel. The team management plan will address the following points (see section IV):

• Organizational structure and team composition
• Shared leadership, contributions, and distributed responsibility for decision making
• Resource sharing and allocation
• Credit assignment
• Coordination and communication plans
• Intra-team data sharing, archiving, and preservation

Because teams will likely include individuals from widely divergent scientific backgrounds, teams must have a shared vision and a defined plan for communication and management of shared responsibilities, interpersonal interactions, and professional credit. It is highly recommended that a scientific project manager or program coordinator is included in the team. Depending on the specific data needs of the project, data/resource sharing and management systems and/or hiring of professional data science staff should also be considered.

2. Timeline and Benchmarks for Success

The research goal for this team science effort should be cohesive, feasible, well-defined, and sufficiently focused so that meaningful outcomes can be achieved within 5 years.

3. Plan for Enhancing Diverse Perspectives (PEDP)

To support the best science, the NIH HEAL Initiative encourages inclusivity in research. Examples of structures that promote diverse perspectives include but are not limited to:

• Transdisciplinary research projects and collaborations
• Engagement from different types of institutions and organizations (e.g., research-intensive, undergraduate-focused, minority-serving, community-based)
• Individual applications and partnerships that enhance geographic and regional heterogeneity
• Investigators and teams composed of researchers at different career stages
• Participation of individuals from diverse backgrounds, including groups historically underrepresented in the biomedical, behavioral, and clinical research workforce (see NOT-OD-20-031), such as underrepresented racial and ethnic groups, those with disabilities, those from disadvantaged backgrounds, and women
• Project-based opportunities to enhance the research environment to benefit early- and mid-career investigators

Applications are required to include a Plan for Enhancing Diverse Perspectives (PEDP) submitted as Other Project Information as an attachment (see Section IV). The PEDP will be assessed as part of the scientific and technical peer review evaluation, as well as considered among programmatic matters with respect to funding decisions. Applicants are strongly encouraged to read the FOA instructions carefully and view examples available from the NIH BRAIN Initiative in their PEDP guidance material.

Here are some important points to consider before applying:

Rigor and Transparency

NIH strives for rigor and transparency in all research it funds. For this reason, the NIH HEAL Initiative explicitly emphasizes the NIH application instructions related to rigor and transparency (https://grants.nih.gov/policy/reproducibility/guidance.htm) and provides additional guidance from individual NIH ICs to the scientific community. For example, the biological rationale for the proposed experiments must be based on rigorous and robust supporting data, which means that data should be collected via methods that minimize the risk of bias and be reported in a transparent manner. If previously published or preliminary studies do not meet these standards, applicants should address how the current study design addresses the deficiencies in rigor and transparency. Proposed experiments should likewise be designed in a manner that minimizes the risk of bias and ensures validity of experimental results.

Prior Consultation with NIH HEAL Initiative Program staff

The NIH HEAL Initiative intends to fund a limited number of applications for this FOA. Therefore, consultation with relevant staff at least 6 weeks prior to the application due date is strongly encouraged. Once applicants have identified overall program objectives and PD/PI participants, HEAL Initiative staff may be able to advise applicants whether the proposed research strategy meets the goals of the NIH HEAL Initiative and mission of the ICs, whether it addresses one or more high priority research areas, and whether it is appropriate for this team-science program. A collaborative program that is closely related to the goal of a PD/PI's existing NIH-funded research might require that funding be relinquished to avoid overlap. HEAL Initiative staff will not evaluate the technical and scientific merit of the proposed program in advance; technical and scientific merit will be determined during peer review using the review criteria indicated in this FOA. During the consultation phase, if the proposed research strategy does not meet the NIH HEAL Initiative's programmatic needs, or is not appropriate as a team-science grant, applicants will be encouraged to consider other funding opportunities.

Non-Responsiveness Criteria:

Applications deemed to be non-responsive will not proceed to review and will be withdrawn. The following are considered non-responsive to this FOA:

• Research outside of the NIH HEAL Initiative mission on Pain.
• Applications that propose a systematic, team based plan to discover and develop small molecule or biologic therapeutics or devices to treat pain since these types of applications are already covered by several FOAs (listed on the NIH HEAL Initiative website at https://heal.nih.gov/funding/open).
• Applications without a well-defined goal that is achievable within the timeframe of the grant and through a collective, integrated effort.
• Applications that propose extrapolations of a single line of research or propose parallel but independent advancement of different areas in pain.
• Clinical Trials designed to answer specific questions about safety, tolerability, efficacy and/or effectiveness of pharmacologic, behavioral, biologic, surgical, or device (invasive or non-invasive) interventions (e.g., phase I, phase II, phase III, or pivotal clinical trials). Such designs should be submitted to an NIH HEAL Initiative's clinical trial-specific funding announcement (listed on the NIH HEAL Initiative website at https://heal.nih.gov/funding/open).

NIH Institute and Center Interests and Guidance

National Institute on Aging (NIA)

NIA is interested in collaborations that support research on underlying human pain biology mechanisms to facilitate the development of innovative, safe, and effective therapeutics for pain-related disorders with aging. NIA is particularly interested in research that addresses important age-related considerations such as multimorbidity, polypharmacy, age-related cognitive decline/impairment, and Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD). Studies should account for important aging and age-related changes in molecular, cellular, pathological, behavioral, physiological, or cognitive processes that may influence the underlying normal and pathophysiological mechanisms of pain processing and therapeutic responses across the lifespan. Investigators developing preclinical aged pain models using rodents and/or non-human primates may consider use of NIA-supported biological resources (e.g., aged rodent and Macaca mulatta colonies). Investigators are encouraged to contact NIA program staff for additional details.

National Cancer Institute (NCI)

NCI is particularly interested in applications focusing on understanding the underlying mechanisms, identifying predictive biomarkers, and stratification of patients, and understanding the impact of co-morbidities associated with cancer- or cancer-treatment related pain. Pain conditions of interest include, but are not limited to: bone cancer pain, oral cancer pain, metastasis-related pain, post-surgical pain, radiation pain, aromatase inhibitor-induced arthralgia, chemotherapy-induced peripheral neuropathy, and immunotherapy-related pain. An ideal team would include basic scientists and clinicians across multiple fields (i.e. oncology, radiology, neurology, palliative care, etc ).

National Center for Complementary and Integrative Health (NCCIH)

NCCIH is interested in collaborative research that would further our mechanistic understanding of complementary and integrative interventions that fit within NCCIH’s mission, including biophysical force-based interventions (e.g., massage, acupuncture, chiropractic manipulations, osteopathic treatments) or other non-pharmacological interventions as well as natural products (e.g., probiotics and microbial based therapeutics, herbs, or supplements). NCCIH is also interested in collaborations that further our understanding of pain pathophysiology in a variety of chronic pain conditions with special emphasis on Sickle Cell Disease Pain, Myofascial Pain, Irritable Bowel Disease Pain, and Joint Pain.

National Heart, Lung, and Blood Institute (NHLBI)

The NHLBI is interested in collaborative research that furthers our understanding of the biology of pain conditions within the mission of NHLBI. Topics of special interest include, but are not limited to, pain associated with blood diseases such as sickle cell disease, hemophilia, deep venous thrombosis; pain associated with cardiovascular diseases such as peripheral artery disease and vasculitis; pain associated with the symptoms and treatment of lung disease such as severe cough, pleurisy, tube thoracostomy, and mechanical ventilation; and pain associated with heart, lung or bone marrow transplantation procedures.

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

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

Section II. Award Information

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

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)

Local 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)

Federal Government

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• 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.

• 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.
  • Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; 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 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.

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. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See Notice of NIH’s Interest in Diversity,NOT-OD-20-031. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities,NOT-OD-22-019.

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.

For this FOA, the application is required to be submitted as a multiple PD/PI application, with a minimum of 3 and a maximum of 6 PDs/PIs. Visit the multiple PD/PI Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide, and the Grant Policy Statement on Multiple Principal Investigators. Minimum allowed efforts by the PDs/PIs are described in the R&R Budget instructions in Part 2. Section IV.2.

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.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. 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 2.3.9.4 Similar, Essentially Identical, or Identical Applications)

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

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

D.P. Mohapatra, Ph.D.
Telephone: 301-496-9964
Fax: 301-402-2060
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

For this specific FOA, the Research Strategy is limited to 30 pages.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

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

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

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

Applications that fail to include these three required attachments will be considered incomplete and will be withdrawn.

1. Team Management Plan (Required 3 pages maximum):

As an "Other Attachment" entitled Team-Management-Plan.pdf , applicants should address how the entire group will function to accomplish program objectives and vision. Team management approaches raised in the subsections listed below should be described in the Plan. Note that a "Multiple PD/PI Leadership Plan" is also required as a separate attachment, and the information in that plan should not be duplicated here. Whereas the Multiple PD/PI Leadership Plan focuses on leadership by and interactions across the PD/PIs, the Team Management Plan focuses on management of the whole team/key personnel. Applicants are encouraged to consult resources to aid in developing effective team-based programs (see e.g., the NCI Collaboration and Team Science Field Guide). Applications that exceed the 3-page limit will be withdrawn.

Organizational structure and team composition: The program management structure should avoid giving any single individual undue authority that prevents contributions from the wider team for setting program priorities, resource distribution, and reward. NIH HEAL Initiative recognizes that strong leadership is required for complex team efforts to be successful, while at the same time effective team leadership requires decision-making based on an amalgam of interests, expertise, and roles, guided by recognized project objectives. Applicants should develop a management structure based on project objectives that effectively promote the proposed research. The structure should account for team composition, institutional resources, and policies. NIH HEAL Initiative does not specify any particular organizational structure, as this may very across research questions and groups.

Inclusion of a scientific project manager or coordinator as a Senior/Key Person with adequate authority is strongly recommended. Describe how the qualifications of this individual are appropriate for such a role and for the subject matter and scale of the proposed project.

Shared leadership, contributions, and distributed responsibility for decision making: The Team Management Plan should include a description of how the PD/PIs will recruit an interdisciplinary team of prospective researchers with a range of backgrounds, expertise, and skills to successfully accomplish the goals of the program. One key consideration is that teams employing complementary approaches and having diverse areas of intellectual and technical expertise are more productive if the process for making decisions incorporates different points of view. The Team Management Plan should describe how major decisions will be made or how conflicts will be resolved. A key characteristic that distinguishes productive teams is the degree that all member contributions are valued. Strategies for building and maintaining group participation to develop collective intelligence are encouraged.

Resource sharing and allocation across the team: Applications should describe management and decision-making processes that promote collective input for allocation of program resources with flexibility when resources may need to be dynamically reallocated to achieve programmatic goals. A plan for how intra-team, institutional, and regional resources that are integral to the team goals will be shared and made accessible to team members should also be included.

Credit assignment: A plan for how credit will be shared especially with early career stage investigators should be included. Methods for attributing contributions to publications should be described to enable individual professional assessment in joint projects.

Coordination and Communication plans: Practical aspects should be described, including frequency and logistics of real time communication across all key personnel, consultants, scholars, early stage investigators etc., and other significant contributors regardless of effort level. If a scientific project manager or coordinator is included, describe his/her role in coordinating team activities and communication.

An important and meaningful impact of team science may come from shaping the next generation of pain scientists. Because of the interdisciplinary expertise of the research groups, trainees are exposed to and can learn diverse scientific approach and methodologies, resulting in multi-faceted, early-stage investigators. Plans for how trainees will be immersed in, and benefit from different approaches taken by the collective team program should be described. This could include shared mentorship, inter-lab meetings, all-hands tutorials, shared meeting and document space, inter-lab visits, and trainee presentations.

Intra-team data sharing, archiving, and preservation: A framework for sharing and/or integrating data across team members must be customized to fit the science and the specific data needs of the project. Plans for data archiving and long-term preservation for team use should also be described. Depending on the needs and challenges of managing team data, applicants may also include and justify data/resource sharing and management systems and/or hiring of professional data science staff.

2. Timeline and Benchmarks for Success (Required- 2 pages maximum)

As an "Other Attachment" entitled Timeline_Benchmarks.pdf , applicants should include a project timeline in the form of a Gantt chart/table (or similar) that includes all major tasks to be performed during the project as well as critical benchmarks for success. The chart should also include estimated start and completion dates for those tasks and should identify the contributions expected from each PD/PI toward accomplishing each task. For a truly integrated collaborative project, it is expected that most or all of the scientific aims will require substantial contributions from more than one PD/PI. This chart will aid reviewers in assessing the feasibility and likelihood that the work plan is adequate for achieving project objectives within the funding period. It will also aid in assessing the degree of integration and collaboration, and the availability of appropriate intellectual and technical expertise for each aim.

3. Plan for Enhancing Diverse Perspectives (PEDP) (Required- 1 page maximum)

In an "Other Attachment" entitled "PEDP.pdf", all applicants must include a summary of strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity. The PEDP should provide a holistic and integrated view of how enhancing diverse perspectives is viewed and supported throughout the application and can incorporate elements with relevance to any review criteria (significance, investigator(s), innovation, approach, and environment) as appropriate. Where possible, applicant(s) should align their description with these required elements within the research strategy section. The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured. The PEDP may be no more than 1-page in length and should include a timeline and milestones for relevant components that will be considered as part of the review. Examples of items that advance inclusivity in research and may be part of the PEDP can include, but are not limited to:

• Discussion of engagement with different types of institutions and organizations (e.g., research-intensive, undergraduate-focused, minority-serving, community-based).
• Description of any planned partnerships that may enhance geographic and regional diversity.
• Plan to enhance recruitment of women and individuals from groups traditionally under-represented in the biomedical, behavioral, and clinical research workforce.
• Proposed monitoring activities to identify and measure PEDP progress benchmarks.
• Plan to utilize the project infrastructure (i.e., research and structure) to support career-enhancing research opportunities for diverse junior, early- and mid-career researchers.
• Description of any training and/or mentoring opportunities available to encourage participation of students, postdoctoral researchers and co-investigators from diverse backgrounds.
• Plan to develop transdisciplinary collaboration(s) that require unique expertise and/or solicit diverse perspectives to address research question(s).
• Publication plan that enumerates planned manuscripts and proposed lead authorship.
• Outreach and planned engagement activities to enhance recruitment of individuals from diverse groups as research participants including those from under-represented backgrounds.

IRB Communications (Optional 5 pages maximum):

This attachment should be entitled "IRB-Communications.pdf". Applicants should submit relevant approval letters and associated attachments. Applications that exceed this page limit will be withdrawn.

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

Applications must include a minimum of three PD/PIs and a maximum of six PD/PIs. Applications that do not include the required minimum of 3 PD/PIs or exceed the maximum of 6 PD/PIs will be considered non-compliant, and will be withdrawn.

R&R Budget

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

A single integrated application budget must cover all aims, personnel, equipment, resource assignments, and other costs of the program, with subcontracts as necessary.

Research Budget: To be successful, programs of this level of complexity are expected to require significant effort from all PDs/PIs involved. Generally, each PD/PI should devote at least 2.4 person months (i.e., the equivalent of 20% effort on a full-year appointment, 26.7% on a 9-month appointment, or 40% on a 6-month appointment) throughout the duration of the award. The total research effort should include their 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.

Certain supporting functions such as equipment, animal research costs, and clinical research costs may be requested if well justified and unique to the institution(s) involved. Within the research budget, equipment, including data sharing and management systems, can be included if well justified. Equipment that duplicates existing institutional or regional shared facilities that are available to investigators must be identified and the proposed duplication should be well justified. Applicants should consider the need to ramp-up programs of this complexity, and propose annual budgets accordingly. Do not request inflationary increases in the overall budget or any of the budget categories. Changes in budget should reflect changes in activities required by the science.

Data sharing costs:

• Applicants may include costs associated with preparing and submitting data to a data archive per NOT-OD-21-015.

PEDP implementation costs:

• Applicants may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement section 7: https://grants.nih.gov/grants/policy/nihgps/html5/section_7/7.1_general.htm).

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

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

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Specific Aims

In the single Specific Aims attachment, the proposed research should be presented as an integrated scientific program with a single set of specific aims organized to address the overall objectives rather than individual PD/PI contributions. Provide a concise description of the goals of the entire project for an impactful scope of work in integrated basic and clinical pain research that will result in a significantly improved understanding of the biology of human pain conditions. Briefly describe how the interdisciplinary team is structured, and how the represented areas of expertise will enhance the approach and outcomes of the project.

Research Strategy

The Research Strategy should fully describe the biomedical problem being addressed, its significance within the relevant scientific field(s), and how successful accomplishment of the goals would provide substantial scientific advances. The research strategy should thoroughly describe the specific human pain condition(s) being studied, what is lacking in the mechanistic understanding of those, and what challenges exist in the clinical management as well as understanding the underlying biology of those.

The Research Strategy should describe how this grant proposal will enable the applicants to challenge existing paradigms, overcome long-standing roadblocks to progress, and/or develop new synergies between different scientific fields. Applications should fully describe the overall goal of the research program, its significance within the relevant scientific field(s), the rigor and status of prior research, current obstacles and challenges, and how a team science approach and outcomes will be transformative and/or enable major advances. The research strategy should present how innovative combinations of scientific fields and/or intellectual viewpoints will enable the project goals to be achieved. The research goal for this team science effort should be cohesive, well-defined, and sufficiently focused so that meaningful and significant outcomes can be achieved within 5 years.

The research strategy should thoroughly describe the underlying premise and scientific foundation of the project, experimental rationale, approaches, and steps taken to assure scientific rigor with attention to the reasons a team-science approach is required. The research strategy should describe how the proposed program’s coordinated research effort will produce significant advances in understanding of the biology of human pain conditions. Applications should justify any plans for technology development or new data sharing and archiving resources that are necessary to achieve program goals. Applications should describe how the resources and infrastructure are adequate for accomplishing the specific aims and supporting team science. Shared resources that are needed to achieve project objectives should be integrated in the research plan. The rationale and use of shared resources should be described within the research plan, and the rationale for their use should be described. Applications requesting resources should include evaluations of the existing resources that are available to the PDs/PIs, but considered inadequate.

Team composition: Applications should justify the need for a larger-scale collaborative approach and explain why the goal of the program could not be accomplished by other means, such as independently funded individual research grants. Applications should describe their plans to recruit prospective investigators from a range of backgrounds, skills, and describe how that variety of expertise may help address the proposed scientific problem. Evidence for synergistic interactions among PDs/PIs that are beyond the additive benefits of additional investigators should be described. The planned effort and expertise by the PDs/PIs should be appropriate and sufficient for the work proposed. If the application includes collaborating investigators who will not receive direct support, it should be described how these investigators will participate in the program. If foreign investigators are involved, it should be described how they are uniquely qualified to participate in the team.

Other required elements: Applications should describe critical research benchmarks (can reference the "Timeline and Benchmarks for Success" Other Attachment), definitive 5-year outcomes, and any innovative aspects of the ideas and approach, including those arising from collaborative interactions. Applications should justify any plans for technology development or new data sharing and archiving resources that are necessary to achieve the program goal. Shared resources that are needed to achieve project objectives should be integrated in the research plan and documented by a letter of agreement. The rationale and use of shared resources should be described within the research plan. Applications requesting resources should include evaluations of the existing resources that are available to the PDs/PIs but that are considered inadequate.

Environment: The Research Strategy should describe the resources and infrastructure available to accomplish the specific aims of the research and support team science. The value of the involvement of multiple departments and institutions should be described in terms of synergy and how it promotes the recruitment of a team of prospective researchers with a variety of backgrounds, expertise, and skills. If foreign investigators are involved, it should be described how they will provide unique resources that are not otherwise available.

Rigor and Transparency: The NIH HEAL Initiative urges investigators to follow the NIH guidance for rigor and transparency in grant applications (https://grants.nih.gov/policy/reproducibility/guidance.htm) and additionally recommends the research practices described by individual NIH ICs. This will ensure that robust experiments are designed, potential experimenter biases are minimized, results and analyses are transparently reported, and results are interpreted carefully. These recommended research practices include, where applicable, expressing clear rationale for the chosen model(s) and primary/secondary endpoint(s), describing tools and parameters clearly, blinding, randomizing, ensuring adequate sample size, pre-specifying inclusion/exclusion criteria, appropriately handling missing data and outliers, implementing appropriate controls, preplanning analyses, and using appropriate quantitative techniques. It is also strongly recommended to indicate clearly the exploratory vs. confirmatory components of the study, consider study limitations, and plan for transparent reporting of all methods, analyses, and results so that other investigators can evaluate the quality of the work and potentially perform replications.

Investigators should indicate whether data presented or cited in the application as key support for the proposed work were collected, analyzed, and reported in a rigorous and transparent manner as indicated above. A plan to address any ambiguity, weaknesses, or limitations in the prior research should be included in the application. Proposed experiments should similarly adhere to these high standards of rigor and transparency.

If proposing a mechanistic trial: Applicants must describe the rigor, robustness, and transparency of supporting data that are being used to justify the proposed mechanistic trial and address any gaps identified. For all trials, the rationale for the trial design, population(s) and hypotheses being tested, and control groups must be described. Potential biases and/or challenges in the study design and protocol should be identified and addressed. For Basic Experimental Studies involving Humans (BESH), the application should describe and address how the expected effect size relates to biologically meaningful differences.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

The following modifications also apply:

NIH intends to maximize the impact of HEAL Initiative-supported projects through broad and rapid data sharing. Consistent with the HEAL Initiative Public Access and Data Sharing Policy (https://heal.nih.gov/about/public-access-data), and in line with the new NIH Policy for Data Management and Sharing (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-21-013.html), all applications, regardless of the amount of direct costs requested for any one year, are required to include a Data Management and Sharing Plan outlining how scientific data and any accompanying metadata will be managed and shared. The plan should describe data types, file formats, submission timelines, and standards used in collecting or processing the data. It is expected that data generated by HEAL Initiative-funded projects will be submitted to study-appropriate domain-specific or generalist repositories in consultation with the HEAL Data Stewardship Group to ensure the data is accessible via the HEAL Initiative Data Ecosystem.

To maximize discoverability and value of HEAL datasets and studies, and facilitate data integration and collaboration, applications submitted in response to this FOA are strongly encouraged to incorporate standards and resources where applicable:

• Applicants are encouraged to ensure that data collected by the study conform to Findable, Accessible, Interoperable, and Reusable (FAIR) principles.
• Applicants are specifically encouraged to incorporate into their planning, an alignment with the guidelines, principles and recommendations developed by the HEAL Data Ecosystem, including but not limited to preparing data to store in selected specified repositories, applying minimal metadata standards, use of core HEAL Clinical Data Elements (CDEs, https://heal.nih.gov/data/common-data-elements), and other necessary requirements to prepare data to connect to the HEAL Data Ecosystem.
• All new HEAL clinical pain studies are required to submit their case-report forms/questionnaires to the HEAL CDE Program. The program will create the CDE files containing standardized variable names, responses, coding, and other information. The program will also format the case-report forms in a standardized way that is compliant with accessibility standards under Section 508 of the Rehabilitation Act of 1973 (29 U.S.C 794 (d)), which require[s] Federal agencies to make their electronic and information technology accessible to people with disabilities. HEAL Initiative clinical studies that are using copyrighted questionaries are required to obtain licenses for use prior to initiating data collection. Licenses must be shared with the HEAL CDE team and the program officer prior to use of copyrighted materials. For additional information, visit the HEAL CDE Program.

The NIH notices referenced below provide additional NIH guidance that should be considered in developing a strong data management and sharing plan. The list is instructive but not comprehensive.

• Elements of an NIH Data Management and Sharing Plan (NOT-OD-21-014).
• NIH has provided guidance around selecting a repository for data generated by NIH-supported research and has developed desirable characteristics for all data repositories (NOT-OD-21-016).
• NIH encourages the use of data standards including the PhenX Toolkit (www.phenxtoolkit.org) (for example, seeNOT-DA-12-008,NOT-MH-15-009).
• NIH encourages researchers to explore the use of the HL7 FHIR (Fast Healthcare Interoperability Resources) standard to capture, integrate, and exchange clinical data for research purposes and to enhance capabilities to share research data (NOT-OD-19-122). The FHIR standard may be particularly useful in facilitating the flow of data with EHR-based datasets, tools, and applications.
• NIH encourages clinical research programs and researchers to adopt and use the standardized set of data classes, data elements, and associated vocabulary standards specified in the United States Core Data for Interoperability (USCDI)standards, as they are applicable (NOT-OD-20-146). Use of the USCDI can complement the FHIR standard and enable researchers to leverage structured EHR data for research and enable discovery.

Awardees conducting research that includes collection of genomic data should incorporate requirements under the NIH Genomic Data Sharing Policy (NOT-OD-14-124,NOT-OD-15-086).

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Section 3 - Protection and Monitoring Plans

3.3 Data Safety and Monitoring Plan (DSMP, for proposals that include a mechanistic trial)

Attachment: DSMP: Applicants must submit a data safety and monitoring plan (DSMP) and should consider Guidelines and Policies for Monitoring Clinical Research in the formation of the plan as required by the appropriate IC. Applicants should:

• (In addition to the general guidelines athttps://grants.nih.gov/grants/how-to-apply-application-guide/forms-f/general/g.500-phs-human-subjects-and-clinical-trials-information.htm#3) include an adequate description and justification of safety risks to participants that includes risks incurred during the trial and for device removal. This description should incorporate how risks will be mitigated.
• Include adequate scientific justification for inclusion/exclusion criteria. Exclusion criteria should avoid discrimination against particular groups.
• Describe plans to incorporate an independent committee to evaluate data safety and monitor patient safety, including what expertise will be included (https://www.ninds.nih.gov/Funding/Apply-Funding/Application-Support-Library/NINDS-Guidelines-Data-and-Safety-Monitoring).
• Describe any plan to address cybersecurity and confidentiality of participants personal data (if applicable).

Section 4 - Protocol Synopsis of the PHS Human Subjects and Clinical Trials Information

Attachment: Statistical Analysis Plan (SAP) for analyses specified in the study protocol: Applicants should provide a SAP for analyses specified in the study protocol. Include the rationale for how missing data will be handled; plans for interim analyses for safety, efficacy, and futility; rationale for recalculation of the sample size midway through the trial (if applicable); and other measures to ensure rigor and transparency of the analysis. Sufficient details should be provided in the SAP about any computer simulations used to investigate the operating characteristics of complex clinical trial designs (such as adaptive designs); to choose between alternative outcome measures; or to determine sample size, accounting for the impact of noncompliance, missing data, subject eligibility criteria, etc. It is particularly important to discuss the range of conditions that were considered in the simulation and why this range was considered appropriate, how robust the findings were across the range of conditions considered, and how the study will adjust for any design deficiencies (e.g., bias, loss of power) the simulations revealed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

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

Foreign Institutions

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

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.

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.

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 fieldof the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the 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 responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applications Involving the NIH Intramural Research Program

The requests by NIH intramural scientists will be limited to the incremental costs required for participation. As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs). These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.

If selected, appropriate funding will be provided by the NIH Intramural Program. NIH intramural scientists will participate in this program as PDs/PIs in accord with the Terms and Conditions provided in this FOA. Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights.

Should an extramural application include the collaboration with an intramural scientist, no funds for the support of the intramural scientist may be requested in the application. The intramural scientist may submit a separate request for intramural funding as described above.

Use of Common Data Elements in NIH-funded Research

Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human participants research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Investigators are encouraged to consult the NIH CDE Repository and describe in their applications any use they will make of NIH-supported CDEs in their projects, when applicable. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological diseases), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a Common Data Element (CDE) Repository Resource Portal" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research.

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

IRB Communications (Optional 5 pages maximum):

Applicants may also submit relevant approval letters and associated attachments as a Post Submission Material. This attachment should be entitled "IRB-Communications.pdf".

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.

In addition, for applications involving clinical trials:

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

Overall Impact

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

For this FOA:

• Is the program of sufficient scope and complexity to warrant a team approach?
• Do the specific aims form a single cohesive program, and if accomplished will these aims advance the stated goals of the program on integrated basic and clinical research in pain?
• To what extent do the overall goal challenge existing paradigms, overcome long-standing roadblocks to progress, and/or develop new synergies between basic and clinical pain research?
• Do the specific aims form a single cohesive program that require an integrated effort, and if accomplished will these aims advance the stated goal of the program?
• Does the description of the specific pain condition(s) and the lack of mechanistic understanding of pain biology convey that there is a significant need for new knowledge in this space?
• If successful, will the proposed program's coordinated research effort produce significant advances in the mechanistic understanding of human pain conditions, and/or mechanistic underpinning of heterogeneity and stratification of patients with specific pain conditions and co-morbidities?
• Are the proposed research strategies and outcomes likely to improve strategies for effective management of human pain conditions?
• Does the application adequately describe whether prior research that serves as the key support for the proposed project employed rigorous practices such as minimization of potential experimenter biases, robust experimental designs, transparent reporting of results and analyses, and careful interpretation? How does the application address ambiguity, weaknesses, or limitations in rigor of the prior research, if applicable?
• PEDP (Attachment): To what extent do the efforts and features described in the Plan for Enhancing Diverse Perspectives (e.g., collaborative arrangements, geographic diversity, institutional support, outreach & engagement activities) contribute to the significance of the project?

In addition, for applications involving clinical trials

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

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance, and organizational structure appropriate for the project?

For this FOA:

• Is the planned effort by the PDs/PIs appropriate and sufficient for the work proposed?
• Is it clear how the applicant intends to recruit prospective investigators from a range ofbackgrounds, skills, and expertise and how the interdisciplinary nature of the team may help address the proposed scientific problem?
• Is it clear that each investigator is necessary and will contribute to achieving the goals of the program?
• Is there evidence for synergistic interactions among PDs/PIs beyond the additive benefits of additional investigators?
• Is the team consists of investigators with interdisciplinary expertise for the proposed research? Do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and meet the activities and timelines of the proposed integrated basic and clinical pain research?
• If the application includes collaborating investigators who will not receive direct support, is it clear how these investigators will participate in the program? If foreign investigators are involved, are they uniquely qualified to participate in the team?
• Team Management Plan (Attachment):
  • Does the team management plan instill confidence that fair and adequate governance processes will be used for decision making, conflict resolution, and resource allocation?
  • Does the plan ensure that all investigators will have a voice in decision making and that no single PD/PI will become overly dominant?
  • Does it provide for effective team leadership and management with distributed responsibility and decision-making processes?
  • Is the team plan sufficiently detailed to create a sustainable environment for maintaining cohesiveness, productivity, and shared vision?
  • Does the management plan include adequate plans for shared professional credit?
  • If shared research resources will be utilized, are adequate plans in place on resource sharing and allocation to ensure that all team members will have the access they require?
  • Are plans for team coordination and communication adequate?
  • To what extent will trainees be involved in and benefit from this team science?
  • If a scientific program manager or coordinator is proposed, are the qualifications and role of this individual appropriate?
  • Are adequate plans presented to recruit a team of prospective researchers with a variety of backgrounds, expertise and skills, and plans to arrive at major decisions, accounting for different points of view?
  • Are adequate plans presented to manage intra-team data sharing, archiving, and preservation?
• PEDP (Attachment): To what extent will the efforts and features described in the Plan for Enhancing Diverse Perspectives (e.g., collaborative arrangements, geographic diversity, institutional support, outreach & engagement activities) strengthen and enhance the expertise required for the project?

In addition, for applications involving clinical trials

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

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

For this FOA:

• Does the program involve innovative ideas or approaches that would be very difficult to pursue through independently funded individual or multiple PD/PI research project grants?
• Does the program involve innovative combinations of scientific fields and/or intellectual viewpoints to address the goals of mechanistic understanding of human pain conditions, and/or mechanistic underpinning of heterogeneity and stratification of patients with specific pain conditions and co-morbidities?
• Is innovation evident in the method that the established basic and clinical pain research areas are integrated?
• PEDP (Attachment): To what extent will the efforts and features described in the Plan for Enhancing Diverse Perspectives (e.g., collaborative arrangements, geographic diversity, institutional support, outreach & engagement activities) meaningfully contribute to innovation?

In addition, for applications involving clinical trials

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

Approach

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

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/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?

For this FOA:

• Is the program presented as a cohesive and fully integrated set of specific aims or objectives?
• Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research?
• Is the description of the interdisciplinary approach likely to result in significant new knowledge in the mechanistic understanding of human pain conditions, and/or mechanistic underpinning of heterogeneity and stratification of patients with specific pain conditions and co-morbidities?
• Does the combination scientific expertise (represented by the PD/PIs) present a compelling case that collaborative and interdisciplinary research will result in a synergistic approach to the understanding of human pain conditions?
• If new databases or resource collections will be developed, are they well justified and clearly essential to the research goals? Does the work plan make adequate use of existing institutional and/or regional resources?
• If new resources or equipment are requested, are they well justified and not redundant with resources available elsewhere in the institution or region?
• Is the plan for dissemination of the results to the public- and private-sector research communities sufficient?
• Does the proposed research incorporate adequate methodological rigor where applicable, including, but not limited to, clear rationale for the chosen model(s) and primary/secondary endpoint(s), clear descriptions of tools and parameters, blinding, randomization, adequate sample size, pre-specified inclusion/exclusion criteria, appropriate handling of missing data and outliers, appropriate controls, preplanned analyses, and appropriate quantitative techniques?
• Do the applicants clearly indicate the exploratory vs. confirmatory components of the study, consider study limitations, and plan for transparent reporting of all methods, analyses, and results so that other investigators can evaluate the quality of the work and potentially perform replications?
• How well does the Data Management and Sharing Plan conform to the requirements of the HEAL Initiative Public Access and Data Sharing Policy, such as providing a summary of the data to be shared, a description of the data reporting standards, a plan for the data archiving, and a timeline for data submission to an archive and sharing data with the research community?
• Timeline and Benchmarks for Success (Attachment):
  • Are the timeline and benchmarks proposed appropriate for accomplishing the specific aims of the research?
  • Does the chart/table provide sufficient detail on the timing and duration of key project tasks?
  • Are the timelines proposed for achieving project goals realistic and inclusive of necessary steps, but also efficient without adding unnecessary steps?
  • Do the contributions from the PD/PIs suggest a high degree of commitment, integration, and collaboration?
• PEDP (Attachment): Are the timeline and milestones associated with the Plan for Enhancing Diverse Perspectives well-developed and feasible?

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

Environment

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:

• Are the resources and infrastructure adequate for accomplishing the specific aims of the research and supporting team science?
• Is there synergy to be gained from the involvement of multiple departments and institutions?
• Will the range of departments and/or institutions involved promote the recruitment of a team of prospective researchers with a variety of backgrounds, expertise, and skills?
• If foreign organizations are involved do they provide unique resources that are not otherwise available?
• PEDP (Attachment): To what extent will features of the environment described in the Plan for Enhancing Diverse Perspectives (e.g., collaborative arrangements, geographic diversity, institutional support, project infrastructure, training and/or mentoring opportunities, outreach & engagement activities) contribute to the success of the project?

In addition, for applications involving clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

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

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

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

Additional Review Criteria

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

For this FOA:

Does the Gantt chart/table (or similar) provide sufficient detail on the timing and duration of key project tasks aswell as benchmarks of success? Are the timelines proposed for achieving project goals realistic and inclusive of necessary steps, but also efficient without adding unnecessary steps? Do the contributions from the PD/PIs suggest a high degree of commitment, integration, and collaboration?

Study Timeline

Specific to applications involving clinical trials

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

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

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

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

Renewals

Not Applicable

Revisions

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.

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

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

Select Agent Research

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

Resource Sharing Plans

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

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

• 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

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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

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.

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 recipient's business official.

Recipients 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.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

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: Recipient 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 recipient 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

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federalwide Research Terms and Conditions
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identity, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html

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. 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.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.
• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
• For guidance on administering programs in compliance with applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/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.html or call 1-800-368-1019 or TDD 1-800-537-7697.

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 and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Not Applicable

3. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

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. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients 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.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

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: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

D.P. Mohapatra, Ph.D.

National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9964
Email: [email protected]

Rachel Altshuler, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5873
Email: [email protected]

Brennan Parmelee Streck, PhD, RN, MPH National Cancer Institute (NCI)
National Cancer Institute (NCI)
Telephone: 301-357-0516
Email:[email protected]

Devon Oskvig, Ph.D.
National Institute on Aging (NIA)
Phone: 301-827-5899
Email: [email protected]

Rebecca Lenzi, PhD
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Phone: 301-402-2446
E-mail: [email protected]

C Brian Bai
National Heart, Lung, and Blood Institute (NHLBI)
Phone: 301-827-5212
E-mail: [email protected]

Mark Egli, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Phone: 301-594-6382
E-mail: [email protected]

Alex Tuttle, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-814-6115
Email: [email protected]

Melissa M Ghim
National Institute of Dental & Craniofacial Research (NIDCR)
Phone: none
E-mail: [email protected]

Rachel Altshuler, PhD
National Cancer Institute (NCI)
Telephone: 240-276-5873
Email: [email protected]

Alexis Bakos, PhD, MPH, RN
National Cancer Institute (NCI)
Phone: 301-921-5970
Email: [email protected]

Helena H. Ahn, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development
Telephone: 301-827-3207
Email: [email protected]

Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9223
Email: [email protected]

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

Jeni Smits
National Institute on Aging (NIA)
Phone: 301-827-4020
Email: [email protected]

Sahar Rais-Danai
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Phone: 301-594-5032
E-mail: [email protected]

Nina Hall
National Heart, Lung, and Blood Institute (NHLBI)
Phone: 301-435-0710
E-mail: [email protected]

Judy Fox
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Phone: (301) 443-4704
E-mail: [email protected]

Debbie Chen
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-594-3788
Email: [email protected]

Diana Rutberg
National Institute of Dental & Craniofacial Research (NIDCR)
Phone: (301) 594-4798
E-mail: [email protected]

Gabriel Hidalgo
National Institute of Dental & Craniofacial Research (NIDCR)
Phone: 301-827-4630
E-mail: [email protected]

Sean Hine
National Cancer Institute (NCI)
Telephone: 240-276-6291
Email: [email protected]

Margaret Young
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-642-4552
Email: [email protected]

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.