Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute on Drug Abuse (NIDA)
Funding Opportunity Title	Comorbid HIV, Chronic Pain, and Substance Use among Older Adults (R21)
Activity Code	R21 Exploratory/Developmental Research Grant Award
Announcement Type	New
Related Notices	August 21, 2013: Removed reference to ASSIST in section IV.3, since ASSIST is currently only available for multi-project applications. May 30, 2013 (NOT-OD-13-074) - NIH to Require Use of Updated Electronic Application Forms for Due Dates on or after September 25, 2013. Forms-C applications are required for due dates on or after September 25, 2013.
Funding Opportunity Announcement (FOA) Number	RFA-DA-14-012
Companion Funding Opportunity	RFA-DA-14-009, R01 Research Project Grant RFA-DA-14-010, R01 Research Project Grant RFA-DA-14-011, R01 Research Project RFA-DA-14-007, U01 Research Project Cooperative Agreements
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.279
Funding Opportunity Purpose	To improve understanding of the intersection of HIV/AIDS and drug abuse, this Funding Opportunity Announcement (FOA) is part of a multipronged 2014 expansion of HIV and AIDS related research within the context of drug and alcohol abuse among understudied populations and in understudied settings that show promise for the development of effective prevention and treatment efforts. In addition to this funding opportunity, others included in the 2014 expansion address HIV/AIDS and substance use among the homeless and unstably housed (RFA-DA-14-009); substance use, HIV, and Black/African American women and young Men who have Sex with Men (MSM) (RFA-DA-14-010); the integration of substance abuse and HIV prevention and treatment within HIV/AIDS service delivery settings (RFA-DA-14-011) and Seek, Test, Treat, and Retain Data Harmonization Coordinating Center (RFA-DA-14-007). For this funding announcement, the National Institute on Drug Abuse (NIDA) invites innovative, exploratory research applications proposing to study the intersection of HIV, chronic pain, and substance use among older adults. Applications could include research to examine risk and protective factors contributing to comorbid HIV, chronic pain, and substance use among older adults; to characterize the adverse medical, mental health and social consequences associated with comorbid HIV, substance abuse, and chronic pain among older adults; or to develop effective prevention and service delivery approaches and behavioral and pharmacological treatments to address these comorbid conditions in older adults. Research is also encouraged on the role of HIV/AIDS-associated conditions, HIV treatment, and/or other biobehavioral/social factors in the context of aging, chronic pain, and substance use. A range of research approaches are of interest, including epidemiologic, prevention science, health services, and intervention studies.

Posted Date	June 10, 2013
Open Date (Earliest Submission Date)	October 15, 2013
Letter of Intent Due Date(s)	October 15, 2013
Application Due Date(s)	November 15, 2013, by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
AIDS Application Due Date(s)	November 15, 2013
Scientific Merit Review	February/March 2013
Advisory Council Review	May 2014
Earliest Start Date	July 2014
Expiration Date	November 16, 2013
Due Dates for E.O. 12372	Not Applicable

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

To improve understanding of the intersection of HIV/AIDS and drug abuse, this Funding Opportunity Announcement (FOA) is part of a multipronged 2014 expansion of HIV and AIDS related research within the context of drug and alcohol abuse among understudied populations and in understudied settings that show promise for the development of effective prevention and treatment efforts. In addition to this funding opportunity, others included in the 2014 expansion address substance use, HIV, and Black/African American women and young Men who have Sex with Men (MSM); the integration of substance abuse and HIV prevention and treatment within HIV/AIDS service delivery settings; and HIV/AIDS and substance use among the homeless and unstably housed.

The number of older adults living with HIV/AIDS in the U.S. has continued to rise over the past two decades. Advances in HIV treatment have meant that more persons with HIV are living longer, but, in addition, rates of newly diagnosed infections among older adults have also been increasing. The Centers for Disease Control and Prevention (CDC) estimates that by 2015, over half of all Americans living with HIV will be over the age of 50. Chronic pain conditions are common and debilitating in persons living with prolonged HIV infection, with a range of HIV-associated comorbid conditions raising the risk for pain syndromes, including HIV-related peripheral neuropathy, osteonecrosis, infection-related and non-infection-related cancers, and neuropathies secondary to antiretroviral therapies. Age-related changes and increased frailty further exacerbate the risk for chronic pain conditions in older adults. In addition, there is some evidence that conditions normally associated with aging (e.g., type 2 diabetes, osteoporosis, heart failure) are occurring earlier among long-term HIV-seropositives. This putative accelerated aging appears to be related to metabolic processes which may be associated with chronic HIV infection itself and/or with long-term antiretroviral use, particularly older antiretroviral medications. Many of these conditions may contribute to chronic pain and related disability among aging persons with HIV. Chronic pain conditions in older adults living with HIV are further complicated by the increased risk of substance abuse among persons with HIV. Limited research has explored the complex interrelationships between comorbid HIV, chronic pain, and substance abuse in older adults.

Through this announcement, NIDA encourages a broad range of research applications to address the complexity of comorbid HIV, chronic pain, and substance use among older adults. Across proposed research strategies, there is an interest in stimulating the development and integration of novel technologies (e.g., imaging, proteomic, and/or metabolomic methodologies) to examine and understand the etiology and biological and behavioral mechanisms associated with these three comorbid conditions in older adults, as well as other comorbidities that may be affected by one or more of these conditions and/or long-term antiretroviral treatment.

Specific areas of research interest include, but are not limited to, the following:

Basic Preclinical and Clinical Research

Research on age-related physiological changes that may influence the emergence of chronic pain conditions and substance use disorders in older adults living with HIV, as well as metabolic processes which may accelerate age-related changes among long-term HIV-seropositives (e.g., telomere dysfunction, cellular senescence).

Research that examines the possible association of physical dependence, produced by either licit or illicit drug use, on the development of addiction in older adults with comorbid HIV and chronic pain.

Studies of the pharmacokinetics, pharmacodynamics, and pharmacogenetics of drug-drug interactions between prescription opioids, antiretrovirals, and other licit and illicit substances (e.g., alcohol, supplements, other prescription medications) among older adults with HIV.

Research on opioid-induced hyperalgesia and its relationship to tolerance and addiction in older adults with HIV.

Clinical neurobiological investigations, including those utilizing neuroimaging, to examine how chronic pain and prescription analgesics affect brain processes and systems among older adults with HIV.

Studies on the unique cognitive and neurological complications associated with HIV, substance abuse, and chronic pain among older adults, to include studies that incorporate well-characterized cognitive challenge tasks and neurological measures.

Epidemiology Research

Basic epidemiologic studies on the interrelationships between HIV, chronic pain, and substance abuse among older adults, including the misuse and diversion of prescription analgesics from both licit and illicit sources.

Studies on the role of comorbid chronic pain and substance abuse in driving new HIV infections among older adults, including among older adults who misuse prescriptions opioids and other medications.

Studies on the role of other comorbid medical and psychiatric conditions on the nature and magnitude of comorbid chronic pain, substance abuse, and HIV among older adults.

Studies on the risk of initiating injection opioid abuse after initial misuse of prescription oral opioids for treatment of chronic pain among older adults, and its association with HIV-risk behaviors, to include the range of factors influencing transition to injection drug abuse at later ages (e.g., adequacy of pain relief from prescription oral analgesics, cost and availability factors).

Studies on the role of physical and cognitive impairment, including HIV-associated neurocognitive disorders, on comorbid HIV, chronic pain, and substance use among older adults.

Studies to identify clinical or demographic sub-groups among older adults with differential susceptibility to comorbid chronic pain, substance use disorders, and HIV, including studies on unique factors among older racial/ethnic minority populations and older men who have sex with men.

Lifespan studies to better understand temporal development of these comorbidities, which may reveal antecedent, concurrent, and sequential relationships with HIV infection.

Prevention, Treatment, and Health Systems Research

Research on approaches to prevention, screening, assessment, and diagnosis for comorbid chronic pain and substance use disorders in older adults living with HIV, including research to develop new approaches and to further validate existing models.

Studies that explore the impact of existing evidence-based drug abuse prevention approaches, or variants of existing approaches, on drug abuse patterns among older adults with comorbid chronic pain and HIV.

Studies to develop and evaluate effective treatment strategies for the management of comorbid chronic pain and substance abuse in older adults living with HIV.

Research on attitudes, knowledge, and patterns of prescribing for comorbid chronic pain and substance use across categories of patients and health care providers and how these attitudes contribute to appropriateness of prescribing practices for older adults with HIV (e.g., differential antiretroviral and/or analgesic prescribing practices based on history of substance abuse, socioeconomic status, race/ethnicity, gender).

Studies on the role of antiretroviral adherence on comorbid chronic pain and substance use among older adults with HIV.

Studies on adherence to treatment regimens for chronic pain and its association with risk of HIV and substance use disorders among older adults.

Studies of the effects of medical marijuana use for chronic pain on antiretroviral adherence and other HIV-related outcomes among older adults.

Studies to develop and evaluate behavioral treatments strategies to address comorbid chronic pain and substance use disorders and/or to prevent abuse of prescribed analgesic medications among older adults with comorbid HIV and chronic pain.

Research to develop, evaluate, and disseminate innovative and effective science based education approaches to ensure health professionals provide access to appropriate behavioral and pharmaco- therapies for chronic pain and substance use disorders among older adults with HIV.

This FOA encourages research applications that focus specifically on older populations. Consistent with the CDC definition of older HIV-infected individuals, applications should involve persons 50 years of age or older. Applicants are strongly encouraged to enroll individuals across the range of older ages, especially individuals at the upper end of the age range (i.e., 70 years or older). Studies that include a younger comparison group (e.g., comparisons between younger and older HIV-infected populations) would be considered acceptable approaches.

For this initiative, NIDA is interested broadly in understanding the complex intersection of aging, chronic pain, HIV/AIDS, and substance abuse, with a particular interest in the misuse and abuse of prescription and non-prescription opioids. Applications are also encouraged that explore the relationship of these comorbid conditions with other addictive substances, including nicotine, marijuana, stimulants, and polysubstance use. Regardless of the substance, applications must incorporate all three comorbid conditions (HIV, chronic pain, and substance abuse) among older adults as a part of their study. Across methodological approaches, studies are expected to include multidisciplinary research teams that include investigators/institutions with an appropriate depth of expertise in HIV, chronic pain, substance abuse, and aging processes/normative aging (e.g., clinically oriented projects would be expected to include multidisciplinary teams with expertise in comprehensive HIV care, geriatrics, pain management, and substance abuse treatment).

National Addiction & HIV Data Archive Program (NAHDAP)

NIDA strongly encourages investigators to deposit and/or utilize data sets affiliated with NAHDAP, hosted by the Inter-university Consortium for Political and Social Research (ICPSR). For details, please see the following website (http://www.icpsr.umich.edu/icpsrweb/NAHDAP/). For questions or additional information specifically on the NAHDAP program, please contact Dr. Kathy Etz at [email protected].

Data Harmonization

NIDA encourages data harmonization to increase comparability, collaboration, and scientific yield of clinical research on drug abuse and HIV. Toward that end, awardees conducting research directly related to comorbid HIV, chronic pain, and substance use among older adults should employ, whenever possible, measures that are consistent across other grants on this topic in order to harmonize data within the following domains: demographic information, substance use history, mental health functioning, HIV risk behavior, HIV testing and counseling, biological markers of HIV, use of and adherence to HIV treatment, and related issues unique to comorbid HIV, chronic pain, and substance use among older adults. Awardees are also expected to use monies within the grant to cover travel expenses to attend annual meetings of all grantees funded under RFA-DA-14-012 on data harmonization, to be held in Washington DC. For additional information and examples of data harmonization in other NIDA grants, please see: For more information please see: http://www.drugabuse.gov/researchers/research-resources/data-harmonization-projects/seek-test-treat-retain/addressing-hiv-in-criminal-justice-system and http://www.drugabuse.gov/researchers/research-resources/data-harmonization-projects/seek-test-treat-retain/addressing-hiv-among-vulnerable-populations.

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 http://grants.nih.gov/grants/guide/notice-files/NOT-DA-07-013.html.

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 The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	NIH intends to commit $1 million in FY2014 to fund an estimated 5-7 awards.
Award Budget	The total combined budget for direct costs for the two-year R21 project period may not exceed $275,000. No more than $200,000 may be requested in any single year. Applicants may request direct costs in $25,000 modules, up to the total direct costs limitation of $275,000 for the combined two-year award period.
Award Project Period	The total project period may not exceed 2 years.

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

Foreign components, as defined in the NIH Grants Policy Statement, are not 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 (PDs/PIs)

All PDs/PIs must have an eRA Commons account and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. 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.

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for 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, 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.

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:

• Number and title of this funding opportunity
• 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)

The letter of intent should be sent to: [email protected]

Applicants are encouraged to send the letter of intent by email to the address above, but if necessary the letter may be sent to:

Director - DA-14-012
Office of Extramural Affairs
National Institute on Drug Abuse/NIH/DHHS
6001 Executive Boulevard, Suite 4243, MSC 9550
Bethesda, MD 20892-9550

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

The forms package associated with this FOA includes all applicable components, required and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

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:

Research Strategy: For this initiative, NIDA is interested broadly in understanding the complex intersection of aging, chronic pain, HIV/AIDS, and substance abuse, with a particular interest in the misuse and abuse of prescription and non-prescription opioids. Applications are also encouraged that explore the relationship of these comorbid conditions with other addictive substances, including nicotine, marijuana, stimulants, and polysubstance use. Regardless of the substance, applications must incorporate all three comorbid conditions (HIV, chronic pain, and substance abuse) among older adults as a part of their study. Across methodological approaches, studies are expected to include multidisciplinary research teams that include investigators/institutions with an appropriate depth of expertise in HIV, chronic pain, substance abuse, and aging processes/normative aging (e.g., clinically oriented projects would be expected to include multidisciplinary teams with expertise in comprehensive HIV care, geriatrics, pain management, and substance abuse treatment).

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) 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.

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.

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 by the Center for Scientific Review and responsiveness by NIDA, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

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).

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? 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?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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?

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?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

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?

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.

Protections for Human Subjects

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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. 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

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

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

Applications from Foreign Organizations

Not Applicable

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) Genome Wide Association Studies (GWAS).

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.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NIDA, 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.

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

Applications will be assigned 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 National Advisory Council on Drug Abuse. 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 the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

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 annual Non-Competing Progress Report (PHS 2590 or RPPR) 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 Commons Help Desk (Questions regarding 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)

Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: [email protected]

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

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-710-0267
TTY 301-451-5936
Email: [email protected]

Jeffrey D. Schulden, M.D.
Epidemiology Research Branch, DESPR
National Institute on Drug Abuse (NIDA)
Telephone: 301-402-1526
Email: [email protected]

Mark Swieter, Ph.D.
Office of Extramural Affairs
National Institute on Drug Abuse (NIDA)
Telephone: 301-435-1389
Email: [email protected]

Heidi Young
Grants Management Branch
National Institute on Drug Abuse (NIDA)
Telephone: 703-243-8267
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 Parts 74 and 92.