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.

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

This funding opportunity announcement (FOA) is being issued by the NIH Adherence Network through the Office of Behavioral and Social Sciences Research (OBSSR) with participation from multiple NIH Institutes and Centers. This FOA calls for research grant applications which address patient adherence to treatment and prevention regimens in healthcare to promote health outcomes. This FOA accepts applications that either propose or do not propose a clinical trial(s).

This FOA encourages Exploratory/Developmental Research Project Grant (R21) applications for research and development of interventions to significantly improve adherence in individuals. These studies should break new ground or extend previous discoveries toward new directions or applications. For example, such projects could assess the feasibility of a novel area of adherence investigation, a new approach that could enhance health-related adherence research, or innovative use of an existing methodology to explore a new scientific area of adherence.

Applications under this FOA are encouraged, but not required, to apply approaches and tools developed under the NIH Common Fund’s Science of Behavior Change (SOBC) Program. These include: use-inspired basic research on mechanisms of change at multiple levels of analysis; assays for self-regulation, interpersonal processes and stress that have evidence as malleable targets for behavior change (see https://osf.io/zp7b4) developed under the SOBC program; and an experimental medicine approach which requires a clear a priori specification of the intended mechanistic target(s) of an intervention, and methods that test the degree to which an experimental manipulation or intervention engages those targets. For more information about the SOBC program, please see: https://commonfund.nih.gov/behaviorchange.

Increased patient adherence to recommended treatment and prevention regimens is an area of the behavioral and social sciences that promises substantial improvements in public health as well as savings in healthcare costs. For these reasons, improving adherence has been identified by the National Institutes of Health (NIH) Adherence Research Network as a top priority.

Poor adherence to healthcare regimens is common across many chronic illnesses and patient populations. This includes adherence to prescribed medications and other recommended prevention, screening, treatment, monitoring, and health behavior regimens. Research across many chronic illness areas has identified sub-optimal adherence to oral medications and even lower adherence to diet and exercise recommendations. Continued evidence of non-adherence in many chronic conditions and insufficient evidence for how to improve adherence highlights the need for transformative research in this area.

Adherence is increasingly understood as a multifaceted concept. First, adherence to a specific health care behavior (e.g., taking a medicine, deciding to follow a diet, or making dietary changes) can involve three dimensions: initiation (i.e., starting the regimen), implementation (i.e., executing the schedule), and persistence (i.e., length of time on regimen before discontinuation). Each dimension of adherence may have unique determinants, and each may require distinct behavioral and social interventions. Second, many recommended treatment and prevention regimens involve multiple health behaviors. For example, recommended treatment for Type 2 diabetes may include monitoring glucose, adjusting diet, increasing activity, and taking medicines to maintain health and quality of life. Third, many individuals experience multiple comorbid conditions which may require different and concurrent courses of therapy, or present unique cognitive, emotional, or social challenges that can interfere with adherence. Adherence may vary across different health behaviors, complex regimens, and comorbid conditions.

Adherence behavior is also dynamic with the potential to change over time. Some health care professionals and researchers may view adherence as a stable and dichotomous property of individuals; i.e., "there are adherent patients, and there are non-adherent patients." This misses how adherence in chronic conditions may vary in response to disease activity, treatment methods, and the course of psychosocial or illness comorbidities. The dynamic nature of adherence underscores the need to improve routine monitoring of individual’s adherence to recommended healthcare regimens, and to re-examine or develop new interventions to support adherence over the course of care. Further, as more individuals live with long-term chronic conditions, adherence may be predicated on the complex interaction of the persons health needs and developmental factors.

Determinants of adherence and non-adherence span a broad ecologic spectrum. They may be influenced by the nature of the condition; the complexity of the regimen and concomitant treatments; individual factors such as sociodemographic characteristics, comorbidities, cognitive functioning, mental health status, health literacy, self-efficacy and motivation for self-management; aspects of the person-provider relationship; social and factors such as an individual’s access to social support, relationships and gender dynamics, and culture; and successively larger structural influences, including factors related to health economics (medication cost, insurance coverage, access to transportation, and cost-sharing) and the characteristics of health care organizations and healthcare delivery approaches. These multilevel adherence determinants invite a range of interventions that target individuals, families, caregivers, health-care providers, communities, and/or healthcare system delivery methods. They also invite careful consideration and assessment of the mechanisms of action in adherence intervention research.

New developments and innovations provide fresh opportunities to advance adherence research with the potential for real impact. Advances in mobile health (mHealth) technologies and informatics provide opportunities to monitor recommended healthcare regimen adherence, to improve measurement precision, and to deliver individualized interventions that are timely, tailored, and interactive. Attention to patient-centered care and shared decision-making models that include the person, family, and caregiver as part of the care team further broadens targets for improving adherence. Differentiated care models suggest matching individuals to different forms of adherence support based on demonstrated need. Growing attention to health behavioral economic approaches suggest new ways to "nudge" behavior in helpful directions. Additionally, healthcare coverage models that are designed to incentivize the delivery of high-quality and cost-efficient care are becoming increasingly common.

Regardless of focus or approach, the next generation of adherence research will benefit from improved scientific rigor. Future studies should clearly define adherence, address intervention mechanisms of action, and compliment self-reported measures with objective assessment of behavior. A Cochrane review of randomized controlled trials of medication adherence interventions in 2014 found many trials were compromised by low statistical power and/or biases resulting from use of self-reported adherence measures when trial participants were not blinded to treatment allocation. The adherence intervention evidence base will therefore require improved rigor and reporting: well-powered trials with appropriate sample sizes that employ and describe objective measures, centralized randomization procedures, and blinded outcome assessors. Randomized trials of interventions can target enrollment to individuals with prior adherence problems to help avoid ceiling effects. Adherence research may also benefit from novel research designs, including sequential randomized designs.

Non-adherence to medical regimens exemplifies the challenges in initiating and sustaining healthful behavior change. Researchers are beginning to make progress in understanding some of the basic mechanisms that account for less-than-optimal initiation and maintenance of behavior change. Applications under this FOA are encouraged, but not required, to apply approaches and tools developed under the NIH Common Fund’s Science of Behavior Change (SOBC) Program. These include: use-inspired basic research on mechanisms of change at multiple levels of analysis; assays for self-regulation, interpersonal processes and stress that have evidence as malleable targets for behavior change (see https://osf.io/zp7b4) developed under the SOBC program; and an experimental medicine approach which requires a clear a priori specification of the intended mechanistic target(s) of an intervention, and methods that test the degree to which an experimental manipulation or intervention engages those targets.

Adherence is pivotal to healthcare regimen effectiveness and can make important contributions to health outcomes. Research that pairs measures of adherence behaviors and social determinants of health with clinical outcomes will help advance the science. Research that demonstrates health benefits and cost-effectiveness of adherence interventions, and that reflects the priorities and considerations of real-world stakeholders (persons with the condition/illness; health care providers, care systems, etc.) can additionally promote intervention dissemination and implementation.

This FOA calls for research applications that address individual adherence to recommended treatment and prevention regimens to promote health, health outcomes, and quality of life. Many NIH Institutes, Centers and Offices have joined together to support this initiative. Applications should be relevant to both the general objectives of the FOA and to the specific research interests of at least one participating Institute or Center. Brief descriptions of the specific interests of the Institutes and Centers follow the cross-cutting list provided below.

Potential study topics and intervention approaches may include, but are not limited to:

• Research to develop novel tools or modify existing approaches to monitor adherence and facilitate delivery of targeted interventions to improve adherence
• Research testing innovative approaches for monitoring and maintaining individual or caregiver adherence to complex health care regimens
• Research to target groups at high risk for non-adherence such as adolescents/young adults and individuals with cognitive impairment, complex illnesses and health regimens, mental health comorbidities, and/or substance abuse
• Studies of adherence-promoting interventions that are delivered through technological tools, such as mobile health technologies and electronic health records, to target health care provider behaviors, patient behaviors, both, and/or provider-patient interactions and feedback
• Research examining interventions designed to optimize adherence through caregivers, peers, or social support networks
• Research to examine the role of shared decision making on adherence
• Research testing the efficacy of interventions at the health care system level that target, for example, health care provider practices (i.e., decision tools, access to resources such as medication plans, electronic medical record practices) as facilitators of patient adherence
• Research to address social and structural determinants of health contributing to racial and ethnic disparities in adherence and associated health outcomes
• Interventions that test multi-level and multi-component interventions (e.g., at the individual, health care provider, and community level) to improve adherence behavior
• Studies that identify competing behaviors, psychosocial concerns, and/or social issues that contribute to non-adherence and associated changes in health outcomes, to inform future interventions and science

Descriptions of the specific interests of the Institutes and Centers follow.

• The National Cancer Institute (NCI) seeks multi-level research from across the translational science continuum aimed at improving adherence to treatment and prevention regimens to reduce cancer risk, improve treatment outcomes, and lower cancer-related morbidity, mortality, and disability. Additional information about priority areas of research are described by the NCI s Division of Cancer Control and Population Sciences.
• The National Institute on Aging (NIA) seeks research on interventions to promote adherence to medical and behavioral regimens aimed at promoting healthy aging in Stages I through IV of the translational intervention development pipeline, as defined by the NIH Stage Model. NIA applications under this FOA are expected to articulate their research aims using the NIH Stage Model framework, identifying the Stage(s) of research proposed. In addition, applications are encouraged to apply the experimental medicine approach, i.e. articulate or test a hypothesis to identify an intervention’s principles/mechanism(s) of action, as described by SOBC. Areas of interest include those that leverage current understanding of psychology of aging or of behavioral and social contexts relevant to aging to promote adherence to exercise, healthful eating, prescribed medications, stress-reducing and/or positive affect inducing behaviors, and medical regimens. Of particular interest is the development of scalable principle-driven interventions that are highly relevant to the needs and capacities of individuals as they age and interventions that incorporate behavioral economic principles and/or technological innovations.
• The National Institute on Alcohol Abuse and Alcoholism (NIAAA) is interested in supporting alcohol prevention research focused on incentives, barriers and disincentives to adherence to health promoting and harm reduction behaviors targeting multiple levels, including family-based, community-based, health care systems and other environmental-level policy-based interventions. NIAAA is also interested in alcohol treatment research focused on understanding the mechanisms that underlie adherence to engaging in and maintenance of behavior change within our empirically-supported alcohol behavioral treatments that target heavy and problematic alcohol use.
• The National Institute of Allergies and Infectious Disease (NIAID) is interested in supporting programs that support the development of biomedical measures to improve adherence to ART, PrEP, and other HIV prevention interventions and strategies. NIAID is also interested in supporting basic and applied research in the behavioral and social sciences to inform the development of novel interventions that enable all HIV infected individuals to achieve durable viral suppression. With implementers, develop and pilot enhanced adherence interventions with demonstrated effectiveness.
• The National Institute on Drug Abuse (NIDA) is interested in research on the development of optimal behavioral strategies to promote adherence to medications and substance use disorder (SUD) treatment. Applications are encouraged for studies that include, but are not limited to: improvements in drug abuse treatment adherence interventions for use in primary care; technologies to boost effects and increase efficiency of adherence interventions, and; interventions to promote adherence to HIV medications.
• The National Institute of Mental Health (NIMH) has interest in adherence research in the context of mental health as well as HIV/AIDS. NIMH is interested in research on adherence interventions that support the NIMH Strategic Plan for Research. All applications that propose clinical trials to test adherence strategies are encouraged to follow the NIMH’s experimental therapeutics approach to intervention development and testing (see NIMH Clinical Trials FOAs). Examples of relevant research projects include but are not limited to the following: Adherence interventions capitalizing on innovations in technology, consistent with the NAMHC workgroup on technology report, Opportunities and Challenges of Developing Information Technologies on Behavioral and Social Science Clinical Research; applications that use existing patient-level data, such as electronic medical records and prescription refill data, to support adherence; adherence approaches to reduce empirically documented disparities in care and outcomes for racial and ethnic minorities and other underserved groups; adherence interventions that support shared decision making and patient engagement; adherence strategies that fit seamlessly into existing clinical practice; and strategies to support use of HIV/AIDS antiretroviral treatment and pre-exposure prophylaxis.
• The National Institute on Nursing Research (NINR) is seeking research on patient-focused adherence strategies to engage individuals, caregivers and families and communities as active participants in self-management and wellness to improve quality of life while living with an acute or chronic condition or multiple conditions.
• The National Institute of Minority Health and Health Disparities (NIMHD) is interested in supporting research and interventions considering determinants from more than one domain or level of influence (see NIMHD Research Framework). Intervention design should be based on theories from minority health and health disparities science. Research must focus on one or more minority or health disparity population (African Americans/Blacks, Hispanics/Latinos, American Indians/Alaska Natives, Asians, Native Hawaiians and Other Pacific Islanders, socioeconomically disadvantaged populations, underserved rural populations, and sexual and gender minority populations). Applications may include but are not limited to multi-disciplinary etiologic and intervention research projects that advance the understanding of the mechanisms, pathways, and processes operating within the domain of medication management, including but not limited to research on the behavioral, social, and structural determinants of medication adherence, medication safety, shared decision making, integrated medical team care, and resilience within home and community settings. Research may propose using available secondary data, health system data and/or collection of primary data.

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

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

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
• Non-domestic (non-U.S.) Entities (Foreign Institutions)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

• 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) (formerly CCR) 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 and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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.

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.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

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).

Buttons to access the online ASSIST system or to download application forms 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.

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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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

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

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

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

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

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

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

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

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

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

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.

Appendix:

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

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.

Delayed Onset Study

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

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

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions.

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. 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, NIH. Applications that are incomplete or non-compliant will not be reviewed.

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.

Important Update: See NOT-OD-18-228 for updated review language for due dates on or after January 25, 2019.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

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

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).

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.

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? 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?

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

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?

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

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?

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

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

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

In addition, for applications proposing clinical trials: Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

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

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

In addition, for applications proposing clinical trials: If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed? Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate? If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial? If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

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.

Study Timeline

Specific to applications proposing clinical trials: Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate? Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

For research that involves human subjects but does not involve one of the six 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 six 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.

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 children 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.

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.

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.

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

Not Applicable.

Not Applicable

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.

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

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).

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).

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.

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

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

As part of the scientific peer review, all applications:

• 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.

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 . 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.

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.

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).

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 http://www.hhs.gov/ocr/civilrights/understanding/section1557/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 http://www.hhs.gov/ocr/civilrights/understanding/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

Not Applicable

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

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

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

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

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 registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, 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)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Nicole Redmond, MD, PhD, MPH
National Heart Lung and Blood Institute (NHLBI)
Telephone: 301-435-0379
Email: [email protected]

Wendy Nelson, PhD, MPH
National Cancer Institute (NCI)
Telephone: 240-276-6971
Email: [email protected]

Luke Stoeckel, PhD
National Institute on Aging (NIA)
Telephone: 301-496-3136
Email: [email protected]

Brett T. Hagman, PhD
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-0638
Email: [email protected]

Usha Sharma, PhD
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-292-4809
Email: [email protected]

Will M. Aklin, PhD
National Institute on Drug Abuse (NIDA)
Telephone: 301-443-3207
Email: [email protected]

Michael C. Freed, Ph.D., EMT-B
National Institute of Mental Health (NIMH)
Telephone: 301-443-3747
Email: [email protected]

Karen Huss, PhD, RN, ANP-BC, FAAN, FAAAAI, FAHA
National Institute of Nursing Research (NINR)
Email: [email protected]
Telephone: 301-594-5970

Derrick C. Tabor, PhD
National Institute on Minority Health and Health Disparities (NIMHD)
Telephone: 301-594-8950
Email: [email protected]

Deborah Young-Hyman, PhD
Office of Behavioral and Social Sciences Research (OBSSR)
Phone: 301-451-0724
Email: [email protected]

OBSSR does not award grants. Please contact one of the IC program contacts listed below for questions regarding funding interest.

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Christina Rinaldi
National Heart Lung and Blood Institute
Telephone: 301-827-8287
Email: [email protected]

Carol A. Perry
National Cancer Institute (NCI)
Telehone: 240-276-6282
Email: [email protected]

Nia Pree
National Institute on Aging (NIA)
Phone: 301-827-6374
Email: [email protected]

Judy Fox
National Institute of Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-4704
Email: [email protected]

Ann Devine
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2988
Email: [email protected]

Ericka Wells
National Institute on Drug Abuse (NIDA)
Telephone: 301-827-6705
Email: [email protected]

Tamara Kees
National Institute on Mental Health (NIMH)
Telephone: 301-443-8811
Email: [email protected]

Ron Wertz
National Institute of Nursing Research (NINR)
Telephone: 301-594-2807
Email: [email protected]

Priscilla Grant, JD
National Institute on Minority Health and Health Disparities (NIMHD)
Telephone: 301-594-8412
Email: [email protected]

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

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