Part 1. Overview Information

Key Dates

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

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

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

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

Conformance to all requirements (both in the Application Guide and the NOFO) 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.



Table of Contents
Part 1. Overview Information
Key Dates
Part 2. Full Text of Announcement
Section I. Notice of 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. Notice of Funding Opportunity Description

Background

Among high-income countries, the United States has the highest maternal mortality rate. The maternal health crisis disproportionately affects Black/African American and American Indian/Alaskan Native women. Disparities also exist by age, education, socioeconomic status, and geographic region. Improving maternal health is a national priority as reflected by the White House Blueprint for Addressing the Maternal Health Crisis. The national focus on the maternal health crisis has resulted in several initiatives by the National Institute of Health (NIH). The NIH Implementing a Maternal Health and PRegnancy Outcome Vision for Everyone (IMPROVE) Initiative is one such effort, which was launched in 2019 to support research to address the high rates of pregnancy-related complications (i.e., severe maternal morbidity) and deaths (i.e., maternal mortality) in the United States. The IMPROVE effort is a multipronged initiative designed to build the evidence base of maternal health-related solutions for all women to promote maternal health equity.

The initiative encompasses several integrated components, including the Maternal Health Research Centers of Excellence (CoEs) which utilize innovative approaches to design and conduct research projects in partnership with communities most affected (i.e., populations with health disparities; maternity care deserts) to reduce preventable causes of maternal deaths and improve health for women before, during, and after pregnancy. With support from a Data Innovation and Coordination Hub and the Implementation Science Hub, the research centers share lessons learned, participate in training and research, and disseminate their results. In addition to conducting research projects and building community partnerships, the centers have a robust training and professional development element to grow the maternal health workforce. Although the IMPROVE Maternal Health Centers of Excellence encompass a wide variety of topics and conditions that impact maternal health, complementary and integrative health approaches are not a central feature of the interventions. Complementary and integrative health approaches are widely used by the public, and they are increasingly recognized as a nonpharmacologic approach to symptom management (e.g., chronic pain, mild depression, anxiety). These approaches have been used by individuals to help prevent, treat, or self-manage various conditions before, during, and after pregnancy, and they can be complementary to conventional health care. However, systematic reviews and meta-analyses of these interventions suggest there is a need for more rigorous studies to improve the evidence base of complementary and integrative approaches with physical and/or psychological inputs (often called mind and body interventions) that can inform maternal health clinical practice guidelines.

Although the scientific literature may provide the rationale for conducting an efficacy or effectiveness trial, investigators may lack critical information about key elements needed to plan and conduct such a trial. Some key aspects that may need further investigation to plan the future clinical trial could include refining or adapting the intervention to specific populations, modalities, or settings; assessing the feasibility, acceptability, and adherence to protocolized interventions; finalizing the intervention delivery method, and determining appropriate outcome(s), or recruitment strategies. Early phase clinical trials supported under this notice of funding opportunity (NOFO) can fill this information gap, thereby improving study design and feasibility. That is, this NOFO will support multi-site feasibility trials that can provide valuable information regarding whether the intervention can be delivered with fidelity by multiple providers across multiple sites; determine feasibility of recruitment, randomization, and retention strategies; and test methods for consistent data collection including follow-up data to minimize missing data. It is expected that multi-site feasibility trials funded by this NOFO will allow investigators to collect preliminary data needed to develop future applications for fully powered efficacy and effectiveness trials of mind and body approaches to promote healthy pregnancies and/or improve maternal health.

Research Objectives of the Mind and Body Multi-Site Feasibility Clinical Trial in Maternal Health (R01)

This limited competition NOFO encourages investigators of the IMPROVE Initiative, particularly the Maternal Health Centers of Excellence, to partner with complementary and integrative health investigators to expand current projects and/or propose new pilot projects to test the multi-site feasibility of utilizing complementary and integrative health approaches with physical and/or psychological therapeutic inputs (often called mind and body interventions) to promote healthy pregnancies and/or enhance maternal health outcomes.

Applications submitted under this NOFO are expected to propose a multi-site feasibility clinical trial that will facilitate the design and execution of a future fully powered multi-site clinical trial (see examples below). To justify the need for a multi-site feasibility clinical trial, applicants must reference their own single-site feasibility trial preliminary data or extant published data (see preliminary data requirements below). If previous multi-site feasibility trials have been published, are completed, or underway, then further feasibility research may not be needed. Applications proposing such iterative or duplicative studies will be considered of low programmatic relevance. The application should address any remaining gaps in knowledge that are needed before conducting a fully powered, multi-site efficacy, effectiveness, pragmatic, or dissemination and implementation trial. Investigators should consult the NCCIH website (https://www.nccih.nih.gov/grants/pilot-studies-common-uses-and-misuses) for more information on the uses and misuses of feasibility studies.

For this NOFO, multi-site feasibility clinical trials are defined as trials that enroll research participants from at least two sites that are geographically distinct and non-overlapping with respect to the population of patients engaging with services and are likely to recruit diverse participants. Demonstrating the ability to deliver an intervention with fidelity across sites is critical to demonstrating the ability to later perform a fully powered multi-site efficacy or effectiveness clinical trial. Multiple sites are necessary in efficacy and effectiveness trials to increase the generalizability of the findings, by increasing the size and diversity of eligible participants to enhance recruitment efforts.

Appropriate goals for multi-site feasibility clinical trials proposed in response to this NOFO include but are not limited to:

• Demonstrate feasibility of recruitment rate, randomization, and retention of participants across multiple sites.     
• Assess whether the intervention can be delivered with fidelity across sites, and/or assess whether minor intervention adaptation is useful to enhance adherence, outcome selection, and/or fidelity.
• Demonstrate acceptability and/or adherence to a protocolized multi-component intervention across sites.
• Demonstrate feasibility in measuring outcomes within designated time frames, training interventionists, and delivering the intervention with fidelity across sites.
• Demonstrate participant adherence to the intervention throughout the study across sites.
• Demonstrate consistent collection of clinical data, including follow-up data across sites.
• Assess feasibility of strategies for integrating a mind and body approach into multiple health care systems to inform the execution of future pragmatic or implementation research trials.
• Determine appropriate control/comparison conditions for future large-scale study.

Design Considerations

Investigators should propose a randomized controlled trial design with at least one intervention arm and one comparator arm. There should be strong rationale for the comparator condition (e.g., time and attention control, usual care, standard of care, sham condition, and/or active comparator[s]) based on the research question you plan to address in the future powered trial. Due to lack of rigor and potential expectancy effects, this NOFO will not support studies proposing a wait list comparator condition.

The complementary or integrative approaches with physical and/or psychological therapeutic inputs (often called mind and body interventions) should include one or more of the following:   

• Physical approaches such, but not limited to, as spinal manipulation or mobilization, massage, tai chi, qi gong, yoga, acupuncture;
• Psychological approaches such as, but not limited to, hypnosis, guided imagery, breathing exercises, progressive relaxation, meditation, biofeedback, mindfulness techniques, or music or other art-based therapies;
• Multi-component interventions  that may include the use of natural products such as naturopathic medicine, traditional Chinese medicine, and Ayurvedic medicine, chiropractic care, or a combination of two or more of the specific complementary health approaches (e.g., massage and biofeedback, or yoga and mindfulness); or integrated approaches to care in which a complementary health approach is used in combination with standard care (e.g., mindfulness or yoga as augmentation to conventional medications);
• Multilevel intervention level (patient, caregivers of patient, clinicians, and health care system) where at least one level of intervention includes a mind and body intervention.

Power Recommendations

Pilot or feasibility studies are carried out in preparation for future large-scale, adequately powered studies and therefore should address key issues of process (e.g., recruitment, retention, feasibility, adherence, and/or fidelity) and/or outcomes assessment (e.g., feasibility of the method, frequency, burden, and duration of data collection procedures). Given the limited sample sizes that can be supported under this R01 grant mechanism, proposing to conduct fully powered tests of clinical outcomes (i.e., efficacy) or underpowered tests of outcomes (i.e., "preliminary efficacy") or attempting to utilize the highly variable point estimate of an effect size for future power calculations of a larger scale study would not be appropriate and are noted as nonresponsive below. As pilot and feasibility studies are not designed (or powered) to address efficacy or effectiveness of an approach or intervention, statistical methods should be mainly descriptive. Applicants should use quantitative benchmarks corresponding to each assessment category in determining trial feasibility. Scientific and/or statistical justification should be provided to demonstrate how the sample size is sufficient to make a feasibility/acceptability determination in accordance with proposed benchmarks. Sample sizes used in pilot studies are not formally powered for testing prespecified hypotheses as conventionally expected for confirmatory studies. Sample sizes for subsequent fully powered studies should be based on an achievable, clinically meaningful improvement due to the intervention in the research population with appropriate power calculations. Investigators should consult the NCCIH website (https://www.nccih.nih.gov/grants/pilot-studies-common-uses-and-misuses) for more information on the uses and misuses of feasibility studies.

Group-Based Interventions 

In some cases, investigators who wish to evaluate the effect of an intervention on a health-related biomedical or behavioral outcome may propose a study in which (1) groups or clusters are assigned to study arms, and individual observations are analyzed to evaluate the effect of the intervention, or (2) participants are assigned individually to study arms but receive at least some of their intervention in a real or virtual group or through a shared facilitator. Investigators should provide a strong rationale for the choice among trial design options. The selection of study design should be guided by decisions about how best to deliver the intervention and by concerns regarding contamination and logistics. Applicants should show that their methods are appropriate given their plans for assignment of participants and delivery of interventions. Additional information is available at https://researchmethodsresources.nih.gov/.

Mechanistic Measures 

There are often questions about whether feasibility trials should include mechanistic aims to evaluate how interventions work. Trials submitted under this NOFO should not include aims to assess the impact/efficacy of an intervention on a mechanism of action or evaluate mediation effects. Mechanistic measures may be included in multi-site feasibility trials for the purpose of determining if collecting the mechanistic measure is feasible, which can inform whether mediation or moderation aims should be included in a future large-scale efficacy or effectiveness trial. Applications would need to justify why the mechanistic outcome(s) should be included in the future efficacy or effectiveness trial. The inclusion of mechanistic measures should not introduce a significant burden for participants or utilize a significant portion of the budget.

Preliminary Data About the Intervention: 

This NOFO is appropriate when there is a clear and compelling rationale, a rigorous empirical basis, and a scientific premise to conduct a multi-site feasibility trial. The following preliminary data from previous studies (preferred from published literature, or the team’s previous research) on a similar intervention, patient population, and age group, as proposed in the current application, are required: 

• Demonstration that an intervention similar to the one proposed in the trial is well tolerated (does not produce frequent severe adverse events).
• Pilot single-site feasibility data on a similar intervention in a similar clinical population to the proposed trial (e.g., a proposed study to examine yoga in postpartum women with anxiety may cite pilot work on yoga in a population of pregnant women with depression and anxiety).
• Demonstrated adherence (e.g., cite a pilot study of similar duration with sufficient adherence).
• Demonstrated retention of participants for a similar study duration (e.g., cite a pilot study that retained a sufficient percentage of participants at the primary outcome time point).
• Information to justify the delivery mode, duration, frequency of the intervention (achieve and expected clinical benefit). For example, the intervention could be delivered as a single 30-minute session once a week for 8 weeks, or as self-paced 5-minute modules over 10 weeks. Preliminary data should demonstrate that the selected doses are feasible and likely to have the greatest impact on clinical outcome and minimize the risk of adverse events.

Preliminary Data about the Research Team:

In addition, all the following information demonstrating the research team’s collective experience conducting clinical trials is required:

• Delivered a similar intervention via the same delivery mode in a clinical trial with fidelity.
• Successfully recruited, randomized, and retained similar participants.
• Successfully randomized participants to similar intervention and control conditions.
• Achieved adherence to a similar intervention study protocol by research staff.
• Retained participants for a similar study duration.
• Completed collection of follow-up data with consistency and minimal missing data.
• Published results from previous completed trials.
• For applications studying the feasibility or acceptability of including a natural product as part of a multi-component intervention, the application must provide published data that the formulation of the natural product proposed has demonstrated efficacy for the condition being studied from at least one fully powered placebo-controlled trial.

Timeline

Investigators should propose a realistic timeline for the startup and completion of the clinical trial and provide contingency plans to proactively confront potential delays or disturbances to the planned trial.

Institute and Center Specific Areas of Interest

National Center for Complementary and Integrative Health (NCCIH) 

NCCIH is interested in applications for multi-site feasibility trials that align with the NCCIH Strategic Plan (https://www.nccih.nih.gov/about/strategic-plans-and-reports). Areas of interest include but are not limited to: 

Promotion of health behaviors, health restoration, emotional well-being, or resilience in birthing individuals;

• Prevention or treatment of symptoms and disorders, such as, obesity, sleep disorders or disturbances, depression, anxiety, chronic stress, post-traumatic stress (disorder), and acute and chronic pain conditions in birthing individuals;   
• Whole person health outcomes including multisystem or multilevel outcomes;
• Minority health and reduction of disparities¹ in areas such as pain, obesity, mental and emotional behavioral health, and maternal health;   
• Assessment of multilevel factors, including social and structural determinants of health (https://www.ninr.nih.gov/researchandfunding/nih-sdohrcc), which impact implementation of the mind and body intervention;
• Cultural and contextual adaptations of complementary and integrative health approaches to promote healthy pregnancies and enhance maternal health outcomes;
• Novel continuum care models to implement complementary health approaches in conjunction with conventional care therapies to address risk of maternal morbidity and mortality and enhance maternal health outcomes;
• Utilization of mHealth approaches.  

When evidence justifies, NCCIH encourages applications to conduct studies in a way that assesses the impact of integrating interventions into relevant settings (e.g., health care systems, Federally qualified health centers, military or veteran health care delivery organizations, community organizations, justice systems, or homeless shelters).

All NIH-funded research must adhere to the Code of Federal Regulations, which outlines specific requirements to enhance protections for pregnant women, human fetuses, and neonates; children; and prisoners (https://grants.nih.gov/policy/humansubjects/policies-and-regulations/vulnerable-populations.html). It is the policy of NIH that individuals of all ages, including children (i.e., individuals under the age of 18) and older adults, must be included in all human subjects research, conducted or supported by NIH, unless there are scientific or ethical reasons not to include them (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-18-116.html).   

¹ NIH-designated health disparity populations include racial and ethnic minorities (African Americans/Blacks, Hispanics/Latinos, American Indians/Alaska Natives, Asian Americans, Native Hawaiians, and Other Pacific Islanders), sexual and gender minorities, socioeconomically disadvantaged populations, underserved rural populations, and people with disabilities.

National Institute of Child Health and Human Development (NICHD)

The National Institutes of Health (NIH) launched the IMPROVE initiative in 2019 in response to high rates of pregnancy-related complications and deaths, also called maternal morbidity and mortality, in the United States. The NIH Implementing a Maternal health and PRegnancy Outcomes Vision for Everyone (IMPROVE) Initiative aims to understand the biological, behavioral, environmental, sociocultural, and structural factors that affect pregnancy-related and pregnancy-associated morbidity and mortality and build an evidence base for improved care and outcomes. The initiative supports research to reduce preventable causes of maternal deaths and severe maternal morbidity and improve health for women before, during, and after delivery, particularly for populations disproportionately affected. 

National Institute of mental Health (NIMH)

The National Institute of Mental Health (NIMH) is interested in supporting applications on pilot hybrid effectiveness implementation research focused on the prevention or treatment of maternal mental health disorders (e.g., depression, anxiety, PTSD) and symptoms (e.g., intrusive thoughts, psychosis). The research supported through this RFA is consistent with NIMH’s priorities for: 1) refining and optimizing preventive and therapeutic mental health interventions with previously demonstrated efficacy for use with broader populations or for delivery routine care, community, or online settings, and 2) research on implementation strategies that support the delivery and sustainability of evidence supported preventive and therapeutic interventions for maternal populations in accessible real-world settings.

NIMH encourages a deployment-focused model of intervention design and testing that considers the perspective of relevant end-users and the key characteristics of the intervention setting.  Accordingly, applications to NIMH must propose to pilot a hybrid effectiveness implementation trial design that proposes to simultaneously explore the clinical impact of the intervention and implementation factors or strategies that impact intervention access, engagement, or sustainability. Consistent with the NIMH experimental therapeutics approach, all applications assigned to NIMH must also specify (1) at least one hypothesized mechanism of action for the intervention and/or implementation strategy, (2) measurement plans designed to feasibly assess the mechanism of action and primary mental health outcomes in the intended intervention setting, and (3) an analytic plan designed to explore changes in the mechanism of action and associations between changes in the mechanism of action and the primary outcome(s).

Projects seeking to adapt established evidence-based practices are required to provide an empirical rationale for the adaptation; a clear hypothesis and plan to address the mechanism by which the adapted intervention will enhance maternal mental health outcomes; and evidence to suggest that the adapted intervention will result in a substantial improvement in maternal mental health outcomes and disparities in access to care.

Applicants are strongly encouraged to contact NIMH program officials regarding the match between the potential application and current priorities and policies.

Specific areas of interest for NIMH include but are not limited to:

• Studies that include evidence supported approaches to prevent, treat, or self-manage maternal mental health disorders or symptoms before, during, and after pregnancy, and which may be complementary to conventional health care.
• Adaptations to evidence supported psychosocial interventions that incorporate complementary approaches to address factors related to suboptimal intervention response, cultural fit, intervention engagement, or adherence.
• Innovative approaches that seek to reduce disparities in maternal mental health intervention access, quality, and outcomes for racial and ethnic minority groups, individuals with limited by language or cultural barriers, sexual and gender minorities, individuals living in rural areas, groups that have economically/socially marginalized, and other underserved groups.
• Personalized, modular, or stepped-care approaches for matching evidence supported psychosocial and complementary intervention components of varying intensity to maternal patient preferences or areas of greatest need.
• Interventions that utilize social media and other digital technology to facilitate or augment maternal mental health access and service delivery.
• Patient- and provider-level interventions designed to promote service access, use, engagement, and retention or improve quality or outcomes of care, especially in understudied areas of maternal mental health such as birth trauma and preterm birth.
• Provider-level interventions, such as training and supervision approaches to increase the uptake, fidelity, and sustained use of evidence-based interventions that meet the needs of understudied maternal mental health disorders and symptoms or populations.
• Studies to improve the evidence base of complementary and integrative approaches that can inform clinical practice and guidelines for maternal mental healthcare.

NIMH will not accept assignment of:

• Applications that do not propose to pilot a hybrid effectiveness implementation trial design.
• Applications that propose to test interventions or implementation strategies in research settings rather than routine care, community, school, or online settings and/or propose the use of research therapists or include other features specific to research or academic contexts.
• Applications that do not propose preliminary exploratory evaluations of the mechanism(s) of action and its impact on the primary mental health outcomes, including the following components section of the application: (1) specified mechanism(s) of action; (2) measurement plans designed to assess the mechanism(s) of action and mental health outcomes in the intervention setting; and (3) a description of the analytic plan for exploring whether intervention-induced changes in the mechanism(s) of action are associated with mental health outcomes.
• Applications that propose adaptations of existing interventions without a compelling empirical justification.
• Applications that use patented medications that lack superior efficacy or safety relative to currently available off-patent medications.
• Applications that propose to test health literacy interventions without explicitly examining the impact on service access, engagement, quality and/or mental health outcomes of care.
• Applications that propose to evaluate service level interventions that incorporate multiple implementation strategies to increase access, use, reach, adoption, and implementation of mental health services.

Office of Research on Women's Health (ORWH)

The Office of Research on Women’s Health (ORWH), part of the NIH Office of the Director, collaborates with 27 NIH Institutes and Centers to promote rigorous research focused on women’s health issues. ORWH supports this NOFO as part of the NIH IMPROVE initiative and highlights the importance of interdisciplinary approaches to address research questions effectively. Applications seeking ORWH co-funding in response to this NOFO should ensure that the proposed work is aligned with at least one goal and objective outlined in the NIH-Wide Strategic Plan for Research on the Health of Women 2024-2028

Office of Disease Prevention (ODP)

The ODP is the lead office at the NIH responsible for assessing, facilitating, and stimulating research in disease prevention. In partnership with the 27 NIH Institutes and Centers, the ODP strives to increase the scope, quality, dissemination, and impact of NIH-supported prevention research. The ODP provides co-funding support for research that has strong implications for disease and injury prevention, health equity, and research that includes innovative and appropriate research design, measurements, and analysis methods.  For this opportunity, ODP is interested in co-funding applications, from currently funded investigators of the IMPROVE Initiative, that test the feasibility of mind and body interventions that promote healthy pregnancies and enhance maternal health outcomes. The ODP does not award grants; therefore, applications must be relevant to the objectives of at least one of the participating NIH ICs listed in this announcement. The ODP only accepts co-funding requests from NIH ICs. For questions regarding IC research and/or funding priorities, be sure to contact the relevant IC Scientific/Research Contact(s) named in this NOFO. For additional information about ODP, please refer to the ODP Strategic Plan or visit prevention.nih.gov. 

Types of Clinical Trials Not Responsive to this NOFO:

Applications proposing the following activities will be deemed nonresponsive:

• Studies proposing to analyze data from a feasibility trial to assess efficacy/effectiveness of an intervention or estimate effect size of clinical outcomes (Pilot Studies: Common Uses and Misuses).
• Trials that do not include an aim to assess the multi-site feasibility, acceptability, fidelity, and/or adherence to the intervention.
• Studies to assess the initial feasibility of a mind and body complementary or integrative health approach (i.e., feasibility should have already been demonstrated in at least a single site), or those proposing substantial adaptations to an existing intervention.
• Studies that do not include a mind-body intervention.
• Studies that propose a waitlist control.
• Studies that are geographically limited (e.g., recruiting from one city or region).
• Studies that do not propose to enhance maternal health outcomes and improve health for women before, during, and after pregnancy.

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

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Eligibility is limited to currently funded IMPROVE investigators and their partners. Specifically, the eligible funded recipients include:

• The Maternal Health Centers of Excellence (RFA-HD-23-035): The Maternal American Indian Rural Community Health (MARCH) Center of Excellence at Avera McKennan Hospital, Community-Hospital-Academic Health Equity Partnerships (NY-CHAMP), Mississippi Delta Center of Excellence in Maternal Health, Addressing Key Social-Structural Risk Factors for Racial Disparities in Maternal Morbidity in Southeastern Wisconsin (ASCEND WI), Maternal Health Multilevel Interventions for Racial Equity (MIRACLE), Center to Advance Reproductive Justice and Behavioral Health among Black Pregnant/Postpartum Women and Birthing People (CORAL), University of Illinois at Chicago (UIC) Maternal Health Research Center of Excellence, Center for Indigenous Resilience, Culture, and Maternal Health Equity (CIRCLE), Equity in Maternal and Birthing Outcomes and Reproductive HeAlth through Community Engagement (EMBRACE), ELEVATE maternal Health Center of Excellence, Preventing Inequalities in Hemorrhage-related Severe Maternal Morbidity (PRIHSM), Southern Center for Maternal Health Equity
• Maternal Health Research Centers of Excellence Data Innovation and Coordinating Hub/Resource center (RFA-HD-23-036): Johns Hopkins University Maternal Health Data Innovation and Coordination Hub
• Maternal Health Research Centers of Excellence Implementation Science Hub/Resource Center (RFA-HD-23-037): Achieving Maternal Equity and Transforming Health through Implementation Science and Training Implementation Science Hub (AMETHIST @ PENN)
• IMPROVE Community Implementation Program (OTA-20-014-C): Arizona State University, Texas Tech University Health Sciences Center, Thomas Jefferson University, University of Nebraska Medical Center
• Understanding the Impact of Healthcare System and Clinician Factors on Disparities in Maternal Morbidity and Mortality (PAR-24-059): RAND Corporation, Northwestern University at Chicago
• Career Enhancement Award to Advance the Study of Intimate Partner Violence (IPV) in the Context of Maternal Morbidity and Mortality Reseach (RFA-OD-24-001)
• Short Courses on Techniques for Measuring Intimate Partner Violence (IPV) in Different Populations (RFA-OD-24-002): Johns Hopkins University, University of North Carolina Chapel Hill, Emory University
• Rapid Acceleration of Diagnostics Technology (RADx^® Tech) for Maternal Health Challenge: Cardiex, Caretaker Medical, HemoSonics, Global Access Diagnostics, Sanguina, Sibel Health, MyLÚA Health, PyrAmes
• Connecting the Community for Maternal Health Challenge: Nurturely of Eugene, Oregon; Central Jersey Family Health Consortium of North Brunswick New Jersey; The Abundance Project, Colorado; Atlanta Birth Center, Georgia; Buffalo Prenatal Perinatal Network, Inc, New York; Claris Health, California; Doula CO-OP of Reno, Nevada; HealthConnect One, Illinois.

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

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

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

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply- 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

• System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

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

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

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for 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 How to Apply-Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility

Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Eligibility is limited to investigators supported by the IMPROVE Initiative, the Maternal Health Centers of Excellence (RFA-HD-23-035).

Applications with Foreign components are encouraged to read NCCIH International Health Research page. Foreign components can include foreign collaborators or consultants, but should not include foreign sites outside of the U.S. or Canada, according to NCCIH’s policy

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 NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity 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:

Jessica McKlveen, PhD
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-8018
Email: jessica.mcklveen@nih.gov

Page Limitations

All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply- Application Guide must be followed.

Biographical Sketches: Document the PD/PI’s experience in leading clinical trials and expertise in the content area of the trial (e.g., intervention, study population, research methods). Even feasibility clinical trials will require a multidisciplinary team (e.g., clinician, biostatistician, data manager, study coordinator), and the application should reflect their hands-on involvement in the design and implementation of the study protocol. Applicants are encouraged to provide strong evidence of the study team's qualifications and ability to conduct the proposed as well as future research, experience as investigative team members, and previous investigative experience in related clinical trials.

We strongly encourage that all clinical trials include a biostatistician as part of the key personnel, and the application should reflect their hands-on involvement in the design and implementation of the study protocol. Applicants are encouraged to provide strong evidence of the study team’s qualifications and ability to conduct the proposed as well as future research and previous investigative experience in related clinical trials.

R&R or Modular Budget

All instructions in the How to Apply- Application Guide must be followed.

The budget for the first year of the grant should reflect the time needed for trial startup.

Applicants must propose no more than $350,000 direct costs per year for up to 3 years of support. The budget for the number of participants included in the trial should be based on the number of participants needed to demonstrate feasibility outcomes, not on the power for assessing efficacy on a clinical outcome, which will not be supported by this NOFO. 

If parts of the costs of the trial are to be provided by sources other than NIH, these contributions must be presented in detail in the budget justification. Include budget support for the publication and dissemination of findings. Applicants should budget for the services of appropriate safety monitoring, e.g. Medical Safety Monitor, Independent Medical Monitor, or Safety Monitoring Committee, as indicated (see https://www.nccih.nih.gov/grants/policies/data-and-safety-monitoring-of-nccihfunded-clinical-research).

R&R Subaward Budget

All instructions in the How to Apply-Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the How to Apply- Application Guide must be followed.

PHS 398 Research Plan

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions:

Research Strategy 

The research strategy should be organized in a manner that will facilitate peer review. The body of the application should present a concise overview of the state of the science, the current status and relevance of the trial, a discussion of the specific protocol, and the approach to data collection, analysis, and dissemination. 

The following criteria should be addressed: 

Importance of the Research: The significance of the proposed future efficacy or effectiveness clinical trial and importance of the question must be clearly stated. It is particularly important to include a discussion of how the future trial will test the proposed hypotheses and how or why there is clinical equipoise. The application should clearly state the need for and timeliness of both the future trial and the proposed multi-site feasibility trial, emphasizing how the results will address an evidence gap and therefore advance knowledge of theory and practice in this area. A discussion of the costs and benefits of the future trials should be included for evaluation of the trial's significance. 

The importance of the proposed multi-site feasibility trial should be described and why it is scientifically necessary to plan the subsequent future trial. Discuss how the proposed trial will test the multi-site feasibility hypothesis and how the results of the trial (positive or negative) will guide decisions about whether a subsequent study is feasible, and/or evidence that additional studies must be completed before proceeding to the full-scale trial. Applications should address the reasons for selection of the intervention. This may include public health impact if subsequent efficacy trials are conducted and achieve positive results, ethical dimensions, and patient perspectives on acceptability of the proposed intervention. Characteristics of any preliminary research results provided in support of the proposed project, whether conducted by the applicant or others, should be described in the application so peer reviewers may evaluate the strength of the supporting evidence. The applicant should also discuss the limitations of those data.  

Explain how the application challenges and seeks to shift current research or clinical practice paradigms or guidelines. 

Rigor and Feasibility: This section should include a description of the supporting data, clinical trial experience, and experimental approach.  

Supporting data: The studies that led to the proposed clinical trial should be presented. Data from pilot studies conducted by the team or published in the literature that show the need for and feasibility of the trial should also be presented. Additional supporting data from other research should be included so the approach chosen is clearly justified and adequately framed. Applications must include the following preliminary data from human studies (preferably published in the literature) using a similar intervention in a similar population to the one proposed in the current study: 

All of the following preliminary data about the intervention (from published literature or the team’s previous research): 

• Demonstration that a similar intervention to the one proposed in the trial is well tolerated (does not produce frequent severe adverse events) in pilot human studies.
• Single-site feasibility data on a similar intervention in a maternal patient population similar to the one that will be studied in the proposed trial (e.g., a proposed study to examine vinyasa yoga in adults with anxiety may cite pilot work on hatha yoga in a population of adults with depression and anxiety).
• Demonstrated adherence (e.g., cite a pilot study of a similar duration with sufficient adherence).
• Demonstrated retention of participants for a similar study duration (e.g., cite a pilot study that retained a sufficient percentage of participants at the primary outcome time point).
• Information to justify the selection of how the intervention is delivered (e.g., format of delivery, duration of individual intervention, frequency of delivery, and timeline of intervention delivery to achieve clinical benefit) in the study. For example, the intervention could be delivered as a single 30-minute session once a week for 8 weeks, or as self-paced 5-minute modules over 10 weeks. Preliminary data should demonstrate that the selected doses are feasible and likely to have the greatest impact on clinical outcome and minimize the risk of adverse events. 

All of the following preliminary data demonstrating the collective team’s experience conducting clinical trials: 

• Delivered a similar intervention via the same delivery mode in a single site clinical trial with fidelity.
• Successfully recruited and accrued similar participants.
• Successfully randomized participants to similar intervention and control conditions.
• Achieved adherence to a similar intervention study protocol by research staff.
• Retained participants for a similar study duration.
• Completed collection of follow-up data with consistency and minimal missing data.
• Published results from previous completed trials.
• A description of why the target population is an appropriate group for addressing the proposed hypotheses and how or if results can be generalized to a broader population.
• A description of the mind and body or multi-component intervention to be tested, including elements of the intervention, proposed methods for assessing fidelity of intervention delivery and intervention performance, time duration of delivery (for clinician-provided interventions) or participant practice (for group or individual/home settings), and frequency of delivery or practice.
• A description of the required training and/or licensure/credentialing of individuals providing the intervention across proposed site(s) if necessary.
• A description and justification for assessments, including clinical, laboratory, physiological, behavioral, patient-centered, or other outcomes.
• Use of patient-reported outcomes, including those available through the Patient-Reported Outcomes Measurement Information System (PROMIS), NIH Toolbox, and Quality of Life in Neurological Disorders (NeuroQoL), as well as nontraditional data collection approaches (e.g., telephone, mobile devices, or web-based systems) need to be described. A description of the laboratory evaluations (as appropriate) and plans to implement and monitor Good Clinical Practices (GCP), Good Laboratory Practices (GLP), and Good Manufacturing Practices (GMP), as appropriate, should be provided.
• Investigators should utilize instruments validated in multiple languages representing the diversity of their participant population.
• A description of the commitment to engagement of the clinical community that will play a critical role in the recruitment, retention, and overall conduct of the clinical trial, including how this clinical trial will be prioritized in the context of other overlapping clinical research.
• Discussion of potential challenges expected in implementing the trial and how these might be overcome.
• A timeline, which could be provided as a table or graph, for reaching important study milestones such as: (a) obtaining regulatory approval of the final protocol, (b) establishing agreements with participating partners, if relevant, (c) finalizing the study procedures and training participating clinical site staff, and (d) starting enrollment and completing all subject follow-up and data collection activities.
• A description of the strategy for timely publication and dissemination of results.
• Description of a future clinical trial: a concise summary of the proposed subsequent fully powered trial, including the study design (efficacy, effectiveness, or pragmatic) and how the proposed multi-site feasibility study will inform the design of that trial.
• Investigators should check https://reporter.nih.gov/ and https://clinicaltrials.gov/ to provide justification that the work proposed is not duplicative of completed or ongoing trials. Applicants should not propose work that duplicates other feasibility studies already funded or other trials that are underway using a similar intervention in a similar population.
• For applications that propose the use of an app or clinical decision support software, applicants must consult with their Institutional Review Board to determine whether the approach may qualify as a medical device. If so, or if in doubt, applicants should contact the U.S. Food and Drug Administration (FDA) prior to applying to determine whether an Investigational Device Exemption (IDE) application is necessary for the proposed clinical research (https://www.fda.gov/medical-devices/software-medical-device-samd/your-clinical-decision-support-software-it-medical-device).

Letters of Support:

Letters of support from clinicians or clinical department chairs whose support is necessary to the successful conduct of the trial should be provided from all participating sites or community organizations. Applicants are also encouraged to include documentation of the commitment of any subcontractors and consultants, as well as service agreements for personnel or facilities. Letters of commitment must be co-signed by the business official of the collaborating center.

If parts of the costs of the trial are to be provided by sources other than NCCIH, provide letter(s) of support signed by an authorized representative.

Specific to this NOFO: In addition, if utilizing a natural product as part of a multi-component intervention, a letter of support should document that sufficient supply of the natural product will be available for testing at the time of award, including expiration date; the supplier will meet CMC specifications; and the supplier will provide the data necessary for the investigator to adhere to NIH policies and FDA regulations. Documentation should include a letter of agreement from the third party supplying the natural product. 

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide.

Other Plan(s): 

All instructions in the How to Apply-Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply- Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- 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 How to Apply- Application Guide must be followed.

Section 2 - Study Population Characteristics

2.5 Recruitment and Retention Plan

Describe the following: (1) planned remote recruitment methods, including use of contact lists, databases, other pre-screening resources, advertisements, outreach, media/social media, and referral networks or groups; (2) any known (based on literature or prior experience) participant or study-related barriers to accrual or participation (list the barriers and describe plans to address them to optimize success); (3) contingency plans for participant accrual if enrollment significantly lags behind accrual benchmarks; (4) participant retention and adherence strategies; and (5) possible competition from other trials for study participants. Investigators are encouraged to review NCCIH Policy: Study Accrual and Retention for Human Subject Research (https://www.nccih.nih.gov/grants/policies/nccih-policy-study-accrual-and-retention-for-human-subject-research).

Applicants must provide strong evidence of the availability of appropriate institutional resources and suitable patient populations. Documentation of the availability of eligible participants must be provided. The application must provide relevant information that addresses the feasibility of recruiting a diverse sample of eligible participants to demonstrate feasibility of meeting the NIH requirements for a representative sample in the future fully powered efficacy or effectiveness trial. 

Section 3 - Protection and Monitoring Plans

3.3 Data and Safety Monitoring Plan

In addition to the NIH application requirements for data and safety monitoring for clinical trials, NCCIH requires independent monitoring for research involving human subjects. Applicants should refer to NIH’s policy on data and safety monitoring (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html), as well as the NCCIH's Guidelines for Data and Safety Monitoring (https://www.nccih.nih.gov/grants/policies/data-and-safety-monitoring-of-nccihfunded-clinical-research). The data and safety monitoring plan must explicitly describe plans to remotely monitor participant safety with appropriate safeguards to minimize risk. The Independent Monitoring Committee (IMC) or Data and Safety Monitoring Board (DSMB) will have the responsibility to review interim and final data, recommend whether the protocol should be modified, and, at each meeting, recommend whether the study should continue or be terminated early. Thus, its ethical responsibilities to the participants, as well as to the integrity of the study, are of paramount importance to NCCIH. The IMC/DSMB will meet in person or by phone at least twice a year. To avoid conflicts of interest in peer review, applicants should not appoint IMC/DSMB members in advance of peer review, or even inquire about possible DSMB members.

Section 4 - Protocol Synopsis

4.5. Will the study use an FDA-regulated intervention?

4.5.a. If yes, describe the availability of Investigational Product (IP) and Investigational New Drug (IND)/Investigational Device Exemption (IDE) status.

If the proposed clinical trial will use a device, natural product (e.g.,botanicals, probiotics, and products marketed as dietary supplement), or drug, this attachment should describe correspondence from the FDA indicating whether the proposed study will require an IND or IDE application. Investigators should describe the process and the associated timeline that will be used to attain all FDA or other applicable regulatory agency approvals necessary to the conduct of the trial. For trials using an FDA-regulated product that requires an IND or IDE application, the grant application must include evidence regarding the outcome of a pre-IND meeting, or other evidence of communication with the FDA. If the protocol is being conducted under a non-U.S. regulatory agency, the applicant should submit a plan for attaining those regulatory approvals. If the protocol is exempt from an IND or IDE, a copy of the exemption letter from the FDA should be provided as part of the PDF file attachment. The FDA has provided guidance indicating that for substances that are Generally Recognized as Safe (GRAS) that are used in a clinical trial to evaluate the product's ability to diagnose, cure, mitigate, treat, or prevent disease, it may require an IND under part 312 (https://www.fda.gov/media/79386/download). If the FDA requires an IND application for the proposed clinical trial, the IND application must be submitted to the FDA, with no clinical hold imposed by the FDA before the application is funded.

Section 5 - Other Clinical Trial-Related Attachments

5.1 Other Clinical Trial-Related Attachments

The following attachments must be included as part of the application. Attachments permit expansion of certain elements that cannot be appropriately described in the research strategy section. All attachments listed below must be provided or the application will not be peer reviewed.

1. Clinical Trial Experience

Applicants must provide a detailed table listing the characteristics of trials that demonstrate key personnel experience in trial coordination in the past 5 years. One table must be provided for each study record, with a unique filename for each study record as an attachment (e.g., “Clinical Trial Experience1.pdf”" “Clinical Trial Experience 2.pdf”" etc.) and must not exceed three pages.

The table columns should include:

• Clinical trial title
• Applicant's role in the trial
• A brief description of the trial design
• Planned enrollment
• Actual enrollment
• Number of sites
• Whether the trial was completed on schedule
• Publication reference(s)

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 How to Apply- Application Guide must be followed.

PHS Assignment Request Form

All instructions in the How to Apply- Application Guide must be followed.

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

See Part 2. 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. 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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 How to Apply-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 Section 7.9.1 Selected Items of Cost.

For trials using an FDA regulated product and requiring an IND application, the applicant must either hold or be able to reference an open IND for the trial, or the applicant must obtain an IND with no clinical-hold from the FDA prior to any award. The details of the IND status of the natural product should be provided in the attachment included in the study record for section 4.5. If the FDA has granted a waiver for either trial proposed in the application, then the applicant can provide this letter as part of the response to item 4.5 in the study record. If the protocol is conducted under a non-US regulatory agency, then equivalent determinations and documentation must be provided to NCCIH prior to a grant award. Funding will not be made until the necessary regulatory approvals are in place for the conduct of the proposed clinical trial. If the product to be studied is on the Drug Enforcement Agency (DEA) controlled substance list, the applicant must describe the DEA license and registrations necessary to complete the proposed trial. Again, no awards will be made until all necessary DEA licenses and registrations are in place.   

Applications must be submitted electronically following the instructions described in the How to Apply - 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 form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply - 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 NCCIH, 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 NCCIH Referral Office by email at jessica.mcklveen@nih.gov when the application has been submitted. Please include the FON and title, PD/PI name, and title of the application.

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at grantdisclosures@oig.hhs.gov.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy

In addition to the NIH policy allowed post-submission materials in NOT-OD-19-083, the following post-submission materials are allowed:

• Revised Clinical Trial Experience Table (e.g., due to updated enrollment numbers, publication of trial results, or newly started clinical trials).
• Revised information about FDA-regulated interventions (updates to IND or IDE status or communications with the FDA) as described in Section 4.

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.

For this particular announcement, note the following:

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.

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 scored review criteria and additional review criteria (as applicable for the project proposed).  An application does not need to be strong in all categories to be judged likely to have a major scientific impact.

Reviewers will consider Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate factor score. 

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

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.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NCCIH, in accordance with NIH peer review policies and practices, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

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

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

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

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 NOFO. 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, consistent with applicable law.

• 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.

Please note that reviewers will not consider race, ethnicity, age, or sex of a researcher, award participant, or trainee, even in part, in providing critiques, scores, or funding recommendations. NIH will not consider such factors in making its funding decisions.

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 Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov. NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

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 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

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

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

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

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

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

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

2. Administrative and National Policy Requirements

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website.
  • HHS recognizes that NIH 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 NOFO.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations.  NIH may terminate awards under certain circumstances.  See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support. 

Successful recipients under this NOFO agree that:

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by any funded entity, recipients and subrecipient(s) are required to: Use health IT that meets standards and implementation specifications adopted in 45 CFR part 170, Subpart B, if such standards and implementation specifications can support the activity.  Visit https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-D/part-170/subpart-B to learn more.

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by eligible clinicians in ambulatory settings, or hospitals, eligible under Sections 4101, 4102, and 4201 of the HITECH Act, use health IT certified under the ONC Health IT Certification Program if certified technology can support the activity. Visit https://www.healthit.gov/topic/certification-ehrs/certification-health-it to learn more.

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

1. ongoing and consistent access to HHS owned or operated information or operational technology systems; and 
2. receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Recipients shall develop plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data. Please refer to NIH Post-Award Monitoring and Reporting for additional information. 

Not Applicable

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

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

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

Finding Help Online: https://www.era.nih.gov/need-help (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: 301-480-7075

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

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

Elizabeth L. Neilson, PhD, MPH, MSN
Office of Disease Prevention (ODP)
Phone: 301-827-5578
Email: Elizabeth.Neilson@nih.gov  

Nahida Chakhtoura, MD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6872
Email: nahida.chakhtoura@nih.gov 

Elena Gorodetsky, M.D., Ph.D.
ORWH - Office of Research on Women's Health
Phone: (301) 594-9004
E-mail: egorod@mail.nih.gov

Tamara Lewis Johnson, MPH, MBA
National Institute of Mental Health (NIMH)
Telephone: (301) 594-7963
Email: tamara.lewisjohnson@nih.gov

Jessica McKlveen, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-594-8018
Email: jessica.mcklveen@nih.gov

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

Margaret Young
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-642-4552
Email: margaret.young@nih.gov

Rita Sisco
National Institute of Mental Health (NIMH)
Telephone: 301-443-2805
Email:siscor@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.

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 2 CFR Part 200.