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 Drug Abuse (NIDA)
National Cancer Institute (NCI)
National Institute on Alcohol Abuse and Alcoholism (NIAAA

Funding Opportunity Title

Integrative Research on Polysubstance Abuse and Disorder (R61/R33 Clinical Trial Optional)

Activity Code

R61/R33 Exploratory/Developmental Phased Award

Announcement Type

New

Related Notices

None

Funding Opportunity Announcement (FOA) Number

PAR-20-035

Companion Funding Opportunity

None

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

 93.279, 93.273, 93.399

Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) is supported by Collaborative Research on Addiction (CRAN) at the National Institutes of Health (NIH), a trans-NIH partnership composed of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute on Drug Abuse (NIDA), and the National Cancer Institute (NCI). The intent of this FOA is two-fold: (1) characterize how the neurobiological alterations, associated behaviors, and public health consequences arising from polysubstance use differ from, or are similar to, those observed in single drug use; (2) promote integrative polysubstance research along a translational pipeline, consisting of basic science research in animals, human-based laboratory investigations, and epidemiological studies. These dual objectives will be accomplished with an Exploratory/Developmental Phased Award (R61/R33) mechanism, where polysubstance research can occur in any of these translational stages during the R61 phase and these findings will be rapidly back- or forward-integrated into another stage during the R33 phase, permitting accelerated bi-directional research exchange.

Key Dates
Posted Date

October 18, 2019

Open Date (Earliest Submission Date)

February 17, 2020

Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Date(s)

March 17, 2020, July 17, 2020, November 17, 2020, March 17, 2021, July 19, 2021, November 17, 2021, March 17, 2022, July 19, 2022, November 7, 2022

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s)

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

AIDS Application Due Date(s)

March 17, 2020, July 17, 2020, November 17, 2020, March 17, 2021, July 19, 2021, November 17, 2021, March 17, 2022, July 19, 2022, November 7, 2022

All applications are due, by 5:00 PM local time of applicant organization. All types of AIDS and AIDS-related applications allowed for this funding opportunity announcement are due on the listed date(s).

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.

Scientific Merit Review

 July 2020, November 2020, March 2021, July 2021, November 2021, March 2022, July 2022, November 2022, March 2023   

Advisory Council Review

October 2020, January 2021, May 2021, October 2021, January 2022, May 2022, October 2022, January 2023, May 2023 

Earliest Start Date

October 2020

Expiration Date

November 8, 2022

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.


There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.
  4. Table of Contents

    Part 1. Overview Information
    Part 2. Full Text of the Announcement

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


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

    Background

    Polysubstance use (PSU) is defined as the use of two or more addictive drugs simultaneously or concurrently and polysubstance use disorder (PSUD) is the presence of 2 or more substance use disorders (SUD). Simultaneous PSU is characterized as the use of multiple drugs at the same time whereas concurrent PSU refers to the use of multiple substances within a specified period of time, but not simultaneously. Polysubstance users report that the simultaneous ingestion of two addictive substances can produce additive/synergistic euphoric effects and concurrent use is intended to alleviate the negative consequences of another drug. For example, the co-administration of heroin and cocaine, otherwise known as “speedballing,” produces enhanced reinforcing effects when compared to the delivery of either drug alone. Alternatively, benzodiazepines, opioids, or alcohol are commonly used to relieve the aversive symptoms during a cocaine “crash,” an anhedonic state that is characterized by general dysphoria, agitation, and anxiety.

    Importantly, the incidence and clinical impact of PSU are increasing. Increases in PSU may be related to demand driven by the above desired effects and/or the increased availability of polysubstance products.  The growing clinical impact is evidenced by the increase in fatal and nonfatal overdoses involving PSU. Epidemiological data from national surveys indicate that approximately 20% to 30% of youth and young adults engage in PSU and the majority of treatment seekers are polysubstance abusers. Polysubstance users typically initiate drug use at an earlier age than single drug users, and PSU occurs more frequently in males. Compared to users of a single drug, polysubstance users are more likely to present with comorbid mental health conditions, misuse or abuse prescription drugs, are at a greater risk for other health complications, and are more likely to report higher ratings on the Addiction Severity Index. Moreover, polysubstance abuse and PSUD are associated with social disadvantages including elevated risk of academic failure and non-completion, higher frequency of employment and legal issues, poorer quality of life, and a greater likelihood of engaging in physical violence. Together, these data suggest that PSU is common and increasing in drug users and is associated with worse health and societal consequences than single drug use.

    While clinicians and epidemiologists have long recognized that PSU is prevalent among drug users, this ‘real-world’ context has not been fully investigated in basic animal and clinical human research. There is a paucity of studies addressing drivers and patterns of PSU, biological effects of PSU and relevant drug interactions that could impact acute and chronic toxicity or effects on substance dependence.  In particular, there is a lack of mechanistic research on topics relevant to polysubstance misuse.  Barriers affecting the integration of PSU into clinical and animal basic research include the need for additional control groups, complexities of data interpretation, and challenges of modeling human phenomena using animal research. Limited investigations of PSU in basic science research hinders a full exploration and comprehension of the underlying processes and mechanisms that underlie poorer health and social outcomes that are associated with this pattern of use. This FOA will address this knowledge gap by requiring a translational component in the research applications to encourage applicants to identify similarities and differences between PSU and single drug use. 

    Purpose

    Collaborative Research on Addiction (CRAN) is a National Institutes of Health (NIH) partnership between the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute on Drug Abuse (NIDA), and the National Cancer Institute (NCI). The mission of CRAN is to provide a strong collaborative framework to leverage resources and expertise that will meet public health needs by broadening the research focus of participating institutes to better address poly- or multiple substance use, abuse, and dependence. To this end, the purpose of this FOA is two-fold: (1) to compare the similarities and differences between PSU and single drug use across antecedent and consequential behavioral, neurobiological, genetic, and epigenetic changes; and (2) to rapidly integrate findings across a translational pipeline, consisting of basic science research in animals, human-based laboratory investigations, epidemiological, therapeutic development, and services research studies. The goal of this initiative is to support investigations on tobacco, alcohol, cannabis, and other licit and illicit drugs of abuse. Applicants should focus on two primary drugs of abuse to facilitate the integration of findings and aid interpretability, with the understanding that the human condition often involves the use of multiple substances. This FOA will not support research projects focused on studying food addiction, gambling, or internet/gaming addictions.

    PSU findings from one stage of the translational trajectory are rarely integrated into another stage, hindering our full understanding of the complexities surrounding PSU and PSUD. For this reason, this program announcement will utilize a R61/R33 mechanism to facilitate the integration of findings across the translational continuum in an expedited and timely manner. The R61 phase of the application can originate in any of these three stages along the translational trajectory, consisting of (1) basic science research in animals, (2) human-based laboratory investigations, and (3) epidemiological, treatment development, or services research studies. These findings will be back or forward translated to another stage during the R33 phase and will assist in bridging the identified “translational gap.” This funding mechanism is intended to encourage our investigators to examine PSU and PSUD with a broader perspective, leveraging the insights gleaned from one stage during the R61 phase to guide and stimulate integrative science across the translational pipeline during the R33 phase. Moreover, the structure of this funding mechanism will capitalize on the many advantages that are found along the translational trajectory while providing an opportunity to address the limitations and challenges that exist within each of these three translational stages. For example, while the data collected from individuals with PSUD can provide rich, multi-dimensional information that cannot be attained from animal models, it is often difficult to ascertain if the outcomes observed in humans stem from PSU or other pre-existing conditions. Hence, the back-translation of findings from the clinic into animal models provides a unique opportunity to address this caveat and permits researchers to identify behavioral, psychological, social, and neurobiological mechanisms under stricter experimental control. Collectively, the data gathered from both human and animal research will enrich our understanding of PSU and any related outcomes.

    Research Scope

    Epidemiological data indicate that PSU is associated with worse health and social outcomes than single drug use. Hence, the intent of this announcement is two-fold: (1) to compare the similarities and differences between PSU and single drug use across antecedent and consequential behavioral, neurobiological, genetic, and epigenetic changes; and (2) to rapidly integrate findings along a translational pipeline, consisting of basic science research in animals, human-based laboratory investigations, and epidemiological studies. Additionally, the structure of this R61/R33 Exploratory/Developmental Phased Award mechanism will allow for more direct and timely communication of findings along a translational continuum, consisting of (1) basic science research in animals, (2) human-based laboratory investigations, and (3) epidemiological, therapeutic development, or services research studies. To facilitate the translation of findings, applicants should focus on two primary drugs of abuse in research supported by this FOA, with the understanding that multiple compounds are used are used by humans who abuse drugs. Whenever possible, applicants should relate the outcomes of PSU to single drug use to determine if the findings observed under the PSU condition are distinct from those found under conditions of single drug administration. The comparison of PSU groups to valid pre-existing data sets of single drug consequences is acceptable, but these data sets should be included in the application or appear in a peer-reviewed publication.

    NIDA priority areas: One priority area is to develop safe and more effective treatments for PSU that include medication-based, device-based, behavior-based and integrative intervention approaches. Approaches of interest include application that may focus on studying new chemical entities (NCEs), already-marketed pharmacotherapies, biologics (immunotherapies such as vaccines and antibodies, enzymes, gene therapies, etc.), devices, digital application, behavioral therapies or combinations of these approaches. These interventions under investigation for PSUD may target one or more of the neuropathological mechanisms, the various clinical stages, and/or the medical/psychiatric complications of the disorders. Furthermore, NIDA encourages applications that examine neurocognitive, neuroaffective, and neurobehavioral risk factors for PSU in the context of a substance use disorder or non-SUD mental illnesses.  Clinical and population studies that incorporate construct-guided phenotyping, human laboratory experiments, and projects that develop and validate new animal model systems are encouraged. Finally, NIDA encourages innovative applications on understanding changes in PSU trends, developing interventions to prevent PSU and PSUD, and understanding the effects of and enhancing treatment services for PSUD. Applications that uncover emergent substance use trends (e.g., dabbing, e-cigarette use, etc.) and/or enhance our understanding of effects of policy changes on emerging PSU and treatment services needs are encouraged (e.g., effects of changes in cannabis policy on opioid use). To address these emerging trends, modeling applications and the use of secondary data sets may be appropriate. Further, if efficacious treatments for PSUD are developed, applications proposing implementation science frameworks are encouraged to the adoption of PSUD services.

    NIAAA priority areas: Research projects should follow priority areas described in the general section of the CRAN FOA below. NIAAA will prioritize applications that examine alcohol and cannabis; and alcohol and opioid drug combinations. Specific NIAAA priority include: Identifying molecular mechanisms, neural circuitry and neurotransmitter systems that mediate alcohol and cannabis and alcohol and opioid PSU and PSUD; Understanding neurocognitive and neuroaffective consequences and mechanisms of combined alcohol and cannabis and alcohol and opioid PSU; Examining pharmacokinetics and pharmacodynamics of alcohol and cannabis and alcohol and opioid combinations to better understand their abuse liability; Understanding the effects of quantity of cannabis consumed, cannabis route of administration, and patterns of alcohol/cannabis co-use (e.g., dose effect, simultaneous vs. concurrent patterns of use) for treatment purposes.

    NCI priority areas: NCI is primarily interested in research areas that examine PSU in the context of the entire cancer control continuum, but predominately as PSU relates to cancer prevention and survivorship. Substances that are known to impact cancer risk and outcomes directly include tobacco, alcohol, and cannabis. Advances in developing interventions and evaluating natural experiments require a better understanding of the causal factors influencing PSU behaviors. NCI is focused on supporting research that leads to better understanding of PSU as a cause of cancer, better interventions aimed at preventing cancer by reducing PSU, and addressing PSU in cancer survivors, including their response to cancer treatments, quality of life, and risk of cancer recurrence. Topics of interest include but are not limited to: Research on the biological, psychological, environmental, and social causes and consequences of the combined use of alcohol and tobacco on cancer-related outcomes; Investigation of the association between PSU and several types of cancer, including, but not limited to, lung, head and neck, esophageal, and testicular cancers; PSU patterns in the context of cancer treatment and survivorship; Studies integrating qualitative, ethnographic, and sociological techniques in laboratory and translation to field settings to identify novel influences of PSU on cancer-related outcomes; Studies of unique social, psychological and biological pathways influencing PSU and cancer in populations disproportionately affected by PSU; Identification and validation of mechanisms and constructs that could contribute to optimizing treatment strategies for PSU (e.g. SMART designs); Research on the determinants of PSU over the life course, including the differential association of such determinants on successful behavior change in people with and without a history of cancer.

    Examples of priority topics where integration of data across the translational stages that can be proposed in the application include, but are not limited to:

    • Understanding pharmacokinetics of different polysubstance combinations underlying PSU toxicity (encouraging opioid+alcohol and opioid+psychostimulants combinations)
    • Developing mechanism-based treatments for PSU overdose
    • Identification of molecular pathways, neural circuitry, and neurotransmitter systems that underlie increased rewarding effects or mediate super-additive pharmacological or behavioral effects of PSU
    • Optimization and implementation of treatment services (i.e., is more effective to focus on one abused substance or multiple substances together?)
    • Identify vulnerable or resilient phenotypes and/or genotypes that predict PSU or response to treatment

    Other topics appropriate for this FOA include, but are not limited to:

    • Health outcomes, such as changes in cancer biomarkers, immune function, toxicity
    • Prevention/intervention strategies for PSUD
    • Differences between sequential or concurrent patterns of drug use
    • Developmental differences in patterns of use or combinations
    • Trajectories of or influences on relapse incidence and/or rates
    • Social factors involved in PSU versus single drug use trajectories, including social media data sets
    • PSU in vulnerable populations (e.g., neonatal exposed individuals, adolescents, aging populations)
    • Sex differences in the acquisition, maintenance, relapse, or treatment of PSU
    • Measures of antecedent or consequential cognitive processes in PSU
    • Accelerated transition to compulsive drug use under different drug use conditions or patterns
    • PSU-induced epigenetic modifications

    The intent of this initiative is NOT to address “gateway” hypotheses (i.e., use of one drug enhances vulnerability of using a second drug). However, applications that contribute to the understanding of concurrent vs sequential contexts are encouraged. Additionally, the goal of this announcement is NOT to support other behavioral addictions, such as food addiction, gambling, or internet/gaming addictions.

    Please note that some of the experimental approaches to modeling PSU and PSU outcomes may not have a direct counterpart across translational stages. For example, it may be difficult to capture the complete drug history profile of human users in animal models, such as the drug dose, lifetime use, comorbid psychiatric conditions, or the route of administration. Additionally, laboratory assessments that examine motivational or cognitive processes in humans may not have an exact complement in animals and effects seen in animals may not always be assessed in the same manner in humans. Investigators are encouraged to utilize the best animal model and procedure to replicate the observed phenomena in humans. Compromises in experimental approaches and modeling should be made and are needed to facilitate the translation of findings. For example, it would be appropriate to examine relapse rates in epidemiological surveys, and then to translate this approach by measuring drug craving in humans and/or examining reinstatement of operant responding in animals. Whenever possible, investigators are encouraged to use the assessments and models that have the most translational potential.

    Applicants are encouraged to provide a description of how the study designs, methods and assessments are complementary such that outcomes at one translational stage enhance the interpretation of outcomes at the other translational stage.

    Milestones

    This funding opportunity uses a R61/R33 Exploratory/Developmental Phased Award mechanism. Support will be provided for up to 5 years, which includes initial support of up to 2 years of the R61 phase, followed by up to 3 years of support for the R33 phase upon successfully meeting R61 milestones. For transition to the R33 phase, awardees must submit the transition package no less than two months before the completion of the R61 phase. The transition plan should include the R61 progress report describing in detail the progress towards the R61 milestones and a description of how research proposed for the R33 phase will be supported by the completion of the R61 phase milestones. These materials will be evaluated by NIH program staff.

    R33 funding decisions will be based on the original R61/R33 peer review recommendations, successful completion of transition milestones, any proposed changes to the R61 research based on R33 findings, program priorities, and availability of funds. It is not expected that all applications will continue to the R33 phase. Due to the integrative nature of this FOA, it is recommended that applicants form “integrative teams” to oversee these two phases and discuss applications in advance with NIH program experts. It is expected that the PSU data gathered during these R61 and R33 phases will serve as preliminary data for future NIH applications on this topic.

    Studies may begin in any stage along the translational trajectory described herein, consisting of (1) basic animal research, (2) human-laboratory or field-based investigations, or (3) epidemiological, treatment development, or services research studies.

    Examples of milestones for the R61 phase include, but are not limited to:

    • Secondary data analysis of existing epidemiology, treatment services data, social media data, imaging, genetic, or human behavioral data sets to identify significant differences between patterns of PSU and single drug use and their outcomes.
    • Analysis of existing biological samples/specimens to characterize changes in biomarkers of PSU vs single drug use.
    • Identification of patterns of polysubstance use in humans to guide experimental approaches in animal research or laboratory studies with human subjects.
    • Exploration of differences between PSU and single drug use trajectories and/or health outcomes in animal models or ongoing human-based laboratory studies.

    The objectives for the R33 phase should be based, at least in part, on findings from the R61 phase. Examples of appropriate goals for the R33 phase include, but are not limited to:

    • Establishment of an animal model of PSU based on data from the R61 phase.
    • Replication and validation of the PSU phenomena observed in the R61 phase in a different translational stage.
    • Characterization of social, behavioral, cognitive, epi/genetic or biological mechanisms based on findings from the R61 phase.
    • Incorporation of new question items into ongoing epidemiological surveys that are based on findings from basic or clinical data collected during the R61 phase.
    • Recruitment of additional PSU participants in ongoing imaging and/or behavioral studies in a laboratory setting based on animal or epidemiological data generated during the R61 phase.

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

    Section II. Award Information
    Funding Instrument

    Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

    Application Types Allowed

    New
    Resubmission

    Revisions
    The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

    Clinical Trial?

    Optional: Accepting applications that either propose or do not 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.

    Award Budget

    Application direct costs are limited to $300,000 during each year of the R61 phase and $500,000 during each year of the R33 phase.

    Award Project Period

     The project period is limited to 2 years for the R61 phase and up to 3 years for the R33 phase. The total project period may not exceed 5 years.  

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

    Section III. Eligibility Information
    1. Eligible Applicants
    Eligible Organizations

    Higher Education Institutions

    • Public/State Controlled Institutions of Higher Education
    • Private Institutions of Higher Education

    The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

    • Hispanic-serving Institutions
    • Historically Black Colleges and Universities (HBCUs)
    • Tribally Controlled Colleges and Universities (TCCUs)
    • Alaska Native and Native Hawaiian Serving Institutions
    • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

    Nonprofits Other Than Institutions of Higher Education

    • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
    • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

    For-Profit Organizations

    • Small Businesses
    • For-Profit Organizations (Other than Small Businesses)

    Governments

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

    Other

    • Independent School Districts
    • Public Housing Authorities/Indian Housing Authorities
    • Native American Tribal Organizations (other than Federally recognized tribal governments)
    • Faith-based or Community-based Organizations
    • Regional Organizations
    • Non-domestic (non-U.S.) Entities (Foreign Institutions)
    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.

    Required Registrations

    Applicant Organizations

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

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

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

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

    Eligible Individuals (Program Director/Principal Investigator)

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

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

    2. Cost Sharing

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

    3. Additional Information on Eligibility
    Number of Applications

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

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

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

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

    2. Content and Form of Application Submission

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

    Letter of Intent

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

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

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

    The letter of intent should be sent to: NIDALetterofIntent@mail.nih.gov.

          Office of Extramural Policy and Review
          National Institute on Drug Abuse/NIH/DHHS
          6001 Executive Boulevard, Suite 4243, MSC 9550
          Bethesda, MD 20892-9550

    Page Limitations

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

    Instructions for Application Submission

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

    SF424(R&R) Cover

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

    SF424(R&R) Project/Performance Site Locations

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

    SF424(R&R) Other Project Information

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

    SF424(R&R) Senior/Key Person Profile

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

    R&R or Modular Budget

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

    R&R Subaward Budget

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

    PHS 398 Cover Page Supplement

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

    PHS 398 Research Plan

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

    Specific Aims: Separate specific aims should be presented for the R61 and R33 phases.

    Research Strategy: The Research Strategy should contain separate sections that describe both the R61 and R33 phases, as appropriate.  Separate research design and methods could be presented as needed for the R61 and R33 phases. It is not necessary to repeat information or details in the R33 section that are described in the R61 section.

    Any preliminary data that will support or justify the proposed hypothesis, rationale or development plan may be included.  However, preliminary data are not required for an R61/R33 application.

    Some of the experimental approaches to modeling PSU and PSU outcomes may not have a direct counterpart across translational stages. For example, it may be difficult to capture the complete drug history profile of human users in animal models, such as the drug dose, lifetime use, comorbid psychiatric conditions, or the route of administration. Additionally, laboratory assessments that examine motivational or cognitive processes in humans may not have an exact complement in animals and effects seen in animals may not always be applicable to humans. Whenever applicable, investigators should describe the most appropriate animal model and procedure to replicate the observed phenomena in humans. Compromises in experimental approaches and modeling should be made and are needed in order to facilitate the translation of outcomes. For example, it would be appropriate to examine relapse rates in epidemiological surveys, and then to translate this approach by measuring drug craving in humans and/or examining reinstatement of operant responding in animals. Whenever possible, investigators are encouraged to describe the assessments and models that have the most translational potential.

    Applicants should provide a description of how the study designs, methods and assessments are complementary such that outcomes at one translational stage enhance the interpretation of outcomes at the other translational stage.

    Since the intent of this announcement is to leverage PSU findings from one phase of the translational trajectory to guide research in another phase, PDs/PIs are not required to provide evidence of prior collaborative relationships. However, the PDs/PIs of both phases should describe a plan to communicate findings with each other throughout the life of the grant.

    Milestone and R61/R33 Transition

    The application must include milestones that are expected to be achieved by the end of the R61 phase. Milestones should be specific, quantifiable, and scientifically justified; they should not be simply a restatement of the specific aims for the R61 phase. All projects should include the following:

    • Clear milestones for the R61 phase and related scientific goals for the R33 phase.
    • The R33 portion of the application should focus on a translational stage that is different from the R61 phase.
    • A unifying and testable hypothesis that will be examined during both the R61 and R33 phase.
    • Applications should include a polysubstance group and, whenever possible, single-drug control groups should be included to determine if the outcomes observed in the PSU group are unique to combined drug use. It is not required to collect new data on single drug consequences if appropriate and comparable prior data already exist. Evidence of these data should be provided in the application.
    • Investigation of two primary drugs of abuse is preferred to facilitate data interpretation. The intent of this announcement is NOT to support other behavioral addictions, such as food addiction, gambling, or internet/gaming addictions.

    Demonstration that feasibility of data collection and analysis is possible within the budget and time constraints for both phases.

    R61 (Phase 1):

    Applicants should include one or more critical experiments for rigorously testing the proposed concept/hypothesis. These experiments must be scientifically justified, specific, and feasible. Applicants should state explicitly the results that support, reject, or are inconclusive regarding testing of their concept/hypothesis, and are strongly encouraged to calculate and report effect size, in addition to statistical significance, whenever possible.

    Milestones:

    Transition from the R61 to the R33 phase is contingent upon the successful completion of proposed milestones. These milestones are to be included as the last element of the Research Strategy section of the application and will be evaluated as part of the scientific and technical merit of the R61/R33 application. The milestones proposed in the application should be well-described, quantifiable, and scientifically justified to allow program staff to assess progress and successful completion of the R61 phase. Include a section labeled "milestones" describing milestones to be achieved during the R61 phase to qualify for the transition to the R33 as part of Research Strategy within the approach section.

    R33 (Phase 2):

    Although the Research Strategy for the R33 Phase is expected to be broad and somewhat speculative due to the unpredictable nature of the explorative research in the R61 Phase, the research strategy for the R33 phase of the award should be described in enough detail for reviewers to evaluate the merit of this component of the application, based on anticipated results.

    It is understood that the proposed milestones for the R33 phase may be revised based on activities during the R61 planning phase. In the event of an award, the PD/PI and NIH staff will negotiate a list of milestones for each year of support.

    Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

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

    NIDA strongly encourages investigators to share data with other investigators.  NIDA  expects that applicants to NIDA funding opportunity announcements: 1) submit their data to one of the NIH data archives for sharing; 2) include specific required elements in the Resource Sharing Plan including a description of whether and how the consents that will be used to obtain that data will affect the research that can be done with that data; and 3) include costs attributed to data preparation and submission to a data archive in grant applications

    Appendix:

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

    PHS Human Subjects and Clinical Trials Information

    When involving 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 SF424 (R&R) Application Guide, with the following additional instructions:

    If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

    Study Record: PHS Human Subjects and Clinical Trials Information

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

    Delayed Onset Study

    Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

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

    PHS Assignment Request Form

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

    Foreign Institutions

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

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

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

    4. Submission Dates and Times

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

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

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

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

    5. Intergovernmental Review (E.O. 12372)

    This initiative is not subject to intergovernmental review.

    6. Funding Restrictions

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

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

    7. Other Submission Requirements and Information

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

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

    For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

    Important reminders:

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

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

    See more tips for avoiding common errors.

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

    Post Submission Materials

    Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

    Section V. Application Review Information
    1. Criteria

    Only the review criteria described below will be considered in the review process.

    Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

    In addition, for applications involving clinical trials:

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

    Overall Impact

    Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

    Scored Review Criteria

    Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

    Significance

    Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? 

    SPECIFIC TO THIS FOA:

    In addition, for applications involving clinical trials

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

    Investigator(s)

    Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

    SPECIFIC TO THIS FOA: If the PD/PIs do not have a prior collaborative relationship due to the translational nature of the application, is the proposed communication plan effective for the PD/PIs communicate findings with each other throughout the life of the grant?

    In addition, for applications involving 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?

    Innovation

    Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

    In addition, for applications involving 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?

    Approach

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

    If the project involves human subjects and/or NIH-defined clinical research, are the plans to address

    1) the protection of human subjects from research risks, and

    2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?  

    SPECIFIC TO THIS FOA: Does the application include investigations in two different stages in the translational pipeline, which are composed of (1) basic science research in animals, (2) human-based laboratory studies, and (3) epidemiological, treatment development, or services research investigations? Is there a unifying and testable hypothesis that transcends both R61 and R33 phases? Does the application provide clear milestones for the R61 phase and related scientific goals for the R33 phase? Are those milestones conducive to accomplishing the study aims? Are the goals of the R33 phase based, in part, on findings collected during the R61 phase?

    When there are differences in species, study designs, methods and assessments across the R61 and R33 phases, does the application provide a description of how the studies are complementary such that the outcomes at one translation stage will enhance the interpretation of outcomes during another translational stage? If the intent of the application is to replicate the PSU phenomenon across translational stages, do the PD/PIs provide a description of how differences in research approaches are complementary across species and study design? If either the R61 or R33 phase proposes to use animal models, do the investigators utilize the most appropriate animal model or procedure to mimic outcomes observed in humans? Whenever applicable, does the application include single-drug controls or prior valid data on single drug outcomes to determine if changes observed in the PSU group are unique to combined drug use? If a R61 or R33 phase study proposes animal models, does the study go beyond studying additive effects of multiple drug use or exposure? If the study lacks preliminary PSU data, does the proposed project seem feasible to complete?

    Has the applicant proposed the required critical experiment(s) for testing the innovative idea? Can these experiments unambiguously test the hypothesis at hand, and are they feasible? Are the proposed milestones of the critical experiments well-defined with quantifiable measures that are appropriate for assessing the success of the R61 Phase of the award? Are the proposed critical experiments sufficient to determine if the project succeeded in accomplishing its specific aims? Is it clear how the R33 Phase of the study will develop and expand once the R61 Phase is completed?

    In addition, for applications involving clinical trials

    Does the application adequately address the following, if applicable

    Study Design

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

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

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

    Data Management and Statistical Analysis

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

    Environment

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

    In addition, for applications involving 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?

    Additional Review Criteria

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

    Study Timeline

    Specific to applications involving 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)?

    Protections for Human Subjects

    For research that involves human subjects but does not involve one of the  categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

    For research that involves human subjects and meets the criteria for one or more of the  categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

    Inclusion of Women, Minorities, and Individuals Across the Lifespan 

    When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

    Vertebrate Animals

    The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

    Biohazards

    Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

    Resubmissions

    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.

    Renewals

    Not Applicable

    Revisions

    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.

    Additional Review Considerations

    As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

    Applications from Foreign Organizations

    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.

    Select Agent Research

    Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

    Resource Sharing Plans

    Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3)  Genomic Data Sharing Plan (GDS).

    Authentication of Key Biological and/or Chemical Resources:

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

    Budget and Period of Support

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

    2. Review and Selection Process

    Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by CSR, 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 council. The following will be considered in making funding decisions:

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

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

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

    Section VI. Award Administration Information
    1. Award Notices

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

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

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

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

    Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that 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.

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

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

    Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the 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). 

    2. Administrative and National Policy Requirements

    All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

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

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

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

    Cooperative Agreement Terms and Conditions of Award

    Not Applicable

    3. Reporting

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

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

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

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

    Section VII. Agency Contacts

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

    Application Submission Contacts

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

    Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
    Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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

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

    Scientific/Research Contact(s)

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

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

    Annette Kaufman, Ph.D., M.P.H.
    National Cancer Institute (NCI)
    Telephone: 240-276-6706
    Email: kaufmana@mail.nih.gov

    David Berrigan, Ph.D., M.P.H
    National Cancer Institute (NCI)
    Telephone:240-276-6752
    Email: berrigad@mail.nih.gov

    Peer Review Contact(s)

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

    Financial/Grants Management Contact(s)

    Lennin Greenwood
    National Institute on Drug Abuse (NIDA) 
    Telephone: 301-827-6686
    Email: lennin.greenwood@nih.gov

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

    Carol Perry
    National Cancer Institute (NCI) 
    Telephone: 240-276-6282
    Email: perryc@mail.nih.gov

    Section VIII. Other Information

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

    Authority and Regulations

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

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