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 National Institute on Drug Abuse (NIDA) supports several HIV/AIDS cohorts involving people with substance use disorders (SUDs). These longitudinal cohorts serve as a resource platform for facilitating collaborations among investigators attempting to address emerging questions related to HIV infection, prevention, and treatment in the context of substance use and SUDs, and foster creativity and efficiency in investigator-initiated research. The purpose of this limited competition FOA is to continue supporting basic, epidemiologic, and clinical research on HIV/AIDS and HIV-associated co-morbidities and co-infections among populations with substance use and SUDs. This FOA ensures that the cohort studies continue to provide further insights into the changing demographics of the HIV epidemic as it relates to the current opioid crisis.

Background

Drug abuse (DA) is a major contributor to the persistence and the occurrence of new HIV/AIDS cases. As per CDC, Injection Drug Use (IDU) contributed to an estimated 9% of newly diagnosed HIV cases in 2017. The rate of drug overdose deaths involving opioids has been on the rise since 1999, and CDC estimates 47,600 deaths in 2017 due to Opioids. Together with the overdose crisis, the opioid epidemic has brought new HIV cases and a marked increase of people with co-infections, particularly hepatitis C (Hep-C). The social and economic costs of the opioid epidemic, together with HIV and HCV comorbidity, are staggering.

Since the start of the HIV epidemic, cohort studies of high-risk infected and uninfected populations have made important contributions to the understanding of HIV virology, seroconversion dynamics, the natural and treated histories of HIV-1 infection, the impact of HIV-associated co-morbidities and complications including the role of substance use and SUDs. Further, longitudinal cohorts of at-risk individuals can provide crucial information about transmission and acute or early phases of infection. NIDA has been supporting several HIV/AIDS cohorts among substance abusing populations to address emerging questions related to HIV infection, prevention, and/or treatment in the context of substance abuse. These cohorts have focused on prospective, observational studies in real world settings to study factors that impact HIV prevention, disease acquisition and progress, treatment success and clinical outcomes.

Research Objectives and Scope

Since the report of initial HIV cases back in early 1980 s, the face of HIV/AIDS has significantly changed from an acute and/or subacute fatal illness into a chronic, manageable illness due to the outstanding advances in HIV treatment. However, new cases continue to occur. In view of this, 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 particular in those who use and have SUDs.

This initiative aims to continue supporting existing cohorts of substance using individuals who are HIV-positive or at risk for HIV infection and foster innovation and targeted expansion. The applicants to this FOA must currently have a current cohort study that has been funded by NIDA under PAR-DA-12-222, focused on the intersection of substance use and HIV. In addition, applicants are strongly encouraged to include specific research projects that focus on infectious co-morbidities particularly HCV, and non-infectious comorbidities especially neurocognitive impairment (NCI) and neurological and mental health disorders associated with HIV, substance use and misuse, and antiretroviral therapy (ART).

With this FOA, NIDA intends to move the cohorts toward serving as a national level resource for data and/or biospecimens and as a platform for a broad spectrum of research addressing HIV in the substance use context. Clinical data and biological samples collected via the cohort(s) are expected to be available for sharing and use by the scientific community and awardees will be expected to participate in collaborative activities including at least one in-person meeting per year in Bethesda, MD, quarterly conference calls with the NIDA AIDS Program leadership, and interaction with researchers at other conference and meeting venues. Therefore, applicants responding to this FOA are asked for current efforts and future plans for the following areas:

a) standardizing data and biological specimen collection protocols across the NIDA-funded cohorts

b) developing common data elements around substance use and SUD and incorporating them into their study

c) participating in data harmonization activities for multiple domains, but especially drug use and HIV related data, when measures for data collection vary

d) engaging in data sharing widely across other NIDA and NIH-funded HIV cohorts

e) linking with other known data and specimen banks

f) establishing collaborations with scientists engaged in basic, clinical, translational and behavioral research related to HIV and SUD to leverage cohort data

Applications need to address NIH highest priority areas of research: Research Priorities | NIH Office of AIDS Research

The applications in response to this limited competition FOA should address research areas including, but not limited to the following topics:

• Impact of injection and non-injection substance use, including specific dominant substances and/or polysubstance abuse, factors on HIV acquisition, transmission, treatment and subsequent disease course
• Studies on the Continuum of Care for co-occurring HIV and Hep C
• Contrast studies of HIV and Substance Use Disorder (SUD) populations in urban, suburban and rural areas
• Impact of opioid use in HIV early identification and continuum of care
• Impact of emergent drug use epidemics (suburban and urban) on HIV identification and continuum of care, including transitions from, e.g., opioids to stimulants
• 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
• Consideration of life course changes in drug use and HIV care, with particular attention to opioid use among persons over age 50 living with HIV with current or previous long-term drug use
• 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
• Research on the immunologic and viral 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
• Methodologic research that addresses novel ways to collect behavioral or biologic data as well as novel ways to analyze and disseminate data to promote reduction of risk and/or uptake and adherence to prevention or treatment services
• Research on the short and long-term effects of HIV, chronic substance use, and prolonged HIV therapy exposure on neurocognitive function, psychiatric status, and substance use.
• 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
• 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
• Characterization of acute clinical events and concomitant infections prevalent in substance using populations (e.g., HCV) and their effects on HIV disease course
• Differential effects of the use of opioid agonists (for example: methadone, buprenorphine) versus opioid antagonists (for example: long-acting naltrexone) in people with HIV and other comorbidities
• Consideration of pre-exposure prophylaxis (PrEP) uptake and adherence, including adoption in novel settings (e.g., needle exchange) or through novel modalities (e.g., telehealth, use of electronic medical record systems)
• Effects of nicotine, marijuana, and synthetic cannabinoids in people with HIV and chronic pain
• Conversion of SUD epidemic from heroin to fentanyl and its effects in HIV
• The effect of emergent pharmacotherapies for SUD in HIV (Lofexidine, long-acting buprenorphine, pregabalin, gabapentin, nabilone, buspirone, etc.) together with novel HIV therapies (long-acting anti-retroviral treatments)

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 from this FOA.

Only applications from grantees previously funded under NIDA funding opportunity announcement, PAR-12-222 are allowed.

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) 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.
• o NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

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. Only PDs/PIs previously funded under the NIDA initiative, PAR-12-222 are eligible to apply, unless prior approval has been obtained for a change in PI/PD has been obtained from the Program Officer for the current grant.

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.

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).

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

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

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: [email protected].

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:

Specific Aims:

List in priority order, the broad, long-range objectives and goals of the proposed research, and indicate how these goals will be accomplished based on the longitudinal cohorts and the proposed studies. Concisely describe the hypothesis or hypotheses to be tested. Indicate how the work proposed fit together to address the overall goals and objectives of the research.

Research Strategy:

The applications in response to this FOA must currently cohort funded under PAR-DA-12-222 that is focused on the intersection of drug use and HIV. In addition, applicants are strongly encouraged to include specific research projects that focus on infectious co-morbidities particularly HCV, and non-infectious comorbidities especially neurocognitive impairment (NCI) and neurological and mental health disorders associated with HIV, substance use and misuse, and antiretroviral therapy (ART).

With this FOA, NIDA intends to move the cohorts toward serving as a national level resource for data and/or biospecimens and as a platform for a broad spectrum of research addressing HIV in the substance use context. Clinical data and biological samples collected via the cohort(s) are expected to be available for sharing and use by the scientific community and awardees will be expected to participate in collaborative activities including at least one in-person meeting per year in Bethesda, MD, quarterly conference calls with the NIDA AIDS Program leadership, and interaction with researchers at other conference and meeting venues. Therefore, applicants responding to this FOA are asked for current efforts and future plans for the following areas:

a) standardizing data and biological specimen collection protocols across the NIDA-funded cohorts

b) developing common data elements around substance use and SUD and incorporating them into their study

c) participating in data harmonization activities for multiple domains, but especially drug use and HIV related data, when measures for data collection vary

d) engaging in data sharing widely across other NIDA and NIH-funded HIV cohorts

e) linking with other known data and specimen banks

f) establishing collaborations with scientists engaged in basic, clinical, translational and behavioral research related to HIV and SUD to leverage cohort

The Research Strategy should:

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

Describe how substance use in the population will be characterized i.e. specific drugs used, level and history of use, form of administration, and/or changing patterns over time including initiation.

Describe the 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.

Include identification and justification of the priority research domains for the cohort study and approaches to achieving the study aims.

Identify high priority research questions that can 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. Information should be provided regarding any new data collection needed to address high priority research questions, including study design, power analyses, along with plans for data collection, informed consent and data pooling/sharing among sites (as appropriate).

Include 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. Given the requirement of data sharing across cohort sites, the discussion should address how proposed data elements could incorporate common or share platforms for priority research collaborations with other research studies including existing or future cohorts, and a plan for sharing data and materials with other investigators.

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

• Behavioral, demographic, and medical data, including general medical history, use of antiretroviral therapy, health service utilization, sexual behavior and health, and substance use (relapse, transitions in drug use) and treatment history
• Computational predictive models related to HIV prevention and/or care continua
• Electronic health records of cohort participant living with HIV and the methods for capturing, storing and incorporating these data into study analyses.
• Clinical and laboratory data, including immune parameters, viral load, and co- infections, including utilization of routine clinical data from associated study sites.
• Biological specimen data, including specimen repository capacity and a plan to allow identification of specimens which meet specific criteria for the purpose of cross-site analyses. Applications should address plans for acquisition, curation, management, inventory and dissemination of data and samples to NIDA-approved repositories, along with training and supervision of staff to ensure adequate performance of these tasks.

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

• Non-HIV and HIV-related diagnoses, e.g., neurologic and mental health disorders or neuropsychological outcomes
• Clinical evaluations such as physical examinations or other specific clinical assessments conducted at the study visits
• Co-infection with Hepatitis C, other hepatitis viruses, and opportunistic infections.

Applications also should describe the administrative and organizational structure for the project and how it will facilitate attainment of the aims and objective of the proposed research.

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:

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

When involving NIH-defined human subjects research, clinical research, and/or clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by NIDA, 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. Any instructions provided here are in addition to the instructions in the policy.

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

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

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 the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this FOA: Is 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 those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Specific to this FOA: Will the Team(s) expertise lead to the success of the assigned team function(s), and how well will the Team(s) contribute to the success of the overall cohort establishment and research study outcome? Is there a coordination and unifying infrastructure in place to support all phases of the cohort establishment and analyses?

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?

Specific to this FOA: How appropriate are the data elements to the specific aims and to the key research collaboration priorities? How innovative are the specimen and data collection, and plans for data harmonization and data sharing?

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

Specific to this FOA: Is there a suitable plan for the development and maintenance of a cohort that is likely to facilitate specific or multicomponent research studies? Are there plans to standardize specimen and data collection and data harmonization across NIDA-funded HIV and DA cohorts? Does the application propose approaches to collaborating with basic and clinical researchers engaged in HIV and SUD research? Are there plans to participate in regular meetings with HIDA AIDS program leadership to discuss progress and evaluate plans for data collection, harmonization, and sharing?

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

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

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

Specific to this FOA: How sound and appropriate is the administrative and organizational structure for facilitating attainment of the objective(s) of the proposed study? How adequate is the plan for biological specimen and associated data collection procedures from the cohort, including specimen labeling, coding, tracking, processing, storing, and inventory? How adequate and reasonable are the plans for acquisition, curation, management, inventory and dissemination of data and samples to NIDA-approved repositories? How adequate is the training plan for site staff to capture all data types (e.g., clinical visit data, biological specimen collection, etc.) to ensure high quality, uniform data collection? If applicable, how does the research project incorporate utilize existing resources (e.g., practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate? How adequately is the clinical research protocol adequately described, and do the consent forms and assent forms provide sufficient detail to clarify the process of subject participation? How adequate are the strategies for oversight and implementation of standardized approaches in the recruitment and clinical characterization of human subjects to ensure a robust clinical sample? How adequately do the data analyses plans describe the study design features, and estimate power and sample size to achieve the goals of the program?

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 categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

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

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

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.

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

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

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

• 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. 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 https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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

Cooperative Agreement Terms and Conditions of Award

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 75and 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 recipients 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 awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for all aspects of the study, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, dissemination of data, tools, and technologies, and collaboration with other investigators. The awardee agrees to accept close coordination, cooperation, and participation of NIDA staff in those aspects of scientific and technical management of the study as stated in these terms and conditions:

1. PD/PIs are required to:

-attend an annual meeting in Bethesda and participate in quarterly conference calls with the NIDA program staff and the leadership of the Collaborating Consortium of Cohorts Producing NIDA Opportunities (C3PNO).

-work with C3PNO in establishing common data elements for drug use and HIV data and apply them in collecting the data when appropriate.

-engage in all NIDA and C3PNO-coordinated activities related to data harmonization and data sharing so that data related to drug use, exposure, and HIV may be combined, and made available widely for use by researchers across US.

-work with C3PNO and NIDA to establish and implement standard procedures for collecting biospecimens.

2. Medical safety and protection of study participants: A Data and Safety Monitoring Plan (DSMP) will be submitted to NIDA for approval for each clinical trial conducted under this award. Approval by the NIDA program official is required before any research study with human subjects can be implemented. Changes to the protocol must first be discussed with and approved by the NIDA Program Official before implementation.

3. Serious Adverse Events: in addition to existing OHRP and institutional requirements, serious adverse events will be reported through the NIDA Serious Adverse Event Tracking and Reporting System (SAETRS) within 72 hours of occurrence. Adverse Events will be reported in the annual progress report.

4. Annual progress reports: these will be submitted by the PD/PI to report on the status of each study, and will include progress, obstacles and steps taken to remedy them, and a summary of any NIDA-approved changes and departures from the approved study protocol, as well as any Human Subjects issues.

5. Organizational Changes: the addition or deletion of sites and partners, or other organizational changes must have the prior written approval of NIDA Program staff.

6. PD(s)/PI(s) will comply and maintain current Good Clinical Practices (GCP).

7. PD(s)/PI(s) will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies. Awardees are expected to publish and publicly disseminate results, data, and other products of the study, concordant with governance policies and protocols. Publications and oral presentations of work performed under this agreement will require appropriate acknowledgment of support by the NIDA/NIH.

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

1. The NIDA Project Scientistl substantial involvement includes the following actions and responsibilities:

• Act as a resource to aid in resolving scientific and regulatory issues as they arise
• Ensure the established protocols are followed and assist in the development of any amendments to the study protocol
• Review and monitor any reported Serious Adverse Events (SAEs)
• Review the DSMB reports
• Evaluate the progress and future study plans

2. The NIDA Scientific Contact and the AIDS Research Program Directors will be involved in the following activities to ensure that the cohort studies are meeting objectives and the scope set forth in the FOA:

• Engage in quarterly conference calls with the Cohort PIs and the leadership of the Collaborating Consortium of Cohorts Producing NIDA Opportunities (C3PNO)
• Discuss opportunities for wide collaborations and presentations at the major scientific meetings
• Evaluate the progress and future study plans

3. The NIDA Program Official will be responsible for the following actions:

• Enforcement of general statutory and policy requirements
• Reviewing and evaluating progress through progress reports or in response to programmatic requests, and regular
• Reviewing and evaluating requests for actions requiring prior NIH approval

4. The NIDA Program Official has the responsibility, following consultation with the Project Scientist, for the review and approval of the Data and Safety Monitoring Plan for the clinical trial.

5. NIDA will provide access to the NIDA Serious Adverse Event Tracking and Reporting System (SAETRS), as long as NIDA support for the system exists, at no cost to the grantee.

6. Study Closure - NIDA may require that a study be closed for reasons including:

• Patient safety
• Failure to achieve enrollment and completion milestones
• Emergence of already conclusive study results
• Emergence of new information that diminishes the scientific importance of the study question.

Once the PD(s)/PI(s) are notified by the Grants Management Branch/NIDA of site closure or that the study should cease, only reasonable personnel and administrative costs may be obligated or charged to the grant award. These costs should be associated with the orderly phase-out, and/or to ensure patient safety for enrolled subjects of the study or site.

Areas of Joint Responsibility include:

• The PD(s)/PI(s) and the PS will work collaboratively in evaluating the most appropriate research methods, data quality control strategies, medical safety monitoring, protocol design and implementation, data analysis and interpretation and publication and dissemination of study results.
• The grantee and NIDA Project Scientist will discuss study progress via conference call on a monthly basis. These meetings will include information concerning study progress, obstacles and steps taken to remedy them and any protocol changes that may need to be considered. Recruitment, retention, and drop-out rates for each research protocol will be discussed as will any Human Subject issues as they arise.

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 members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. 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, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Richard Jenkins, PhD
National Institute on Drug Abuse (NIDA)
Telephone: 301-443-1932
Email: [email protected]

Vasundhara Varthakavi, DVM, PhD
AIDS Research Program at NIDA
National Institute on Drug Abuse (NIDA)
Telephone: 301-443-2146
Email: [email protected]

Gerald McLaughlin, PhD
National Institute on Drug Abuse (NIDA)
Telephone: 301-827-5819
Email: [email protected]

Cheryl Nathaniel
National Institute on Drug Abuse (NIDA)
Telephone: 301-827-6703
Email: [email protected]

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

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