Required Application Instructions

It is critical that applicants follow the 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) invites applications for international collaborative research on drug abuse and drug addiction. NIDA is the single largest supporter of research on the causes, consequences, prevention, and treatment of drug addiction in the world. The mission of the Institute is to bring the power of science to bear on drug abuse and addiction through support and conduct of research across a broad range of disciplines, and ensure rapid and effective dissemination and use of results to improve prevention, treatment, and policy. The International Program extends the Institute mission internationally through programs that: 1) take advantage of unique opportunities to advance scientific knowledge through research, 2) address the global impact of addiction on public health through activities that build research capacity internationally, and 3) effectively disseminate and share the knowledge gained through NIDA-supported research to scientists, treatment providers, and policy makers around the world. Activities sponsored and coordinated by the International Program include:

• Support of international collaborations to conduct research that allow U.S. scientists to take advantage of unique research opportunities.
• Development of bilateral and multilateral interchanges with other countries and international organizations to share research knowledge for mutual benefit.
• Administration of fellowships and professional development activities for U.S. and non-U.S. addiction researchers.
• Co-sponsorship of meetings and symposia with other countries or international organizations.
• Dissemination of NIDA research and International Program activities to a broad international audience.

Several NIH and NIDA International Program tools help scientists identify potential research partners and build international partnerships. For more information, see these sections of the website:

• NIDA International Program Web site: http://www.drugabuse.gov/international
• Collaboration Tools: http://www.drugabuse.gov/international/collaboration-tools
• Find a Research Partner: http://www.drugabuse.gov/international/research-funding-landing

In summary, the International Program advances NIDA s mission through fostering international cooperation in drug abuse and addiction research, while integrating NIDA’s Divisional research priorities and crosscutting research issues within the frameworks of NIDA, NIH, and HHS health policy and U.S. economic and foreign policy considerations.

This funding opportunity announcement is part of NIDA s effort to encourage rigorous collaborative international research and will provide funding for projects conducted in whole or in part outside the U.S. The research must be conducted by U.S. investigators in collaboration with non-U.S.-based investigators. Either the U.S. or the non-U.S. investigator may serve as Program Director(s)/Principal Investigator(s) (PD(s)/PI(s), but the project must include significant contributions of resources by each participant. Resources may include in kind contributions of personnel, access to study populations, laboratory and other research facilities, etc., as well as funding. This is a broad call for innovative research and applications are encouraged in all areas of science addressing drug addiction including but not limited to prevention, basic science, epidemiology, treatment and health services. Of particular interest are projects that take advantage of a unique set of resources or subject populations that would otherwise be difficult to access domestically.

The R21 activity code is intended to encourage exploratory and developmental research projects by providing support for the early and conceptual stages of these projects. These studies may involve considerable risk but may lead to a breakthrough in a particular area, or to the development of novel techniques, agents, methodologies, models, or applications that could have a major impact on a field of biomedical, behavioral, or clinical research. Projects of limited cost or scope that use widely accepted approaches and methods within well-established fields are better suited for the R03 small grant activity code.

A 2014 United Nations (UN) high-level review of drug strategies concluded that the world drug problem remains a common and shared responsibility that persistently and negatively impacts public health, government, civil society, and economic prosperity around the world. The UN Commission on Narcotic Drugs review called for increased international cooperation to improve public health systems; reduce drug-related HIV; and adopt comprehensive, evidence-based prevention, treatment, and social rehabilitation and integration interventions, especially for vulnerable populations and people who inject drugs.

Global prevalence of past-year use of illicit substances by people aged 15 to 64 has remained stable during the past few years, ranging from 4.6% in 2008 to 5.2% in 2012, according to the World Health Organization (WHO) 2014 World Drug Report. Prevalence of problem drug use among people aged 15 to 64 was virtually unchanged, dropping to 0.8% in 2012 from the 0.9% reported annually between 2007 and 2011. This global stability masks wide regional and national variations in drugs, use patterns, treatment availability, and surveillance efforts.

Drug use killed about 183,000 people in 2012 through fatal overdose and deaths attributed to drug-related HIV, suicide, and accidents. WHO and the United Nations Office on Drugs and Crime (UNODC) reported that illicit drug use is 1 of the top 20 health risk factors globally, and that drug use represented a much larger proportion of the burden of disease among people between the ages of 20 and 30. The greatest burden of disease and most drug-related deaths are associated with use of opiates and opioids, but all drugs of abuse are associated with an increased risk of HIV/AIDS, hepatitis, tuberculosis, suicide, overdose deaths, schizophrenia, and cardiovascular diseases.

A joint estimate by UNODC, WHO, the Joint United Nations Programme on HIV/AIDS (UNAIDS), and the World Bank concluded that 12.7 million people injected drugs in 2012, but prevalence of injecting drug use is 4.6 times higher than the global average in Eastern and Southeastern Europe. Globally, more than half of the people who inject drugs have hepatitis C and 13.1% have HIV infection. In 2014, UNAIDS reported that injection drug use is found in every country and HIV prevalence in 74 countries was 28 times higher among people who inject drugs. HIV prevalence was much higher among people who inject drugs in Southwest Asia (28.8%) and Eastern/Southeastern Europe (23.0%). On average, injection drug use is associated with 30% of new HIV infections outside sub-Saharan Africa.

Globally, resources are extremely limited for the prevention and treatment of drug-related HIV. According to the 2014 World Drug Report, 16 countries account for 45% of the people who inject drugs and 66% of the people who have HIV infection and inject drugs. Only low levels of prevention services such as opioid substitution therapy are available in those countries. Prisoners are more likely to use drugs particularly through injection drug use than the general population but access to prevention and treatment interventions is even more restricted for prisoners.

The number of new psychoactive substances continues to expand exponentially. The 2014 World Drug Report notes that 348 substances had been identified by December 2013, an increase of 38.6% in 18 months and far more than the 234 psychoactive substances controlled through international treaties. The market for new psychoactive substances also expanded geographically, with an additional 24 countries identifying use of synthetics between July 2012 and December 2013. Increasingly, these new psychoactive substances, cannabis, heroin, MDMA, and cocaine are available over online, virtual marketplaces known as the dark net.

The 2014 World Drug Report found that cannabis use had increased between 2009 and 2012, and that the proportion of treatment admissions for cannabis abuse had increased, particularly in the Americas, Europe, and Oceania. Opioid use also increased between 2009 and 2012, particularly nonmedical use of pharmaceuticals. Heroin and opium use remained the primary reason people sought treatment, particularly in Asia and parts of Europe, and data indicates that variations in price and availability prompted many drug users to alternate between nonmedical use of prescription opioids and heroin. Treatment demand for cocaine was most common in the Americas, while use of amphetamine-type stimulants propelled treatment demand in Asia and Oceania. Access to drug abuse treatment varied widely: Globally, 1 in 6 problem drug users had access to treatment, but access ranged from 1 in 18 in Africa to 1 in 3 in North America.

As the U.S. agency charged with applying scientific methods to better understand drug abuse and addiction, NIDA is also a global leader in drug abuse research and education. The Institute remains committed to supporting innovative research to expand scientific knowledge that government leaders can use to develop evidence-based public policy and clinicians can use to deliver more effective prevention and treatment interventions. The Institute supports this international mission because it recognizes that addiction knows no borders and that no country can solve the problem by acting alone.

This funding opportunity announcement encourages applications in all areas of NIDA-supported science, including basic laboratory studies, clinical studies, epidemiological studies, community-based studies, and services research. The intent of this program is to stimulate state-of-the-science collaborative research between investigators from domestic U.S. institutions and researchers in other countries. Funds are being made available to take advantage of new opportunities to establish collaborative relationships with scientists conducting research or with a potential to conduct research in other countries as well as to support new research projects from established collaborators. NIDA is also very interested in establishing relationships with research-funding organizations in other countries in order to leverage the limited resources available globally for drug abuse research. The inclusion of funding organizations in other countries, as collaborators, has the potential to improve the focus and quality of the research, and to help make any findings that result from the FOA more readily available and useful globally. Resources may include in-kind contributions of personnel; access to study populations, laboratory, and other research facilities, etc.; as well as funding. It should be emphasized that these examples are not intended to be prescriptive, or to exclude other creative means of achieving the same goals, as long as the efforts directly complement the objectives of this FOA. Rather, NIDA seeks to encourage such collaborations and any additional means to increase the effectiveness of the funds provided for this program.

Research priority areas have been identified that are international in scope, are associated with substantial detrimental health consequences, and for which international collaborative research may provide a unique opportunity to expand our knowledge and ability to effectively respond. While this call is meant to be very broad and inclusive, the following areas of research are current priority areas:

Research on marijuana, its acute and chronic effects, especially on the neurobiology and function of the brain, are encouraged. In addition, research on the impacts of policies and laws regarding marijuana possession and use are encouraged.

Active drug use is often associated with increased risk of HIV transmission, non-adherence to HAART or lapses in HIV treatment. Studies are needed to discern the best strategy to reach and test high-risk individuals and initiate and monitor HAART therapy for those who test positive. Known as Seek, Test, Treat, and Retain, this approach has been shown to reduce viral load and also HIV incidence at the population level.

Amphetamine type stimulant abuse and synthetic and other designer drug abuse are growing problems in the United States and around the world. Studies are encouraged to assess the nature and extent of amphetamine type stimulant abuse and synthetic and other designer drug abuse, their short and long term sequelae and prevention and treatment approaches.

Inhalant abuse continues to be an under-recognized public health problem in many countries. Studies are encouraged to improve epidemiological data on the nature and extent of abuse, to develop and implement effective prevention programs, to better understand the neurobiological impacts of these agents, and to increase public awareness of their impact.

Smoking during pregnancy studies are encouraged to increase our knowledge of the prenatal impact of smoking and the effects of early exposure to tobacco in young people and adolescents on development of addiction and other diseases and on cognitive development.

Drugged driving studies are encouraged to develop and utilize accurate drug testing technologies to assess the prevalence of driving under the influence of drugs, the role of drugs in accidents, and to assess the costs and benefits of laws and other programs to reduce the incidence and impact of drugged driving.

Other areas of interest include, but are not limited to:

Implementation research can help to determine how best to provide comprehensive, integrated sustainable HIV/AIDS prevention and treatment interventions for drug users, especially interventions to prevent or treat HIV infection.

To date, several promising integrated behavioral and biomedical approaches have shown positive outcomes in decreasing the rate of new HIV infections, promoting greater adherence to HIV treatment and overall medical management, improving engagement and retention in HIV care, and reducing substance abuse. Examples of these successful interventions include, but are not limited to: targeting use of and adherence to ART; screening and risk reduction; engagement and long-term retention in HIV care; and overall medical management for co-morbid conditions such as substance use, mental health disorders, and co-infections such as Hepatitis C and TB. However, there remains a large gap in translation from research models into combination approaches that are effective in real world settings. This FOA encourages implementation research to explore mechanisms to successfully transfer and sustain efficacious integrated combination preventive and treatment interventions for at-risk and HIV+ populations in real-world settings. Applications should address issues of scale-up in diverse settings, effectiveness and cost-effectiveness, and how to best integrate diverse evidence-based interventions to optimize their impact;

Development of surveillance systems to track and respond to emerging drug epidemics, identifying abuse of novel drugs; optimal ways to respond to emerging epidemics and consider the range of linked services (e.g., drug treatment, primary care, health, social, recreational, educational, juvenile justice) for defined populations in various cultural settings;

Optimal ways to respond to emerging epidemics and evaluate the impact of a range of linked services (e.g., drug treatment, primary care, health, social, recreational, educational, juvenile justice) for defined populations in various cultural settings;

Research on systems or practices that enhance technology transfer and investigate how to integrate research findings into practice in a timely manner across different cultures and regulatory bodies; this may include a new research methodology or approach (e.g., valid/reliable cross-cultural measure of quality of care), rapid testing of drug use for screening drivers, or physician based education on smoking cessation treatments for pregnant women);

Research to adapt and test innovative prevention interventions or treatments; test replicability of established prevention/treatment programs, identify key intervention components that impede or account for success in the adaptation process; culturally related barriers and facilitators to implementation; and processes and mechanisms that increase program fidelity and the potential for sustainability;

Identification of factors that underlie treatment-seeking behavior in different countries and address the unmet need for treatment (for example, outreach interventions aimed at children at highest risk for inhalant abuse);

Secondary data analysis of existing data sources and when available comparison of international data;

Basic biomedical studies are needed to understand the genetic and biological basis for HIV infection and persistence, AIDS-related disease progression, and related co-infections or co-morbidities, in combination with use of licit or illicit substances (including alcohol, tobacco, cannabis, stimulants, opiates). Effects of past or continuing chronic substance use, including smoking and polysubstance use, on factors that impact disease progression and responses to current therapies as well as responses to potential vaccines or new treatment strategies are encouraged;

Recent advances in statistical genetics, molecular biology, and genomic approaches have greatly accelerated the ability to identify the etiology of diseases that have a genetic basis. Genetic approaches, such as genome-wide association studies, deep sequencing, or whole genome sequencing are needed to identify chromosomal loci, gene variants, and haplotypes in non-US based populations to examine genetic associations with phenotypes and endophenotypes of addiction vulnerability with or without co-morbid disorders, including HIV-1 infection.

Research that takes advantage of particular population characteristics (e.g., genotype, drug use patterns, cultural sanctions) to isolate and study variables underlying risk for drug addiction and impact of use;

Basic research in behavior, cognition and neurobiology that capitalizes on unique opportunities in populations of abusers that are characterized by different patterns of abuse than is typically seen in the United States; for example, select groups that use unusual routes of administration, drug combinations, or whose abuse is directed at only one particular drug of abuse rather than the polydrug abuse that typifies users and addicts in the United States;

Preclinical and other human or animal laboratory studies relevant to the study of addiction and addictive processes. For example: basic research that expands our knowledge of the impact of drug use on brain development among children and adolescents, as well as knowledge regarding gene and environment interactions.

Development of computational and modeling approaches to study addiction including but not limited to computational neuroscience, neuro- and behavioral economics, multiscale modeling, population modeling and other mathematical and or modeling approaches. We encourage collaborative research resources that facilitate multi-disciplinary projects of international scope.

Small and big data approaches to predictive modeling identifying populations deemed to garner the most benefit from the limited resources available to provide drug abuse treatment. This includes data analysis from standard and non-standard data sources. Novel data acquisition modalities including mobile sensors and mobile phone applications will also be considered

In summary, the overall purpose of this FOA is to support state-of-the-science research between investigators from domestic U.S. institutions and researchers in other countries. Priority will be given to projects that address linkages between HIV/AIDS and drug abuse, marijuana, amphetamine type stimulants abuse, synthetic and other designer drug abuse, inhalant abuse, smoking during pregnancy, and drugged driving; as well as research projects that address NIDA's Divisional research priorities and crosscutting research issues.

HIV/AIDS Counseling and Testing Policy for the National Institute on Drug Abuse: In light of recent significant advances in rapid testing for HIV and in effective treatments for HIV, NIDA has revised its 2001 policy on HIV counseling and testing. NIDA-funded researchers are strongly encouraged to provide and/or refer research subjects to HIV risk reduction education and education about the benefits of HIV treatment, counseling and testing, referral to treatment, and other appropriate interventions to prevent acquisition and transmission of HIV. This policy applies to all NIDA funded research conducted domestically or internationally. For more information see https://grants.nih.gov/grants/guide/notice-files/NOT-DA-07-013.html.

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

Points to Consider Regarding Tobacco Industry Funding of NIDA Applicants: The National Advisory Council on Drug Abuse (NACDA) encourages NIDA and its grantees to consider the points it has set forth with regard to existing or prospective sponsored research agreements with tobacco companies or their related entities and the impact of acceptance of tobacco industry funding on NIDA's credibility and reputation within the scientific community. Please see http://www.drugabuse.gov/about-nida/advisory-boards-groups/national-advisory-council-drug-abuse-nacda/council-statements/points-to-consider-regarding- for details.

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

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to 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).

In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows. The NIH will accept submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions 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: Do not use the Appendix to circumvent page limits. 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 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 a 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 described throughout the SF424 (R&R) Application Guide.

Part I. Overview Information contains information about Key Dates. 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.

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. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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.

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 our Post Submission Application Materials policy.

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 focus their evaluation on 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.

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).

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

Reviewers will 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 the 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:

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?

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.

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

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

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 Wide Association Studies (GWAS) /Genomic Data Sharing Plan.

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 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 submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

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

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.

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.

Additionally, ICs may specify any special reporting requirements for the proposed clinical trial to be included under IC-specific terms and conditions in the NoA. For example: If the proposed clinical trial has elevated risks, ICs may require closer programmatic monitoring and it may be necessary to require the awardee to provide more frequent information and data as a term of the award (e.g., to clarify issues, address and evaluate concerns, provide documentation). All additional communications and information related to programmatic monitoring must be documented and incorporated into the official project file. 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.nig.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.

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 progress report, 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.

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)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: https://grants.nih.gov/support/index.html
Email: [email protected]

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

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

Steven Gust, Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-443-6480
Email: [email protected]

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

Pam Fleming
National Institute on Drug Abuse (NIDA)
Telephone: 301-253-8729
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.