Vol. 18, No. 5, February 17, 1989 NOTICES NEW INDIVIDUAL FELLOWSHIP FORM ...........................(84/183)........... 1 Division of Research Grants Index: RESEARCH GRANTS DATED ANNOUNCEMENTS (RFPs AND RFAs) RODENT DISEASE DIAGNOSTIC LABORATORIES (RFP) .............(189/237).......... 2 National Institute of Environmental Health Sciences Index: ENVIRONMENTAL HEALTH SCIENCES CHEMISTRY SUPPORT SERVICES FOR THE NATIONAL TOXICOLOGY PROGRAM (RFP) ........ 3 National Institute of Environmental Health Sciences (241/274) Index: ENVIRONMENTAL HEALTH SCIENCES PATHOGENESIS AND NATIONAL HISTORY OF HUMAN PAPILLOMA VIRUSES (RFA) .......... 3 National Institute of Allergy and Infectious Diseases (277/311) Index: ALLERGY, INFECTIOUS DISEASES COORDINATING CENTER FOR MATCHING PATIENTS TO ALCOHOLISM TREATMENTS (RFA) ....................................(321/424, 644/1209)..... 4 National Institute on Alcohol Abuse and Alcoholism Index: ALCOHOL ABUSE, ALCOHOLISM CLINICAL RESEARCH UNITS FOR MATCHING PATIENTS TO ALCOHOLISM TREATMENTS (RFA) ....................................(427/535, 1212/1915).... 5 National Institute on Alcohol Abuse and Alcoholism Index: ALCOHOL ABUSE, ALCOHOLISM ONGOING PROGRAM ANNOUNCEMENTS RESEARCH ON SERVICES FOR MENTALLY ILL PERSONS .............(531/556)......... 6 National Institute of Mental Health Index: MENTAL HEALTH ERRATUM NEW APPROACHES TO STUDYING EPSTEIN-BARR VIRUS ONCOGENESIS ..(564/579)........ 7 National Cancer Institute Index: Cancer NOTICES NEW INDIVIDUAL FELLOWSHIP FORM P.T. 22; K.W. 1014002, 1014006 Division of Research Grants The revised application form for competing Public Health Service Individual National Research Service Awards, PHS 416-1, revised 7/88, is now available. This revision, which contains major changes, should be used for the May 10, 1989 receipt date and subsequent deadlines. Any old forms (PHS 416-1, Rev. 6/85) should be discarded. An article on the changes in the new form will appear soon in the NIH Guide for Grants and Contracts. Direct any questions to Mr. Nicholas Moriarty, Program Analyst, Division of Research Grants, Westwood Building, Room A25, National Institutes of Health, Bethesda, Maryland 20892, Telephone: (301) 496-7221. The sources of application kits are identified below. NIH Postdoctoral and Senior Fellowships: Individual copies are available from: Office of Grants Inquiries Division of Research Grants National Institutes of Health Westwood Building, Room 449 Bethesda, Maryland 20892 Telephone: (301) 496-7441 Multiple copies are available from: Administrative Services Office Division of Research Grants National Institutes of Health Westwood Building, Room 438 Bethesda, Maryland 20892 Telephone: (301) 496-9797 There are separate postdoctoral and senior fellowship program announcements included with the kits. NIH Nursing Predoctoral Fellowships: National Center for Nursing Research predoctoral fellowship applications are available from the same sources as identified above for NIH Postdoctoral and Senior Fellowships. National Cancer Institute Oncology Nurse Fellowship applications are available from: Cancer Training Branch National Cancer Institute National Institutes of Health Executive Plaza North, Room 232 Rockville, Maryland 20892 Telephone: (301) 496-8580 Minority Access to Research Career (MARC) Program: MARC Honors Undergraduate Research Training Grant Predoctoral and Faculty Fellowship Award applications to be submitted from eligible minority institutions and Visiting Scientist Award applications to be submitted by scientists at majority institutions are available from: Director, MARC Program National Institutes of General Medical Sciences National Institutes of Health Westwood Building, Room 9A-18 Bethesda, Maryland 20892 Telephone: (301) 496-7941 Alcohol, Drug Abuse, and Mental Administration Predoctoral and Postdoctoral Fellowship applications are available from the following offices: National Institute of Alcohol and Alcohol Abuse National Clearing House of Alcohol and Drug Information P.O. Box 2345 Rockville, Maryland 20852 Telephone: (301) 468-2600 Vol. 18, No. 5, February 17, 1989 - Page 1 National Institute of Drug Abuse Grants Management Officer Parklawn Building, Room 10-25 5600 Fishers Lane Rockville, Maryland 20857 Telephone: (301) 443-6710 National Institute of Mental Health Grants Awards and Operations Section Grants Management Branch Parklawn Building, Room 7C-15 5600 Fishers Lane Rockville, Maryland 20857 Telephone: (301) 443-4014 National Center for Health Services Research and Health Care Technology Assessment (NCHSR) Postdoctoral Applications are available from: NCHSR Parklawn Building, Room 18A-20 5600 Fishers Lane Rockville, Maryland 20857 Telephone: (301) 443-3091 DATED ANNOUNCEMENTS (RFPs AND RFAs) RODENT DISEASE DIAGNOSTIC LABORATORIES RFP AVAILABLE: NIH-ES-89-13 P.T. 34; K.W. 0780000, 1002002, 0755010 National Institute of Environmental Health Sciences The purpose of this procurement shall be to evaluate rodents (344/N rats and B6C3F1 hybrid mice) used by the National Institute of Environmental Health Sciences (NIEHS) in various studies and reviews in order to detect rodent pathogens and diseases encountered in NIEHS testing laboratories. This evaluation will be based upon an analysis of serum samples which will be shipped to the contractor. This work will be divided into two tasks. There shall be one cost reimbursement level-of-effort type contract for each Task (total two contracts) for a term of five years, each funded on an incremental basis. Offerors may submit proposals for either Task I or Task II or both. Separate contractors will be selected for Task I and Task II. No single contractor will be awarded both tasks. Under Task I, the contractor will provide for routine comprehensive health evaluation of rodents. Under Task II, the contractor will provide research expertise in rodent diseases and confirmation of routine evaluations performed under Task I. The proposed Task I contract listed here is a 100 percent small business set aside. The proposed Task II contract as listed here shall remain open for full and open competition. This work shall be performed in accordance with the Good Laboratory Practice regulations established by the FDA for Nonclinical Laboratory Studies (Federal Register, Friday, December 22, 1978, Part II, pp. 59986-60025) and the NTP Health and Safety Minimum Requirements for Contract Laboratories Performing Work for the Systemic Toxicology Branch. The Government estimates that approximately 2.5 technical persons equivalent effort in serology, microbiology, parasitology, histology, and administrative support and approximately 0.4 person equivalent of pathologist(s) and laboratory animal medicine specialist(s) per year for Task I and for Task II; and that the project will require approximately 1.0 technical person equivalent effort in serology, microbiology, parasitology, histology, and administrative support and approximately 0.2 person equivalent of pathologist(s) and laboratory animal medicine specialist(s) per year. All responsible sources may submit a proposal which will be considered by NIEHS. Expected release date for the RFP is February 23, 1989, with the proposal due on April 14, 1989. Request should reference RFP NIH-ES-89-13 and should be forwarded to: National Institute of Environmental Health Sciences Contracts and Procurement Management Branch, OM Attn: Mr. James H. Locus, Jr. 79 T.W. Alexander Drive, 4401 Building P.O. Box 12874 Research Triangle Park, North Carolina 27709 Vol. 18, No. 5, February 17, 1989 - Page 2 CHEMISTRY SUPPORT SERVICES FOR THE NATIONAL TOXICOLOGY PROGRAM RFP AVAILABLE: NIH-ES-89-14 P.T. 34; K.W. 0780000, 0780017, 1007009 National Institute of Environmental Health Sciences The objective of this project is to provide chemistry support services to the National Toxicology Program. Two awards are anticipated. Services required under Contract I are: bulk chemical procurement, bulk chemical handling, bulk chemical shipment, bulk chemical analysis, bulk chemical reprocurement and analysis, dosage formulation developmental studies, routine dosage formulation analysis, bulk chemical reanalysis, referee analysis of dosage formulations, analysis of biological samples, synthesis of test chemicals, investigation of alternate vehicles, special bulk analysis, special dosage formulation analysis, and microencapsulation of test materials. Services required under Contract II are the same as for Contract I except investigation of alternate vehicles and microencapsulation are not required. This is an announcement of an anticipated request for proposals. RFP NIH-ES-89-14 will be issued on or about February 15, 1989, with a closing date for receipt of proposals of April 18, 1989. Requests should reference RFP NIH-ES-89-14 and should be forwarded to: National Institute of Environmental Health Sciences Contracts and Procurement Management Branch, OM ATTN: Susan D. Kinney, Contract Specialist P.O. Box 12874 79 T.W. Alexander Drive 4401 Building, Research Commons Research Triangle Park, North Carolina 27709 PATHOGENESIS AND NATURAL HISTORY OF HUMAN PAPILLOMA VIRUSES RFA AVAILABLE: 89-AI-02 (Extension of Due Date and Award Date) P.T. 34; K.W. 0715125, 1002045, 0765033, 0715182, 0710070 National Institute of Allergy and Infectious Diseases Revised Application Receipt Date: May 8, 1989 Revised Letter of Intent Date: April 3,1989 Revised Award Date: April 1, 1990 RFA # AI-89-02 on the Pathogenesis and Natural History of Human Papilloma Viruses appeared in the NIH Guide for Grants and Contracts, page 2, Vol. 17, No. 42, December 16, 1988, with an originally announced due date of March 9, 1989. The National Institute of Allergy and Infectious Diseases announces the extension of the due date for these applications to May 8, 1989. Letters of intent are requested at least one month before the grant submission deadline. The earliest possible award date will be extended to April 1, 1990. All of the known applicants have been contacted by NIAID staff to advise them of the revised due date. If additional information about the RFA deadline is needed, prospective applicants should contact: William P. Allen, Ph.D. Chief, Bacteriology and Virology Branch National Institute of Allergy and Infectious Diseases Westwood Building, Room 738 9000 Rockville Pike Bethesda, Maryland 20892 The full, revised RFA (general description and guidelines) and consultation may be obtained from Dr. Allen. Vol. 18, No. 5, February 17, 1989 - Page 3 COORDINATING CENTER FOR MATCHING PATIENTS TO ALCOHOLISM TREATMENTS RFA AVAILABLE: AA-89-02A P.T. 34; K.W. 0404003, 0755015, 0755018 National Institute on Alcohol Abuse and Alcoholism Application Receipt Date: May 4, 1989 PURPOSE The purpose of this cooperative agreement is to support a Coordinating Center to work with Clinical Research Units to conduct multi-site trials of patient-treatment matching in the alcoholism treatment field. RESEARCH OBJECTIVES The objective of the project for which applications are solicited by this Request for Cooperative Agreement Applications (RFA AA-89-02A) is to support a Coordinating Center to work with and support Clinical Research Units to conduct a patient-treatment matching study, using a common protocol, at multiple sites in order to investigate the efficacy of particular strategies for matching patients to alcoholism treatment regimens. MECHANISM OF SUPPORT The study will involve the cooperation of scientists from: (1) a single Coordinating Center, (2) multiple Clinical Research Units, and (3) the National Institute on Alcohol Abuse and Alcoholism (NIAAA) Division of Clinical and Prevention Research. The primary governing body of the study will be the Steering Committee comprised of representatives of each of the Clinical Research Units, a representative from the Coordinating Center, the NIAAA Staff Collaborator, and a statistician. Applications for the Coordinating Center may be submitted by public or private nonprofit or for-profit organizations, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal Government. The award for the Coordinating Center will be made in the form of a cooperative agreement. The Coordinating Center will organize the Steering Committee meetings, reproduce and score instruments, train personnel from all sites in the use of data collection instruments and common research protocols, and assure that treatments are implemented according to the specifications of the final research protocol. The Coordinating Center will be a single institution with the ability to collect, process, and analyze data. Support may be requested for a period of up to 5 years. Annual awards will be made subject to continued availability of funds and progress achieved. It is estimated that approximately $2 million will be available in FY 1989 to support a single Coordinating Center and from five to nine Clinical Research Units. APPLICATION PROCEDURES Prospective applicants are asked to submit a letter of intent by April 7, 1989, to the staff contact person listed at the end of this notice. This RFA is a one-time request for applications. Applicants who also wish to apply for consideration as a Clinical Research Unit should submit a separate application with the title "Clinical Research Units for Matching Patients to Alcoholism Treatments RFA AA-89-02B." THE RFA LABEL FOUND IN THE PHS 398 KIT MUST BE AFFIXED TO THE BOTTOM OF THE FACE PAGE OF THE ORIGINAL COMPLETED APPLICATION FORM, PHS 398, AND DUPLICATED ON ALL COPIES. FAILURE TO USE THIS LABEL COULD RESULT IN DELAYED PROCESSING OF YOUR APPLICATION SUCH THAT IT MAY NOT REACH THE REVIEW COMMITTEE IN TIME FOR REVIEW. THERE WILL BE NO OBLIGATION TO REVIEW SUCH APPLICATIONS. Send or deliver the completed application and four signed, exact photocopies of it to: Division of Research Grants Westwood Building, Room 240 National Institutes of Health Bethesda, Maryland 20892** SEND TWO ADDITIONAL COPIES OF THE APPLICATION TO THE ADDRESS LISTED BELOW. IT IS IMPORTANT TO SEND THESE TWO COPIES AT THE SAME TIME AS THE ORIGINAL AND Vol. 18, No. 5, February 17, 1989 - Page 4 FOUR COPIES ARE SENT TO THE DIVISION OF RESEARCH GRANTS IN ORDER TO INSURE THAT THE APPLICATION WILL BE REVIEWED IN COMPETITION FOR THIS RFA. Office of Scientific Affairs National Institute on Alcohol Abuse and Alcoholism Parklawn Building, Room 16C-20 5600 Fishers Lane Rockville, Maryland 20857 Applications must be received by May 4, 1989. An application not received by this date will be considered ineligible. INQUIRIES For further information contact: John Allen, Ph.D. Chief, Treatment Research Branch Division of Clinical and Prevention Research National Institute on Alcohol Abuse and Alcoholism Parklawn Building, Room 16C-03 5600 Fishers Lane Rockville, Maryland 20857 Telephone: (301) 443-0796 CLINICAL RESEARCH UNITS FOR MATCHING PATIENTS TO ALCOHOLISM TREATMENTS RFA AVAILABLE: AA-89-02B P.T. 34; K.W. 0404003, 0755015, 0785035 National Institute on Alcohol Abuse and Alcoholism Application Receipt Date: May 4, 1989 PURPOSE The purpose of this cooperative agreement is to support Clinical Research Units to conduct multi-site trials of patient-treatment matching in the alcoholism treatment field. RESEARCH OBJECTIVES The objective of the project for which applications are solicited by this Request for Cooperative Agreement Applications (RFA AA-89-02B) is to conduct a patient-treatment matching study, using a common protocol, at multiple sites in order to investigate the outcome of particular strategies for matching patients to alcoholism treatment regimens. MECHANISM OF SUPPORT The study will involve the cooperation of scientists from: (1) a single Coordinating Center, (2) multiple Clinical Research Units, and (3) the National Institute on Alcohol Abuse and Alcoholism (NIAAA), Division of Clinical and Prevention Research. The primary governing body of the study will be the Steering Committee comprised of representatives of each of the Clinical Research Units, a representative from the Coordinating Center, the NIAAA Staff Collaborator, and a statistician. Applications for the Clinical Research Units may be submitted by public or private nonprofit or for-profit organizations, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal Government. Applications will consist of a proposal for a multi-site study of patient-treatment matching to include a clinical trial of particular matching techniques. Awards for Clinical Research Units will be made in the form of a cooperative agreement. Clinical Research Units may include more than one treatment facility. Support may be requested for a period of up to 5 years. Annual awards will be made subject to continued availability of funds and progress achieved. It is estimated that approximately $2 million will be available in FY 1989 to support a single Coordinating Center and from five to nine Clinical Research Units. APPLICATION PROCEDURES Prospective applicants are asked to submit a letter of intent by April 7, 1989, to the staff contact person listed at the end of this notice. Vol. 18, No. 5, February 17, 1989 - Page 5 This RFA is a one-time request for applications. Applicants who also wish to apply for consideration as the Coordinating Center should submit a separate application with the title "Coordinating Center for Matching Patients to Alcoholism Treatments RFA AA-89-02A." THE RFA LABEL FOUND IN THE PHS 398 KIT MUST BE AFFIXED TO THE BOTTOM OF THE FACE PAGE OF THE ORIGINAL COMPLETED APPLICATION FORM, PHS 398, AND DUPLICATED ON ALL COPIES. FAILURE TO USE THIS LABEL COULD RESULT IN DELAYED PROCESSING OF YOUR APPLICATION SUCH THAT IT MAY NOT REACH THE REVIEW COMMITTEE IN TIME FOR REVIEW. THERE WILL BE NO OBLIGATION TO REVIEW SUCH APPLICATIONS. Send or deliver the completed application and four signed, exact photocopies of it to: Division of Research Grants Westwood Building, Room 240 National Institutes of Health Bethesda, Maryland 20892** SEND TWO ADDITIONAL COPIES OF THE APPLICATION TO THE ADDRESS LISTED BELOW. IT IS IMPORTANT TO SEND THESE TWO COPIES AT THE SAME TIME AS THE ORIGINAL AND FOUR COPIES ARE SENT TO THE DIVISION OF RESEARCH GRANTS IN ORDER TO INSURE THAT THE APPLICATION WILL BE REVIEWED IN COMPETITION FOR THIS RFA. Office of Scientific Affairs National Institute on Alcohol Abuse and Alcoholism Parklawn Building, Room 16C-20 5600 Fishers Lane Rockville, Maryland 20857 Applications must be received by May 4, 1989. An application not received by this date will be considered ineligible. INQUIRIES For further information contact: John Allen, Ph.D. Chief, Treatment Research Branch Division of Clinical and Prevention Research National Institute on Alcohol Abuse and Alcoholism Parklawn Building, Room 16C-03 5600 Fishers Lane Rockville, Maryland 20857 Telephone: (301) 443-0796 ONGOING PROGRAM ANNOUNCEMENTS RESEARCH ON SERVICES FOR SEVERELY MENTALLY ILL PERSONS P.T. 34; K.W. 0715129, 0730000, 0730050, 0730070, 0785035 National Institute of Mental Health The National Institute of Mental Health (NIMH) announces a revision of its announcement on Research on Services for the Severely Mentally Ill (August 1987). The revision gives more emphasis to clinical-level studies of service practices in which client outcome is assessed in relation to alternative management strategies. The revised announcement also gives emphasis to relating research on services for severely mentally ill persons to other NIMH initiatives, such as encouraging linkage of university-based research to public systems of care. For further information on this revised announcement, potential applicants may contact: Charles Windle, Ph.D., or Ann A. Hohmann, Ph.D., M.P.H. Biometric and Clinical Applications Branch Division of Biometry and Applied Sciences National Institute of Mental Health Parklawn Building, Room 18C-14 5600 Fishers Lane Rockville, Maryland 20857 Telephone: (301) 443-4233 Vol. 18, No. 5, February 17, 1989 - Page 6 ERRATUM NEW APPROACHES TO STUDYING EPSTEIN-BARR VIRUS ONCOGENESIS RFA AVAILABLE: 89-CA-08 P.T. 34; K.W. 0715035, 1002045, 0785140 National Cancer Institute Application Receipt Date: August 3, 1989 Letter of Intent Receipt Date: June 3, 1989 The above referenced RFA originally published in Volume 18, Number 2, January 20, 1989 issue of the NIH Guide to Grants and Contracts contained an error. Section IV indicated that the earliest possible start date for initial awards would be April 1, 1989. The correct earliest possible start date would be April 1, 1990. Vol. 18, No. 5, February 17, 1989 - Page 7 FULL TEXT OF RFAs FOR ONLINE ACCESS DEPARTMENT OF HEALTH AND HUMAN SERVICES PUBLIC HEALTH SERVICE ALCOHOL, DRUG ABUSE, AND MENTAL HEALTH ADMINISTRATION NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM P.T. 34; K.W. 0404003, 0755015, 0755018 Request for Cooperative Agreement Applications Matching Patients to Alcoholism Treatments RFA AA-89-02A, Coordinating Center January 1989 (Catalog of Federal Domestic Assistance No. 13.273) PURPOSE The purpose of this cooperative agreement is to support a Coordinating Center to work with Clinical Research Units to conduct multi-site trials of patient-treatment matching in the alcoholism treatment field. BACKGROUND AND RATIONALE Recent alcoholism treatment outcome research shows that matching particular clients to specific treatment modalities may significantly enhance treatment effectiveness. Examples of such research include several studies suggesting that varying degrees of severity of emotional or life adjustment problems in patients require different intensities of treatment (McLellan, et al., 1983). Other studies indicate that patients who think in abstract, analytical ways do better with therapists having similar methods of conceptualizing (McLachlan, 1974). A recent study of aftercare found that alcohol abusers who could clearly identify stimuli associated with their drinking had fewer relapses in programs designed to teach coping skills for high- risk situations than they did with more generalized treatments (Annis, 1987). Another recent project has found that depressed or highly anxious alcohol and/or other drug abusers do better if they receive individual psychotherapy and alcohol and/or other drug abuse counseling rather than the counseling alone (Woody, 1988). Although important findings about patient-treatment matching from individual studies have been reported, their utility to the alcoholism treatment field is limited due to questions about generalizability. Because individual studies have rarely offered the opportunity to test standardized treatment regimens in multiple samples, it is difficult to determine whether conclusions about patient-treatment matching can be generalized from the specific population studied to other populations and to different settings. Research in this area has also been impeded by samples that are generally too small to permit precise measurement of the effect of patient-treatment matching on treatment outcome. Multi-site trials, therefore, represent a valuable strategy for the study of alcoholism treatment since they help ensure generalizability and usefulness to the alcohol treatment field. Multi-site trials offer two primary advantages in this regard. First, they make the recruitment of large samples possible. This markedly reduces error and allows for sophisticated statistical analyses that assess the effects of multiple factors on treatment outcomes. Second, by allowing the use of standardized research protocols, multi-site studies provide the capacity to compare treatment effects for different subtypes of clients in different sites, thereby enhancing the generalizability of results. In addition, multi-site trials, with their large samples and standardized techniques, also allow for the possibility of simultaneous testing of more than one strategy and of exploration of interactions between strategies. The availability of new monies to evaluate treatment provides NIAAA with the capacity to fund multi-site patient-treatment matching research. Such research provides an opportunity for public and private treatment programs to work collaboratively with experienced university-affiliated treatment outcome research experts in investigating promising patient-treatment matching strategies. The statutory authority for this program is section 1922 of the Public Health Service Act as amended by the Anti-Drug Abuse Act of 1988 (PL 100-690). PROJECT OBJECTIVE The objective of the project for which applications are solicited by this Request for Cooperative Agreement Applications (RFA AA-89-02A) is to support a Coordinating Center to work with and support Clinical Research Units to conduct a patient-treatment matching study, using a common protocol, at multiple sites in order to investigate the efficacy of particular strategies for matching patients to alcoholism treatment regimens. PROJECT COMPONENTS This study will involve the cooperation of investigators from a Coordinating Center, Clinical Research Units, and the NIAAA Division of Clinical and Prevention Research. Separate applications are being solicited for a Coordinating Center (RFA AA-89-02A) and for Clinical Research Units (RFA AA-89-02B) to participate in this collaborative study. Particulars of design requirements are discussed under APPLICATION REQUIREMENTS. Coordinating Center The function of the Coordinating Center is to coordinate the aspects of the project that involve cross-site support. This will include activities such as data collection, processing, and analysis; training personnel from all Clinical Research Units; reproducing and scoring instruments; monitoring compliance with the common research protocol; and organizing the Steering Committee meetings. While Clinical Research Units with expertise in the particular treatment approaches employed in the trials will conduct the training regarding treatment protocols, the Center will coordinate this activity, will provide training regarding all other aspects of the research, and will assure that the project is implemented according to the specifications of the final research protocol. The Coordinating Center will also be responsible for the executive secretariat functions of organization of Steering Committee meetings and preparation of reports from the Steering Committee to the NIAAA Project Officer. (The role and composition of the Steering Committee is discussed under CONDUCT AND OVERSIGHT OF THE COOPERATIVE STUDY.) Clinical Research Units The function of the Clinical Research Units is the conduct of the common study of patient-treatment matching developed by the Steering Committee, including subject enrollment, implementation of treatment protocols, and data collection. In addition, Clinical Research Units with expertise in the selected treatment(s) will provide training to the other Units in implementation of the treatment protocol. APPLICATION REQUIREMENTS Applications for the Coordinating Center should identify automated data processing resources, previous experience with large scale data collection efforts, and relevant staff expertise. The applicant also must delineate proposed procedures for data collection, processing, and analysis; development of an appropriate database; training of Clinical Research Unit personnel; and preparation and distribution of measurement instruments. The applicant must also specify procedures to ensure the quality of the data and monitor compliance of the Clinical Research Units with the common research protocol. Requirements for the protection of human subjects must be completed at the time of application, even though a second IRB review may be required after the final study plan is developed. CONDUCT AND OVERSIGHT OF THE COOPERATIVE STUDY Steering Committee A Steering Committee will constitute the primary governing body of the study. This group will have responsibility for the direction of the multi-site study, developing the final study plan, implementing the study, monitoring study progress, and reporting study results. The study plan will include the research design, assessment instruments, protocols, and detailed implementation procedures. All major scientific decisions will be determined by majority vote of the Steering Committee. Since the use of common protocols is crucial to the success of the project, all participating Clinical Research Units must agree to abide by the study design and the policies developed by the Steering Committee. It is important to note that the final study plan may not be identical to any of the individual proposals; it may be based on a study proposed in one of the awardee's applications or it may combine elements of studies proposed by more than one Clinical Research Unit. The Steering Committee will also develop policies on data sharing, on access to data and materials, and on publication authorship. Publication policies will be written and authorship decided using procedures developed by the Steering Committee. Principal investigators may publish results from a single Clinical Research Unit but must obtain prior approval from the Steering Committee. The quality of publications resulting from the study will be the responsibility of authors; no NIAAA clearances will be required except for NIAAA staff who serve as coauthors (see NIAAA Staff Participation). The Steering Committee will be composed of: the principal investigator of the Coordinating Center, the principal investigators of the Clinical Research Units, the NIAAA Staff Collaborator, and a statistician. Additional non-voting consultants may be appointed to the Steering Committee as needed. The Steering Committee will normally meet up to four times a year (usually in the Washington, D.C. area). Up to six meetings may be required the first year to develop the study plan and research protocols. Applicants should include budgets for travel to these meetings in their applications and should assure that adequate provisions are made to allow principal investigators to participate fully in Steering Committee activities. If a Steering Committee decision regarding the design, implementation, or continuation of a trial is not acceptable to an awardee, and a mutually acceptable compromise cannot be reached, the awardee may, within 30 days of notification of the Steering Committee decision, request a review of the decision by an Arbitration Panel composed of one nominee chosen by the awardee, one chosen by NIAAA, and one with pertinent expertise chosen by the first two nominees. This Panel will make a decision within 60 days of the request. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action in accordance with PHS regulations at 42 CFR part 50, subpart D, and HHS, Grant Administration Regulations at 45 CFR part 74, and HHS regulations at 45 CFR part 16. Project Advisory Committee NIAAA will establish a Project Advisory Committee composed of at least five experts in the alcohol research field, including a statistician, who are not directly involved in the conduct of the study. The Advisory Committee will have two specific responsibilities: peer review of the final study plan and ongoing project oversight. Once the final study plan and research protocols have been developed, the Advisory Committee will conduct a peer review and will submit a written review report to the Institute. In terms of oversight, the Committee will monitor both data and safety aspects of the study. In addition, annual reports prepared by the Steering Committee (with the assistance of the NIAAA Staff Collaborator and the Coordinating Center) on behalf of the awardees will be provided to the Advisory Committee for review and comment. It is also expected that the Project Officer will seek Advisory Committee input on matters concerning study progress, especially at times of movement from one phase to another. NIAAA Staff Participation The NIAAA Staff Collaborator will be a voting member of the Steering Committee, but not its chair. He/she will participate in the development of the final study plan, in quality control, and in coordination of the project, but will not participate in activities that directly involve clinical testing or treatment of human subjects. The Staff Collaborator may also participate in data analysis and interpretation and in the preparation of publications. He/she may cooperate with the awardees in adjustments of protocols and preparation of reports of trial results. In instances where significant involvement in the design of trials and/or analysis of results has occurred, the Staff Collaborator may cooperate with awardees as a co-author in preparing publications of data resulting from the trials. In this regard, he/she will be subject to the publication/authorship policies governing all participants. In addition, publications involving NIAAA staff require internal clearances. The NIAAA Project Officer will oversee the Coordinating Center and will be responsible for periodic review and approval of the progress of the trials. The Project Officer is also responsible for monitoring the conduct and fiscal management of the project. The Director of the NIAAA Division of Clinical and Prevention Research will participate in the Steering Committee as an ex officio (non-voting) member to provide expertise in the area of multi-site clinical trials. TIMETABLE FOR THE STUDY It is envisioned that the study will be conducted in three phases over a total of 5 years. Phase I will involve the establishment of the Steering Committee and the development of a common study plan, including the matching criteria to be employed, and selection and/or development of specific research protocols. Review of the plan by the Project Advisory Committee will also occur. The developmental phase will be completed in 9 to 12 months. Phase II will involve pilot testing in all Clinical Research Units of the instruments and the research protocols. It will also involve testing of procedures to be used by the Coordinating Center. Preliminary data will be analyzed and protocols will be revised according to findings of the pilot project. The Project Advisory Committee will review the resulting study plan. The testing phase will be completed in 9 to 12 months. In Phase III, multi-site clinical trials of matching strategies will be implemented at the clinical sites according to the final study plan. Data on patient characteristics, treatment, and outcomes will be collected. Data will be analyzed and publications prepared. This phase will take 3 to 3 1/2 years. MECHANISM OF SUPPORT The administrative and funding mechanism to be used to support these clinical trials will be a cooperative agreement between the awardees and NIAAA. Under a cooperative agreement, researchers define the details of the proposed project within the guidelines of the RFA, agree to accept close coordination and guidance by the Steering Committee in all aspects of the scientific and technical management of the common project, and retain primary responsibility for performance of the research, in accordance with terms formally negotiated and mutually agreed on prior to the award. Under a cooperative agreement, Institute staff collaborate with the investigators on the common project. The major difference between a cooperative agreement and a research grant is the substantial programmatic involvement of NIAAA staff above and beyond the levels regularly required for traditional program management of grants. Significant programmatic involvement is needed because this RFA has the scientific objective of conducting multi-site trials of patient-treatment matching protocols using common intake and outcome measures as well as standardized treatment protocols (see PROJECT OBJECTIVES). Cooperative Agreements are subject to the same administrative requirements as grants. All pertinent DHHS, PHS, and ADAMHA grant regulations, policies, and procedures are applicable. Business management aspects of these awards will be administered in accordance with DHHS and PHS grant administrative requirements. Additional terms specific to this cooperative agreement program will be included in the Notice of Award. ELIGIBILITY Applications may be submitted by public or private nonprofit or for-profit organizations such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal Government. Women and minority investigators are encouraged to apply. PERIOD OF SUPPORT Support may be requested for a period of up to 5 years. Annual awards will be made subject to continued availability of funds and progress achieved. In Year 4 of the project the NIAAA will initiate a review to determine whether this program should be continued and if so, the appropriate support mechanism. Consideration will be given to options, such as (1) competitive renewal of existing cooperative agreement awards, (2) recompetition under the cooperative agreement mechanism, including both competitive renewals and new awards, or (3) future support of research in this area through the regular investigator-initiated research grant program. REVIEW PROCEDURES The Division of Research Grants, NIH, serves as a central point for receipt of applications for most discretionary PHS grant programs. Applications received under this announcement will be assigned to an Initial Review Group (IRG) in accordance with established PHS Referral Guidelines. The IRG, consisting primarily of non-Federal scientific and technical experts, will review the applications for scientific and technical merit during the summer of 1989. Notification of the review recommendations will be sent to the applicant after this initial review. Applications will receive a second-level review based on policy as well as scientific merit considerations by the National Advisory Council on Alcohol Abuse and Alcoholism in September 1989. Only applications recommended for approval by the Council may be considered for funding. Applications submitted in response to this announcement are not subject to the intergovernmental review requirements of Executive Order 12372, as implemented through Department of Health and Human Service regulations at 45 CFR Part 100 and are not subject to Health Systems Agency review. REVIEW CRITERIA Factors considered in evaluating the merit of applications for the Coordinating Center include: 1. The overall understanding of the project and the adequacy of the proposed approach. 2. Experience, competence, willingness, and availability of the Principal Investigator and other key personnel in performing the functions of the Coordinating Center. 3. Adequacy of plans and resources for collecting/ maintaining data, establishing an appropriate database, assuring data integrity, instructing on the correct use of research protocols, and monitoring adherence to research design specifications such as those described in this RFA. 4. The plan for the executive secretariat function needed principally in Phase I of the study, including the issues to be addressed and the special expertise needed. 5. The plans for collaboration and interaction with the Clinical Research Units. 6. Availability of adequate facilities, including computer data management, data analysis and repository facilities, and of other needed resources. 7. Appropriateness of budget estimates for the proposed activities. 8. Adequacy of procedures for the protection of human subjects. AWARD CRITERIA AND AVAILABILITY OF FUNDS Applications recommended for approval by the National Advisory Council on Alcohol Abuse and Alcoholism will be considered for funding on the basis of overall scientific and technical merit of the proposal as determined by peer review, NIAAA program needs and balance, and the availability of funds. In FY 1989, it is estimated that approximately $2 million will be available to support a single Coordinating Center and from five to nine Clinical Research Units. If further sites or additional patients are needed and/or if funds available for this effort increase, there may be an opportunity for new applicants to compete for funding of Clinical Research Units in FY 1990 and/or for competing supplemental applications from FY 1989 awardees. Because of the need to retain flexibility in the conduct of this study, and based on the funds available to the project, it may be necessary to adjust budget levels at the beginning of each budget period. Therefore, funding levels may be subject to re-negotiation between the Institute and each of the awardees throughout the project prior to the final award of funds. METHOD OF APPLYING Prospective applicants are asked to send a letter of intent, briefly describing goals, staffing, and resources of the planned Coordinating Center. This letter is requested only to provide an indication of the number and scope of applications. It is not binding and will not enter into the review of any application subsequently received. Letters of intent should be received by the Treatment Research Branch contact identified at the end of this RFA by April 7, 1989. State and local agencies may use form PHS 5161-1 (revised 4/88) to apply; all other applicants must use the regular research grant application form, PHS 398 (revised 9/86). When applying, type on page one, item 2 of PHS 398, the name and number of the RFA: Matching Patients to Alcoholism Treatments, RFA AA-89-02A, Coordinating Center. The page limit of 20 pages (for sections A through D on the PHS 398 application form) will be strictly enforced. Applicants who also wish to apply for consideration as a Clinical Research Unit should submit a separate application entitled: Matching Patients to Alcoholism Treatments, RFA AA-89-02B, Clinical Research Units. Application kits containing the necessary forms and instructions (PHS 398) may be obtained from institutional business offices or offices of sponsored research of most universities, colleges, medical schools, and other major research facilities. Applications may also be obtained from: The National Clearinghouse for Alcohol and Drug Information, Box 2345, Rockville, Maryland 20852 (telephone: 301/468-2600). SUBMISSION The signed original and four permanent, legible copies of the complete application should be submitted to: Division of Research Grants, NIH Westwood Building, Room 240 Bethesda, Maryland 20892** In order to accommodate the expedited review schedule, applicants are requested to send two complete copies directly to: National Institute on Alcohol Abuse and Alcoholism Office of Scientific Affairs Parklawn Building, Room 16C-20 5600 Fishers Lane Rockville, Maryland 20857 The RFA label in the PHS 398 application kit must be affixed to the bottom of the original face page and be duplicated on all copies. Failure to use the RFA label and to follow instructions could result in delayed processing of the application such that it may not reach the review committee in time for review. APPLICATION RECEIPT AND REVIEW SCHEDULE Applications for FY 1989 funding must be received by May 4, 1989. Applications not received by May 4 will be ineligible and will be returned without review. The following timetable summarizes the receipt and review schedule: Letter of Intent April 7, 1989 Application Receipt Date May 4, 1989 Initial Review by the IRG Summer, 1989 NIAAA Advisory Council Review September, 1989 Anticipated Award Date September 30, 1989 TERMS AND CONDITIONS OF SUPPORT The section entitled CONDUCT AND OVERSIGHT OF THE COOPERATIVE STUDY will be made part of the terms and conditions of award. The specific terms, conditions, and details of the scope and nature of the interaction between NIAAA and the awardees, and arbitration procedures pertaining to them will be incorporated in the Notice of Award. Cooperative agreement funds may be used for expenses clearly necessary to carry out the research project being supported by the award. Expenses may include direct costs which can be specifically identified with the project and allowable indirect costs for the applicant Institution. Investigators should note that funds may not be used to establish, add a component to, or operate a treatment, rehabilitation, or prevention intervention service program per se. Support for research-related treatment, rehabilitation, or prevention services and programs may be requested only for costs required by the research. Such expenses must be clearly justified in terms of research needs. Awards will be administered in accordance with the PHS Grants Policy Statement, (Revised, 1/87), which is available for $4.50 from the Superintendent of Documents, U.S. Government Printing Office, Washington, D.C. 20402. When ordering copies, the GPO stock number GPO 017-020-00092-7 should be referenced. Federal regulations at Title 42 CFR Part 52, "Grants for Research Projects," and Title 45 CFR Part 74, "Administration of Grants," are applicable to these awards. Title 42 CFR Part 2 "Confidentiality of Alcohol and Drug Abuse Patient Records" may also be applicable to these awards. STAFF CONTACT Inquiries and correspondence should be directed to: John Allen, Ph.D. Chief, Treatment Research Branch NIAAA, Room 16C-03 5600 Fishers Lane Rockville, Maryland 20857 (301) 443-0796 REFERENCES McLellan, A.T., Woody, G.E., Luborsky, L., O'Brien, C.P., and Druly, K.A. Predicting response to alcohol and drug abuse treatments. Arch Gen Psychiatry, 40:620-625, 1983. McLachlan, J.F.C. Therapy strategies, personality orientation and recovery from alcoholism. Canada Psychiatry Associate J., 19: 25-30, 1974. Annis, H.M. Effective treatment for drug and alcohol problems: What do we know? Invited address presented at the Annual Meeting of the Institute of Medicine National Academy of Science, Washington, D.C., October 21, 1987. Woody, G.E., McLellan, A.T., Luborsky, L., O'Brien, C.P., Blaine, J., Fox, S., Herman, I., Beck, A.T. Psychiatric severity as a predictor of benefits from psychotherapy. The Penn-VA study. AM J Psychiatry 140:1172-1177, 1984. Annis, H.M. and Chan, D. The differential treatment model: Empirical evidence from a personality topology of adult offenders. Criminal Justice and Behavior, 10:159-173, 1983. McLachlan, J.F.C. Benefit from group therapy as a function of patient-therapy match and conceptual level. Psychotherapy, Research and Practice, 9: 317-323, 1972. DEPARTMENT OF HEALTH AND HUMAN SERVICES PUBLIC HEALTH SERVICE ALCOHOL, DRUG ABUSE, AND MENTAL HEALTH ADMINISTRATION NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM P.T. 34; K.W. 0404003, 0755015, 0785035 Request for Cooperative Agreement Applications Matching Patients to Alcoholism Treatments RFA AA-89-02B, Clinical Research Units January 1989 (Catalog of Federal Domestic Assistance No. 13.273) PURPOSE The purpose of this cooperative agreement is to support Clinical Research Units to conduct multi-site trials of patient-treatment matching in the alcoholism treatment field. BACKGROUND AND RATIONALE Recent alcoholism treatment outcome research shows that matching particular clients to specific treatment modalities may significantly enhance treatment effectiveness. Examples of such research include several studies suggesting that varying degrees of severity of emotional or life adjustment problems in patients require different intensities of treatment (McLellan, et al., 1983). Other studies indicate that patients who think in abstract, analytical ways do better with therapists having similar methods of conceptualizing (McLachlan, 1974). A recent study of aftercare found that alcohol abusers who could clearly identify stimuli associated with their drinking had fewer relapses in programs designed to teach coping skills for high- risk situations than they did with more generalized treatments (Annis, 1987). Another recent project has found that depressed or highly anxious alcohol and/or other drug abusers do better if they receive individual psychotherapy and alcohol and/or other drug abuse counseling rather than the counseling alone (Woody, 1988). Although important findings about patient-treatment matching from individual studies have been reported, their utility to the alcoholism treatment field is limited due to questions about generalizability. Because individual studies have rarely offered the opportunity to test standardized treatment regimens in multiple samples, it is difficult to determine whether conclusions about patient-treatment matching can be generalized from the specific population studied to other populations and to different settings. Research in this area has also been impeded by samples that are generally too small to permit precise measurement of the effect of patient-treatment matching on treatment outcome. Multi-site trials, therefore, represent a valuable strategy for the continued study of alcoholism treatment outcomes since they help ensure generalizability and usefulness to the alcohol treatment field. Multi-site trials offer two primary advantages in this regard. First, they make the recruitment of large samples possible. This markedly reduces error and allows for sophisticated statistical analyses that assess the effects of multiple factors on treatment outcomes. Second, by allowing the use of standardized research protocols, multi-site studies provide the capacity to compare treatment effects for different subtypes of clients in different sites, thereby enhancing the generalizability of results. In addition, multi-site trials, with their large samples and standardized techniques, also allow for the possibility of simultaneous testing of more than one strategy and of exploration of interactions between strategies. The availability of new monies to evaluate treatment provides NIAAA with the capacity to fund multi-site patient-treatment matching research. Such research provides an opportunity for public and private treatment programs to work collaboratively with experienced university-affiliated treatment outcome research experts in investigating promising patient-treatment matching strategies. The statutory authority for this program is section 1922 of the Public Health Service Act as amended by the Anti-Drug Abuse Act of 1988 (PL 100-690). PROJECT OBJECTIVE The objective of the project for which applications are solicited by this Request for Cooperative Agreement Applications (RFA AA-89-02B) is to conduct a patient-treatment matching study, using a common protocol, at multiple sites in order to investigate the outcome of particular strategies for matching patients to alcoholism treatment regimens. PROJECT COMPONENTS This study will involve the cooperation of investigators from a Coordinating Center, Clinical Research Units, and the NIAAA Division of Clinical and Prevention Research. Separate applications are being solicited for a Coordinating Center (RFA AA-89-02A) and for Clinical Research Units (RFA AA-89-02B) to participate in this collaborative study. Particulars of design requirements are discussed under RESEARCH SPECIFICATIONS and APPLICATION REQUIREMENTS. Coordinating Center The function of the Coordinating Center is to coordinate the aspects of the project that involve cross-site support. This will include such activities such as data collection and processing, training personnel from all Clinical Research Units, reproducing and scoring instruments, monitoring compliance with the common research protocol, and organizing the Steering Committee meetings. While Clinical Research Units with expertise in the particular treatment approaches employed in the trials will conduct the training regarding treatment protocols, the Center will coordinate this activity, will provide training regarding all other aspects of the research, and will assure that the project is implemented according to the specifications of the final research protocol. The Coordinating Center will also be responsible for the executive secretariat functions of organization of Steering Committee meetings and preparation of reports from the Steering Committee to the NIAAA Project Officer. (The role and composition of the Steering Committee is discussed under CONDUCT AND OVERSIGHT OF THE COOPERATIVE STUDY.) Clinical Research Units The function of the Clinical Research Units is the conduct of the common study of patient-treatment matching developed by the Steering Committee, including subject enrollment, implementation of treatment protocols, and data collection. In addition, Clinical Research Units with expertise in the selected treatment(s) will provide training to the other Units in implementation of the treatment protocol. RESEARCH SPECIFICATIONS Although well-justified, innovative matching strategies suitable for multi-site trials will be considered, preference will be given to Clinical Research Unit applicants proposing strategies which have been shown experimentally to be efficacious in the treatment of alcoholism, drug abuse, or other behavioral dysfunction or which have a sound rationale for likely success. Patient-treatment matches that consider two or more patient characteristics or treatment factors simultaneously (for example, patient emotional stability and locus of control matched to degree of structure in treatment) may also be proposed. Several previous matching strategies for which some evidence of efficacy exists include: 1. Treatment Intensity - Alcoholic patients with both severe alcohol dependence and life adjustment problems do better in a structured full hospital treatment program then in a partial hospitalization program (McClellan, Woody, Luborsky, O'Brien, and Druly 1983). 2. Treatment Modality a. Alcoholic patients who are severely anxious or depressed do better in treatment which includes individual psychotherapy (Woody et al., 1984). b. Alcoholic patients who are high in self-esteem seem to do better with confrontation than those who are low in self-esteem (Annis and Chan, 1983). 3. Treatment Specificity - Patients who can identify specific high-risk drinking situations seem to do better in relapse prevention programs based on training in specific coping skills than those which use a conventional treatment program approach (Annis, 1987). 4. Counselor Characteristics - Patients who are matched to counselors on the basis of cognitive style (as tending to abstractly analyze issues) do better than those who are mismatched (McLachlan et al., 1972, 1974). The purpose of this list is not to be exhaustive nor preclude applicants from suggesting other types of matches. Nevertheless, investigators must specify what types of matches they would be unable or unwilling to employ in terms of matching on patient characteristics, treatment intensity, treatment type (behavioral or pharmacological), and counselor characteristics. Drinking outcome must be measured as a dependent variable in this study. Abstinence and measures of drinking behavior other than abstinence, e.g., quantity/frequency of drinking, days to first drink, may be used. Self-reported alcohol consumption should be validated by measures such as collateral reports, biochemical correlates of drinking, and direct measures of the physical presence of alcohol in the system. Also, improvements in life functioning, e.g., occupational performance, level of social functioning, health status, and legal offenses should be included. In addition to these outcomes, estimates of the costs associated with alternative treatment regimens are highly desirable (but not required). NIAAA urges Clinical Research Unit applicants to give attention, where feasible and appropriate, to the inclusion of women and minorities in study populations. If minorities and women are not included in a given study, a clear rationale for their exclusion should be provided. Investigators are reminded that merely including an arbitrary number of women and/or minority group participants in a given study does not guarantee generalizability of the results; thought should be given to the way in which women and/or minority participants fit into the overall study design. APPLICATION REQUIREMENTS Applications for a Clinical Research Unit will consist of a proposal for a study of patient-treatment matching which includes a clinical trial of particular matching technique(s). Applications are to describe fully the researcher's model and rationale for the proposed matching strategy and are to include detailed information concerning research design, measurement, and data analysis. In particular, applications must specify the following information: o Patient variables, including specific diagnostic and matching criteria, outcome measures and validation methods, and other relevant subject information to be collected should be specified in the application. The rationale for selection of diagnostic criteria, whether the DSM-III or some other guidelines, must also be given. Because of the heterogeneity of alcoholic populations, proposals should also clearly characterize their study populations with respect to relevant clinical and demographic factors. o Treatment variables in the matching paradigm must be defined, and the proposed treatment protocol defined. The number of facilities (if more than one) to be involved in the proposed patient-treatment match should be indicated. Relevant information about the characteristics of each participating treatment program, including type of patient served, treatment modalities currently employed, and the intensity/duration of treatment should be provided. Available information on client compliance with treatment, treatment outcome data, and pilot data on any matching that is in use should be given. Letters from the directors of the proposed treatment sites conveying their willingness to participate in the research should also be included. Such letters should also specify the types of matching they would be unable or unwilling to do. o The number of subjects likely to be available for the study during the entire enrollment period should be estimated based on the assumption that the proposed match is part of the final study protocol. The estimate should take into account the proposed criteria for subject selection, percentage of eligible subjects likely to refuse to participate, and the attrition rate during the study. Power analyses for the proposed study should be provided. o Mechanisms to ensure data quality and adherence to protocols in individual sites should be addressed. For example, procedures to assure reliable assessment of diagnosis and other patient variables, including staff training, reliability checks, and follow-up methods, should be described. Information on the experience of the staff with patient intake assessment should be provided. Previous experience, if any, in conducting treatment effectiveness research should be cited. Clinical Research Unit applicants with expertise in particular treatment approaches are encouraged to propose provision of training in related treatment protocols to other Units. Such training will be conducted in collaboration with the coordinating center. Clinical Research Unit applicants must also provide evidence of the capability of their studying matching strategies other than those they propose. Applicants should therefore comment on their ability to conduct research using different matching strategies At a minimum, strategies listed in the RESEARCH SPECIFICATIONS section (1-4) must be discussed. Particular emphasis should be placed on subject availability and ability to provide alternate treatment modalities. Requirements for the protection of human subjects must be completed at the time of application, even though a second IRB review may be required after the final study plan is developed. CONDUCT AND OVERSIGHT OF THE COOPERATIVE STUDY Steering Committee A Steering Committee will constitute the primary governing body of the study. This group will have the responsibility for the direction of the multi-site study, developing the final study plan, implementing the study, monitoring study progress, and reporting study results. The study plan will include the research design, assessment instruments, protocols, and detailed implementation procedures. All major scientific decisions will be determined by majority vote of the Steering Committee. Since the use of common protocols is crucial to the success of the project, all participating Clinical Research Units must agree to abide by the study design and the policies developed by the Steering Committee. It is important to note that the final study plan may not be identical to any of the individual proposals; it may be based on a study proposed in one of the awardee's applications or it may combine elements of studies proposed by more than one Clinical Research Unit. The Steering Committee will also develop policies on data sharing, on access to data and materials, and on publication authorship. Publication policies will be written and authorship decided using procedures developed by the Steering Committee. Principal investigators may publish results from a single Clinical Research Unit but must obtain prior approval from the Steering Committee. The quality of publications resulting from the study will be the responsibility of authors; no NIAAA clearances will be required except for NIAAA staff who serve as coauthors (see NIAAA Staff Participation). The Steering Committee will be composed of: the principal investigator of the Coordinating Center, the principal investigators of the Clinical Research Units, the NIAAA Staff Collaborator, and a statistician. Additional non-voting consultants may be appointed to the Steering Committee as needed. The Steering Committee will normally meet up to four times a year (usually in the Washington, D.C. area). Up to six meetings may be required the first year to develop the study plan and research protocols. Applicants should include budgets for travel to these meetings in their applications and should assure that adequate provisions are made to allow principal investigators to participate fully in Steering Committee activities. If a Steering Committee decision regarding the design, implementation, or continuation of a trial is not acceptable to an awardee, and a mutually acceptable compromise cannot be reached, the awardee may, within 30 days of notification of the Steering Committee decision, request a review of the decision by an Arbitration Panel composed of one nominee chosen by the awardee, one chosen by NIAAA, and one with pertinent expertise chosen by the first two nominees. This Panel will make a decision within 60 days of the request. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action in accordance with PHS regulations at 42 CFR part 50, subpart D, and HHS, Grant Administration Regulations at 45 CFR part 74, and HHS regulations at 45 CFR part 16. Project Advisory Committee NIAAA will establish a Project Advisory Committee composed of at least five experts in the alcohol research field, including a statistician, who are not directly involved in the conduct of the study. The Advisory Committee will have two specific responsibilities: peer review of the final study plan and ongoing project oversight. Once the final study plan and research protocols have been developed, the Advisory Committee will conduct a review and will submit a written report to the Institute. In terms of oversight, the Committee will monitor both data and safety aspects of the study. In addition, annual reports prepared by the Steering Committee (with the assistance of the NIAAA Staff Collaborator and the Coordinating Center) on behalf of the awardees will be provided to the Advisory Committee for review and comment. It is also expected that the Project Officer will seek Advisory Committee input on matters concerning study progress, especially at times of movement from one phase to another. NIAAA Staff Participation The NIAAA Staff Collaborator will be a voting member of the Steering Committee, but not its chair. He/she will participate in the development of the final study plan, in quality control, and in coordination of the project, but will not participate in activities that directly involve clinical testing or treatment of human subjects. The Staff Collaborator may also participate in data analysis and interpretation and in the preparation of publications. He/she may cooperate with the awardees in adjustments of protocols and preparation of reports of trial results. In instances where significant involvement in the design of trials and/or analysis of results has occurred, the Staff Collaborator may cooperate with awardees as a co-author in preparing publications of data resulting from the trials. In this regard, he/she will be subject to the publication/authorship policies governing all participants. In addition, publications involving NIAAA staff require internal clearances. The NIAAA Project Officer will oversee the Coordinating Center and will be responsible for periodic review and approval of the progress of the trials. The Project Officer is also responsible for monitoring the conduct and fiscal management of the project. The Director of the NIAAA Division of Clinical and Prevention Research will participate in the Steering Committee as an ex officio (non-voting) member to provide expertise in the area of multi-site clinical trails. TIMETABLE FOR THE STUDY It is envisioned that the study will be conducted in three phases over a total of 5 years. Phase I will involve the establishment of the Steering Committee and the development of a common study plan, including the matching criteria to be employed, and selection and/or development of specific research protocols. Review of the plan by the Project Advisory Committee will also occur. The developmental phase will be completed in 9 to 12 months. Phase II will involve pilot testing in all Clinical Research Units of the instruments and the research protocols. It will also involve testing of procedures to be used by the Coordinating Center. Preliminary data will be analyzed and protocols will be revised according to findings of the pilot project. The Project Advisory Committee will review the resulting study plan. The testing phase will be completed in 9 to 12 months. In Phase III, multi-site clinical trials of matching strategies will be implemented at the clinical sites according to the final study plan. Data on patient characteristics, treatment, and outcomes will be collected. Data will be analyzed and publications prepared. This phase will take 3 to 3 1/2 years. MECHANISM OF SUPPORT The administrative and funding mechanism to be used to support these clinical trials will be a cooperative agreement between the awardees and NIAAA. Under a cooperative agreement, researchers define the details of the proposed project within the guidelines of the RFA, agree to accept close coordination and guidance by the Steering Committee in all aspects of the scientific and technical management of the common project, and retain primary responsibility for performance of the research, in accordance with terms formally negotiated and mutually agreed on prior to the award. Under a cooperative agreement, Institute staff collaborate with the investigators on the common project. The major difference between a cooperative agreement and a research grant is the substantial programmatic involvement of NIAAA staff above and beyond the levels regularly required for traditional program management of grants. Significant programmatic involvement is needed because this RFA has the scientific objective of conducting multi-site trials of patient-treatment matching protocols using common intake and outcome measures as well as standardized treatment protocols (see PROJECT OBJECTIVES). Cooperative Agreements are subject to the same administrative requirements as grants. All pertinent DHHS, PHS, and ADAMHA grant regulations, policies, and procedures are applicable. Business management aspects of these awards will be administered in accordance with DHHS and PHS grant administrative requirements. Additional terms specific to this cooperative agreement program will be included in the Notice of Award. ELIGIBILITY Applications may be submitted by public or private nonprofit or for-profit organizations such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal Government. Women and minority investigators are encouraged to apply. A Clinical Research Unit may involve a single treatment facility or may include more than one facility. PERIOD OF SUPPORT Support may be requested for a period of up to 5 years. Annual awards will be made subject to continued availability of funds and progress achieved. In Year 4 of the project the NIAAA will initiate a review to determine whether this program should be continued and if so, the appropriate support mechanism. Consideration will be given to options, such as (1) competitive renewal of existing cooperative agreement awards, (2) recompetition under the cooperative agreement mechanism, including both competitive renewals and new awards, or (3) future support of research in this area through the regular investigator-initiated research grant program. REVIEW PROCEDURES The Division of Research Grants, NIH, serves as a central point for receipt of applications for most discretionary PHS grant programs. Applications received under this announcement will be assigned to an Initial Review Group (IRG) in accordance with established PHS Referral Guidelines. The IRG, consisting primarily of non-Federal scientific and technical experts, will review the applications for scientific and technical merit during the summer of 1989. Notification of the review recommendations will be sent to the applicant after this initial review. Applications will receive a second-level review based on policy as well as scientific merit considerations by the National Advisory Council on Alcohol Abuse and Alcoholism in September 1989. Only applications recommended for approval by the Council may be considered for funding. Applications submitted in response to this announcement are not subject to the intergovernmental review requirements of Executive Order 12372, as implemented through Department of Health and Human Service regulations at 45 CFR Part 100 and are not subject to Health Systems Agency review. REVIEW CRITERIA Factors to be considered in evaluating the merit of applications for Clinical Research Units include: 1. Scientific merit of research approach and methodology, including theoretical and empirical justification for the proposed matching system and adequacy of the research design, measures, procedures, and data analysis. 2. Ability of the treatment facility to participate in research involving a variety of patient-treatment matches other than those proposed, especially those listed under RESEARCH SPECIFICATIONS (1-4). 3. Research experience, competence, and willingness of the Principal Investigator and staff to conduct the proposed studies. 4. Adequacy of time that the Principal Investigator and staff would be able to devote to the proposed study. 5. Adequacy of facilities and resources, including access to a sufficient number of subjects and established treatment sites to allow completion of meaningful studies within the proposed project period. 6. Utility of the proposed research to applied clinical practice (i.e., extent to which results are likely to develop findings which will improve the treatment of alcoholism). 7. Potential replicability and generalizability. 8. Previous experience in conducting research on alcoholism treatment effectiveness. 9. Appropriateness of budget estimates for the proposed activities. 10. Adequacy of procedures for the protection of human subjects. AWARD CRITERIA AND AVAILABILITY OF FUNDS Applications recommended for approval by the National Advisory Council on Alcohol Abuse and Alcoholism will be considered for funding on the basis of overall scientific and technical merit of the proposal as determined by peer review, NIAAA program needs and balance, and the availability of funds. In FY 1989, it is estimated that approximately $2 million will be available to support a single Coordinating Center and from five to nine Clinical Research Units. If further sites or additional patients are needed and/or if funds available for this effort increase, there may be an opportunity for new applicants to compete for funding in FY 1990 and/or for competing supplemental applications from FY 1989 awardees. Because of the need to retain flexibility in the conduct of this study, and based on the funds available to the project, it may be necessary to adjust budget levels at the beginning of each budget period. Therefore, funding levels may be subject to re- negotiation between the Institute and each of the awardees throughout the project prior to the final award of funds. METHOD OF APPLYING Prospective applicants are asked to send a letter of intent, briefly describing the scientific goals, staffing, subject population, and resources of the proposed project. This letter is requested only to provide an indication of the number and scope of applications. It is not binding and will not enter into the review of any application subsequently received. Letters of intent should be received by the Treatment Research Branch contact identified at the end of this RFA by April 7, 1989. State and local agencies may use form PHS 5161-1 (revised 4/88) to apply; all other applicants must use the regular research grant application form, PHS 398 (revised 9/86). When applying, type on page one, item 2 of PHS 398, the name and number of the RFA: Matching Patients to Alcoholism Treatments, RFA AA-89-02B, Clinical Research Units. The page limit of 20 pages (for sections A through D on the PHS 398 application form) will be strictly enforced. If a Clinical Research Unit proposes more than 1 component, the 20 page limit (for PHS 398 sections A-D) applies to each component. Applicants who also wish to apply for consideration as a Coordinating Center should submit a separate application entitled: Matching Patients to Alcoholism Treatments, RFA AA-89-02A, Coordinating Center. Application kits containing the necessary forms and instructions (PHS 398) may be obtained from institutional business offices or offices of sponsored research of most universities, colleges, medical schools, and other major research facilities. Applications may also be obtained from: The National Clearinghouse for Alcohol and Drug Information, Box 2345, Rockville, Maryland 20852 (telephone: 301/468-2600). SUBMISSION The signed original and four permanent, legible copies of the complete application should be submitted to: Division of Research Grants, NIH Westwood Building, Room 240 Bethesda, Maryland 20892** In order to accommodate the expedited review schedule, applicants are requested to send two complete copies directly to: National Institute on Alcohol Abuse and Alcoholism Office of Scientific Affairs Parklawn Building, Room 16C-20 5600 Fishers Lane Rockville, Maryland 20857 The RFA label in the PHS 398 application kit must be affixed to the bottom of the original face page and be duplicated on all copies. Failure to use the RFA label and to follow instructions could result in delayed processing of the application such that it may not reach the review committee in time for review. APPLICATION RECEIPT AND REVIEW SCHEDULE Applications for FY 1989 funding must be received by May 4, 1989. Applications not received by May 4 will be ineligible and will be returned without review. The following timetable summarizes the receipt and review schedule: Letter of Intent April 7, 1989 Application Receipt Date May 4, 1989 Initial Review by the IRG Summer, 1989 NIAAA Advisory Council Review September, 1989 Anticipated Award Date September 30, 1989 TERMS AND CONDITIONS OF SUPPORT The section entitled CONDUCT AND OVERSIGHT OF THE COOPERATIVE STUDY will be made part of the terms and conditions of award. The specific terms, conditions, and details of the scope and nature of the interaction between NIAAA and the awardees, and arbitration procedures pertaining to them will be incorporated in the Notice of Award. Cooperative agreement funds may be used for expenses clearly necessary to carry out the research project being supported by the award. Expenses may include direct costs which can be specifically identified with the project and allowable indirect costs for the applicant Institution. Investigators should note that funds may not be used to establish, add a component to, or operate a treatment, rehabilitation, or prevention intervention service program per se. Support for research-related treatment, rehabilitation, or prevention services and programs may be requested only for costs required by the research. Such expenses must be clearly justified in terms of research needs. Awards will be administered in accordance with the PHS Grants Policy Statement, (Revised, 1/87), which is available for $4.50 from the Superintendent of Documents, U.S. Government Printing Office, Washington, D.C. 20402. When ordering copies, the GPO stock number GPO 017-020-00092-7 should be referenced. Federal regulations at Title 42 CFR Part 52, "Grants for Research Projects," and Title 45 CFR Part 74, "Administration of Grants," are applicable to these awards. Title 42 CFR Part 2 "Confidentiality of Alcohol and Drug Abuse Patient Records" may also be applicable to these awards. STAFF CONTACT Inquiries and correspondence should be directed to: John Allen, Ph.D. Chief, Treatment Research Branch NIAAA, Room 16C-03 5600 Fishers Lane Rockville, Maryland 20857 (301) 443-0796 REFERENCES McLellan, A.T., Woody, G.E., Luborsky, L., O'Brien, C.P., and Druly, K.A. Predicting response to alcohol and drug abuse treatments. Arch Gen Psychiatry, 40:620-625, 1983. McLachlan, J.F.C. Therapy strategies, personality orientation and recovery from alcoholism. Canada Psychiatry Associate J., 19: 25-30, 1974. Annis, H.M. Effective treatment for drug and alcohol problems: What do we know? Invited address presented at the Annual Meeting of the Institute of Medicine National Academy of Science, Washington, D.C., October 21, 1987. Woody, G.E., McLellan, A.T., Luborsky, L., O'Brien, C.P., Blaine, J., Fox, S., Herman, I., Beck, A.T. Psychiatric severity as a predictor of benefits from psychotherapy. The Penn-VA study. AM J Psychiatry 140:1172-1177, 1984. Annis, H.M. and Chan, D. The differential treatment model: Empirical evidence from a personality topology of adult offenders. Criminal Justice and Behavior, 10:159-173, 1983. McLachlan, J.F.C. Benefit from group therapy as a function of patient-therapy match and conceptual level. Psychotherapy, Research and Practice, 9: 317-323, 1972.