RFA-DA-00-007: HIV THERAPY FOR DRUG USERS: ACCESS, ADHERENCE, EFFECTIVENESS

Department of Health
and Human Services (HHS)

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HIV THERAPY FOR DRUG USERS: ACCESS, ADHERENCE, EFFECTIVENESS Release Date: December 20, 1999 RFA: DA-00-007 National Institute on Drug Abuse Letter of Intent Receipt Date: February 28, 2000 Application Receipt Date: March 29, 2000 THIS REQUEST FOR APPLICATIONS (RFA) USES THE MODULAR GRANT AND JUST-IN- TIME CONCEPTS. IT INCLUDES DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT MUST BE USED WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS RFA. PURPOSE The National Institute on Drug Abuse (NIDA) invites applications for research on access, adherence and effectiveness relevant to the treatment of drug users with HIV. Treatment and management of HIV/AIDS in drug users is complicated by social, behavioral, clinical and pharmacological factors which may alter the long-term effectiveness of HIV therapies. Poorer access to health care and the difficulties in managing and sustaining complex treatment regimens for HIV, have limited the numbers of drug users who are on combination antiretroviral therapy. While engagement of drug users into HIV care through accessible programs, such as primary care linked with methadone treatment, has demonstrated reduced morbidity and improved survival, providers may consider drug users as high-risk for developing drug resistant HIV infection due to a perceived inability to adhere to complex medical regimens. As a result, drug users may not be considered good candidates for anti-retroviral therapy or to receive the clinical support necessary to take chronic medications correctly. Further understanding of the factors influencing adherence and development of effective interventions are critical for improved clinical outcomes and prevention of development of resistance to antiretroviral medications. Determining patterns of use of therapies and the impact of episodic or intermittent patterns of adherence, as well as the impact of ongoing injection, are important to understanding selection of drug-resistant strains of HIV. Due to an underrepresentation of drug users in clinical studies of HIV therapies, there is a lack of data on potential risks of drug interactions and toxicity. Interactions between illicit drugs and HIV therapies, as well as pharmacotherapies for substance abuse, mental health conditions, and for other diseases common in drug users, may cause morbidity, influence adherence, and reduce the effectiveness of HIV treatment. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of Healthy People 2000, a PHS-led national activity for setting priority areas. This RFA, HIV Therapy for Drug Users: Access, Adherence, Effectiveness, is related to the priority areas of alcohol and other drugs, HIV infection, and sexually transmitted diseases. Potential applicants may obtain a copy of Healthy People 2000 at http://odphp.osophs.dhhs.gov/pubs/hp2000. ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign for-profit and non- profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the federal government. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. MECHANISM OF SUPPORT The mechanism of support for this RFA will be the investigator-initiated research project grant (R01). Applicants are advised to contact NIDA program staff listed under INQUIRIES for additional information. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. Specific information on individual research mechanisms can be obtained from the NIDA home page at http://www.nida.nih.gov/Funding.html. Support may be requested for a period of up to 5 years for R01 grants. Modular budgeting procedures apply for grants up to $250,000. See http://grants.nih.gov/grants/funding/modular/modular.htm for further information about modular budgets. FUNDS AVAILABLE NIDA intends to commit approximately $3,000,000 in FY 2000 to fund approximately seven new grants in response to this RFA. An applicant may request a project period of up to 5 years. Because the nature and scope of the research proposed may vary, it is anticipated that the size of each award will also vary. Although the financial plans of NIDA provide support for this program, awards pursuant to this RFA are contingent upon the availability of funds and the receipt of a sufficient number of applications of outstanding scientific and technical merit. RESEARCH OBJECTIVES Background The advent of combined antiretroviral therapy has resulted in dramatic reductions in both morbidity and mortality due to HIV/AIDS. Benefits for drug users from these potent combination therapies have lagged behind those of other populations. While data from selected samples demonstrate improvement in the numbers of drug users receiving combination therapy, deaths due to HIV/AIDS among drug users have declined at a significantly lower rate compared with other risk groups. Limited access to care, an important predictor of inconsistent medical care and poorer survival, remains a significant problem for drug users. Studies have shown that injection drug users tend to seek medical care later in their disease course and are less likely than other groups to receive HIV-related therapy. Psychiatric co-morbidity, common among drug users, as well as ongoing substance abuse, have been shown to be associated with poorer levels of adherence. Drug users have high rates of co- morbid medical conditions, including renal, hepatic, and neurologic disease, as well as bacterial pneumonia, tuberculosis, and hepatitis B and C. These prevalent conditions complicate the medical management of HIV-infected drug users and increase the risk of toxicities and drug-drug interactions from use of multiple therapies and ongoing substance use. Drug users co-infected with hepatitis C and HIV who are being treated with protease inhibitors may be at particular risk for hepatotoxicity or acute hepatitis. Recent data have shown that chronic methadone treatment increases plasma levels of AZT, that protease inhibitors can inhibit metabolism of both methadone and buprenorphine, and that nevirapine can induce opiate withdrawal in patients on methadone. Further understanding of the complex components of treating HIV-infected drug users is important to the development of improved clinical management approaches. . Areas of Research Focus This initiative will support research on a broad range of HIV care-related issues, including, 1) access issues related to receipt of HIV-related treatment and outreach strategies to improve access; 2) factors influencing initiation of HIV treatment and long-term adherence to HIV treatment regimens; 3) the development of intervention strategies to improve use of and adherence to complex medical regimens in a variety of settings; 4) the development and testing of behavioral treatments as an integral component of comprehensive approaches designed to reduce risk behaviors, prevent transmission of infection, and enhance adherence with medications and care, 5) the occurrence of beneficial and deleterious behavior risk changes as a result of HIV therapy, 6) factors influencing long-term therapeutic effectiveness, development of viral resistance, disease progression, and medical outcomes, 7) consequences of the use of therapies in drug users--including toxicities and pharmacologic interactions of antiretrovirals with drug abuse treatment medications (methadone, LAAM, buprenorphine), illicit substances, medications for dual diagnosis patients and for other diseases common in drug-users--and with alternative/complimentary therapies for drug users with HIV infection; 8) clinical management approaches for drug users on multiple medical therapies for HIV and associated infectious and non-infectious conditions associated with drug use; and 9) bioethical considerations involving availability of care, provider attitudes, and clinical management approaches. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale or justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This new policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing research involving human subjects should read the NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research, published in the Federal Register on March 28, 1994 (FR 59 14508- 14513) and in the NIH Guide for Grants and Contracts, Volume 23, Number 11, March 18, 1994, available on the web at: http://grants.nih.gov/grants/guide/notice-files/not94-100.html. NIH POLICY AND GUIDELINES ON THE INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS: It is the policy of NIH that children (i.e., individuals under the age of 21) must be included in all human subjects research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. This policy applies to all initial (Type 1) applications submitted for receipt dates after October 1, 1998. All investigators proposing research involving human subjects should read the NIH Policy and Guidelines on the Inclusion of Children as Participants in Research Involving Human Subjects that was published in the NIH Guide for Grants and Contracts, March 6, 1998, and is available at the following URL address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html. Investigators also may obtain copies of these policies from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning these policies. NATIONAL ADVISORY COUNCIL ON DRUG ABUSE RECOMMENDED GUIDELINES FOR THE ADMINISTRATION OF DRUGS TO HUMAN SUBJECTS The National Advisory Council on Drug Abuse recognizes the importance of research involving the administration of drugs to human subjects and has developed guidelines relevant to such research. 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 home page at www.nida.nih.gov/HSGuide.html or may be obtained by calling (301) 443-2755. LETTER OF INTENT Prospective applicants are asked to submit by February 28, 2000, a letter of intent that includes a descriptive title of the proposed research; the name, address, telephone number, and institution of the Principal Investigator; names of other key investigators and their respective institutions (if applicable); and the title and number of this RFA in response to which the application will be submitted. Although a letter of intent is not required, it is not binding and is not a factor in the peer review of the application. The information it contains is helpful, however, in planning for the review of applications because it allows NIDA staff to estimate the potential review workload and avoid conflict of interest in the review. The letter of intent is to be sent to: Director, Office of Extramural Program Review National Institute on Drug Abuse 6001 Executive Boulevard, Room 3158, MSC 9547 Bethesda, MD 20892-9547 Telephone: (301) 443-2755 FAX: (301) 443-0538 APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 4/98) is to be used in applying for these grants. Application kits are available at most institutional offices of sponsored research and may be obtained from the Division of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone (301) 710-0267, E-mail: [email protected]. SPECIFIC APPLICATION INSTRUCTIONS FOR MODULAR GRANTS The modular grant concept establishes specific modules in which direct costs may be requested, as well as a maximum level for requested budgets. Only limited budgetary information is required under this approach. The just-in-time concept allows applicants to submit certain information only when there is a possibility for an award. It is anticipated that these changes will reduce the administrative burden for the applicants, reviewers, and Institute staff. The research grant application form PHS 398 (rev. 4/98) is to be used in applying for these grants, with the modifications noted below. BUDGET INSTRUCTIONS Modular Grant applications will request direct costs in $25,000 modules, up to a total direct cost request of $250,000 per year. (Applications that request more than $250,000 direct costs in any year must follow the traditional PHS 398 application instructions.) The total direct costs must be requested in accordance with the program guidelines and the modifications made to the standard PHS 398 application instructions described below: PHS 398 FACE PAGE - Items 7a and 7b should be completed, indicating Direct Costs (in $25,000 increments up to a maximum of $250,000) and Total Costs [Modular Total Direct plus Facilities and Administrative (F&A) costs] for the initial budget period. Items 8a and 8b should be completed indicating the Direct and Total Costs for the entire proposed period of support. DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD - Do not complete Form Page 4 of the PHS 398. It is not required and will not be accepted with the application. BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT - Do not complete the categorical budget table on Form Page 5 of the PHS 398. It is not required and will not be accepted with the application. NARRATIVE BUDGET JUSTIFICATION - Prepare a Modular Grant Budget Narrative page (see http://grants.nih.gov/grants/funding/modular/modular.htm for sample pages). At the top of the page, enter the total Direct Costs requested for each year. This is not a Form page. Under Personnel, list key project personnel, including their names, percent of effort, and roles on the project. No individual salary information should be provided. However, the applicant should use the NIH appropriation language salary cap and the NIH policy for graduate student compensation in developing the budget request. For Consortium/Contractual costs, provide an estimate of total costs (Direct plus F&A) for each year, each rounded to the nearest $1,000. List the individuals/organizations with whom consortium or contractual arrangements have been made, the percent effort of key personnel, and the role on the project. Indicate whether the collaborating institution is foreign or domestic. The total cost for a consortium/contractual arrangement is included in the overall requested Modular Direct Cost amount. Include the letter of intent to establish a consortium. Provide an additional narrative budget justification for any variation in the number of modules requested. BIOGRAPHICAL SKETCH - The Biographical Sketch provides information used by reviewers in the assessment of each individual's qualifications for a specific role in the proposed project, as well as to evaluate the overall qualifications of the research team. A biographical sketch is required for all key personnel, following the instructions below. No more than three pages may be used for each person. A sample biographical sketch may be viewed at: http://grants.nih.gov/grants/funding/modular/modular.htm. - Complete the educational block at the top of the Form page; - List position(s) and any honors; - Provide information, including overall goals and responsibilities, on research projects ongoing or completed during the last three years; and - List selected peer-reviewed publications, with full citations. CHECKLIST - This page should be completed and submitted with the application. If the F&A rate agreement has been established, indicate the type of agreement and the date. All appropriate exclusions must be applied in the calculation of the F&A costs for the initial budget period and all future budget years. The applicant should provide the name and phone number of the individual to contact concerning fiscal and administrative issues if additional information is necessary following the initial review. The RFA label available in the PHS 398 (rev. 4/98) application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the title and number of this RFA must be typed in Item 2 on the face page of the application form, and the YES box must be marked. The RFA number must be typed on the label as well. The sample RFA label is available at: http://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been modified to allow for this change. Please note this is in pdf format. Submit a signed, typewritten original of the application, including the Checklist, and three signed photocopies in one package to: CENTER FOR SCIENTIFIC REVIEW NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) At the time of submission, two additional copies of the application must be sent to: Director, Office of Extramural Program Review National Institute on Drug Abuse 6001 Executive Boulevard, Room 3158, MSC 9547 Bethesda, MD 20892-9547 Rockville, MD 20852 (for express/courier service) Applications must be received by March 29, 2000. If an application is received after that date, it will be returned to the applicant without review. The Center for Scientific Research (CSR) will not accept any application in response to this RFA that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The CSR will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the CSR and for responsiveness by NIDA. Incomplete and/or non-responsive applications will be returned to the applicant without further consideration. Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NIDA in accordance with the review criteria stated below. As part of the initial merit review, a process will be used by the initial review group in which applications receive a written critique and undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of the applications under review, will be discussed, assigned a priority score, and receive a second level review by the NIDA National Advisory Council. REVIEW CRITERIA The goals of NIH-supported research are to advance the understanding of biological systems, improve the control of disease, and enhance health. In the written comments, reviewers will be asked to discuss the following aspects of the application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that the application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. (1) Significance: Are the goals and objectives of this application relevant to this RFA? Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods that drive this field? (2) Approach: Are the conceptual framework, design, methods, and analyses adequately developed, well-integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? (3) Innovation: Does the project employ novel concepts, approaches, or method? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies? (4) Investigator: Is the investigator appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers (if any)? (5) Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support? In addition to the above criteria, in accordance with NIH policy, all applications will also be reviewed with respect to the following: The adequacy of plans to include both genders, minorities, and their subgroups, as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. The adequacy of plans to make data available to other investigators in a timely fashion. The reasonableness of the proposed budget and duration in relation to the proposed research. The adequacy of the proposed protection for humans, animals, or the environment, to the extent they may be adversely affected by the project proposed in the application. The adequacy of plans for including children as appropriate for the scientific goals of the research. Schedule: Letter of Intent: February 28, 2000 Application Receipt Date: March 29, 2000 Special Review Meeting: Summer 2000 Council Review: September 2000 Earliest Start Date: September 29, 2000 AWARD CRITERIA Award criteria that will be used to make award decisions include: scientific merit as determined by peer review, availability of funds, and programmatic priorities. INQUIRIES Inquiries concerning this RFA are strongly encouraged. The opportunity to clarify issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Elizabeth Lambert, M.S. Center on AIDS and Other Medical Consequences of Drug Abuse National Institute on Drug Abuse 6001 Executive Boulevard, Room.5198, MSC 9593 Bethesda, MD 20892-9593 Telephone: (301) 402-1933 FAX: (301) 443-4100 E-mail: [email protected] Direct inquiries regarding fiscal matters to: Gary Fleming, J.D., M.A. Grants Management Branch National Institute on Drug Abuse 6001 Executive Boulevard, Room 3131, MSC 9541 Bethesda, MD 20892-9541 Telephone: (301) 443-6710 FAX : (301) 594-6847 E-mail: [email protected] Direct inquiries regarding review matters to: Teresa Levitin, Ph.D. Director, Office of Extramural Program Review National Institute on Drug Abuse 6001 Executive Boulevard, Room 3158, MSC 9547 Bethesda, MD 20892-9547 Telephone : (301) 443-2755 FAX: (301) 443-0538 E-mail: [email protected] AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.279. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and are administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

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