Department of Health and Human Services
Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Mental Health (NIMH)
National Institute on Aging (NIA)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institute on Drug Abuse (NIDA)
National Institute of Nursing Research (NINR)
National Institute on Minority Health and Health Disparities (NIMHD)
National Center for Complementary and Integrative Health (NCCIH)

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 Behavioral and Social Sciences Research (OBSSR)
Office of Research on Women’s Health (ORWH)

Funding Opportunity Title

HEAL Initiative: Effectiveness Trials to Optimize, Implement, Scale, and Sustain the Collaborative Care Model for Individuals with Opioid Use Disorders and Mental Health Conditions (U01 Clinical Trial Required)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

New

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-MH-19-525

Companion Funding Opportunity

None  

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.242, 93.213, 93.866, 93.273, 93.279, 93.307, 93.361, 93.313      

Funding Opportunity Purpose

In April 2018, the National Institutes of Health (NIH) launched the HEAL (Helping to End Addiction Long-term) Initiative, an aggressive, trans-agency effort to speed scientific solutions to stem the national opioid public health crisis. In response to this initiative, the National Institute of Mental Health (NIMH), in partnership with other NIH Institutes, proposes research to adapt the Collaborative Care Model (referred to henceforth as collaborative care) – a specific service delivery model for treating mental/behavioral health conditions in primary care settings – to meet the needs of individuals with opioid use disorders (OUDs) and co-occurring mental health conditions. Effectiveness clinical trials are envisioned to develop, optimize, implement, scale, and sustain collaborative models that offer Medication Assisted Treatment for OUD alongside indicated treatment for mental health conditions that commonly co-occur with OUD and are treatable in primary care.    

Key Dates
Posted Date

December 10, 2018

Open Date (Earliest Submission Date)

March 1, 2019

Letter of Intent Due Date(s)

March 1, 2019

Application Due Date(s)

April 1, 2019, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

No late applications will be accepted for this Funding Opportunity Announcement.

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.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

May/June 2019

Advisory Council Review

August 2019

Earliest Start Date

October 2019

Expiration Date

April 2, 2019

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow 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 the 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 1. Overview Information
    Part 2. Full Text of the Announcement

    Section I. Funding Opportunity Description
    Section II. Award Information
    Section III. Eligibility Information
    Section IV. Application and Submission Information
    Section V. Application Review Information
    Section VI. Award Administration Information
    Section VII. Agency Contacts
    Section VIII. Other Information

    Part 2. Full Text of Announcement
    Section I. Funding Opportunity Description

     This funding opportunity announcement (FOA) is being offered as 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 will bolster 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://www.nih.gov/research-training/medical-research-initiatives/heal-initiative.

    The current NIMH FOA will support effectiveness clinical trials that develop, optimize, and test collaborative care models based in primary care to furnish indicated treatment for people with opioid use disorders (OUDs) and co-occurring mental health conditions. In these collaborative care models, Medication Assisted Treatment (MAT) must be offered alongside indicated treatments for other mental health conditions that commonly co-occur with OUD (e.g., depression, anxiety, and/or PTSD).

    Background

    National survey data suggest around 2.1 million Americans ages 12 years and older had an opioid use disorder (OUD) in 2016; and that, among adults who misused opioids in the prior year, 15.6% also had a serious mental illness and 42.8% had any mental illness. OUDs are also associated with various serious co-occurring physical health conditions, as well as high risk of premature death via accidental overdose, other accident mortality, and suicide (via intentional self-poisoning, as well as by other means). In 2016, 42,000 people died from opioid overdoses in the US, which represents a five-fold increase since 1999.

    Substantial evidence documents the effectiveness of certain medications, particularly buprenorphine and methadone, for treating OUDs, especially when such medications are combined with behavioral health counseling and delivered via coordinated Medication Assisted Treatment (MAT). MAT can significantly increase rates of recovery and reduce risk of fatal and non-fatal overdose. Despite a 2015 Practice Guideline from the American Society of Addiction Medicine that focuses on the use of medications in the treatment of substance use disorders involving opioid use, and a recommendation within the CDC Prescribing Guideline that clinicians offer MAT for patients with OUD, MAT remains underutilized. Only around one in five people with OUD receive any specific treatment, and only a minority of those receive MAT. Even among individuals who do receive indicated OUD treatments, effectiveness in current usual practice is limited.

    Geographic availability of clinicians who provide MAT and other indicated OUD treatments is highly variable and is especially limited in rural and other areas where OUD morbidity and mortality rates have risen steeply.  The Substance Abuse and Mental Health Services Administration (SAMHSA) reports that approximately half of US counties lack even one practicing mental/behavioral health specialty clinician. Of counties that do have providers certified to prescribe buprenorphine for OUD, most providers practice well under the patient caps, with 40% of certified providers not prescribing any buprenorphine. Together, these factors identify an urgent need for better models of care for individuals with OUD, to improve access, quality, and clinical outcomes.

    Over 80 randomized controlled trials demonstrate the effectiveness of collaborative care for improving clinical and service delivery outcomes among patients presenting in primary care with various common mental/behavioral health conditions, particularly mood and anxiety disorders, including those with co-occurring physical health problems. Collaborative care programs have been implemented and tested in diverse health care settings, including network and integrated systems, and private and public providers; different practice sizes; and different patient populations, including both insured and uninsured/safety-net populations. Compared to usual practice, collaborative care improves mental and physical health outcomes, functioning, and labor market outcomes; is associated with reductions in suicidality; increases access to care and improves quality of care; reduces disparities in quality and outcomes; and is relatively cost-effective and in some cases, is cost-saving. As such, collaborative care holds promise as an effective, scalable, sustainable, and readily implementable service delivery model for people with complex needs.

    In collaborative care, care is provided to a panel of patients by a treatment team. Team members include the primary care provider, a care manager, and a behavioral health specialty consultant. The care manager supports the patient and the primary care provider through a variety of treatment coordination activities. These activities include proactive follow-up of treatment adherence, tolerance, and response, alerting treatment team members when the patient is not improving; supporting medication management; facilitating communication among the treatment team; and delivering brief interventions like motivational interviewing, behavioral activation, and problem-solving therapy. The behavioral health specialty consultant, who has expertise and authority to prescribe medications, advises the primary care treatment team regarding patients who present diagnostic challenges or who are not adequately adhering, tolerating, or responding to treatment. Such consultation can be provided in person, or via tele- or web/video-conference to help address geographic scarcity. Teams may be augmented to include clinicians who furnish psychotherapy or other indicated treatments, or such treatments can be furnished via referral. Collaborative care programs follow the principles of measurement-based care, treatment-to-target, stepped care, and shared patient-provider decision making. In collaborative care, new cases are identified thorough routine screening, and patients’ progress is closely tracked using validated instruments. Treatment is adjusted – stepped up – if patients are not improving as expected.

    Evidence supporting collaborative care is strongest for common mental disorders but is less robust for OUD and other substance use disorders. While collaborative care trials focusing on common mental disorders have typically included patients with co-occurring substance use disorders, research has typically not examined effectiveness separately for those with and without such co-occurring conditions. 

    This FOA will support research to address unanswered questions regarding the adaptation, effectiveness, and implementation of collaborative care for individuals with OUD and co-occurring mental health conditions. This research will complement studies conducted within OUD specialty care clinics by testing integrated treatment models appropriate for diverse primary care settings, where many patients with OUDs and mental health conditions already seek care, and that are more plausibly available in areas where behavioral health specialty providers are - and are likely to remain - scarce.

    The anticipated effectiveness trials will channel the efforts of the scientific community to develop and implement pragmatic, effective, scalable, and sustainable solutions to the formidable public health challenges of OUD, which affect the lives and welfare of millions of Americans.


    Public Law 115-141, the Consolidated Appropriations Act of 2018 (signed March 23, 2018) includes a requirement that grantees from for-profit applicant organizations must provide a 50% match and/or in-kind contribution of all federally awarded dollars under the grant award (direct costs, as well as facilities and administrative costs) for research related to opioid addiction, development of opioid alternatives, pain management and addiction treatment.

    Matching Requirement: A grantee from a for-profit organization funded under this funding opportunity announcement must match funds or provide documented in-kind contributions at a rate of not less than 50% of the total-Federally awarded amount, as stipulated by Public Law 115-141, the Consolidated Appropriations Act of 2018.The applicant will be required to demonstrate that matching funds and/or in-kind contributions are committed or available at the time of, and for the duration of, the award. Applications must identify the source and amount of funds proposed to meet the matching requirement and how the value for in-kind contributions was determined. All matching funds and/or in-kind contributions must be used for the portion of allowable project costs not paid by Federal funds under the grant award.  NIH will not be the recipient, nor serve as a pass-through entity, of any such matching funds and/or in-kind contributions required under this announcement.  See 45 CFR 75.306 for additional details.

    Research Objectives

    NIH is interested in supporting effectiveness trials that develop, optimize, and test collaborative care models based in primary care to furnish indicated treatment for people with OUD and co-occurring mental health conditions. The collaborative care model must include MAT for OUD--specifically including indicated medications such as buprenorphine and/or methadone--as a component of care.  The comparative effectiveness trials should be designed to support rapid implementation, scalability, and sustainability of collaborative care approaches, should findings be positive.

    Two categories of patients would be the primary foci for enhancing quality of care and improving clinical outcomes via the collaborative care model:

    • Individuals presenting or referred to primary care who are identified with an OUD and one or more co-occurring mental health conditions and who, based on shared patient-provider decision-making, choose to receive treatment for these conditions in primary care;
    • Individuals with an OUD and one or more co-occurring mental health condition presenting to a hospital emergency department or other acute care setting with non-fatal overdose, intentional self-harm, or other OUD-related emergent risk, and who prefer to receive follow-up outpatient care after discharge in primary care (including because they lack access to specialty care).

    To meet the needs of people with OUD and mental health conditions, applicants should seek to answer these important primary research questions:

    • When integrating MAT and indicated treatment for mental health conditions, and when compared to standard care or other adaptions of collaborative care, how effective is collaborative care for improving patient outcomes with respect to (1) OUD, i.e., reducing or eliminating opioid use; (2) co-occurring mental health conditions, i.e., symptom response or remission; (3) functioning; and (4) risk for premature mortality, via accidental overdose, suicide, or other manner?
    • How can routine screening practices in primary care and as part of collaborative care be improved to identify new patients with OUD and mental health conditions?
    • When compared to standard care, how much does collaborative care improve access to and engagement with evidence-based services? That is, what is the reach of collaborative care into the target population?
    • How can collaborative care be optimized to introduce MAT to existing primary care practices already offering collaborative care for depression, anxiety, or other mental health conditions?
    • How can collaborative care for MAT and mental health conditions be introduced to primary care practices not providing collaborative care?
    • What patient, provider, and health system-level strategies are most effective to implement, bring to scale, and sustain collaborative care in diverse primary care practice settings for people with OUD and mental health conditions?

    NIH is particularly interested in clinical trial designs which can secondarily answer the following questions:

    • Does treatment of mental health conditions also improve outcomes for people with OUDs?
    • What are the clinical and treatment engagement tradeoffs associated with sequencing mental health treatment ahead of treatment for OUD? How can designs that study treatment sequencing inform clinical practice guidelines for co-occurring disorders and inform shared patient-provider decision making during initial treatment planning?
    • Can improved collaborative care for OUD and mental disorders be considered “primary prevention” for acute overdose, suicide behaviors, and/or accidental death - catastrophic outcomes for which individuals with OUD have very elevated risk?
    • Can collaborative care be part of a care pathway for individuals with OUD who have been identified via presentation to a hospital emergency department or other acute care setting with non-fatal overdose or suicide attempt? And if so, under what conditions would this pathway be reasonable and effective in the context of other alternatives (e.g., immediate inpatient hospitalization if beds are available, emergency department boarding followed by inpatient hospitalization, telehealth consultation with a behavioral health specialist, warm handoff to an outpatient behavioral health specialist, usual care discharge home)?
    • Given the public health urgency to furnish high value services that are effective, scalable, and sustainable in real-world practice, NIH is additionally interested in answering these questions:
    • How well do existing financing models support the implementation of collaborative care models for treating individuals with OUD and co-occurring mental health conditions? What are the major barriers to wider implementation of collaborative care for these purposes, and practical options for addressing them?
    • What are the best strategies to ensure collaborative care models are implemented, adopted, scaled, and sustained in routine practice, to include rural and Native American settings, and other settings of high need which may be under resourced?

    Institute Interests

    NCCIH 

    • The mission of NCCIH is to define, through rigorous scientific investigation, the usefulness and safety of complementary and integrative health interventions and their roles in improving health and health care. in the context of this FOA, NCCIH is interested in studies that will evaluate the impact of adding evidence-based complementary approaches for mental health conditions that are commonly co-occurring with OUD, such as mood disorders, anxiety, or sleep disorders, to determine if they have a measurable impact on improving OUD outcomes. Applicants are encouraged to discuss applications the NCCIH contact listed in Section VII. Agency Contacts.

    NIAAA

    • Given the substantial co-occurrence of OUD, mental health issues, and alcohol use disorder, service delivery models that emphasize integration of care for behavioral health in general medical settings are of particular importance.  In the context of this FOA, NIAAA is interested in studies that will assess whether and how the benefits of collaborative care models extend beyond patients’ OUD and mental health outcomes to other co-occurring behavioral health conditions, particularly heavy drinking and alcohol use disorder. In addition, NIAAA encourages studies that will examine the influence of alcohol drinking history and current drinking on the efficacy of collaborative care models as applied to OUD and co-occurring mental health conditions.  Applicants are encouraged to discuss applications with the NIAAA contact listed in Section VII. Agency Contacts.

    OBSSR

    • Although OBSSR does not accept assignment of applications or manage awards that are funded through this announcement, OBSSR does encourage applications relevant to the OBSSR mission and may provide co-funding support to ICs that do manage the awards. OBSSR is specifically interested in studies that apply evidence-based approaches for behavioral change (e.g., provider prescribing practices, adherence to treatment and management recommendations for both the practitioner and patients, provider/patient communications, resilience and other topics) to improve outcomes within the collaborative care model. 

    ORWH

    • The Office of Research on Women’s Health (ORWH) is part of the Office of the Director of NIH and works in partnership with the 27 NIH Institutes and Centers to ensure that women's health research is part of the scientific framework at the NIH, and throughout the scientific community. In general, ORWH is interested in research that considers the influence of sex and gender on health and disease, and the total health of women across the full spectrum of research. ORWH encourages interdisciplinary approaches and would be interested in partnering to support research that examines ways to integrate evidence-based practices, interventions, and policies into practice settings to improve the health of women.  The Trans-NIH Strategic Plan for the Health of Women covering FY 2019 - 2023 is available on the ORWH website (https://orwh.od.nih.gov) for additional guidance.
    Scale and Scope of Research Covered Under This Announcement

    This FOA is intended to support trials that are statistically powered to provide a definitive answer regarding the effectiveness of collaborative care for people with OUD and co-occurring mental health conditions in comparison to usual care practices or alternative intervention/services approaches. The study should also be designed to address hypotheses regarding predictors and moderators of effectiveness and questions regarding the action of mediators and mechanisms that underlie improvements to service delivery, implementation, scalability, and sustainability of collaborative care.

    This FOA is intended to only fund strategies that optimize and test collaborative care for OUD and co-occurring mental health conditions. This FOA is not intended to test other models of integration (e.g., co-location of a behavioral health provider into primary care in the absence other elements like care management services or application of measurement-based care).  It is also not intended to support other efforts like the development of treatment guidelines and education of primary care providers, in the absence of collaborative care. 

    Core elements of collaborative care include 1) a prepared primary care practice (e.g., routine screening for indicated conditions; real-time availability and use of a disease registry for measurement-based care and treat-to-target practices); 2) care management services (in-person and/or telehealth); 3) a behavioral health consultant (in-person and/or telehealth) with prescription privileges and who has collaborative care expertise; 4) delivery of indicated treatments for common mental health conditions encountered in primary care settings (e.g., depression, anxiety, and/or PTSD) that are integrated within a collaborative care model; and 5) shared patient-provider decision making.

    NIH envisions an intervention arm that integrates both MAT for OUDs and treatment for indicated mental health conditions within a collaborative care model of service delivery. Here, the behavioral health consultant must also advise directly on MAT services (or ensure regular expert consultation is available to the care team about MAT). Workflows, decision support tools, principles of measurement-based care and treatment-to-target, strategies to engage patients in care, etc. that are used in collaborative care for patients with mental health conditions should also be adapted (if necessary) and used as part of MAT services that are integrated with collaborative care.

    Comparison conditions could include the following: 1) usual care for OUD plus usual care for mental health conditions, 2) MAT for OUD plus usual care for mental health conditions, 3) usual care for OUD plus collaborative care for mental health conditions, 4) MAT for OUD that is separate from collaborative care for mental health conditions plus collaborative care for mental health conditions, and/or 5) usual care where MAT for OUD plus indicated treatment for mental health conditions is integrated within a collaborative care framework and where manipulations in the intervention arm might include specific components of treatment, service delivery, and/or strategies for implementation.

    Study sites should be representative and in areas of high need. The proposed projects should be multi-site and potentially include entire states like New Hampshire, West Virginia, New Mexico, Kentucky, or Ohio.

    Projects must specify the patient outcomes that will be the focus of treatment; provide detailed rationale for the choice of outcomes; and describe valid and standardized methods for how those outcomes will be measured. Wherever possible, projects should utilize existing validated, standardized instruments of patient outcomes, which are available for many mental disorders and for functioning.

    Given the urgency for rapid implementation of pragmatic and effective interventions to stem the opioid crisis, projects must demonstrate a deployment-focused model of design and testing. That is, studies should take into account key characteristics of the settings, providers, and intervention elements (e.g., training, supervision, infrastructure, and capacity to pursue measurement-based care) and factors related to implementation (reach, effectiveness, adoption, and maintenance). Designs should be pragmatic, and procedures and infrastructure unique to research (e.g., recruitment and follow-up strategies) should have minimal impact on clinical care and should not confound the interpretation of intervention effects or the generalizability of findings to non-research settings. A deployment focus is crucial to ensure that clinical trials that test collaborative care for people with OUDs and co-occurring mental health conditions have sufficient external validity to support broad implementation of evidence-based practices outside of a clinical trial context.

    NIH will give priority to studies that leverage existing equities (e.g., practice networks, clinical trial networks, research-practice partnerships) rather than those that need to create research and clinical infrastructure de novo. Collaborations between academic researchers and clinical or community practice partners or networks are expected. When possible, studies should capitalize on existing infrastructure. Examples include practice-based research networks such as the NIMH-sponsored Mental Health Research Network (MHRN), the NIDA supported Clinical Trials Network, the NCATS Trial Innovations Network, the AHRQ Clinical Directors Network, and other clinical infrastructure (e.g., federal qualified health centers, rural health clinics, other integrated care settings supported by federal partners like HRSA or SAMHSA. Other examples may include leveraging electronic medical records, administrative data bases, and patient registries to increase the efficiency of participant recruitment (i.e., more rapid identification and enrollment) and to facilitate the collection of moderator data (e.g., patient, provider, and setting characteristics), longer-term follow-up data, and broader, stakeholder-relevant outcomes (e.g., mental health and general health care utilization, value and efficiency of intervention approaches).

    Effective prevention, treatment, and management of OUD and mental health conditions have the potential to reduce morbidity and mortality associated with intentional injury (i.e., suicide attempts and deaths, see: www.suicide-research-agenda.org) and accidental overdose. Lack of attention to the assessment of these outcomes has limited our understanding regarding the degree to which MAT and indicated mental health treatment might offer prophylaxis. Accordingly, NIMH encourages effectiveness research that includes assessment of suicidal behavior to advance understanding of how effective prevention and treatment of mental disorders might impact suicide-relevant outcomes. 

    For multi-site trials, use of single IRBs is expected.

    This funding announcement is intended to invite single applications that will use subcontracts to fund research being conducted at multiple clinical sites and/or fund investigators at multiple research institutions.

    This RFA is not intended to support the development and testing of novel treatment modalities for the conditions being targeted here, i.e., new psychotherapies, medications, devices, or other treatments that are not yet indicated for OUD or relevant mental health conditions. Rather, this RFA is intended to support innovations in the delivery of existing efficacious treatment, when integrated as part of an optimized collaborative care model. Similarly, this RFA is also not intended to support the development and testing of new screening or patient outcome instruments. Wherever feasible and appropriate, projects should utilize existing validated and standardized instruments to screen for OUD and other substance use, as well as for common mental health conditions, as well as existing validated and standardized instruments to assess patient outcomes related to OUD, specific mental health conditions, functioning, and other relevant patient outcomes.

    Examples of studies that are considered low priority to this FOA include the following:

    • Studies that do not include these core elements of the collaborative care model to be tested:1) A prepared primary care practice (e.g., routine screening for indicated conditions; real-time availability and use of a disease registry for measurement-based care and treat-to-target practices for a panel of patients); 2) Care management services (in-person and/or via telehealth); 3) A behavioral health consultant with prescription privileges, with collaborative care expertise and with MAT expertise (if the behavioral health consultant does not have the prerequisite expertise, applicants must provide a plan for how that expertise will be obtained and provided to the care team); 4) Integration of MAT for OUD within the collaborative care model; 5) Indicated treatment for mental health conditions commonly seen in primary care settings (e.g., depression, anxiety, and/or PTSD); and 6) Shared patient-provider decision making. 
    • Projects that do not demonstrate a deployment-focused model of design and testing. That is, studies that do not take into account key characteristics of the settings, providers, and intervention elements.
    • Designs that are not pragmatic, and/or do not have procedures and infrastructure unique to research (e.g., recruitment and follow-up strategies) that have minimal impact on clinical care and minimal impact on trial results.
    • Projects that do not explicitly inform understanding regarding whether collaborative care engages putative change mechanisms (i.e., targets) related to service delivery that are presumed to account for improved outcomes.

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

    Section II. Award Information
    Funding Instrument

    Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

    Application Types Allowed

    New

    The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

    Clinical Trial?

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

    Need help determining whether you are doing a clinical trial?

    Funds Available and Anticipated Number of Awards

    NIH intends to commit an estimated $10 million (total costs) per year to fund 3-4 awards.

    Award Budget

    Application budgets are not limited but need to reflect the actual needs of the proposed project.

    Award Project Period

    The total project period for an application submitted to this funding announcement may not 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)

    Governments

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

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

    Required Registrations

    Applicant Organizations

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

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

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

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

    Eligible Individuals (Program Director/Principal Investigator)

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

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

    2. Cost Sharing

    For grantees from a for-profit organization, this FOA does require cost sharing, as defined in the NIH Grants Policy Statement.  More information on cost matching requirements is in Section IV.2 R&R or Modular Budget

    3. Additional Information on Eligibility
    Number of Applications

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

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

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

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

    2. Content and Form of Application Submission

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

    Letter of Intent

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

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

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

    The letter of intent should be sent to:

    Email: nimhpeerreview@mail.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 with the following additional instructions:

    Key Personnel should document their expertise conducting collaborative care clinical trials; their expertise delivering or researching MAT; their familiarity with state and federal regulations pertaining to MAT delivery; their knowledge about Medicaid, Medicare, and commercial insurance benefit packages associated with collaborative care and MAT; their expertise implementing collaborative care programs in diverse geographic areas; their expertise collecting and integrating de-identified, person-level data gathered across multiple clinics and using standardized data to improve the quality of mental health services and individual patient outcomes; and their success conducting services and/or intervention research with individuals who have complex needs, including success in identifying and recruiting such participants into research studies.

    Applicants should document their experience working in community practice primary care and other relevant settings (e.g., the emergency department) and with administrators and clinic leaders to integrate standardized assessment methods and health information technology into routine clinical care and in establishing collaborations across diverse mental health care stakeholders, such as patients, families, clinicians, researchers, administrators and payors to create organizational and/or cultural change in mental healthcare delivery. Applications should include information demonstrating the investigator’s or co-investigator’s capacity to identify, recruit, randomize, and retain individuals who have OUDs and mental health conditions in numbers sufficient to support an adequately powered randomized clinical trial. Investigators should also demonstrate experience in clinical trials management.

    R&R or Modular Budget

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

    Budget Justification related to for-profit entities: All requests from for-profit entities must document the matching (non-Federal) component and the federal (non-matching) component in the total project budget. That is, the requested budget plus the cost-matching budget must be detailed in tabular format to document the cost-matching (non-Federal) component and the federal (non-cost matching) component. The amount of matching is subject to adjustment based on total allowable costs incurred.  All costs and contributions used to satisfy the matching requirement must be documented by the recipient, including how the value for in-kind contributions was determined, and are subject to audit. The cost matching requirement is not negotiable for for-profit organizations.


    Cost Matching Requirement for For-profit Applicants

    Cost matching or documented in-kind contributions is required for for-profit organizations responding to this FOA.  The for-profit awardee is required to match funds or provide at least a 50% matching of funds or documented in-kind contributions at a rate of not less than 50% of the for the total-Federally awarded amount (direct costs, as well as facilities and administrative costs), as stipulated by Public Law 115-141, the Consolidated Appropriations Act of 2018.   
    Federal funds may not be used as a source of matching funds. Generally, cost matching requirements may not be met from the following sources:
    a) Costs borne by another Federal grant or sub award;
    b) Costs or contributions toward cost sharing on another Federal grant, a Federal procurement contract, or any other award of Federal funds;
    c) Cost of services or property financed by income earned by contractors under a contract from the recipient (or sub recipient);
    (d) Program income; and
    (e) Patient incentives.
    The for-profit organization will be required to demonstrate that matching funds and/or in-kind contributions are committed or available at the time of, and for the duration of, the award. Applicants must submit budgets that clearly document the total costs, the source and amount of matching funds, and how valuation was determined in the case of in-kind contributions, as well as the Federal and Institutional (non-Federal) components of the budget. All matching funds and/or in-kind contributions must be used for the portion of allowable project costs not paid by Federal funds under the grant award.  NIH will not be the recipient, nor serve as a pass-through entity, of any such matching funds and/or in-kind contributions required under this announcement.  See 45 CFR 75.306 for additional details.
    Budget Justification: All for-profit applicants must document the matching (non-Federal) component and the federal (non-matching) component in the total project budget. That is, the requested budget plus the cost-matching budget must be detailed in tabular format to document the cost-matching (non-Federal) component and the federal (non-cost matching) component. The amount of matching is subject to adjustment based on total allowable costs incurred.  All costs and contributions used to satisfy the matching requirement must be documented by the recipient, including how the value for in-kind contributions was determined, and are subject to audit. The cost matching requirement is not negotiable for for-profit organizations.

    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: 

    Research Strategy

    Applications must describe a feasible mechanism for scientific integration of research procedures and overall managerial and administrative responsibilities across participating clinic sites. The common research protocol must specify mechanisms for cross-site coordination of clinical assessment, data collection, training and supervision for the care team, fidelity monitoring, and database management to assure reliability and quality control. The research grant application is expected to include central data coordination and statistical analysis support for the overall project. In addition, the Research Strategy should include the following information.

    Describe the process for establishing and convening a Steering Committee, including the composition, roles/responsibilities, and schedule for convening regular and ad hoc steering committee meetings

    Significance

    Explain the importance of the problem or critical barrier to progress that the proposed project addresses. Describe the scientific premise for the proposed project, including consideration of the strengths and weaknesses of published research or preliminary data crucial to the support of your application. Explain how the proposed project will improve scientific knowledge, technical capability, and/or clinical practice in one or more broad fields.

    Indicate how scientific knowledge, technical capability, clinical practice and/or health policy for the treatment and management of OUD and co-occurring mental health conditions could be improved if the aims of the project are achieved. Indicate how successful completion of the project aims could change the concepts, methods, technologies, treatments, and services, that drive care for individuals with OUDs and co-occurring mental health conditions.

    Justify the practical impact of the collaborative care intervention to be tested in terms of the estimated hypothesized effect size compared with already available approaches. Address the potential impact of the collaborative care intervention in terms of both (1) the empirical basis for the anticipated effect size (e.g., citing data from prior collaborative care trials, trials testing MAT, and/or trials of indicated treatments for mental health conditions in primary care settings), and (2) the clinical meaningfulness of the anticipated increment in effects compared to existing approaches.

    As appropriate, address the degree to which the study can answer questions of secondary interest to NIH. For example:

    • Explain how treating mental health conditions may improve outcomes for OUD.
    • Describe the importance and implications of an evidence-based approach to treatment sequencing for people with co-occurring OUD and MH disorders.
    • Address the degree to which the collaborative care model can be adoptable, scalable, and sustainable in routine practice settings, given typically available resources (e.g., trained, skilled providers), typical service structures (including existing financing models), and typical service use patterns. Address how the collaborative care model can increase both the reach and effectiveness of care for people with OUDs and co-occurring mental health conditions, when compared to usual care practices.

    Innovation

    Explain how the application challenges and seeks to shift current research or clinical practice paradigms. Describe any novel theoretical concepts, approaches or methodologies, instrumentation or interventions to be developed or used, and any advantage over existing methodologies, instrumentation, or interventions. Explain any refinements, improvements, or new applications of theoretical concepts, approaches or methodologies, instrumentation, or interventions.

    Propose innovations in care integration, including:

    • Innovations in clinical workflows, recommendations for treatment sequencing, identification and management of patients at high risk for overdose or suicide, quality of care metrics, and integration of mental health treatment and MAT within collaborative care.
    • Innovations to improve the care pathway for people with OUD and mental health conditions into collaborative care from other settings like emergency departments, specialty care outpatient treatment programs (OTPs), other community settings, or other primary care practices that are ill-equipped to treat individuals with OUD and mental health conditions. 
    • Innovative strategies to rapidly increase intensity of services to address the short-term needs of people in crisis when such services do not exist.

    Highlight how innovative research strategies and design/analytic elements (e.g., adaptive sequential randomization, equipoise stratification) are incorporated, as appropriate, in order to enhance the study's potential for yielding practice-relevant information.

    Responsive applications will include innovations in workforce development, such as innovations in telehealth services, training and supervision models, and/or maximizing functions of non-physician providers with prescription privileges (e.g., NPs, PAs, and psychologists) to increase access to services and reach of collaborative care in areas of highest need and to inform future prescribing guidelines and rules for psychotropic medications and buprenorphine.

    Approach

    Describe the overall strategy, methodology, and analyses to be used to accomplish the specific aims of the project. Describe the experimental design and methods proposed and how they will achieve robust and unbiased results. Unless addressed separately in the Resource Sharing Plan, include how the data will be collected, analyzed, and interpreted, as well as any resource sharing plans as appropriate. Discuss potential problems, alternative strategies, and benchmarks for success anticipated to achieve the aims. If the project is in the early stages of development, describe any strategy to establish feasibility, and address the management of any high risk aspects of the proposed work.

    Provide a brief overview of the target population for whom existing services are inadequate and the settings where the collaborative care is to be tested.

    Discuss barriers and facilitators associated with collaborative care implementation, scalability, and sustainment at the sites where the study is to be conducted and how these factors might affect generalizability of research findings to other primary care practices.

    The approach must detail how projects will use a deployment-focused model of design and testing. That is, studies should take into account key characteristics of the settings, providers, and intervention elements (e.g., training, supervision, infrastructure, and capacity to pursue measurement-based care) and factors related to implementation (reach, effectiveness, adoption, and maintenance). Designs should be pragmatic, and procedures and infrastructure unique to research (e.g., recruitment and follow-up strategies) should have minimal impact on clinical care and minimal impact on trial results.  The approach should describe how the collaborative care model to be tested has external and face validity and how it can be feasibly delivered outside of a clinical trial context, should it be effective. Elements of a deployment focused model include the following:

    • A study powered to detect meaningful clinical improvements in OUDs (via MAT) and mental health conditions (via indicated treatments) and/or service delivery outcomes (e.g., improvements in access, reach, or continuity of care) and/or implementation outcomes (e.g., scalability or sustainability)
    • Study samples that are representative of community practice populations; study settings that are diverse and representative; and interventions, screening instruments, and decision support tools that are feasibly integrated into provider workflows, that are evidence supported, and that can be scaled and sustained.
    • Assessment and/or testing of patient-, provider- and clinic-level factors that might impact implementation, along with corresponding analyses that will be used to examine whether/how these factors impact adoption, scalability, sustainability, and patient outcomes, especially in settings and locations of highest need.
    • Assessment plans that describe the assessment of suicidal behavior and related outcomes using strategies that can facilitate integration and sharing of data (e.g., see NOT-MH-15-009 and https://www.phenxtoolkit.org/ for constructs and corresponding assessment strategies), as appropriate, or provide a rationale for excluding such measures if they are not included. Accordingly, plans should provide the rationale for the selection of suicide-related constructs and corresponding assessment instruments (e.g., measures of ideation, attempts), the time periods assessed (e.g., lifetime history, current), and the assessment schedule for administration (e.g., baseline, during intervention, post-intervention, follow up), considering the nature of the target population, participant burden, etc. Plans should also address provisions for clinical management when suicidal behavior is reported. In situations where it is not appropriate or feasible to include assessment of suicide outcomes due to the nature of the intervention (e.g., services interventions that target provider behavior or systems-level factors), the target population (e.g., very young children), or unique issues related to participant burden or safety/monitoring concerns, the application should provide an appropriate justification for excluding these assessments.
    • Projects that utilize existing health care billing/financing mechanisms wherever possible, i.e., for primary care services, prescription medications, psychotherapy, laboratory testing, and all other relevant services. This includes billing codes for services delivered through collaborative care via CPT 99492/99493/99494, formerly G0502/G0503/G0504.
    • Patient-related clinical services that are supported through existing billing and financing mechanisms. In the event that study-related interventions and services cannot be supported through existing mechanisms, a justification should be provided.
    • Projects that leverage existing research practice partnerships and clinical infrastructure to 1) capitalize on existing research infrastructure whenever possible; (2) create efficiencies such that research dollars do not support clinical infrastructure that is unsustainable upon trial completion; and 3) ensure key research questions are highly relevant to the practice community and findings from the study will be used to change current practice. If applicants choose not to leverage partnerships and equities, applicants must provide a detailed justification. Examples include practice-based research networks like the NIMH-supported Mental Health Research Network and the NCATS leveraged and Agency for Healthcare Research and Quality-funded Clinical Directors Network and the Rockefeller Practice Based Research Network; other clinical trials networks like NIDA’s Clinical Trials Network and the NCATS Trial Innovation Network; care platforms funded by other federal agencies like the Substance Abuse and Mental Health Services Administration the  Health Resources & Services Administration) with various community primary care practices (e.g., Federally Qualified Health Centers, designated Rural Health Clinics, other rural practices, integrated healthcare systems) and possibly other healthcare settings like emergency departments.
    • Sites that are representative and in areas of high need. The proposed projects should be multi-site, in areas where OUD mortality has risen particularly steeply, and cover geographic areas the size of entire states.
    • A study adequately powered to answer primary questions about of outcomes related to clinical effectiveness, including mortality (accidental and intentional death); service delivery (e.g., reach, access, continuity); and implementation (e.g., adoption, scalability, sustainability).
    • Data capture approaches (e.g., approaches that leverage existing electronic health record infrastructure) that are highly efficient, valid, and minimally burdensome to patients and providers.
    • Design considerations that disambiguate outcomes associated with study participation (e.g., patient completes follow-up assessments as reported in a CONSORT) from engagement with broad collaborative care services (e.g., patient is responsive to care manager outreach calls), and from individual treatment elements delivered as part of collaborative care (e.g., patient takes buprenorphine as prescribed and attends regular counseling sessions as part of MAT).
    • Study designs that are pragmatic and that control for and/or minimize the impact of research personnel or procedures on study outcomes.

    Applicants should propose the comparison group(s) that allow for meaningful comparisons, in light of a robust evidence base that supports the widespread implementation of collaborative care. Describe how findings will be interpretable and inform practice if the outcomes are positive, if outcomes are negative, and if there is heterogeneity in the directionality of outcomes?

    Applicants should provide adequate detail about the collaborative care model(s) to be tested and the comparator(s). Required elements of the collaborative care model to be tested must include the following:

    1) A prepared primary care practice (e.g., routine screening for indicated conditions; real-time availability and use of a disease registry for measurement-based care and treat-to-target practices for a panel of patients);

    2) Care management services (in-person and/or via telehealth);

    3) A behavioral health consultant with prescription privileges, with collaborative care expertise and with MAT expertise (if the behavioral health consultant does not have the prerequisite expertise, applicants must provide a plan for how that expertise will be obtained and provided to the care team);

    4) Integration of MAT for OUD within the collaborative care model;

    5) Indicated treatment for mental health conditions commonly seen in primary care settings (e.g., depression, anxiety, and/or PTSD); and

    6) Shared patient-provider decision making.

    Elements of MAT and its integration with collaborative care should be described. This description could include the care processes, medication type and dosing, and integration with other elements of collaborative care during the three phases of MAT (e.g., induction, stabilization, and maintenance).

    Projects must specify the patient outcomes that will be the focus of treatment; provide detailed rationale for the choice of outcomes; and describe valid and standardized methods for how those outcomes will be measured. Wherever possible, projects should utilize existing validated, standardized instruments of patient outcomes, which are available for many mental disorders and for functioning.

    Consistent with the NIMH experimental therapeutics approach, (http://www.nimh.nih.gov/about/director/2012/experimental-medicine.shtml), these clinical trials will test the effectiveness of collaborative care for people with OUD and co-occurring mental health conditions on primary outcomes of interest, but should also explicitly inform understanding regarding whether collaborative care engages  putative change mechanisms (i.e. targets) related to service delivery that are presumed to account for improved outcomes. (see NIMH web page on Clinical Trials). The results of these trials will advance knowledge regarding change mechanisms and have utility regardless of trial outcomes (e.g., in the event of negative results, information about whether the intervention was successful at engaging its targets can facilitate interpretation).

    • Applicants should detail the plan to explicitly address whether the intervention engages the mechanisms that are presumed to underlie the effects of collaborative care as a service delivery model (e.g., the mechanism that account for changes in service delivery, public health outcomes or changes in the effectiveness of the implementation strategy) and include the following: (1) a conceptual framework that clearly identifies the target(s)/mechanism(s) and the empirical evidence linking the target(s)/mechanism(s) to the clinical symptoms, functional deficits, or patient-, provider- or system-level behaviors/processes that the intervention seeks to improve; (2) plans for assessing engagement of the target(s)/mechanism(s) using valid measures that are as direct, efficient, and objective as is feasible in the effectiveness context, including the specific measures, the assessment schedule, and the justification for the assessment strategy (e.g., evidence regarding the validity and feasibility of the proposed measures in the effectiveness context); and (3) a statistical analysis plan for data analyses that will be used to examine whether the intervention engages the target(s) and whether intervention-induced changes in the target(s) are associated with clinical benefit (i.e., mediation).
    • Applicants should not necessarily specify the conceptual basis, assessment plan, and analytic strategy, as detailed above, for the target(s)/mechanism(s) corresponding to each component of collaborative care.  Instead, applicants should do so only for service delivery or implementation-oriented change mechanisms believed to be crucial ingredients to effective collaborative care delivery. In this way, future adaptions of collaborative care for the target population might retain those key ingredients deemed effective and shed those elements deemed non-essential. 
    • Valid and reliable measures of change in the hypothesized target(s)/mechanism(s) will provide useful information about key change mechanisms that account for intervention effects. NIMH encourages the use of measures that are as direct and objective as is feasible in clinical practice setting, including valid measures of the construct that extend beyond self-reports and other subjective measures (e.g., data extracted from EHRs) and span more than one level of assessment, if possible and appropriate.

    If applicable, describe how the project will address questions of secondary interest to NIH such as whether treating mental health conditions will improve OUD-related outcomes.

    Letters of Support

    For-profit applicants must include a letter(s) of support confirming that the required secured cost matching (cash; in-kind commitments such as salary, consultant costs, equipment) is available and confirm that the essential personnel have the authority within the organization to allocate resources. 

    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, with the following modification:

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

    In order to facilitate the goal of advancing research through widespread data sharing among researchers, investigators funded under this FOA are expected to share those data via the National Database for Clinical Trials related to Mental Illness (NDCT; http://ndct.nimh.nih.gov/; see NOT-MH-14-015 and NOT-MH-15-012). Established by the NIH, NDCT is a secure informatics platform for scientific collaboration and data-sharing that enables the effective communication of detailed research data, tools, and supporting documentation. NDCT links data across research projects through its Global Unique Identifier (GUID) and Data Dictionary technology. Investigators funded under this FOA are expected to use these technologies to submit data to NDCT.

    To accomplish this objective, it will be important to formulate a) an enrollment strategy that will obtain the information necessary to generate a GUID for each participant, and b) a budget strategy that will cover the costs of data submission. The NDCT web site provides two tools to help investigators develop appropriate strategies: 1) the NDCT Budgeting Spreadsheet http://ndct.nimh.nih.gov/preplanning/budget - a customizable Excel worksheet that includes tasks and hours for the Program Director/Principal Investigator and Data Manager to budget for data sharing; and 2) plain language text to be considered in your informed consent http://ndct.nimh.nih.gov/preplanning/informed-consent. Investigators are expected to certify the quality of all data generated by grants funded under this FOA prior to submission to NDCT and review their data for accuracy after submission. Submission of descriptive/raw data is expected semi-annually (every January 15 and July 15); submission of all other data is expected at the time of publication, or prior to the end of the grant, whichever occurs first (see Data Sharing Expectation http://ndct.nimh.nih.gov/preplanning/#tab-1 for more information); Investigators are expected to share results, positive and negative, specific to the cohorts and outcome measures studied by using the Study functionality(see http://ndct.nimh.nih.gov/results). The NDCT Data Sharing Plan is available for review on the NDCT web site (http://ndct.nimh.nih.gov/wp-content/uploads/NDCT_Data_Sharing_Policy_20141002.pdf). NDCT staff will work with investigators to help them submit data types not yet defined in the NDCT Data Dictionary http://ndct.nimh.nih.gov/submit/data-dictionary

    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 NIH-defined human subjects research, clinical research, and/or 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 with the following additional instructions:

    Section 2 - Study Population Characteristics

    2.5 Recruitment and Retention Plan

    Recruitment and Retention Plan. Applications must provide a clear description of:

    1. Recruitment and Referral sources, including detailed descriptions of the census/rate of new cases and anticipated yield of eligible participants from each source;

    2. Procedures that will be used to monitor enrollment and track/retain participants for follow-up assessments;

    3. Strategies that will be used to ensure a diverse, representative sample;

    4. Potential recruitment/enrollment challenges and strategies that can be implemented in the event of enrollment shortfalls (e.g., additional outreach procedures, alternate/back-up referral sources);

    5. Strategies that will allow for the study team to take advantage of new opportunities (e.g., policy changes or new financing mechanisms that have immediate practice implications);

    6. Evidence to support the feasibility of enrollment, including descriptions of prior experiences and yield from research efforts employing similar referral sources and/or strategies.

    2.7 Study Timeline

    Study Timeline: Applications must provide a timeline for reaching important study benchmarks such as: (1) finalizing the study procedures and training participating clinical site staff; (2) finalizing the intervention manual and assessment protocols, including fidelity measures/procedures, where applicable; (3) enrollment benchmarks; (4) completing all subject assessments and data collection activities, including data quality checks; (5) analyzing and interpreting results; and (6) preparing de-identified data and relevant documentation to facilitate data sharing, as appropriate.

    Applications should include plans for critically evaluating and revising these milestones on a regular basis

    Section 3 - Protection and Monitoring Plans

    3.5 Overall Structure of the Study Team

    Provide a management plan that details how the PD(s)/PI(s) will manage the proposed project, who will oversee the day-to-day clinical and research activities associated with the project. This plan should include how the study team will support achievement of the aims and milestones.  

    Section 5 - Other Clinical Trial-related Attachments

    5.1 Other Clinical Trial-related Attachments

    Applicants must upload the attachments for Intervention Manual/Materials as separate files, as applicable. Applicants must use the "Intervention Manual/Materials", appended with 1, 2, 3, etc. as needed, to name these other attachments files.

    As appropriate, this may include screenshots of mobile interventions, technological specifications, training manuals or treatment algorithms.

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

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

    See more tips for avoiding common errors.

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

    In order to expedite review, applicants are requested to notify the NIMH Referral Office by email at nimhreferral@mail.nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

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

    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.

    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 research strategy describe a feasible mechanism for scientific integration of research procedures and overall managerial and administrative responsibilities across participating clinic sites? Does the common research protocol address specify mechanisms for cross-site coordination of clinical assessment, data collection, training and supervision for the care team, fidelity monitoring, and database management to assure reliability and quality control? Is the central data coordination and statistical analysis support adequate for the overall project?

    Is this clinical trial necessary to inform a change in clinical practice or health care policy? Will the findings of this trial advance scientific understanding about how to treat and manage people with OUDs and co-occurring mental health disorders?

    Does the application justify the practical effect of the collaborative care intervention in terms of the estimated hypothesized effect size (on the primary trial outcome), compared with already available approaches? Does the application adequately address both (1) the empirical basis for the anticipated effect size (e.g., citing appropriate data or literature on collaborative care and/or MAT), and (2) the clinical meaningfulness of the anticipated increment in effects compared to existing approaches?

    As appropriate, how well does the application seek to answer research questions of secondary interest to NIH?  For example:

    • Does the application address how treating mental health conditions may improve outcomes for OUD?
    • Does the application describe the importance and implications of an evidence-based approach to treatment sequencing for people with co-occurring OUD and MH disorders?
    • If the approach is successful, is it scalable and sustainable, and could it be implemented into practice given typically available resources (e.g., trained, skilled providers), typical service structures (including health care financing), and typical service use patterns?  

    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?  

    Are key personnel familiar with state and federal regulations pertaining to MAT delivery?  Are they familiar with commercial insurance and Medicaid and Medicare benefits for MAT and collaborative care?

    As appropriate, does the trial involve collaborations and/or input from community practice partners/providers, consumers, and relevant policy makers in a manner that informs the research and helps to ensure the results will have immediate utility?

    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 application propose innovations to improve care integration in terms of clinical workflow, treatment sequencing, identification and management of high risk patients, or to improve care pathways into collaborative care from other settings (e.g., the emergency department)?

    How well does the study incorporate innovative research strategies and design/analytic elements (e.g., adaptive sequential randomization, equipoise stratification) in order to enhance the study's potential for yielding practice-relevant information?

    Does the project adequately propose innovations in workforce development, such as innovations in telehealth services, training and supervision models, and or maximizing functions of non-physician providers with prescription privileges (e.g., NPs, PAs, and psychologists) to inform future prescribing guidelines and rules?

    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? 

    How well does the application describe the target population and the settings where collaborative care is to be tested?

    Does the application adequately discuss barriers and facilitators associated with implementation, scalability, and sustainment of collaborative care at the sites where the study will be conducted and how these factors might affect generalizability of research findings to other primary care practices?

    Do the applicants take a deployment-focused model of design and testing? That is, do studies take into account key characteristics of the settings, providers, and intervention elements (e.g., training, supervision, infrastructure, and capacity to pursue measurement-based care) and factors related to implementation (reach, effectiveness, adoption, and maintenance)?  How pragmatic is the study design? Will procedures and infrastructure unique to research (e.g., recruitment and follow-up strategies) likely have minimal impact on clinical care and minimal impact on trial results? Should the to-be-tested collaborative care model be effective, can it be feasibly delivered outside of a clinical trial context?  Specifically:

    • Is the study powered adequately to answer primary questions about clinical outcomes (to include mortality), service delivery outcomes (e.g. access, continuity, reach), and implementation outcomes related to adoption, scalability, and sustainability?
    • How representative are study populations and study settings to community practice populations? Are relevant patient, provider, and clinic-level factors assessed and manipulated? Will the approach generate findings that can inform screening and treatment guidelines that may influence how care is delivered to people with OUD and mental health problems?
    • Do applicants adequately leverage research practice partnerships, networks, or other clinical infrastructure? If so, do they demonstrate efficiencies or practice relevance by doing so? If not, have they provided adequate for justification for why?
    • Are sites in areas of high need where OUD and co-occurring mental health disorders are prevalent?  Does the multi-site trial cover large geographic areas where OUD mortality has risen particularly steeply?
    • Are projects equipped to utilize existing health care billing/financing mechanisms whenever possible (e.g., use of CPT codes 99492/99493/99494, formerly G0502/G0503/G0504), and are projects designed to inform how existing mechanisms can be used as part of a sustainable business process, should clinics deliver collaborative care for people with OUDs and mental health problems once the research concludes?
    • Are data capture approaches valid efficient, minimally burdensome to study participants?
    • Is the study designed to differentiate outcomes associated with study participation (e.g., patient completes follow-up assessments as reported in a CONSORT), engagement with broad collaborative care services (e.g., patient is responsive to care manager outreach calls), and individual treatment elements delivered as part of collaborative care (e.g., patient takes buprenorphine as prescribed and attends regular counseling sessions as part of MAT)?
    • Is the design pragmatic such that it can control for and/or minimize the impact of research personnel or procedures on study outcomes?

    Will the selected comparison group(s) allow for meaningful comparisons, given the robust evidence supporting widespread implementation of collaborative care? Will findings be interpretable and inform practice if the outcomes are positive, if outcomes are negative, and if there is heterogeneity in the directionality of outcomes?

    How adequately described is the collaborative care model to be optimized and tested? Are all core elements of the model included and consistent with acceptable practice? These are the 6 required core elements:

    1) A prepared primary care practice (e.g., routine screening for indicated conditions; real-time availability and use of a disease registry for measurement-based care and treat-to-target practices for a panel of patients);

    2) Care management services (in person and/or via telehealth);

    3) A behavioral health consultant with prescription privileges, with collaborative care expertise and with MAT expertise (if the behavioral health consultant does not have the prerequisite MAT expertise, applicants must provide a plan for how that expertise will be obtained and provided to the care team);

    4) Integration of MAT for OUD within the collaborative care model;

    5) Indicated treatment for mental health conditions commonly seen in primary care settings (e.g., depression, anxiety, and/or PTSD); and

    6) Shared patient-provider decision making.

    Is MAT appropriately described (e.g., to include the induction, stabilization, and maintenance phases) and integrated with other elements of collaborative care?

    Does the project specify the patient outcomes that will be the focus of treatment; provide detailed rationale for the choice of outcomes; and describe valid and standardized methods for how those outcomes will be measured?  Are existing validated, standardized instruments of patient outcomes, which are available for many mental disorders and for functioning, utilized?

    How well does the study design address whether the intervention engages the services-oriented change mechanism(s) presumed to underlie the effects of collaborative care (the mechanism(s) that accounts for changes in clinical/ functional outcomes, changes in provider behavior, etc.)? To what extent does the application include (1) a conceptual framework that identifies the presumed mediator(s)/change mechanism(s); (2)  plans for assessing engagement of the target(s)/mechanism(s), including the specific measures, the assessment schedule, and the justification for the assessment strategy ; and (3) an appropriate  analytic strategy a to examine whether the collaborative care engages the presumed target(s)/mechanism(s) and whether collaborative care-induced changes in the mechanism(s) are associated with benefit in the primary endpoints (i.e., mediation)?

    How well does the application answer questions of secondary interest to NIH such as whether treating mental health conditions will improve OUD-related outcomes?

    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?

    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 protections for high risk patients in this research context assessed against an appropriate standard of care that is not artificially high for the target population? Will study procedures to manage risk contaminate care as usual or the intervention(s) being tested? That is, have applicants appropriately balanced the need to protect human subjects with the need to conduct trials that are highly generalizable to the practice settings.

    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? 

    As appropriate, are the plans achievable for establishing necessary agreements with all partners (e.g., single IRB) in a timely manner?

    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.

    Collaboration

    Are sufficient and feasible mechanisms in place to ensure collaboration across sites to achieve scientific integration of research procedures, overall managerial and administrative responsibilities, appropriate quality control and reliability assurance, and planning for data management, analysis and reporting of results? Are there adequate plans for shared decision making among PDs/PIs with regard to personnel, clinical decisions, changes in study protocol, and authorship?

    Is the process for establishing and convening a Steering Committee adequate?

    Study Timelines

    Are milestones achievable and appropriate for the trial?  Are milestones being evaluated regularly?

    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) Data Sharing Plan; (2) Sharing Model Organisms; and (3)  Genomic Data Sharing Plan (GDS).

    Authentication of Key Biological and/or Chemical Resources:

    For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

    Budget and Period of Support

    Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

    Specific to this FOA:

    How likely is it that the plans for cost matching will be adequate?

    2. Review and Selection Process

    Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NIMH, 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:

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

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

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

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

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

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

    Section VI. Award Administration Information
    1. Award Notices

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

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

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

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

    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 of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/ 

    Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the application as well as all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.  Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

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

    Special award condition specific to this FOA: A grantee from a for-profit organization funded under this announcement must match funds or provide documented in-kind contributions at a rate of not less than 50% of the total-Federally awarded amount, as stipulated by Public Law 115-141, the Consolidated Appropriations Act of 2018.  See 45 CFR 75.306 for additional details. Matching funds must be non-Federal funds set aside for this project and are available from the source(s) identified in the application, as committed to by the recipient. Cost matching will be evaluated by the awarding office to ensure that this requirement is being met. Compliance with the matching requirement must be verified on an annual basis and must be documented in the annual and final FFR.

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

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

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

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

    Cooperative Agreement Terms and Conditions of Award

    The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

    The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

    The PD(s)/PI(s) will have the primary responsibility for:

    • Define the details of the project within the guidelines of this FOA.
    • Assume responsibility and accountability to the applicant organization and to NIH for performance and proper conduct of all research in accordance with the Terms and Conditions of Award.
    • Accept close coordination, cooperation, and participation of NIH program staff in the scientific, technical, and administrative management of the grant.
    • Provide milestones and cost for the grant to NIH program staff as requested (usually at the onset of the award and annually thereafter, but also at other times as requested).
    • Chair and coordinate the activities of the Steering Committee. The Chair is responsible for preparing meeting agendas, scheduling and chairing meetings, and preparing concise minutes which will be delivered to Steering Committee members within 2 weeks of the meeting. Virtual meetings are appropriate.
    • Serve as a member of the Steering Committee and fulfill related duties outlined below in Areas of Joint Responsibility; inform the NIMH Program Official of all major interactions with other members of the Steering Committee.
    • Adhere to NIMH policies regarding intellectual property and other policies that might be established during the course of this project activity. Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.
    • A data sharing plan is expected; investigators funded under this FOA are expected to share data via the National Database for Clinical Trials related to Mental Illness (NDCT; http://ndct.nimh.nih.gov/; see NOT-MH-14-015 and  NOT-MH-15-012).
    • The PI will have responsibility for depositing all data collected under this award, including de-identified patient-level data, in the NIMH Data Archive (see NDA; https://data-archive.nimh.nih.gov/), consistent with achieving the goals of the program. All data collected are expected to be deposited into NDA every 12 months, as appropriate and consistent with achieving the goals of the program.
    • Publication or oral presentation of work done under this agreement will require appropriate acknowledgment of NIMH support, including the assigned cooperative agreement award number.
    • Share data and resources according to the data release and resource sharing policies developed for and by this project as appropriate and consistent with achieving the goals of the project.
    • Fully disclose algorithms and software source code and analytic approaches to all site clinics and on a publicly accessible site (e.g., github)
    • Not disclose confidential or protected information obtained from sites or patients.
    • Submit data for quality assessment and/or validation in any manner specified by the Steering Committee and/or the NIMH program staff to ensure scientific rigor.
    • Accept and implement the common guidelines and procedures approved by the Steering Committee and NIMH.
    • Coordinate and collaborate with awardees of this and other HEAL initiatives to improve dissemination of important findings, identify and analyze common data elements (especially for low base rate events) to assist with decision making and improve overall public health impact of this trans-NIH HEAL initiative. 
    • Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

    NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

    • An NIMH Program Official will be responsible for the normal scientific and programmatic stewardship of the award, including programmatic monitoring and assistance in the coordination of the overall project and implementation of the data and research resource sharing plans, and will be named in the award notice.
    • The NIMH Program Official may attend and participate in steering committee meetings as a non-voting member.
    • The NIMH reserves the right to terminate or curtail the clinical trial (or an individual component of the award) in the event of inadequate progress, data reporting, insufficient use of this resource, or safety issues.
    • The NIMH Program Officer will interact with the PD(s)/PI(s) on a regular basis to monitor progress. Monitoring may include: regular communication with the PI and his/her staff, periodic site visits for discussion with the awardee research team, observation of field data collection and management techniques, fiscal reviews, and other relevant stewardship matters.
    • The NIMH Program Officer may also identify additional extramural staff from NIMH and other participating organizations that have appropriate experience and expertise to collaborate with the study team to review study designs and methods, participation in study analyses, and review of scientific reports and articles. 
    • In addition to the Program Official, an NIH Project Scientist(s) may be named to the Steering Committee as a voting member. The role of the NIMH Project Scientist(s) is one of substantial involvement above and beyond the normal program stewardship role of a Program Official. The participation of the Project Scientist(s) is intended to assist the Steering Committee in its efforts to ensure that the broad scientific goals of NIH are reflected in the final design, implementation, and reporting of results of the trial. 
    • The role of the NIH Project Scientist(s) is to assist, participate in deliberations, and facilitate discussion, but not to direct activities. This level of staff involvement does not alter the awardee’s dominant role and prime authority in conducting the activities of the trial. The NIH Project Scientist(s) may cooperate with the awardee as author or co-author of resulting publications in accordance with publication policies developed by the Steering Committee. Publications involving NIH staff must follow NIH publication policies.

    Areas of Joint Responsibility include:

    • A governing Steering Committee will be established to assist in ensuring that the aims of the trial are achieved and milestones are met. The Steering Committee will be composed of the PD(s)/PI(s); key personnel; the NIH Project Scientist(s); senior members of the local treatment team or clinic leadership; and additional members that reflect the diversity of mental health and addiction stakeholders, such as patients and relatives, clinicians, health system administrators, and health care policy makers from local, state, or federal government. Experts in learning health care, measurement-based treatment, health information technology, health informatics, computational modeling, bioethics, and other areas may also be included, as appropriate.
    • Steering Committee members will meet periodically, but not fewer than twice per year, to plan research activities, review study progress, and establish priorities, policies, and procedures. Each member will have one vote in any decision to be made by the Steering Committee with respect to study policies and procedures. The NIH Project Scientist(s) will be a voting member of the Steering Committee. Adoption of policies and procedures will require a majority vote. 
    • NIH Program Officials may attend Steering Committee meetings as non-voting participants.

    Dispute Resolution:

    Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

    3. Reporting

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

    A final Research Performance Progress Report (F-RPPR), invention statement, and the expenditure data portion of the Federal Financial Report, including Federal and non-Federal share for cost matching, are required for closeout of an award, as described in the NIH Grants Policy Statement.

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

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

    Section VII. Agency Contacts

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

    Application Submission Contacts

    eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)
    Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
    Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

    General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
    Email: GrantsInfo@nih.gov (preferred method of contact)
    Telephone: 301-945-7573

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

    Scientific/Research Contact(s)

    Michael C. Freed, Ph.D., EMT-B
    National Institute of Mental Health (NIMH)
    Telephone: 301-443-3747
    Email: michael.freed@nih.gov

    Coryse St. Hillaire-Clarke
    National Institute on Aging (NIA)
    Telephone: 301-496-9350
    Email: sthillaireclacn@mail.nih.gov

    Ivana Grakalic, Ph.D.
    National Institute on Alcohol Abuse and Alcoholism (NIAAA)
    Telephone: 301-443-7600
    Email: ig33z@nih.gov

    Shelly Su, Ph.D.
    National Institute on Drug Abuse (NIDA)
    Telephone: 301-402-3869
    Email: shelley.su@nih.gov

    Martha Matocha, Ph.D.
    National Institute of Nursing Research (NINR)
    Telephone: 301-594-2775
    Email: matocham@mail.nih.gov

    Benyam Hailu, M.D.
    National Institute on Minority Health and Health Disparities (NIMHD)
    Telephone: 301-594-8696
    Email: benyam.hailu@nih.gov

    Wendy Weber, N.D., Ph.D., M.P.H.
    National Center for Complementary and Integrative Health (NCCIH)
    Telephone: 301-402-1272
    Email: weberwj@mail.nih.gov

    Rebecca DelCarmen-Wiggins, Ph.D.
    Office of Research on Women’s Health (ORWH)
    Telephone: 301-451-8689
    Email: rdelcarm@mail.nih.gov

    Peer Review Contact(s)

    David Sommers, Ph.D.
    National Institute of Mental Health (NIMH)
    Telephone: 301-443-7861
    Email: dsommers@mail.nih.gov

    Financial/Grants Management Contact(s)

    Tamara Kees
    National Institute of Mental Health (NIMH)
    Telephone: 301-443- 8811
    Email: tkees@mail.nih.gov

    Jeffrey Ball
    National Institute on Aging (NIA)
    Telephone: 301-402-7732
    Email: ballj@nia.nih.gov

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

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

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

    Priscilla Grant
    National Institute on Minority Health and Health Disparities (NIMHD)
    Telephone: 301-594-8412
    Email: grantp@mail.nih.gov

    Shelley Carow
    National Center for Complementary and Integrative Health (NCCIH)
    Telephone: 301-594-3788
    Email: carows@mail.nih.gov

    Section VIII. Other Information

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

    Authority and Regulations

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

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