Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Neurological Disorders and Stroke (NINDS)

National Eye Institute (NEI)

National Institute on Aging (NIA)

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

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

National Institute on Drug Abuse (NIDA)

National Institute of Dental and Craniofacial Research (NIDCR)

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

National Center for Complementary and Integrative Health (NCCIH)

National Center for Advancing Translational Sciences (NCATS)

Funding Opportunity Title
HEAL Initiative: Interdisciplinary Teams to Elucidate the Mechanisms of Device-Based Pain Relief (RM1 Clinical Trial Optional)
Activity Code

RM1 Research Project with Complex Structure

Announcement Type
New
Related Notices

  • September 30, 2021 - Notice of NEI, NIA, NIAAA, NIAMS, NIDA and NIDDK's Participation in RFA-NS-22-016. See Notice NOT-NS-22-031.

Funding Opportunity Announcement (FOA) Number
RFA-NS-22-016
Companion Funding Opportunity
None
Assistance Listing Number(s)
93.853, 93.213, 93.121, 93.350, 93.867, 93.866, 93.273, 93.846, 93.279, 93.847
Funding Opportunity Purpose

This funding opportunity announcement (FOA) is designed to support interdisciplinary research teams of multiple PD/PIs to investigate the mechanism of action of device-based pain relief with the overall goal of optimizing therapeutic outcomes for FDA-approved or -cleared technologies. Teams must leverage appropriate multi-disciplinary expertise to develop new principles and methods for experimentation, analysis, and interpretation. Teams are encouraged to consider objectives that will produce major advances in the understanding of device-based pain relief.

Key Dates

Posted Date
August 31, 2021
Open Date (Earliest Submission Date)
October 03, 2021
Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
November 03, 2021 Not Applicable Not Applicable March 2022 May 2022 July 2022

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

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

Expiration Date
November 04, 2021
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) Instructions in the 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.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

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 HEAL Initiative aims to support the development of safe and effective devices to treat pain with little or no addiction liability. This funding opportunity announcement (FOA) is designed to support interdisciplinary research teams of multiple PD/PIs to investigate the mechanisms of action of pain relief using FDA-approved or -cleared medical devices with the overall goal of optimizing therapeutic outcomes for these technologies. Program teams are expected to accomplish goals that require considerable synergy and collaborative interactions. Teams must leverage appropriate multi-disciplinary expertise to develop new principles and methods for experimentation, analysis, and interpretation. Project goals should not be achievable with a collection of individual efforts or projects. Teams are encouraged to consider objectives that will produce major advances in the understanding of device-based pain relief that are likely to improve strategies for pain management.

Background

The NIH HEAL Initiative:

This funding announcement is part of the NIH’s Helping to End Addiction Long-term (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 about the HEAL Initiative is available at: https://heal.nih.gov/.

The NIH HEAL Initiative will require a high level of coordination and sharing between investigators. It is expected that NIH HEAL Initiative 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.

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. Therapeutic devices provide a significant opportunity to offer a class of non-opioid therapies for pain that reduces or eliminates the need for opioid prescription and can provide treatment options for those who have no other effective ways to manage their pain. The outcomes of this program have the potential to ignite significant improvements in device-based clinical therapies for pain relief. Although several therapeutic devices for pain relief have received FDA Premarket Approval (PMA) or 510(k) clearance and are being disseminated clinically, many have shown variability in outcomes between individuals, or may reach a plateau in the pain relief they provide. Examples of these technologies include spinal cord stimulation (SCS) and dorsal root ganglion (DRG) stimulation for chronic low-back pain, transcutaneous magnetic stimulation (TMS) and vagus nerve stimulation (VNS) for migraine and cluster headache, and transcutaneous electrical nerve stimulation (TENS) for pain. Although several industry efforts to translate device-based treatments have shown success, many lack a strong mechanistic rationale from the sources of innovative basic science that the SPARC ProgramBRAIN Initiative, and other NIH funding are now providing. In the case of SCS for example, the mechanism for pain relief induced by electrical stimulation is largely unknown. To address these limitations, it is necessary to better understand the mechanisms underlying medical devices for pain relief, to identify physiological markers of pain relief, and to determine how therapeutic approaches affect them. Improving this understanding will point to ways in which existing therapeutic approaches can be improved or optimized. The identification of new approaches will lead to better patient outcomes in the areas of 1) greater patient stratification by responder characteristics, 2) improved therapeutic efficacy with decreased side effects, 3) reduction in number of revision surgeries to move implanted leads, and 4) expansion of therapeutic benefits to patient populations suffering from additional sources of pain. In addition, having a broader body of knowledge in this space may lead to new, innovative ways of designing true sham-controlled efficacy trials—often a challenge for device-based therapies.

Program Approach and Scope

To accomplish these goals, applications are being solicited from interdisciplinary teams to utilize multi-faceted approaches to discovering the mechanisms of device-based pain relief for FDA-approved or -cleared therapies. Device technologies within scope of this FOA only include medical devices for pain that have already received FDA Premarket Approval (PMA) or FDA Premarket Notification 510(k). Devices that are exempt from Premarket Notification 510(k) are not within scope of this FOA. Projects should also propose/investigate methods for implementing new or optimized therapeutic procedures that have a high likelihood of improving the standard of care.

Types of research supported through this program include clinical studies and/or trials (see additional guidance below), small- or large-animal studies, and computational models. Model systems, including the possibility of multiple species ranging from invertebrates to humans, may be employed (and should be appropriately justified) in order to inform mechanistic hypotheses that can be tested in human-subjects research.

Overall, the research should be carried out by a multi-, inter-, or transdisciplinary team of researchers who will address a highly significant translational research theme or challenge in device-based pain therapies. Projects should employ multi-component teams of research expertise that seek to cross boundaries of interdisciplinary collaboration—these may include neuroscientists, clinicians, statisticians, physicists, mathematicians, engineers, veterinary scientists, computer scientists, data scientists, and others as appropriate. The goal will be to support programs with a systematic, team-science approach that can realize meaningful outcomes within the next 3–5 years. Projects are expected to result in mechanistic knowledge to inform enhanced clinical approaches with FDA-approved or -cleared devices for pain relief. Specific deliverables should include evidence-based models of pain pathways, therapeutic mechanisms of action, and/or validated computational models. Applicants are also expected to describe how the results of their studies will be disseminated widely to the public- and private-sector research communities and suggest potential implementation strategies to increase the likelihood of adoption into clinical therapies.

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

Mechanistic studies should be focused on developing an understanding of the mechanism of action of an intervention. For studies that seek to understand how the neuromodulatory interventions work, objective and/or quantitative measures should be used (where possible) to examine the effects of dosage level and treatment duration. To evaluate the validity of the proposed mechanism of action of the intervention, such studies should also demonstrate that the intervention target has been modulated and whether there are off-target effects. It is expected that proposed clinical studies or trials will include activities that are using a device for an approved use (also known as “on-label” use) and only require approval by an Institutional Review Board (IRB) to begin the clinical activities. Only in extenuating circumstances (where there is a unique or advantageous opportunity for significant new knowledge) will projects be accepted that require an investigational device exemption (IDE) from the FDA.

Program Organization

Recent reports (e.g., Enhancing the Effectiveness of Team Science) have evaluated the benefits of a team science approach to scientific inquiry, and the need to create flexible funding opportunities that enable interdisciplinary research teams to accomplish goals that could not be achieved individually. Applications submitted to this FOA are expected to propose a single, well-integrated research plan of sufficient scope, complexity, and impact to justify the investment of significant resources. 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 should be sufficiently challenging, ambitious, and innovative that the proposed research cannot be achieved by a single investigator or small group of investigators. Therefore, a multiple PD/PI application is required, and applications must include a minimum of three PD/PIs who are all necessary to provide sufficient research capacity and the relevant expertise to address the proposed scientific problem. Each PD/PI should bring a distinct scientific viewpoint or expertise necessary to pursue the interdisciplinary approach being proposed in the application. Applications that propose extrapolations of a single line of research or propose parallel but independent advancement of different areas are not responsive to this FOA.

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 Team Science Field Guide). In addition to the required multiple PD/PI leadership plan, applications are expected to develop a comprehensive team management plan that addresses the following points:

  • Appropriate organizational structure and team composition
  • Shared leadership, contributions, and distributed responsibility for decision making
  • Resource allocation
  • Conflict resolution

If teams include individuals from widely divergent scientific backgrounds, applicants may wish to address how they will develop trust and a shared vision, as well as how shared responsibilities, interpersonal interactions, and professional credit will be managed. Additionally, applicants may want to consider a scientific project manager or program coordinator as part of the management plan.

In addition to scientific diversity, applicants should strive to incorporate diversity in their team management plan. Research shows that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogenous teams. Scientists and trainees from diverse backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems. There are many benefits that flow from a diverse NIH-supported scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved or health disparity populations participate in, and benefit from health research, and enhancing public trust. Please refer to Notice of NIH's Interest in Diversity NOT-OD-20-031 for more details.

Prior Consultation with HEAL Program Staff

HEAL intends to fund a limited number of applications. 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 staff may be able to advise applicants whether the proposed research strategy meets the goals of HEAL 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 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 HEAL's programmatic needs, or is not appropriate as a team-science grant, applicants will be encouraged to consider other funding opportunities.

Non-Responsive Activities: Applications that include the following activities will be considered non-responsive, will be withdrawn, and will not be reviewed:

  • Projects focused on medical devices for pain that are not FDA-approved (PMA) or FDA-cleared (510(k)) (i.e. projects on devices exempt from Premarket Notification 510(k) will not be accepted).
  • Projects focused on drug-delivery devices.
  • Clinical trials designed primarily to determine the safety, tolerability, and/or clinical efficacy of an intervention.
  • Clinical studies or clinical trials focused on device interventions that are not FDA-approved (PMA) or FDA-cleared (510(k)).
  • Delayed-onset clinical studies.
  • Applications that propose extrapolations of a single line of research or propose parallel but independent advancement of different areas.

.

  • Projects not considered to be in the mission(s) of the participating ICs of the HEAL Initiative.

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

Section II. Award Information

Funding Instrument

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

Application Types Allowed
New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?

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

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

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

NIH intends to fund an estimate of 3 awards for fiscal year 2022. Future year amounts will depend on annual appropriations.

Award Budget

Application budgets are not limited, but should be consistent with the number of PDs/PIs and the complexity and needs of the proposed program. Application budgets should rarely exceed $1,500,000 direct costs per year. Annual inflationary increases are not allowed.

Award Project Period

Applications may request up to five years of support.

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

Eligible Organizations

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 Governments

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

Other

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

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

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

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

Required Registrations

Applicant organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

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.

The application is required to be submitted as a multiple PD/PI application with a minimum of 3 PDs/PIs, all of whom must have an appointment at a domestic institution. Scientists employed solely by foreign institutions may not serve as one of the PD(s)/PIs of the multiple PD/PI team, although they may be included in the application as collaborators/co-investigatorsconsultants or other significant contributors. 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.  This means that the NIH will not accept:

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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:

Eric Hudak, Ph.D.
Email: NINDS-Devices@nih.gov

Page Limitations

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.

Instructions for Application Submission

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.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

Facilities and Other Resources:

Describe aspects of the institutional environment that support team science. Describe the institutional and regional research resources that will be utilized to accomplish the goals of the program, and how access to these resources will be ensured for team members.

Other Attachments:

Team Management Plan (Required – 3 pages maximum):

Applications that exceed this limit will be withdrawn. This attachment should be entitled “Team-Management-Plan.pdf”. 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. Rather, this attachment should contain an overall team management plan that addresses how the entire group will function to accomplish program objectives and vision. Inclusion of a project manager or coordinator as a Senior/Key Person with adequate authority is recommended. If a project manager or coordinator is included, describe how the qualifications of this individual are appropriate for such a role and for the subject matter and scale of the proposed project.

The Team Management Plan should include a description of how the PD/PIs will establish and sustain a diverse and interdisciplinary team of researchers with an optimal range of backgrounds, expertise, and skills to successfully accomplish the goals of the program. There is evidence 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. 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.

The management structure should account for team composition, institutional resources, and policies. Practical aspects should be described, including real-time communication, intra-team data sharing, data archiving, and long-term preservation for team use.

The team management plan should describe management and decision-making processes that promote collective input for the overall project objectives and for oversight and reallocation of program resources, recognizing that resources may need to be dynamically reallocated to achieve programmatic goals. Methods for attributing contributions to publications should be described to enable individual professional assessment in joint projects. The overall management plan should include all key personnel, consultants, and other significant contributors regardless of effort level. It is recommended that the Team Management Plan include procedures for evaluating scientific progress and overall support for program objectives of each of the PDs/PIs and key personnel.

Gantt Chart (Required 1 page maximum):

Applications that exceed this limit will be withdrawn. This attachment should be entitled “Gantt.pdf”. Applicants should include a project timeline in the form of a Gantt chart (or similar) that includes all major tasks to be performed during the project. 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.

IRB Communications (Optional 5 pages maximum):

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

SF424(R&R) Senior/Key Person Profile

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

Applications must include a minimum of three PD/PIs. Applications that do not include the required minimum of 3 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. The contact PD/PI is required to devote at least 30% of their time available for research to this award, while other PDs/PIs are required to devote at least 25% of their time available for research to this 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.

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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 that will result in a significantly improved understanding of the mechanisms underlying device-based pain relief. 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 therapeutic device and pain indication being studied, what is lacking in the mechanistic understanding of how the device relieves pain, what challenges exist in the clinical application of the technology, and the typical range of patient outcomes. The goals of the research proposed should be achievable within a 5-year timeframe.

The research strategy should describe how this team-science grant will enable the applicants to challenge existing paradigms, overcome long-standing bottlenecks to substantial progress, and/or develop new synergies between different scientific fields. The research strategy should describe how innovative combinations of scientific fields and/or intellectual viewpoints will enable the project goals to be achieved. Applications should justify the need for a larger-scale collaborative approach and explain why the goals of the program could not be accomplished by other means, such as independently funded individual research grants. Innovative solutions by any means can be proposed.

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 the mechanistic understanding of device-based pain relief. Applications should describe critical research benchmarks and any innovative aspects of the 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 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. Applications should also describe how the results of their studies will be disseminated widely to the public- and private-sector research communities and suggest potential implementation strategies to increase the likelihood of adoption into clinical therapies. Technology development should not be the primary goal of this team-science grant program.

For applications proposing clinical research, describe how the results of the study will improve the mechanistic understanding of pain relief with the device, how the results will contribute to an integrated model of device-based pain relief, how the study will contribute to understanding the subtypes of patients with acute or chronic pain, and whether the study will inform responder characteristics for the device therapy being studied.

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 Clinical Data Elements (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, see NOT-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).

Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the 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

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:

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.

Delayed onset studies are not responsive and will not be accepted.

PHS Assignment Request Form

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

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

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

4. Submission Dates and Times

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

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

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

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

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

Post Submission Materials

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

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? Does the description of the pain population, the device, and the lack of mechanistic understanding of pain relief convey that there is a significant need for new knowledge in this space? Does the described range of patient outcomes with this device provide a compelling case that this patient population is in need of an improved therapy? Is the problem such that definitive outcomes can be accomplished during the funding period? If successful, will the proposed program's coordinated research effort produce significant advances in the mechanistic understanding of device-based pain relief? Are the proposed implementation strategies likely to enhance device-based clinical approaches to treating pain?

Specific to applications proposing clinical research:

Are the results of the proposed study likely to improve the mechanistic understanding of pain relief with the device? Will the results contribute to an integrated model of device-based pain relief? Will the study contribute to understanding subtypes of patients with acute or chronic pain? Will the study inform responder characteristics for the device therapy being studied?

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? Are the critical mass and diversity of investigator backgrounds and expertise sufficient to 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? Do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and meet the proposed activities and timelines? 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 give one confidence that fair and adequate governance processes will be used for decision making? Does the plan allow for flexibility in pursuing the aims and allocation of resources? Does it provide for effective team leadership and management with distributed responsibility and decision-making processes? Does the management plan include adequate plans for shared professional credit? If shared research resources will be utilized, are plans adequate to ensure that all team members will have the access they require? If a project manager or coordinator is proposed, are the qualifications and role of this individual appropriate? Are adequate plans presented to establish and sustain a team of researchers with an optimal range of backgrounds, expertise and skills, and plans to arrive at major decisions, accounting for different points of view?

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 research grants? Does the program involve innovative combinations of scientific fields and/or intellectual viewpoints to address its goals? Is innovation evident in the method that the established areas of science are combined?

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:

Research Strategy:

Is the program presented as a coherent 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 device-based pain relief? Is this new knowledge likely to result in optimized approaches for the treatment of this pain condition with the device? Are the timeline and benchmarks proposed appropriate for accomplishing the specific aims? Are any plans for technology development necessary to address the scientific problems and specifically focused on these problems as opposed to being more general technology development goals? Does the combination scientific expertise (represented by the PD/PIs) present a compelling case that this will result in a synergistic approach to the problem? 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?

How well does the Data Management and Sharing Plan conform to the requirements of the HEAL Initiative Public Access and Data Sharing Policy (https://heal.nih.gov/about/public-access-data), such as providing a summary of the data to be shared, a description fo 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?

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?

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.

Gantt Chart (Attachment)

Does the Gantt chart 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?

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

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

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

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Sharing Model Organisms; and (2)  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.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Neurological Disorders and Stroke Council (NANDSC). The following will be considered in making funding decisions:

  • 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.

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

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

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 awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

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

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

2. Administrative and National Policy Requirements

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. More information is provided at Award Conditions and Information for NIH Grants.

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. This includes ensuring programs are accessible to persons with limited English proficiency. 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 http://www.hhs.gov/ocr/civilrights/understanding/section1557/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.

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 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

3. Reporting

When multiple years are involved, awardees 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.

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

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

Section VII. Agency Contacts

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

Application Submission Contacts

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: GrantsInfo@nih.gov (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: support@grants.gov

Scientific/Research Contact(s)

Eric Hudak, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1779
Email: NINDS-Devices@nih.gov

Houmam H Araj
National Eye Institute (NEI)
Phone: (301) 435-8166
E-mail: ha50c@nih.gov

Devon Oskvig, Ph.D.
National Institute on Aging (NIA)
Phone: 301-827-5899
Email: devon.oskvig@nih.gov

Mark Egli
National Institute On Alcohol Abuse And Alcoholism (NIAAA)
Phone: 301-594-6382
E-mail: megli@mail.nih.gov

Leslie K Derr, PhD
National Institute Of Arthritis And Musculoskeletal And Skin Diseases (NIAMS)
Phone: (301) 594-8174
E-mail: derrl@mail.nih.gov

Dana K. Andersen, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Phone: 410-868-0638
E-mail: andersendk@mail.nih.gov

Will Aklin
National Institute On Drug Abuse (NIDA)
Phone: 301-827-5909
E-mail: aklinwm@mail.nih.gov

Bobbieann Mount
National Center For Advancing Translational Sciences (NCATS)
Phone: 301-435-0824
E-mail: bobbieann.mount@nih.gov

Merav Sabri, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301- 496-2583
E-mail: merav.sabri@nih.gov

Melissa M Ghim, PhD
National Institute Of Dental & Craniofacial Research (NIDCR)
Phone: (301) 529-6570
E-mail: ghimm@mail.nih.gov

Peer Review Contact(s)

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9223
Email: nindsreview.nih.gov@mail.nih.gov

Financial/Grants Management Contact(s)

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: ChiefGrantsManagementOfficer@ninds.nih.gov  

David Madoo
National Center For Advancing Translational Sciences (NCATS)
Phone: 301-761-6703
E-mail: david.madoo@nih.gov

Shelley Headley
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-594-3788
Email: shelley.headley@nih.gov

Diana Rutberg, MBA
National Institute Of Dental & Craniofacial Research (NIDCR)
Phone: (301) 594-4798
E-mail: dr258t@nih.gov

Karen Robinsonsmith
National Eye Institute (NEI)
Phone: (301) 451-2020
E-mail: kyr@nei.nih.gov

Paolo Arguinzoni-Urrutia
National Institute on Aging (NIA)
Phone: 301-827-5985
Email: paolo.arguinzoni-urrutia@nih.gov

Judy Fox
National Institute On Alcohol Abuse And Alcoholism (NIAAA)
Phone: (301) 443-4704
E-mail: jfox@mail.nih.gov

Erik Edgerton
National Institute Of Arthritis And Musculoskeletal And Skin Diseases (NIAMS)
Phone: 301-594-7760
E-mail: erik.edgerton@nih.gov

Elizabeth Gutierrez
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Phone: 301-594-8844
E-mail:gutierrezel@mail.nih.gov

Pamela G Fleming
National Institute On Drug Abuse (NIDA)
Phone: 301-480-1159
E-mail: pfleming@mail.nih.gov

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.

Authority and Regulations

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.


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