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

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

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

Purpose

The purpose of this limited competition FOA is to continue to support basic, epidemiologic, and clinical research on HIV/AIDS, HIV/HCV co-infections among substance abusing populations in the existing NIDA-funded cohorts under the FOAs PAR12-222 and PA 09-236, four of which will terminate in 2018 (see the list in Section III- Eligibility Information) if additional funds are not provided for them to continue resulting in the loss of exceptionally important well-characterized and maintained cohorts of subjects with HIV/AIDS and substance abuse. The funded projects have contributed highly significant findings to the scientific field of HIV/AIDS and substance abuse. This limited competition FOA will continue to support these four cohorts ([a] MSM and Substances Cohort at UCLA Linking Infections Noting Effects [MASCULINE], UCLA; [b] The AIDS Linked to the Intravenous Experience {ALIVE} Study, Hopkins; [c] Effects of HIV, Cocaine, and Prolonged ART Use on Subclinical Cardiovascular Disease, Hopkins; [d] Incidence of HIV Infection in a Cohort of IV Drug Users, Hopkins) that will conduct highly innovative multi-disciplinary research. This research will characterize the long-term, natural and treated history of HIV/AIDS and other co-occurring infections in the current cohorts of men and women, and recruit and retain new subjects into the cohort to provide insight into the changing demographics of the HIV epidemic among substance abusing populations in the U.S. Therefore, this FOA encourages applications from only those investigators whose projects will terminate in January 2018.

Research Objectives

Background

The National Institute on Drug Abuse supported a number of HIV/AIDS cohorts among substance abusing populations. These cohorts will address emerging and high priority research on HIV/AIDS and other opportunistic infections. These cohorts continue to serve as a strong resource platform for current and future collaborative efforts with other investigators to address emerging questions related to HIV infection, prevention, and/or treatment in the context of substance abuse, as well as to foster the creativity and efficiency of investigator-initiated research. The purpose of this Limited Competition Funding Opportunity Announcement (FOA) is to: (i) encourage applications from the currently funded cohort projects under FOAs PAR12-222 and PA 09-236, mentioned in purpose above, that will terminate in 2018 to enable maintenance of the existing cohorts, (ii) continue to address new emerging and/or high priority research on multidisciplinary aspects of HIV/AIDS and substance abuse, and (iii) provide support for retaining HIV/AIDS participants into the cohort(s) to provide insight into the demographics of the HIV epidemic among this high risk population in the US. This FOA will also continue to provide a strong resource platform for current and future collaborative efforts with other investigators to address new and emerging questions related to HIV infection, prevention, and/or treatment in the context of substance abuse, as well as to foster the creativity and efficiency of investigator initiated research goals. This limited competition FOA will not support establishment of new cohorts.

Research areas: The proposed FOA will continue to support multi-disciplinary multi-component basic, behavioral, and clinical research to cover multiple areas of research including but not limited to: (i) impact of community or individual level treatment and prevention modalities related to substance abuse and HIV/AIDS, (ii) engagement and retention in care, adherence to treatment regimens, (iii) study HIV and HIV-comorbidities progression and outcomes, (iv) impact of long-term drug use on progression of HIV/AIDS and HIV-comorbidities; (v) immunologic and virologic responses to HIV therapy, (vi) progression of HIV, HIV/HCV disease, (viii) infections associated medical and health consequences (neuroAIDS, cardiac, hepatic, renal, drug-drug interactions etc.) in drug abusing populations; and (ix) study impact/role of microbiome in HIV and HIV/HCV infections in substance abusing populations.

Despite the overall decline in new HIV infections worldwide, substance use continues to be a major driver of global infection, in association with sexual risk behaviors as well as through parenteral transmission. HIV prevalence among non-injecting drug users has also grown, and polysubstance use, including alcohol, marijuana, and cigarette smoking, is common among HIV-infected populations. Lack of treatment engagement, as well as treatment failure, continue to be major challenges among those with substance abuse issues. It therefore remains crucial to understand the role of substance use in the context of HIV diagnosis, prevention and treatment strategies, pathogenesis, and disease outcomes, as well as its role in HIV-associated co-infections, complications and co-morbidities.

Prospective, observational cohort studies in real world settings have informed current understanding of factors that impact HIV acquisition, prevention and progression, treatment success and clinical outcomes. Since the start of the HIV epidemic, cohort studies of high-risk infected and uninfected populations have made crucial contributions to understanding the biology of HIV, seroconversion dynamics, the natural and treated histories of HIV-1 infection, and the impact of associated co-morbidities, co-infections, and complications. Because HIV-infected individuals with access to antiretroviral treatment are living longer with HIV, as new prevention and treatment approaches are introduced, it will be important to better understand the complex host, viral, and environmental factors that influence disease progression and outcomes in people living with HIV. In addition, longitudinal cohorts involving at-risk individuals can provide crucial information about transmission and acute or early phases of infection.

This initiative is intended to support only those cohorts that are terminating in 2018 and will include substance using individuals who are HIV positive or at risk for infection. The applications in response to this FOA may include specific research projects that focus on the intersection of HIV/AIDS and substance use, and should serve as a platform for a wide range of research efforts by the investigator, collaborators, and other researchers utilizing data and/or specimens collected from these studies as part of independent, investigator-initiated research grants. Research aims included in submitted applications may be broad or narrow, given the diverse topics of interest to this FOA, such as identifying the determinants of susceptibility or resistance to infection; HIV prevention; barriers to optimal HIV care; the health effects of multiple co-morbidities and co-infections, such as HCV; disease progression and response to both substance abuse and HIV treatment; the impact of aging; factors including pharmacokinetics/pharmacodynamics affecting adherence to antiretroviral treatment and other pharmacotherapeutic and behavioral interventions; and understanding determinants and consequences of comprehensive care for chronic comorbid diseases, substance abuse, and mental health issues. Populations of particular interest may include injection and non-injection substance users, sexual minorities (including men who have sex with men (MSM)), racial and ethnic minority women, youth/adolescents, and high-risk heterosexual couples.

The National Institute on Drug Abuse encourages comparability, collaboration, and scientific yield of research funded under this FOA. The capacity of cohort studies to address both broad and specific research questions that take into account the heterogeneity among HIV-infected and at-risk individuals, the diversity of disease severity, patterns and history of substance use, comorbidities, and demographic variables, would be greatly enhanced by harmonization using a common set of core measures. Common elements for interval data collection provide opportunities for multiple cohorts addressing a variety of issues to collaborate on priority questions of mutual interest which a single cohort may not be able to address. Awardees funded under this FOA will be expected to participate in collaborative activities, including annual meetings to determine how to best to harmonize data. Applications in response to this FOA should include funds for investigators to attend an annual meeting in Washington, D.C. as part of the budget request.

The scope of the application should address the following key points:

1. A rationale and purpose for the proposed continuation or expansion of an existing cohort involving HIV and substance abuse, including characteristics of the population to be studied;

2. The cohort must serve as resource platform for current and future collaborative efforts with other investigators to address new and emerging questions related to HIV infection, prevention, and/or treatment in the context of substance abuse, as well as to foster the creativity and efficiency of investigator initiated research goals;

3. Characterization of substance use in the population to be studied, such as specific drugs used, form of administration, level and history of use, and/or changing patterns over time including initiation;

4. Measurement, technologic, and/or methodologic approaches for the design, conduct and analyses of cohort studies of HIV/AIDS and substance use, including discussion of cohort outreach and retention approaches to ensure long-term follow-up of participants;

5. Identification and justification of the priority research domains for the cohort study and how the study aims will be achieved;

6. Identification of high priority research questions the investigator proposes to be explored through collaboration with other investigators, including those involved in other cohort studies. This may include but is not limited to developing standardized assessments and outcome measures that support comparative studies among substance-using populations, pooling of data across cohorts, and/or identification of complex relationships such as gene-gene and gene-environment interactions;

7. Discussion of proposed data elements, such as clinical data, biologic specimens, socio-behavioral data, or treatment variables that will support the study aims, and a schedule for collection of these elements for prospective intervals. In addition, the discussion should address the potential of the proposed data elements to inform a common or shared platform for priority research collaborations with other research studies, as well as a plan for sharing data and materials with other investigators.

Data elements of interest for this FOA include but are not limited to:

(a) Behavioral, demographic, and medical data, including general medical history, use of antiretroviral therapy, health service utilization, sexual behavior and health, and substance use and treatment history,

(b) Clinical and laboratory data, including immune parameters, viral load, and co-infections,

(c) Biological specimen data, including capacity for a specimen repository and a plan to allow identification of specimens which meet specific criteria for collaborative efforts

Additional data elements as appropriate to the specific study aims as well as to key research collaboration priorities could include but are not limited to:

(i) AIDS-related and non-AIDS diagnoses, e.g., cardiovascular and cerebrovascular disease, kidney and liver disease, lung infections, bacteremia, neurologic or neuropsychological outcomes

(ii) Clinical evaluation such as physical examinations or other specific clinical assessments collected at study visits

The scientific agenda of this FOA is the development and maintenance of a cohort that will facilitate specific or multicomponent research studies including, but not limited to, the following areas of interest:

(i) Impact of injection and non-injection substance use, including specific dominant substances and/or polysubstance abuse, and other socio-behavioral factors on HIV acquisition, transmission, treatment and subsequent disease course;

(ii) Impact of community or individual-level treatment and prevention modalities related to substance use and/or HIV/AIDS, structural factors, or policy changes on HIV incidence, engagement and retention in care, adherence to treatment regimens, and/or disease progression and outcomes;

(iii) Long-term natural and treated history of HIV infection in the context of substance use, such as the clinical course of HIV disease following long-term exposures to different combinations of therapies, unstructured treatment interruptions, and various co-morbidities;

(iv) Research on the immunologic and virologic responses to HIV therapy, including demographic, genetic, psychological, behavioral, viral resistance, and immunologic predictors of response that inform when to initiate treatment and how to optimize response over the long term in the context of substance use;

(v) Research on the short and long-term effects of HIV, chronic substance use, and prolonged HIV therapy exposure on cardiovascular disease, lipodystrophy, liver disease, neurocognitive function, psychiatric status, substance use, kidney disease, diabetes, and other outcomes;

(vi) Studies of the effects of aging and substance use on the clinical course of HIV, HIV therapy, and response to HIV therapy, including consideration of how normal psychological, neurocognitive, biological, and physical processes of aging are affected by HIV treatment and disease progression

(Vii) Pathogenesis research that takes advantage of longitudinally collected specimens, examining the intersection of HIV infection and substance use with disease outcomes, including genomics, epigenomics, proteomics, metabolomics, or systems biology approaches;

(viii) Characterization of acute clinical events and concomitant infections prevalent in substance using populations (e.g., HCV, TB) and their effects on HIV disease course.

Special Considerations

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

Points to Consider Regarding Tobacco Industry Funding of NIDA Applicants: The National Advisory Council on Drug Abuse (NACDA) encourages NIDA and its grantees to consider the points it has set forth with regard to existing or prospective sponsored research agreements with tobacco companies or their related entities and the impact of acceptance of tobacco industry funding on NIDA's credibility and reputation within the scientific community. Please see (http://ww2.drugabuse.gov/about/organization/nacda/points-to-consider.html) for details.

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

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

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

Eligible Organizations

Applications may be submitted only by the currently NIDA-funded cohort investigators funded under the FOAs PAR 12-222 and PA 09-236 that are terminating in 2018. Therefore, only the following awardee organizations with funded projects may apply for this limited competition:

[a] University of California (UCLA), Los Angeles; 'MSM and Substances Cohort at UCLA Linking Infections Noting Effects [MASCULINE]',

[b] Johns Hopkins University, Baltimore, Maryland; 'The AIDS Linked to the Intravenous Experience {ALIVE} Study';

[c] Johns Hopkins University, Baltimore, Maryland; 'Effects of HIV, Cocaine, and Prolonged ART Use on Subclinical Cardiovascular Disease';

[d] Johns Hopkins University, Baltimore, Maryland; 'Incidence of HIV Infection in a Cohort of IV Drug Users'.

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 (PD(s)/PI(s))

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

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

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

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

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

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

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

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

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

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

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.

Applicants are encouraged to send the letter of intent by email to the email address above but as an alternative the letter may also be sent to:

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

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

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

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

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

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

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

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

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

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

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

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

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

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

See more tips for avoiding common errors.

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

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

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

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

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

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Are there a clear rationale and purpose for the proposed continuation of an existing cohort involving HIV and substance abuse, including characteristics of the population to be studied?

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?

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? Are the additional data elements appropriate to the specific aims and to key research collaboration priorities?

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

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

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.

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

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

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

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

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

Not Applicable

For Renewals, the committee will consider the progress made in the last funding period.

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.

Not Applicable

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

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

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

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by 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:

• Will be reviewed and will receive a priority score of scientific merit.
• 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. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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

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

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

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

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

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 http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.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

If this FOA is not a cooperative agreement, make no changes to this section. If it IS a cooperative agreement, fill out the template Cooperative Agreement Terms and Conditions of Award as appropriate. THEN, copy and paste all the text from that template into this section, replacing Not Applicable (below) with your text.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipient(s) in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardee(s) for the project as a whole, although specific tasks and activities may be shared among the awardee(s) and the NIH as defined below.

The PD(s) PI(s) will have the primary responsibility for:

The PD(s)/PI(s) will have the primary authority and responsibility of carrying out several activities as detailed above under Section III-Eligibility Information, subpart- 3-Other Special Eligibility Criteria'. Awardee(s) should be advised that they will retain custody of and primary rights to their data developed under the award, subject to current Government policies regarding rights of access consistent with current DHHS, PHS, and NIH policies.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

An NIH Project Scientist (PS) will have substantial programmatic involvement that is above and beyond the normal stewardship role in the award and will be named in the award notice. The responsibilities of the PS include involvement during conduct of the activity, through technical assistance, advice, coordination, and/or other assistance activities that is above and beyond normal program stewardship for grants. The PS will participate in the definition of objectives and approaches used by the CC Director in coordinating activities of the NIDA-funded U01 cohort studies. However, the dominant role and prime responsibility for the activity reside with the awardee(s) for the project as a whole, but not necessarily for each task.

Additionally, an agency program official (PO) program will be responsible for the programmatic stewardship of the award and will be named in the award notice. The Government, via the PO, will have access to data generated under this Cooperative Agreement and may periodically review the data and progress reports. The NIDA PO may use information obtained from the data for the preparation of internal reports on the activities of the study. However, awardees will retain custody of and have primary rights to all data developed under these awards.

Areas of Joint Responsibility include:

The PD(s)/PI(s) and the PS will work closely in evaluating the most appropriate methods used to coordinate activities of the NIDA-funded U01 cohorts and study effectiveness of the virtual repository developed under this U01 cooperative agreement.

During performance of the award, the PS, with assistance from other scientific program staff who are designated based on the research topic and their relevant expertise, may provide appropriate assistance, advice, and guidance. The role of the NIH PS will be to facilitate and not to direct the activities of the center. It is anticipated that decisions in all activities will be reached by consensus between the Program Director/Principal Investigator and the NIH PS, and that NIDA staff will be given the opportunity to offer input into this process. The PS will facilitate liaison activity for partnerships, and provide assistance with access to NIDA-supported resources and services.

The release of each annual funding increment by NIDA will be based on the NIDA PO review of progress towards achieving the previously agreed upon research goals, interim objectives and milestones. NIDA reserves the right to terminate or curtail activities of the funded U01 project in the event of inadequate progress, poor quality, or other major breach of the approved project.

The specific timelines, interim objectives and funding levels agreed to by the awardee and the NIDA shall be included in the terms and conditions of award. Given the nature of the activities of the U01 funded projects, it is recognized that timelines and interim objectives may require revision and re-negotiations during the project period. The Program Director/Principal Investigator and NIDA PO must agree to all such revisions.

The PD(s)/PI(s) will be responsible for the timely submission of all the activities performed under this Cooperative Agreement. These activities include but not limited to coordination of activities (detailed above under Section III-Eligibility Information, subpart- 3-Other Special Eligibility Criteria') being conducted under funded U01 cohort projects and establishment of the virtual repository and its utility by U01 cohort investigators and their collaborators. This Cooperative Agreement will require appropriate acknowledgement of NIDA support. Timely publication of major findings is encouraged.

Dispute Resolution:
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three academic members who are not involved in the study will be convened. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

NIDA Staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

i) In addition to the Program Official who will be responsible for normal program stewardship, the cooperative agreement will be assigned a Project Scientific Officer (PS) with multidisciplinary expertise in HIV/AIDS, co-occurring opportunistic infections and substance use. The PS will be substantially involved in this project beyond the normal stewardship of an NIDA Program Official by ensuring the established studies are followed and assisting in overseeing the quality of the study.

ii) The PS will serve as a resource to aid in resolving scientific issues as they arise.

iii) The PS will facilitate the access to other U01 funded investigators at no cost to the grantee.

iv) Study Closure The PS may require that a study be closed for reasons including but not limited to: a) failure to establish successful collaborations with the funded U01 investigators, and b) failure to establish the required virtual repository of basic and clinical data from thousands of enrolled patients for collaborations between and among U01 researchers and their current and future collaborators. Once notified by the Grants Management Branch, NIDA, of site (coordination center) closure, the funded site should cease. Only reasonable personnel and administrative costs associated with the orderly phase-out may be obligated or charged to the grant award.

Areas of Joint Responsibility Include:

i) The awardee and NIDA PS will confer on the most optimal strategy to ensure and monitor coordination between and among U01 funded researchers and their collaborators compliance.

ii) Proposals for the design and implementation of each new research activity will be discussed between the awardee and NIDA PS before a decision is made to proceed with the proposed research or administrative activity. Both parties shall agree on the most appropriate protocol design and outcome measures for activity.

iii) Status reports in the format of conference calls with NIDA PS will take place on a bi-monthly basis. These reports will include information concerning but not limited to results of collaborations and the establishment of the biorepository and its utility by researchers and their collaborators. Status reports will also discuss the results of each ongoing or research activity in progress as they become available.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three academic members who are not involved in the study will be convened. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

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

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

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

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

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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

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

Jag H. Khalsa, MS, PhD.
National Institute on Drug Abuse (NIDA))
Telephone: 301-827-5928
Email: jkhalsa@nih.gov

Mark Swieter, PhD
National Institute on Drug Abuse
Telephone: 301-827-5844
Email: mswieter@mail.nih.gov

Cheryl Nathaniel
National Institute on Drug Abuse (NIDA)
Telephone: 301-827-6703
Email: nathanic@nida.nih.gov

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

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