Alcohol Treatment, Pharmacotherapy, and Recovery Research (R34 Clinical Trial required)

Alcohol Treatment, Pharmacotherapy, and Recovery Research (R34 Clinical Trial required) is sponsored by National Institute on Alcohol Abuse and Alcoholism (NIAAA) - NIH. This R34 planning grant supports clinical trials focused on alcohol treatment, pharmacotherapy, and recovery research.

PAR-25-193: Alcohol Treatment, Pharmacotherapy, and Recovery Research (R34 Clinical Trial required) This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Institute on Alcohol Abuse and Alcoholism ( NIAAA ) Funding Opportunity Title Alcohol Treatment, Pharmacotherapy, and Recovery Research (R34 Clinical Trial required) March 31, 2025 - This funding opportunity was updated to align with agency priorities.

Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084 .

August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198 . August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy.

See Notice NOT-OD-22-189 . Funding Opportunity Number (FON) Companion Funding Opportunity See Section III. 3.

Additional Information on Eligibility . Assistance Listing Number(s) Funding Opportunity Purpose The National Institute on Alcohol Abuse and Alcoholism solicits applications for an R34 Clinical Trial Required mechanism focusing on alcohol treatment and recovery research.

This NOFO will focus broadly on topics relevant for treatment of and recovery from alcohol use disorder (AUD), including: medications development, precision medicine, behavioral therapies and mechanisms of behavioral change (MOBC), recovery, translational research, and innovative methods and technologies for AUD treatment and recovery.

Funding Opportunity Goal(s) To develop a sound fundamental knowledge base which can be applied to the development of improved methods of treatment and more effective strategies for preventing alcoholism and alcohol-related problems.

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) supports research in a broad range of disciplines and subject areas related to biomedical and genetic factors, psychological and environmental factors, alcohol-related problems and medical disorders, health services research, and prevention and treatment research.

Open Date (Earliest Submission Date) The following table includes NIH standard due dates marked with an asterisk. Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed 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.

Required Application Instructions 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.

Use the NIH ASSIST system to prepare, submit and track your application online. 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. Workspace to prepare and submit your application and eRA Commons to track your application. Part 1.

Overview Information 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 The purpose of this PAR is to advance research on various topics that fall within NIAAA’s Division of Treatment and Recovery (DTR).

DTR’s research interests are wide-ranging but typically encompass broad categories such as medications development; behavioral therapies, including mechanisms of behavioral change (MOBC); recovery; translational research; and innovative methods and technologies for alcohol use disorder (AUD) treatment. Other areas of interest include topics focusing on special-emphasis and underserved populations.

Specific examples include research related to health disparities, age, sex, race and ethnicity, co-occurring disorders, and military populations. AUD is a global health problem, affecting more than 76 million adults worldwide, including over 14. 5 million Americans, and resulting in a myriad of medical, psychological, social, economic, and personal problems.

AUD ranks among the leading causes of decreased disability-adjusted life-years and ranks third in preventable causes of death in the United States. The total economic cost to society in the United States is a staggering $249 billion each year.

Research is needed to develop effective treatments for AUD and to better understand the complex nature of recovery across a broad range of topic areas and populations, as described in detail below. This NOFO uses the R34, Grant Planning Program, to address these topics.

The focus of applications responding to this announcement may focus on: Establishment of the research team Development of tools for data management and research oversight Development of a trial design or experimental research designs Finalization of the protocol Preparation of an operations/procedures manual Pilot studies or collection of feasibility data for subsequent research projects, excluding the collection of preliminary data or the conduct of pilot studies to support the rationale for a clinical trial During the past 2 decades, progress has been made in developing efficacious medications and behavioral therapies to treat AUD.

Currently, there are three medications approved by the U.S. Food and Drug Administration (FDA) for the treatment of alcohol dependence: disulfiram, oral and long-term injectable naltrexone, and acamprosate. In addition, nalmefene recently was approved in Europe. However, given the heterogeneous nature of AUD, many patients show only limited or no response to these medications.

Because of this, developing and evaluating new, more efficacious and safe medications remains a top priority. All studies must be conducted in humans. Examples of high-priority research areas appropriate for evaluation in clinical trials include, but are not limited to, investigations that: Evaluate the efficacy and safety of experimental medications (either repurposed or novel compounds) that bind to new targets to treat AUD.

Assess the efficacy and safety of medications to treat comorbid AUD and psychiatric (e.g., posttraumatic stress disorder [PTSD]) disorders. Determine who responds favorably during the trial by exploring clinical and behavioral characteristics and biological markers. Explore new human laboratory paradigms that will help predict efficacy in clinical trials of experimental medications.

Leverage relationships with pharmaceutical and biotechnology companies to identify new compounds for testing in clinical trials. Several behavioral therapies have shown efficacy in treating AUD. These include cognitive behavioral therapy, motivation enhancement therapy, twelve-step facilitation, brief intervention, contingency management, community reinforcement approach, and mindfulness therapy.

Although progress has been made in developing a broad menu of treatment options, not all individuals with AUD respond to today’s behavioral therapies. Incorporating new scientific discoveries and technologies into behavioral treatment may improve clinical outcomes and help disseminate different, more effective, treatments in clinical practice.

Examples of high-priority research areas appropriate for evaluation in clinical trials include, but are not limited to, investigations that evaluate evidence-based behavioral therapies in real-world treatment settings, especially for culturally complex, special emphasis, and underserved populations.

Use dynamic and person-centered statistical modeling approaches to evaluate how heterogeneity impacts alcohol use behavior within specific AUD treatments. Conduct micro-intervention studies to isolate and test the importance of key treatment-related mediators and moderators. Develop new and adapt existing interventions for AUD based on emerging findings from research on MOBC.

Translate evidence-based MOBC best practices into clinical practice. Engage in complex research designs (e.g., dismantling studies), which enhance support and provide evidence for the mechanisms underlying established AUD behavioral treatments Recovery from AUD is complex and highly individualized.

NIAAA is interested in research to learn more about the risk and resiliency factors related to recovery and relapse, including the factors that allow some people to recover without receiving formal treatment. This research will inform the development of additional effective treatment interventions, as well as strategies to sustain recovery.

To fully clarify the concept of recovery and to improve consistency across recovery research, NIAAA developed an operational definition of “recovery” from AUD ( LINK ). The definition involves remission from AUD and cessation from heavy drinking. Moreover, recovery is associated with improvements in dimensions of well-being, quality of life, and biopsychosocial functioning.

Examples of high-priority research areas appropriate for evaluation in clinical trials include, but are not limited to, investigations that: Explore the neurobiological, psychological, environmental, social, and spiritual factors that influence post-treatment recovery.

Identify novel mechanisms of behavioral change (MOBC) that help maintain behavior change in recovery (e.g., self-regulation), and evaluate how knowledge about these mechanisms can be applied to recovery.

Determine the trajectories of recovery in subgroups of people with different cultural and socioeconomic backgrounds, cognitive abilities, and medical histories, including examining sex-related differences in trajectories of recovery within these groups.

Characterize the relationships among relapse severity, frequency, and timing in the recovery process, including how relapse impacts the potential for long-term recovery and improvement in biopsychosocial functioning. Understand the role of understudied mutual support groups, as well as spirituality and religion, in treatment and recovery from AUD.

Identify the factors associated with so-called spontaneous or “natural” recovery and how these factors can be applied to change the behavior of those in treatment. Explore continuing care treatments and interventions that aim to support long-term recovery.

Define and measure dimensions of functioning and well-being associated with recovery (e.g., which of these dimensions of functioning and well-being are positively vs. negatively associated with recovery? Which of these dimensions of functioning and well-being are the most integral in recovery? To what degree might these functioning measures be feasible in clinical practice?)

Clinical research examines the neurobiological, cognitive, emotional, and genetic processes underlying addiction and offers ways for applying those findings to practice and predicting treatment outcomes.

Examples of high-priority research areas appropriate for evaluation in clinical trials include, but are not limited to, investigations that: Translate key neuroscience research findings (e.g., neurobiological, cognitive, emotion regulation, and genetic) to develop more effective treatments.

Innovative Methods and Technologies for AUD Treatment and Recovery New technology (e.g., mobile, computer, and web-based applications) has the potential to expand both the accessibility and effectiveness of a variety of treatments and interventions. Research is needed to further advance digital technology for the diagnosis, intervention, treatment, and maintenance of recovery from AUD.

Developing new analytical approaches can be critical for evaluating treatment, such as tracking results in subpopulations of people with AUD, comparing linear and dynamic models of clinical findings, conducting trajectory analysis and growth mixture modeling to capture changes in recovery over time, and developing and implementing adaptive clinical trial designs and statistical analyses.

Examples of high-priority research areas appropriate for evaluation in clinical trials include, but are not limited to, investigations that: Apply new technology (e.g., mobile devices, computer, web-based applications) to evidence-based behavioral treatments to improve the effectiveness of telemedicine and to reach remote and underserved, vulnerable populations.

Investigate new ways of capturing real-time data in clinical trials and treatment protocols (e.g., interactive voice response technology, smartphones, and alcohol sensors). Explore new analytical methods for evaluating treatment and recovery. Special-Emphasis Populations Research examining disparities in access to and quality of treatment for harmful drinking and AUD typically has not kept pace with other areas of investigation.

Thus, there is a need for more research to develop and implement effective treatments for marginalized and vulnerable populations. It is important to understand how the social determinants of health (i.e., environmental, social, cultural, and economic factors) influence outcomes and sustainability of effects.

There is a need for greater emphasis on developing novel, accessible, cost-effective, culturally grounded treatment interventions in medically underserved populations. Special areas of interest also include research examining the role of harmful drinking in creating and exacerbating disparities in the onset, progression, and treatment of other health conditions.

Examples of high-priority research areas appropriate for evaluation in clinical trials include, but are not limited to, investigations that: Develop and implement effective treatments tailored to populations affected by health disparities in a variety of clinical and nontraditional settings. Determine how social/cultural factors influence treatment accessibility, effectiveness, and long-term recovery.

Develop measures to assess care delivery models to better understand the issues underlying disparities (e.g., health literacy, access to health care, confidence in the proximal health system, socioeconomic status, sociocultural beliefs and practices related to alcohol use, multi-morbidity with other health issues, and personal health care).

AUD Patients with Psychiatric Comorbidity AUD patients often suffer from comorbid psychiatric disorders, such as depression, anxiety, PTSD, insomnia, bipolar disorder, and schizophrenia.

This population experiences poorer treatment outcomes, and tends to have higher rates of clinical impairment, psychosocial and medical problems, utilization of health services, and suicide, as well as lower quality of life than patients who suffer from AUD alone. Developing effective personalized treatment strategies is essential in treating multiple disorders.

For example, how can treatments be integrated to address both mental health disorders and AUD? How does treatment of one disorder affect the outcome of the other? How do the disorders interact to increase the severity and clinical course of each disorder?

Examples of high-priority research areas appropriate for evaluation include, but are not limited to, investigations that: Integrate treatment for co-occurring AUD and mental health conditions to address the heterogeneity that exists among patients.

Explore how behavioral interventions and medications can be combined to treat AUD patients with co-occurring PTSD; anxiety; depression; insomnia; and other mental health conditions, including timing of interventions (serial vs. concurrent), separate vs. fully integrated treatment, and dose/frequency of treatment components.

Identify which types of services, service providers, and treatment settings work best for specific subgroups receiving treatment. Determine how the treatment of one disorder can influence the risks and outcomes for other disorders. Historically, men have tended to drink at higher rates and experience more alcohol-related problems than women.

However, in recent years, the sex-gap has narrowed. Women are increasingly likely to have rates of drinking and heavy drinking similar to those observed in men, to be diagnosed with AUD, and to experience the negative consequences of drinking (such as car crashes). Moreover, many of alcohol’s harmful physiological effects have been found to occur more rapidly and severely in women than men.

This includes blackouts, liver inflammation, brain atrophy, cognitive deficits, certain cancers, negative affect during withdrawal, and stress and anxiety-induced relapse. More research is needed to better understand sex differences in alcohol use and alcohol-related consequences.

Examples of high-priority research areas appropriate for evaluation in clinical trials include, but are not limited to, investigations that: Develop new strategies for alcohol screening, diagnosis, and interventions; and tailor these approaches to women in a variety of settings, including prenatal care and specialty health care. Examine the effects of stress, early childhood trauma, and co-occurring disorders on women’s drinking.

Determine the effectiveness of standard treatment approaches, such as group counseling and relapse prevention, in single-sex vs. mixed-sex groups. Develop innovative strategies to improve coordination of care for women and their families across primary care, maternal health services, specialty alcohol treatment services, and other integrated health system components.

Adolescents and Young Adults Although recent data show that U.S. adolescents in general are drinking less alcohol, when they do drink, they consume alcohol in ways that are particularly harmful. Many young adults are also drinking heavily, and experience myriad associated negative consequences.

These include an increased risk for alcohol overdose, blackouts, falls, drowning, unplanned sexual encounters, intimate partner violence, and co-occurring mental health conditions. Epidemiological data clearly show an association between early onset of drinking (particularly before age 14) and later alcohol-related problems. Finally, research also shows that alcohol may cause changes in the developing brain.

Because the human brain continues to develop past adolescence and into young adulthood, young people are at particularly high risk for experiencing alcohol-related harms. Future research needs to examine whether alcohol-related brain changes occurring in adolescence and young adulthood have long-term consequences. Research also needs to examine how treatment strategies can be better tailored to this special population.

Examples of high-priority research areas appropriate for evaluation in clinical trials include, but are not limited to, investigations that: Develop and test integrated behavioral treatments in adolescents and young adults with AUD that are tailored to the developmental, biological, psychological, emotional, and social needs of these ages.

Test novel approaches (e.g., sequential, multiple assignment, randomized trials–[SMART] trials)to adapt interventions at the individual level and/or to account for comorbidity and cultural factors or other considerations specific to the participants. In the United States, 1 in 10 older adults engages in binge drinking. Alcohol misuse is increasing in this population, in both men and women, with potentially serious consequences.

Drinking among older adults contributes to accelerated aging in some brain regions, including the frontal cortex, leading to impaired cognitive function and resulting in deficits in learning, memory, and motor function. Developing and evaluating early intervention approaches may help to stem these brain effects.

Examples of high-priority research areas appropriate for evaluation in clinical trials include, but are not limited to, investigations that: Develop screening and behavioral and pharmaceutical therapies targeted to older adults. Identify vulnerabilities in high-risk subgroups of older adults, including those with physical and/or mental health comorbidities; women; and people with cultural, socioeconomic, immigrant, and sex status.

Applications that focus on the following topics will not be considered responsive to this NOFO and will not be reviewed: Efficacy and dissemination studies of brief interventions for high risk and understudied populations (e.g., individuals who are not 4-year college students or graduates, individuals experiencing poverty or comorbidity).

Approaches that focus on enhancing positive health or other behaviors that might have an indirect positive effects on drinking, sleep improvement, and fitness, Role of life events and social factors as contributors to changes in the patterns of drinking.

This includes understanding how the positive social effects of drinking influence the initiation and escalation of drinking, and how social forces and life events facilitate change are needed. Link changes in environmental factors such as the relative availability and price of alcohol and alcohol-free rewards associated with changes in drinking, and how to leverage these factors in treatment.

Preclinical animal studies, only human studies are allowed in this PAR. Studies that include substances other than alcohol or on poly-substance use disorders Clinical trials on prevention Clinical trials in community settings (community centers, college campuses etc.) Clinical Trials that include organ-associated diseases.

Basic experimental studies involving humans (BESH) 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 Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity. Application Types Allowed The OER Glossary and the How to Apply Application Guide provide details on these application types.

Only those application types listed here are allowed for this NOFO. Required: Only accepting applications that propose clinical trial(s). Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. Direct costs are limited to $450,000 over the R34 project period, with no more than $225,000 in direct costs allowed in any single year. The total project period for an application submitted in response to this NOFO may not exceed 3 years.

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 Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education 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 (Other than Small Businesses) 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 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 Non-domestic (non-U.S.) Entities (Foreign Organizations) Non-domestic (non-U.S.) Entities (Foreign Organizations) 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 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.

Eligible Individuals (Program Director/Principal Investigator) Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with 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. 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 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 ). 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. All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed. Instructions for Application Submission 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.

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

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.

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.

Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement , and procedures for foreign organizations described throughout the How to Apply- Application Guide. 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. All NIH awards are subject to the terms and conditions, cost principles, and other considerations