Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute on Drug Abuse (NIDA)

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

National Institute of Nursing Research (NINR)

National Institute on Minority Health and Health Disparities (NIMHD)

National Center for Complementary and Integrative Health (NCCIH)

National Cancer Institute (NCI)

All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers. The following NIH Offices may co-fund applications assigned to those Institutes/Centers.

Division of Program Coordination, Planning and Strategic Initiatives, Office of Disease Prevention (ODP)

Funding Opportunity Title
HEAL Initiative: Research Studies to Develop and Implement Interventions to Prevent Opioid Misuse in Community Health Centers (R61/R33 Clinical Trial Required)
Activity Code

R61/R33 Exploratory/Developmental  Phased Award

Announcement Type
New
Related Notices

NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022

Funding Opportunity Announcement (FOA) Number
RFA-DA-23-048
Companion Funding Opportunity
None
Assistance Listing Number(s)
93.279, 93.361, 93.393, 93.273, 93.307, 93.213
Funding Opportunity Purpose

This funding opportunity announcement (FOA) is part of the Helping to End Addiction Long-term (HEAL) Prevention Initiative, a portfolio of research focused on the prevention of opioid misuse and opioid use disorder funded under NIH’s HEAL Initiative. The National Institute on Drug Abuse (NIDA) seeks to address the urgency and magnitude of the opioid crisis by developing and testing new or adapted interventions to prevent opioid misuse among patients served by community health centers (CHCs), and/or developing and testing implementation strategies for screening and referral to preventive interventions for misuse of opioids and other substances among patients served by CHCs. Research will be supported through exploratory/developmental phase awards (R61/R33) that may not exceed 5 years, allocating up to two years of funding for development of the project and up to four years for a full test of the research aims.

Key Dates

Posted Date
July 26, 2022
Open Date (Earliest Submission Date)
October 08, 2022
Letter of Intent Due Date(s)

October 8, 2022

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
November 08, 2022 Not Applicable Not Applicable February 2023 May 2023 July 2023

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

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

Expiration Date
November 09, 2022
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

The National Institute on Drug Abuse (NIDA) seeks to establish the evidence base for interventions that can effectively prevent opioid and other substance misuse in community health centers (CHCs), a setting which serves populations at increased risk for substance misuse. While there are effective interventions to prevent substance misuse, generally, there is a gap in interventions designed for use in CHCs, and knowledge as to the factors that support implementation of those interventions is lacking. This FOA seeks to address the urgency and magnitude of the opioid crisis in populations that experience health disparities by developing and testing new or adapted interventions to prevent opioid misuse among patients served by community health centers (CHCs), and/or by developing and testing implementation strategies for screening and referral to preventive interventions for misuse of opioids and other substances among patients served by CHCs.

This 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/.

Background

CHCs are well positioned to serve as a formal point of entry into evidence-based opioid misuse prevention services because they reach a large population impacted by the opioid crisis and are located across the nation in areas with limited health care resources. CHC patients are more likely to experience social and health conditions (e.g., mental disorder diagnosis) that are risk factors for substance misuse and negatively impact their overall health, suggesting prevention may be beneficial for this population. In recent years, CHCs have increased their capacity to provide mental health and substance use treatment services, with 93% of health centers providing mental health treatment and 67% providing substance use treatment services. Despite this capacity, screening for substance use risk (rather than treatment need) and referral to prevention services is uncommon.

Research Goals

This initiative seeks research that will ultimately enhance the capacity of CHCs to screen patients for opioid and substance use risk and refer them to or provide opioid and other substance use prevention services. The two areas of research interest are studies to: (1) develop and test new or adapted interventions to prevent opioid misuse among patients served by community health centers (CHCs), and/or (2) develop and test implementation strategies for screening and referral to preventive interventions for misuse of opioids and other substances among patients served by CHCs.

Research Topics

Research projects should be developed in consultation and partnership with CHCs. Strong partnerships are critical for ensuring that proposed research activities are responsive to the needs of the community and maximize the likelihood that interventions developed and tested can be sustained. Applicants are strongly encouraged to address issues of patient/stakeholder engagement; scalability beyond the study sites/settings; sustainability beyond the funding period; and whether the proposed implementation strategy/process reduces inequities in service availability, access, utilization, cost, quality, or outcomes.

Applications should focus on primary prevention, developing and testing strategies that CHCs can take to scale in order to prevent the initiation of opioid/substance use or misuse and/or the progression to opioid or other substance use disorder. Applications may include universal prevention interventions that are intended to be delivered to the entire CHC patient population (or all CHC patients in a particular age range) or selective or indicated prevention interventions that focus on a particular sample with demonstrated risk factors for substance use. Investigators should provide a rationale for their level of intervention and a description of how they are defining their target population within the CHC setting.

Examples of priority areas for the two categories of research supported are identified below.

Intervention research

Intervention research applications should be theory based, developing and testing prevention intervention strategies that can be easily integrated into the CHC setting, addressing the unique needs of the community served. Intervention studies may test new interventions or include efficacy and/or effectiveness studies of established interventions that are adapted for CHCs. Intervention studies should test critical components of the prevention strategies for CHC patients to understand the intervention components that impact outcomes. Additionally, the measurement of implementation outcomes and inclusion of economic analyses is encouraged where feasible.

Topics of interest include but are not limited to:

  • Studies to test models of integrating into CHCs existing, effective or promising, substance use prevention strategies that use established techniques (e.g., motivational interviewing, skill building). The integration should involve the inclusion of natural providers for the delivery of the intervention.
  • Research on interventions designed to prevent substance misuse by directly addressing known risk factors for substance misuse, such as:
    • Interpersonal violence, community violence, and/or maltreatment
    • Mental disorders (e.g., depression, anxiety, post-traumatic stress disorder, serious mental illness, suicide ideation and behaviors)
    • Attention deficit and hyperactivity disorder (ADHD)
    • Acute or chronic pain
    • Social determinants of health that impact substance use, including experiencing racism, homelessness, and/or economic and food insecurity
  • Studies of evidence-based substance use prevention interventions that are adapted to incorporate technology, such as mobile health and telehealth delivery or models of consultation, or program delivery.
  • Testing of strategies to overcome stigma related to substance use and its consequences, such as discrimination based on risk factors for substance misuse and substance using behavior. This might include incorporation of content and activities to reduce self-stigma on the part of participant populations, stigma in delivery of basic services for people experiencing risk for substance use (e.g., discriminatory channels for service; interactions withadministrative/non-service provider staff).

Implementation research

Implementation research applications should inform strategies to increase uptake, effectiveness, and sustainability of screening and referral to prevention among patients served by CHCs. Implementation research topics of interest include, but are not limited to:

  • Research to test implementation factors that support evidence-based prevention interventions in CHCs that have been tested in other settings, including:
    • Research to address system fragmentation that impacts referral to prevention services (e.g., gaps for persons transitioning from pediatric or adolescent medicine practices to adult medicine practices; access for persons in specialty settings or social services systems who need linkage to health/behavioral health and prevention services)
    • Studies of organizational and provider factors that contribute to implementation and sustainability of prevention interventions
    • Testing of screening and referral strategies to improve enrollment and completion of prevention services delivered by the CHC
    • Testing of implementation strategies to support CHC-based screening and referral to preventive services provided by other entities (e.g., local health department, community behavioral health center)
  • Research of instruments or strategies to identify individuals at risk for substance use, including research to test
    • risk-profiles from electronic health records to facilitate case identification, active referral and linkage to prevention interventions, and or consultation models
    • innovative tools for identifying individuals at risk for substance misuse and engaging them in prevention services, including in prenatal care, dental care, specialist pain management, and other specialties
  • Application of human factors research to test strategies to improve screening effectiveness, reduce provider burden, and improve implementation feasibility and sustainability of prediction algorithms, electronic health record tools, clinical decision support tools, or other technology
  • Research to understand whether, to what extent, and under what conditions policies and/or novel funding strategies (e.g., Medicaid waivers, reimbursement for telehealth or consultation) improve uptake and sustainability of screening and referral to prevention interventions.

While not required, projects that capitalize on funding streams and technical assistance resources available to CHCs that promote sustainability are highly encouraged.

National Institute of Nursing Research

The National Institute of Nursing Research (NINR) supports research to solve pressing health challenges and inform practice and policy - optimizing health and advancing health equity into the future. NINR discovers solutions to health challenges through the lenses of health equity, social determinants of health, population and community health, prevention and health promotion, and systems and models of care. Drawing on the strengths of nursing’s holistic, contextualized perspective, core values, and broad reach, NINR funds multilevel and cross-sectoral research that examines the factors that impact health across the many settings in which nurses work, including homes, schools, workplaces, clinics, justice settings, and the community.

For this FOA, NINR is particularly interested in:

  • Studies that address and mitigate the effects of social determinants of health on intervention uptake and effectiveness
  • Studies that address and mitigate the effects of health system structural factors to achieve equity in intervention uptake and effectiveness
  • Studies in community health centers that use a holistic and contextualized approach to address issues of substance misuse and co-occurring pain
  • Studies of systems-level interventions or new models of care in community health centers to prevent opioid misuse while addressing pain management needs

National Cancer Institute

The National Cancer Institute (NCI) leads, conducts, and supports cancer research across the nation to advance scientific knowledge and help all people live longer, healthier lives. The NCI is interested in supporting intervention research for individuals being screened for cancer as well as cancer survivors in the following areas that include, but are not limited to:

  • Increase collaboration and coordination between oncologist and primary care providers (PCPs) and other pain specialists, in treating and/or monitoring treatment-induced long-term pain to facilitate safe prescribing practices and prevent opioid misuse and OUD
  • Strategies that utilize patient navigators or community health workers to improve pain management or prevent OUD in cancer survivors
  • Improving the quality of pain assessment and management among cancer survivors or patients with precancerous conditions (e.g., cirrhosis, chronic pancreatitis) to reduce the use of opioids
  • Utilizing evidence-based approaches that recommend non-opioid management to treat pain
  • Investigating how community health centers can extend their outreach by using remote interventions (i.e., telemedicine, use of electronic ambulatory devices) to assess, report, and manage pain due to cancer, cancer treatment, or pain from precancerous conditions
  • Testing pain reporting mechanisms that are culturally and linguistically tailored for individuals with limited English proficiency or with limited health literacy
  • Investigating novel approaches to assessing pain among different racial/ethnic groups

Design, Analysis, and Sample Size for Intervention Studies that Assign and/or Deliver Interventions in Groups or Clusters

Projects are encouraged to consider special research designs and methods for analysis and sample size that may be required in the following conditions:

  1. Participants are assigned to study arms in groups or clusters (e.g., families, clinics, communities, counties, states) and observations taken on individual participants are analyzed for intervention effects. Appropriate intervention study designs include but are not limited to a parallel group- or cluster-randomized trial, a stepped-wedge group- or cluster randomized trial, a rigorous quasi-experimental design such as a group- or cluster-level regression discontinuity design or an interrupted time-series design, or a rigorous alternative.
  2. Participants are assigned individually to study arms but receive at least some of their intervention in a group (in-person or virtual) or through a shared facilitator or provider. Appropriate study designs include an individually randomized group-treatment trial, a rigorous quasi-experimental design such as an individual-level regression discontinuity design, or a rigorous alternative.

Methods consistent with plans for assignment of participants and delivery of interventions should be documented in the application. Additional information and examples are available at?https://researchmethodsresources.nih.gov/.

R61/R33 Phases and HEAL Requirements

Phases of the Award and Milestones

Support for this research will be provided in two phases using the R61/R33 Exploratory/Developmental Phased Award mechanism for up to 5 years. This includes initial support of up to 2 years for the R61 phase, followed by up to 4 years of support for the R33 phase. Transition to the R33 phase is contingent upon successfully meeting R61 milestones. The first phase (R61) is a planning phase that is expected to include scientific and operational development and planning activities. Examples of activities that could be included are: partnership development and operationalization of stakeholder collaboration to support the project; development and feasibility testing of study elements including measurements, CHC clinical procedures, electronic health record, and other data availability; intervention adaptation; recruitment planning; and meeting study and administrative requirements (e.g., IRB approval, data use agreements, HEAL collaborative participation). This phase will identify and meet pre-specified milestones ensuring that the results of this phase inform and provide a foundation for the second phase of the research. (See Section IV for more information on required milestones for the R61 award.)

The R33 phase will be a clinical trial to test an intervention and/or implementation of prevention intervention in a CHC setting. For transition to the R33 phase, recipients will be required to submit the transition package no less than two months before the completion of the R61 phase. The transition plan should include the R61 progress report describing in detail the progress towards the R61 milestones and a description of how research proposed for the R33 phase will be supported by the completion of the R61 phase milestones. These materials will be evaluated by NIH program staff to determine if the milestones were met.

R33 funding decisions will be based on the original R61/R33 peer review recommendations, successful completion of transition milestones, any proposed changes to the R33 research based on R61 findings, program priorities, and availability of funds. Funding of the R61 phase and completion of milestones does not guarantee funding of the R33 phase of the project.

Key Definitions

Community Health Center: Community Health Centers (CHCs) are safety net clinics that provide primary and preventive health care and health education to populations with limited access to health care. CHCs address social determinants of health and provide enabling services to reduce mortality and health disparities. CHCs include health centers designated by Health Resources and Services Administration’s (HRSA) Health Center Program, including Federally Qualified Health Centers (FQHCs), which serve special populations, including individuals and families experiencing homelessness, migratory and seasonal agricultural workers, and residents of public housing, FQHC “look-alikes,” and school-based health centers. CHCs also includes other primary care-based clinics that serve communities with limited access to care, including IHS Community Health Representatives, rural health care centers, HIV primary care clinics, and nurse-managed health clinics.

Funding decisions will prioritize diversity in projects based on geographic distribution, types of CHCs, and patient populations served. Applicants are encouraged to partner with CHCs in communities that serve populations that are not often represented in research.

Special considerations

Applications will be considered non-responsive if they do not include:

  • Aims for both the R61 and R33 phases of the project.
  • Milestones for transition from the R61 to R33 phase of the project.
  • Documentation of partnership with a CHC, as defined by this FOA, that will serve as a research partner and site for the study.
  • Outcomes related to prevention of substance use. Applications that only include pain-related outcomes will not be considered.

Studies that propose interventions that focus solely on changing provider prescribing behavior will be considered non-responsive.

Diversity

In addition to scientific diversity, applicants should strive to incorporate diversity in their team development 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. In spite of tremendous advancements in scientific research, information, educational and research opportunities are not equally available to all. NIH encourages institutions to diversify their student and faculty populations to enhance the participation of individuals from groups that are underrepresented in the biomedical, clinical, behavioral, and social sciences. Please refer to Notice of NIH's Interest in Diversity NOT-OD-20-031 for more details.

PI Meeting Attendance

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 such as inclusion of common data elements and outcome measures across studies.

Points to Consider Regarding Tobacco Industry Funding of NIDA Applicants

The National Advisory Council on Drug Abuse (NACDA) encourages NIDA and its grantees to consider the points it has set forth with regard to existing or prospective sponsored research agreements with tobacco companies or their related entities and the impact of acceptance of tobacco industry funding on NIDA's credibility and reputation within the scientific community. Please see (http://ww2.drugabuse.gov/about/organization/nacda/points-to-consider.html) for details.

Establishment of a Standard delta-9-THC Unit to be used in Research

Applications proposing research on cannabis or its main psychotropic constituent delta-9-THC are required to measure and report results using a standard delta-9-THC unit in all applicable human subjects’ research. The goal is to increase the comparability across cannabis research studies. A standard delta-9-THC unit is defined as any formulation of cannabis plant material or extract that contains 5 milligrams of delta-9-THC. A justification should be provided for human research that does not propose to use the standard unit. Please see https://grants.nih.gov/grants/guide/notice-files/NOT-DA-21-049.html NOT-DA-21-049 for additional details.

National Advisory Council on Drug Abuse Recommended Guidelines for the Administration of Drugs to Human Subjects

The National Advisory Council on Drug Abuse (NACDA) recognizes the importance of research involving the administration of drugs with abuse potential, and dependence or addiction liability, to human subjects. Potential applicants are encouraged to obtain and review these recommendations of Council before submitting an application that will administer compounds to human subjects. The guidelines are available on NIDA's Web site at http://www.drugabuse.gov/funding/clinical-research/nacda-guidelines-administration-drugs-to-human-subjects.

Data Harmonization for Substance Abuse and Addiction via the PhenX Toolkit

NIDA strongly encourages investigators involved in human-subjects studies to employ a common set of tools and resources that will promote the collection of comparable data across studies and to do so by incorporating the measures from the Core and Specialty collections, which are available in the Substance Abuse and Addiction Collection of the PhenX Toolkit (www.phenxtoolkit.org). Please see NOT-DA-12-008 (http://grants.nih.gov/grants/guide/notice-files/NOT-DA-12-008.html) for further details.

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

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?

Required: Only accepting applications that propose clinical trial(s).

Funds Available and Anticipated Number of Awards

The HEAL Initiative intends to commit $5.25 million in FY 2023 to fund 5-7 awards.

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.

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

Award Budget

Application budgets must reflect the actual needs of the proposed project. The R61 phase is limited to a budget of no more than $350,000 in direct costs per year. Unless well-justified, it is strongly recommended that applicants not request a budget of more than $750,000 in direct costs per year for the R33 phase.

Award Project Period

The maximum project period is 5 years. This includes up to 2 years for the R61 phase and up to 4 years for the R33 phase, with the total project period for both phases not to exceed 5 years.

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 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
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.

  • 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.

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 diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. 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.

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 susequent 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, prospecitve 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: FOAReviewContact@csr.nih.gov

Page Limitations

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

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.

SF424(R&R) Senior/Key Person Profile

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

R&R Budget

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

Budgets for both phases (R61/R33) must be included; the R33 budget will undergo reassessment during the R61 planning phase.

The budget must include personnel at all participating organizations or health care systems with expertise relevant to the project, which might include clinical investigators and staff with expertise in the administrative aspects of clinical trials oversight.

Applications should budget for study personnel to participate in NIH HEAL Prevention Initiative activities. For budgeting purposes, include travel costs to support the attendance of one PD/PI (one person) to attend a 2-day, in-person HEAL Investigators Meeting in the greater Washington D.C. area, annually for the duration of the award.

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

The application should contain separate Specific Aims sections for the R61 and R33 phases and aims for both phases must fit in the one-page, single attachment.

Research Strategy

Exploratory/Developmental Phased Award

The research strategy should present an overview of the state of the science, current status and relevance of the proposed research and clinical trial, a detailed discussion of the specific protocol and approach to data collection, and demonstrate consideration of long-term sustainability and scalability of the proposed efforts. The research strategy should also include a description of the team’s experience with: (a) developing, testing, and implementing prevention interventions; (b) the identified study population (individuals who receive services from CHCs); and (c) collaboration with CHCs.

The following criteria should be addressed:

Significance: The R61 and R33 should clearly address a single set of research questions and goals, with the R61 phase building capacity, developing infrastructure, and establishing feasibility for the clinical trial, which will be conducted in the R33 phase. Given this integration, only one Significance section is needed.

The application should demonstrate an in-depth understanding of the significance of the opioid public health crisis for the population of focus of the study, and broadly for those who receive health care services from CHCs. The significance of the proposed clinical trial, justification of the target population and need for the specific intervention proposed, and importance of the research questions must be clearly stated. The application should make clear the need for and timeliness of the study with emphasis on how the results will expand the evidence base and contribute to sustainable interventions in CHCs for preventing opioid misuse or use disorder.

Innovation: Given the integration of the R61/R33 phases, only one Innovation section is needed. The application should demonstrate knowledge of the common barriers to delivering effective preventive interventions in CHCs and describe how the proposed research will be innovatively designed to address and inform solutions to those barriers. The applications should describe how the proposed research is innovative, as relevant, in terms of the population of focus, intervention adaptations, intervention delivery, the investigative and clinical team, the integration of the intervention within the CHC, data collection protocols, economic analysis, dissemination and sustainability plans, or other potential sources of innovation.

Approach: The application should contain separate Approach sections for the R61 and R33 phases, as described below. It is not necessary to repeat any information or details in the R33 section that are already described in the R61 section.

Preliminary data, extensive background material or preliminary information are not required for an R61/R33 application; however, they may be included if available. Appropriate justification for the proposed approach can be provided through literature citations, data from other sources, or, when available, from investigator-generated data.

R61 (Phase 1) Approach:

The focus of the R61 phase is the pilot/foundational work needed to inform a clinical trial. Applications should include the R61 phase activities that will lead to an established governance structure that includes adequate representation of CHC administrators, clinicians, and patients; development of a memorandum of understanding between the awardee and CHC partner; and a formalized or planned data use agreements between the awardee and its CHC partner.

Applicants may propose pilot/feasibility testing in the R61 phase approach. Pilot/feasibility testing may include fine-tuning an intervention or adapting an evidence-based intervention or implementation strategy for use in their partner CHC.

Investigators should indicate in their application their willingness to collaborate on the development and use of standardized measurement protocols, and coordination of assessment or intervention approaches with other projects funded through this FOA as part of the HEAL Prevention Initiative. Applicants are encouraged to leverage the availability of existing data collection platforms such as the HRSA Uniform Data System (UDS) data elements. At the end of the R61 phase of the project, grantees must demonstrate their ability to access and report these data elements.

Each awardee will be responsible for training and certification of personnel, which can be included in the R61 phase of the project.

The following should be included in the R61 approach section:

  • Plans for relationship development with partner CHCs, including the formal establishment of a partnership and identification of a CHC representative as key personnel
  • Plans for pilot/feasibility testing of intervention components, if applicable
  • Plans to complete clinical study and administrative requirements related to the study (e.g., IRB approval, data use agreements)
  • Plans for data coordination with the HEAL Prevention Initiative

The R61 Approach section application must include milestones that are expected to be achieved by the end of the R61 phase. Milestones should be specific, quantifiable, and scientifically justified; they should not be simply a restatement of the specific aims for the R61 phase. Applicants must include a discussion of the suitability of the proposed milestones for assessing success in the R61 phase, and a discussion of the implications of successful completion of these milestones for the proposed R33 phase of the project.

Milestones should be identified in the following areas:

  1. solidifying structural/functional partnerships with CHC site(s);
  2. pilot/feasibility testing of any intervention components, if applicable;
  3. plans to complete NIH regulatory requirements related to the study, including completion of IRB review, data use agreements, and required HEAL initiative participation;
  4. strategies for standardizing or coordinating data efforts.

R33 (Phase 2) Approach:

The proposed study designs to test the efficacy or effectiveness of the proposed intervention and/or address implementation-related research questions must be rigorous. Multiple site studies are allowed but not required for this FOA. The R33 phase of the project should clearly describe the approach and address how it will contribute to the sustainable prevention services in CHCs, including:

  • The study design, justifying why the design is appropriate for the proposed research questions and how threats to internal validity will be mitigated.
  • The primary and secondary outcomes that will be evaluated and the proposed measures. The expected sample size for the clinical trial, nature of the comparison/control group, expected attrition, power estimation, and methods for handling missing data.
  • The analytical plan, including plans to examine whether the intervention or implementation strategies are associated with and account for changes in the outcomes of interest, including any core components of the interventions or strategies that impact the change.
  • Plans for inclusion of the CHC partner as a meaningful contributor to the research, including the inclusion of CHC representatives as key personnel and CHCs as research sites.
  • The timeline of activities to be completed in the R33 phase of the project.
  • A discussion of any impediments that could require an addendum to the research plan or timeline with a discussion of alternative approaches.

Site Selection:

Applicants must propose to include one or more CHCs to serve as research sites and achieve the necessary sample size or otherwise enhance the scientific value of the study sample. In the R61 phase approach, applicants must provide evidence of organizational support by the CHC partner and plans to formalize that partnership during the R61 phase. In the R33 phase approach section, applicants should demonstrate their ability to recruit participants in each CHC site involved in the study, to implement measurement and intervention protocols in the study population, to provide appropriate oversight, and to maintain high rates of retention throughout the study.

For this RFA, partner CHCs may include community-based health centers, including FQHCs, FQHC look-alikes, school-based health centers, rural health clinics, IHS-funded Community Health Representatives, HIV primary care clinics, and nurse-managed health clinics. (See Key Definitions, Section I).

To increase the likelihood of the research supporting implementation and long-term sustainability in real world settings, applicants are encouraged to put together a multi-disciplinary team. Applicants are required to propose CHC staff as members of the research team and demonstrate how theywill contribute meaningfully to the project. Applicants are also encouraged to consider other community stakeholders who may contribute to the research and are appropriate research team members. At the time of application, CHC staff roles may be identified but individual staff members do not need to be named as research team members CHC staff are not required to be named as key personnel in the application, but at least one CHC representative must be named key personnel at the end of the R61 phase.

If investigators are located long distances from the CHC research site(s), applicants must demonstrate plans for working with the site(s) are adequate.

Letters of Support

Include letters of support/agreement for any collaborative arrangements, subcontracts, or consultants. For activities to be conducted at an institution other than the applicant institution, a letter of assurance or comparable documentation, signed by the collaborator as well as the institutional officials, must be submitted with the application.

At the time of application submission, the CHC partnership should be demonstrated by including a letter of support from CHC leadership. Letters should include a commitment from each site to enroll proposed subjects, adhere to the study protocol, collect and transmit data in an accurate and timely fashion, and operate within the proposed organizational structure.

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.

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), 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. Data generated by HEAL Initiative-funded projects must 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. Guidelines for complying with the HEAL Public Access and Data Sharing Policy can be found at https://heal.nih.gov/data/complying-heal-data-sharing-policy. Resources and tools to assist with data related activities can be found at https://www.healdatafair.org/.

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.
  • To the extent possible, HEAL awardees are expected to integrate broad data sharing consent language into their informed consent forms and align study consent language with data access and re-use requirements as defined by repository HEAL investigators select to store their HEAL data long-term.

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.

  • NIH has provided 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 examples, see NOT-DA-12-008, NOT-MH-15-009.)
  • Data should be organized according to a standard model that is widely accepted within the field. An example for the clinical research studies would be the OMOP Common Data Model, which has also been successfully adapted for use with observational (including survey) studies more generally. In addition, the HL7 FHIR® (Fast Healthcare Interoperability Resources) standard (NOT-OD-19-122) may facilitate 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. In addition to USCDI, OMOP, and FHIR standards for enhanced interoperability, investigators and data centers should align their data collection and management practices with recommended guidance emerging from the HEAL CDE and Data Ecosystem programs.
  • 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.

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.

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 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.

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

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.

For this particular announcement, note the following:

An R61/R33 grant application need not have preliminary data/information or extensive background material, however, they may be included if available. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Reviewers will assign a single impact score for the entire application, which includes both the R61 and R33 phases.

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?

Does the application demonstrate understanding of the opioid crisis and the population of focus in the proposed research?

Will the proposed research build on past research and expand the evidence base for preventing opioid misuse or use disorder among those receiving health services in CHCs?

Will the proposed research inform sustainability of CHC-based prevention?

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?

Specific to this FOA:

Do the investigators commit adequate effort to successfully fulfill the program needs?

Are the plans for CHC partnerships adequate to provide the research team with expertise on feasibility, implementation, and sustainability of the intervention?

Is a CHC representative named as key personnel or are there demonstrated plans to identify a CHC representative as key personnel by the end of the R61 phase of the project?

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

Innovation

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

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

Approach

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

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

Are the milestones for the R61 phase well specified?

Does the length of the R61 phase seem appropriate for the scope of work proposed?

Are plans for the R33 phase well-articulated, including specification of research questions?

Do the plans for the R33 phase build in a logical way on the R61 phase?

Does the application take into account issues of equity, scalability, and sustainability of the intervention or approach?

Is there substantial and appropriate integration of CHC stakeholders in the research team?

Does the research team include adequate CHC and community representation that can ensure that the research will be acceptable and relevant for the setting?

If investigators are located long distances from the research site, are plans for working within the site adequate?

Are the Data Sharing plans adequate? Do they address how the applicants will ensure rapid release of data, including metadata, in a way that will be useful to the community?

Does the application adequately describe how the center will closely work with the NIH HEAL Initiative’s Data Ecosystem (https://heal.nih.gov/data/heal-data-ecosystem), to maximize sharing and dissemination of datasets and digital resources to the pain research and therapeutics development communities.

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?

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.

Is the study timeline for the R61 and R33 phases of the project described in detail, taking into account planning, relationship building, feasibility testing, 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., CHC data, including those found in electronic medical records or administrative database) 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 challenges formalizing partnerships with CHCs or enrollment shortfalls)?

Study Timeline


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

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 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 Council on Drug Abuse. 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.
  • Geographic distribution of projects.

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:

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.

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.

Cooperative Agreement Terms and Conditions of Award

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.

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: 301-637-3015

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)

Sarah Steverman, PhD, MSW
National Institute on Drug Abuse (NIDA)
Telephone: 301-827-5435
Email: sarah.steverman@nih.gov

Laura Elizabeth Kwako, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Phone: 301-451-8507
E-mail: laura.kwako@nih.gov

Alexis Bakos, PhD, MPH, RN
National Cancer Institute (NCI)
Phone: 301-921-5970
Email: alexis.bakos@nih.gov
 

Karen A. Kehl, PhD, RN
National Institute of Nursing Research (NINR)
Telephone: 301-594-8010
Email: karen.kehl@nih.gov

Beda Jean-Francois
National Center for Complementary & Integrative Health (NCCIH)
Phone: 202-313-2144
Email: beda.jean-francois@nih.gov

Priscah Mujuru, DrPH, MPH, RN
National Institute on Minority Health and Health Disparities (NIMHD)
Phone: 301-594-9765
E-mail: mujurup@mail.nih.gov

Denise L Stredrick, Ph.D
Office of Disease Prevention (ODP)
Phone: 301-594-7553
E-mail: stredrid@mail.nih.gov

Peer Review Contact(s)

Center for Scientific Review (CSR)
Email:CSR (SEP) Review FOAReviewContact@csr.nih.gov

Financial/Grants Management Contact(s)

Pamela Fleming
National Institute on Drug Abuse (NIDA)
Telephone: 301-480-1159
Email: pfleming@nih.gov

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

Sean Hine
National Cancer Institute (NCI)
Phone: 240-276-6291
Email: hines@mail.nih.gov
 

Ron Wertz
National Institute of Nursing Research (NINR)
Telephone: 301-594-2807
Email: wertzr@mail.nih.gov

Debbie Chen
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-594-3788
Email: debbie.chen@nih.gov

Priscilla Grant, JD
National Institute on Minority Health and Health Disparities (NIMHD)
Phone: 301-594-8412
E-mail: pg38h@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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