Full Text DA-94-002 BEHAVIORAL THERAPIES DEVELOPMENT PROGRAM NIH GUIDE, Volume 22, Number 41, November 12, 1993 RFA: DA-94-002 P.T. 34 Keywords: Drugs/Drug Abuse Behavioral/Social Studies/Service National Institute on Drug Abuse Letter of Intent Receipt Date: February 11, 1994 Application Receipt Date: March 11, 1994 PURPOSE Behavioral therapies are frequently the only treatments available to drug-dependent individuals. (The term, "behavioral therapies," is used here in a broad sense and includes various forms of psychotherapy, behavior therapy, skills training, counseling, and other rehabilitative therapies.) Even where medications are available, behavioral therapies are an integral component of treatment. Considerable progress has been made over the past decade in developing effective behavioral therapies for drug abuse and dependence. These recent research advances suggest that the field is ready to move ahead with a major initiative in this area. Recognizing the importance of behavioral therapies for drug abuse and dependence, the National Institute on Drug Abuse (NIDA) is launching a Behavioral Therapies Development Program. It is intended to: (1) complement and dramatically expand work underway within the Clinical and Experimental Therapeutics Research Branch, Division of Clinical Research, NIDA and (2) parallel NIDA's Medications Development Program. The release of this Request for Applications (RFA) coincides with the commencement of NIDA's Behavioral Therapies Development Program and represents NIDA's ongoing commitment to support behavioral therapy drug abuse and dependence research. It is NIDA's intention to support scientifically sound and clinically relevant behavioral therapy research that will potentially have a meaningful impact on the efficacy of drug abuse/dependence treatment. Through the Behavioral Therapies Development Program, support may be sought to identify, evaluate, and standardize behavioral therapies for the treatment of drug abuse and dependence. Ultimately, therapies found to be efficacious through rigorous testing, will be disseminated to clinicians. Although substantial work has already been done, this initiative will target for funding, in a systematic way, essential research on behavioral therapies for drug abuse and dependence. This will include, in particular, critical areas of research that have been overlooked in the past. The purpose of this RFA is to introduce a major research effort on behavioral therapies for drug abuse and dependence. Behavioral therapy research has been conceptualized, for the purposes of this initiative, to consist of three phases. For the Behavioral Therapies Development Program to succeed, it is essential that all three phases of behavioral therapy research receive appropriate support. Therefore, it is NIDA's intention to support: (1) Phase I research (including the development, refinement, and pilot efficacy testing of behavioral interventions for drug dependence); (2) Phase II research (efficacy testing and replication of promising piloted behavioral therapies; and (3) Phase III research (studies to test the generalizability and transferability of behavioral therapies proven efficacious in Phase II studies). 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, Behavioral Therapies Development Program for Drug Abuse and Dependence, is related to the priority area of alcohol and other drugs. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by foreign and domestic, for-profit and non-profit organization, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. Foreign institutions are not eligible for First Independent Research Support and Transition (FIRST) (R29) Awards. MECHANISM OF SUPPORT Support mechanisms include: Research projects grants (R01), small grants (R03), and FIRST awards (R29). Investigators may also respond to this RFA under the Interactive Research Project Grant (IRPG) mechanism. Additional requirements for the IRPG mechanism are described in PA-93-078. Most investigator-initiated research is supported by regular research grants. Research grants are awarded to institutions on behalf of Principal Investigators who have designed and will direct a specific project or set of projects. FUNDS AVAILABLE It is anticipated that approximately $3 million will be available to support the first year of the behavioral therapies research program. Because the nature and scope of the research proposed in response to this RFA may vary, the size of an award will also vary. However, it is anticipated that approximately eight new awards will be made under this announcement. RESEARCH OBJECTIVES Background and Rationale Recent results from research studies indicate great promise for the efficacy of behavioral therapies for drug dependence. For example, Higgins and Budney (1993) reported using the community reinforcement approach (Hunt and Azrin, 1973; Azrin, 1976) to treat cocaine-dependent individuals. Their results were extremely encouraging, with a large number of subjects achieving initial abstinence from cocaine. Carroll et al. (1993) found evidence that while a behavioral therapy (as compared to standard treatment without the behavioral therapy) does not always increase an individual's ability to maintain abstinence from drugs while the patient is in treatment, behavioral interventions may, indeed, help patients maintain the gains that they have made after they are out of treatment. Specifically, they found that whether cocaine abusers were provided relapse prevention or clinical management, they all improved during treatment. However, at 6 and 12-month followup, only those who had received the relapse prevention were able to maintain the gains they made in treatment. While considerable progress has been made, engagement and retention in treatment and relapse following treatment remain concerns. NIDA is undertaking the Behavioral Therapies Development Program with the goal of addressing these concerns and substantially improving the efficacy of behavioral treatments for drug abuse. NIDA's Behavioral Therapies Development Program delineates three phases of behavioral therapy research. Phase I, the earliest phase of behavioral therapy research, therapy development, is viewed as a multi-stage process. It involves identifying promising clinical and research findings relevant to drug abuse treatment, generating and formulating new behavioral therapies, operationally defining the therapies in manuals, and pilot testing and refining the therapies. With the Behavioral Therapies Development Program, support for Phase I research is intended to continue and intensify. Phase II research consists of small-scale efficacy testing of promising therapies identified in Phase I, as well as studies examining the efficacy of components of therapies. Most of the behavioral treatment research that NIDA has supported in the past has been of this type. Phase II also involves the replication, at other sites, of efficacy studies with positive results. Under the Behavioral Therapies Development Program, Phase II clinical trials and component analysis studies will be emphasized more strongly, as is the case for replication studies. Phase III entails the testing of therapies that have been shown to be efficacious in more than one controlled Phase II clinical trial. This involves establishing the generalizability and transferability of these therapies, and determining their usefulness within community-based treatment programs. For drug abuse treatment to succeed, it is essential that all phases of behavioral therapy research receive sufficient emphasis and support. Through the Behavioral Therapies Development Program, NIDA will greatly increase its support of the early phases of behavioral therapy development, small-scale controlled clinical trials of fully developed therapies (including replications), and studies in community-based treatment programs of the most promising therapies identified in the Phase II clinical trials. This RFA is intended to introduce this initiative by encouraging research grant applications in any one of the three phases of behavioral therapy research. Specific Areas of Interest Areas of interest include, but are not limited to, the following: Phase I Research: Investigators are encouraged to submit applications to develop new or modify existing behavioral therapies that: (1) appear promising for the treatment of drug-dependent and abusing individuals; and (2) have a convincing rationale or theoretical basis. Therapies of interest include but are not limited to the following: 1. Discrete therapy modules that address specific problems common among drug-dependent individuals, and that can be implemented in conjunction with other therapeutic services. For example, an investigator may wish to develop a four-session, highly focused, job-seeking skills module that can be easily implemented by a wide range of practitioners, to effectively increase appropriate job-seeking behavior. Other examples include, but are not limited to, modules to engage ambivalent drug- dependent individuals in treatment, to address "denial," or to increase assertiveness in female drug addicts who feel pressured by others to use drugs. 2. Therapies designed specifically to engage and retain individuals in treatment. An example could be a therapy that: (1) is sensitive to the motivational level of the client, (2) is specifically designed to respond to the needs of the individual, whatever his or her motivational level might be, and (3) actively works to increase an individual's desire to remain in treatment. 3. Therapies to impact specific client characteristics. Such therapies are based upon theories regarding measurable psychological, behavioral, or interpersonal constructs. Examples include therapies to overcome cognitive deficits, family dysfunction, or social skill deficiencies, where these constructs are hypothesized to be causally related to drug abuse and where they may be quantified. Investigators may propose the development of measures where relevant to the development and assessment of the therapy. 4. Therapies for abusers of specific drugs. This may include, but is not limited to, therapies to treat cocaine, heroin, benzodiazepine dependence, or dependence upon several drugs. 5. Therapies to treat comorbid populations. This may include therapies to treat drug abuse/dependence in individuals who have, for example, psychotic, mood, anxiety, personality disorders, or one of the disruptive behavior disorders of childhood and adolescence such as an attention-deficit/hyperactivity, conduct, or oppositional defiant disorder. This may also include behavioral therapies aimed at integrating drug dependence and mental health treatment approaches in dually diagnosed populations, where the ultimate goal of the therapy is to decrease drug use. 6. Therapies for specific ethnic, racial, or cultural groups. This includes therapies that are culturally sensitive and address the unique needs and perspectives of minorities or cultural groups. 7. Therapies for women. Such therapies may be aimed, for example, at meeting the emotional and cognitive needs of drug-abusing pregnant or parenting women, or of women who have or are experiencing physical/sexual abuse. 8. Therapies for adolescents. Such therapies may be aimed, for example, at addressing the problems associated with active drug abuse or dependence on the part of the youth during the early, middle, and/or late adolescent stages of development. 9. Therapies for families. Such therapies should address drug abuse from the perspective of the whole family rather than from the viewpoint of an individual family member. 10. Therapies for use in community settings. Therapies need to be developed for use in outreach programs and other non-traditional settings that access drug abusers who avoid the formal drug abuse treatment system. An application for a grant to develop a therapy should include an explicit, logical, consistent, and coherent statement describing the theoretical basis for that therapy, and the population for whom it is intended. A thorough literature review documenting relevant research and clinical findings should also be included. Although, of course, a manual for a therapy will not exist prior to an application to develop such a manual, the nature of the therapy to be developed should be described in as much detail as possible in the application. Components of the psychotherapy, behavior therapy, or drug counseling approach to be developed should be operationally defined wherever possible. Applicants proposing client characteristic specific therapies, should address the issue of whether theoretically based diagnostic systems or client assessment scales tailored to their therapy need development. If one theorizes, for example, that certain heroin addicts either began or maintained heroin use due to interpersonal conflicts, and that the resolution of these conflicts will decrease drug use, a measure of interpersonal conflicts should either exist, or be developed with a therapy based upon treating these conflicts. The development of a theoretically based therapy should include measures of client attributes directly related to that therapy. Where necessary, investigators may develop new or refine existing client assessment scales to measure the impact of the proposed theoretically-based therapy. Methods that will be used to develop these instruments should be described in detail. Close attention should be paid to the psychometric characteristics of these measures (i.e., validity, internal consistency, inter-rater and test-retest reliability). Applicants should also address the issue of how they intend to measure what is actually occurring in the therapy they are proposing to develop. The credibility of any treatment research depends on the ability to determine the extent to which that treatment was actually administered, and administered correctly. In the development of any therapy, therefore, emphasis should be placed upon the development of psychometrically sound therapist competence and adherence scales, process measures, and instruments measuring the integrity and fidelity of the therapy. Applicants should describe the instruments they intend to develop, and the methods that they will use to ensure they are developing valid and reliable measures. In the development of a new therapy for drug dependence, a broad range of issues relevant to efficacy and safety must be addressed. Pilot efficacy testing of newly developed/modified therapies, therefore, should be considered an integral part of any therapy development process. The applicant should describe, in detail, the nature of any pilot testing intended. Any pilot testing proposed should be based upon sound, scientific methods. Phase II Research Phase II research establishes the efficacy of therapies, and the efficacious components of therapies. In Phase II research control and comparison groups are operationally defined, standardized, and manualized. However, early in Phase II, it may be appropriate to compare a therapy with "treatment as usual." Investigators should have clearly delineated research questions, and should carefully choose their control/comparison groups to answer those questions. It is appropriate, but not required, that investigators design studies to answer not only if their therapy works, but why it works. Specific areas of Phase II research include, but are not limited to: 1. Comparative Behavioral Therapy Research. Controlled clinical trials that examine the relative efficacy of behavioral therapies and attempt to determine which therapies are best for which individuals, and under what conditions, are encouraged. Studies that investigate the relative efficacy of individual, group, or family psychotherapy; behavior therapy; skills training; drug abuse counseling; or other rehabilitative approaches in various special populations are also encouraged. Applicants proposing comparative behavioral therapy research studies are encouraged to examine the interactions of relevant therapist/patient characteristics with therapy type and to assess the relative contribution of therapist, patient, and type of therapy to outcome. For example, contingency management has been shown to be efficacious for some individuals, but not for others (Stitzer et al., 1993). Investigators proposing a clinical trial using contingency management in one group may wish, therefore, to design the study such that they may determine the characteristics of patients for whom this intervention is or is not helpful. (This type of study may be done, of course, within or outside the context of a comparative clinical trial). Another example of a study examining client characteristics is a study which attempts to determine the relative efficacy of a cognitive therapy in individuals with varying levels of cognitive ability. For these studies, it is imperative that investigators accurately measure and control for the psychiatric diagnosis and problem severity level of the patients. It is also necessary that clear definitions of outcome variables be specified, and that valid and reliable measures of outcome be used. It is important that therapists/counselors providing the therapy be systematically trained, that manuals be used to guide the therapies, that valid and reliable therapist competence and adherence scales be used, and that the treatment process be measured accurately. For all efficacy studies, it is expected that adequate followup assessments be planned. It is also important that these studies use procedures and methods that can be replicated. It is strongly suggested that pilot data showing that a counseling or psychotherapy strategy is promising be provided when proposing comparative research involving this therapy. These pilot data should indicate that the utilization of the therapy approach shows promise in its ability to produce a decrease in drug use, dropout rate, or psychiatric symptoms. 2. Research To Integrate Behavioral Therapies with Pharmacotherapies. Where effective pharmacotherapies are available, research projects that attempt to maximize the efficacy of that pharmacotherapy through integration with behavioral therapy, or vice versa, are encouraged. 3. Component Analysis Research. Knowing the effective components of treatment can greatly aid in improving the quality of treatment. Theoretically based research that attempts to determine the effective components or combination of components in drug dependence psychotherapies, behavior therapies, or counseling strategies is encouraged. 4. Replications. Applications that propose to replicate a behavioral therapy for drug abuse/dependence study that has positive findings are strongly encouraged. Applications that propose to generalize the efficacy of a promising therapy in another population are also encouraged. Where the investigator believes that significant modification of the therapy is needed before it can be tested in another population, investigators are referred to the section of this RFA entitled, "Phase I Research." It is recognized that for many research questions asked in the field of psychotherapy, behavior therapy, and counseling, no perfect research design may exist. Where there is more than one way to answer a proposed research question, investigators are urged to state their theoretical, ethical, and practical reasons for choosing one control group or one research design over another (see Borkovec, 1990, 1993). Investigators are also encouraged to address the issues of selection bias and attrition (Howard et al., 1990; Howard et al., 1993), and any other pertinent methodological issues. Phase III Research. Where behavioral therapies have been shown to be efficacious in a clinical trial, and where replication has borne out the contention that the therapy is, indeed, efficacious, investigators may propose to carry out a study to address the therapy's transferability, generalizability to other populations, and applicability in community-based drug abuse treatment programs. It is incumbent upon the applicant proposing any Phase III research to review the relevant literature on the behavioral therapy to be researched, and to clearly delineate the reasons that it is ready for a Phase III study. An example of a Phase III study might involve an investigator using a therapy that has been rigorously tested in a replicated controlled clinical trial, packaging that therapy, including development of training manuals and other training materials, to be used in a community setting. The investigator might then pilot the therapy in the community clinic, refine the therapy package, and ultimately test the usefulness of the packaged therapy in the community setting. Applicants are expected to develop applications that are focused on one phase; that is, investigators may choose to focus on either Phase I, Phase II or Phase III research. However, where it is justifiable, investigators may develop proposals to include a research component consistent with another phase (e.g., a Phase II research application may include a small Phase I component). If a subject is identified as being at risk for HIV acquisition and/or transmission, HIV testing and counseling should be offered to the subject in accordance with current guidelines. Furthermore, in high-risk populations, investigators are encouraged to assess the effect of the new therapy on the acquisition/transmission of associated infectious disease, including HIV. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements will be required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale should be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information should be included in the form PHS 398 in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research includes human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by February 11, 1994, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains allows NIDA staff to estimate the potential review workload and to 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 5600 Fishers Lane, Room 10-42 Rockville, MD 20857 Telephone: (301) 443-2755 APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and may be obtained from the Office of Grant Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 240, Bethesda, MD 20892, telephone 301/710-0267. The RFA label in the PHS 398 (rev. 9/91) application form must be affixed to the bottom of the original face page. 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. In addition, the RFA title and number must be typed in Item 2a on the face page of the application form and the YES box must be marked. Applications for the FIRST Award (R29) must include at least three sealed letters of reference attached to the face page of the original application. FIRST Award (R29) applications submitted without the required number of reference letters will be considered incomplete and will be returned without review. Submit a signed, typewritten original of the application and three signed photocopies in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission, two additional copies of the application must also be sent to: Director, Office of Extramural Program Review National Institute on Drug Abuse 5600 Fishers Lane, Room 10-42 Rockville, MD 20857 Applications must be received by March 11, 1994, and will be reviewed according to the following review schedule: Application Receipt Date: March 11, 1994 Initial Review: June 1994 Advisory Council: September 1994 Earliest Date of Award: September 1994 Applications received after the above receipt date will be held for the next regular receipt date and reviewed under standard circumstances. However, such applications may not be considered for the Fiscal Year 1994 funding set aside under this RFA. REVIEW CONSIDERATIONS The Division of Research Grants, NIH, serves as a central point for receipt of applications for most discretionary DHHS grant programs. Applications received under this announcement will be assigned to an initial review group (IRG) convened by the NIDA in accordance with established PHS referral guidelines. The IRGs, consisting primarily of non-Federal scientific and technical experts, will review the applications for scientific and technical merit in accordance with the standard NIH peer review procedures. Notification of the review recommendations will be sent to the applicant after the initial review. Applications will receive a second-level review by the National Advisory Drug Abuse Council, whose review may be based on policy considerations as well as scientific merit. Only applications recommended for further consideration by the Council may be considered for funding. AWARD CRITERIA The anticipated date of award is September 30, 1994. Applications recommended for further consideration by an appropriate Advisory Council will be considered for funding on the basis of overall scientific and technical merit of the application as determined by peer review, appropriateness of budget estimates, program needs and balance, policy considerations, adequacy of provisions for the protection of human subjects, and availability of funds. Upon completion of the project's period of award made under this RFA, grantees may submit competitive renewal applications. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Lisa Onken, Ph.D. National Institute on Drug Abuse 5600 Fishers Lane, Room 10A-30 Rockville, MD 20857 Telephone: (301) 443-0108 Direct inquiries regarding fiscal matters to: Gary Fleming, J.D., M.A. Chief, Grants Management Branch National Institute on Drug Abuse 5600 Fishers Lane, Room 8A-54 Rockville, MD 20857 Telephone: (301) 443-6710 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, Section 301, and administered under PHS policies and Federal Regulations at Title 42 CFR 52 "Grants for Research Projects", Title 45 CFR Part 74 & 92, "Administration of Grants" and 45 CFR Part 46, "Protection of Human Subjects". Title 42 CFR Part 2, "Confidentiality of Alcohol and Drug Abuse Patient Records" may also be applicable to these awards. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. References Azrin, N. "Improvements in the community reinforcement approach to alcoholism," Behavior Research and Therapy, 14: 339-348, 1976. Borkovec, T.D. "Control groups and comparison groups in psychotherapy outcome research," In Onken, L. Simon and Blaine, J.D. (Eds.) Psychotherapy and counseling in the treatment of drug abuse, NIDA Research Monograph #104, Department of Health and Human Services Publication Number (ADM)90-1722, 1990. Borkovec, T.D. "Between-group therapy outcome research: Design and methodology," In Onken, L. Simon, Blaine, J.D., and Boren, J.J. (Eds.) Behavioral Treatments for Drug Abuse and Dependence, NIDA Research Monograph, Department of Health and Human Services, 1993. Carroll, K.M., Rounsaville, B.J., Nich, C., Gordon, L.T., Wirtz, P.W., and Gawin, F.H. "One year follow-up of psychotherapy and pharmacotherapy for cocaine dependence: Delayed emergence of psychotherapy effects." Submitted for publication. Higgins, S.T. and Budney, A.J. "Treatment of cocaine dependence via the principles of behavior analysis and behavioral pharmacology," In Onken, L. Simon, Blaine, J.D., and Boren, J.J. (Eds.) Behavioral Treatments for Drug Abuse and Dependence, NIDA Research Monograph, Department of Health and Human Services, 1993. Howard, K.I., Cox, M., and Saunders, S.M. "Attrition in substance abuse comparative treatment research: The illusion of randomization," In Onken, L. Simon and Blaine, J.D. (Eds.) Psychotherapy and counseling in the treatment of drug abuse, NIDA Research Monograph #104, Department of Health and Human Services Publication Number (ADM)90-1722, 1990. Howard, K.I., Krause, M.S. and Lyons, J. "When clinical trials fail: A guide to disaggregation," In Onken, L. Simon, Blaine, J.D., and Boren, J.J. (Eds.) Behavioral Treatments for Drug Abuse and Dependence, NIDA Research Monograph, Department of Health and Human Services, 1993. Hunt, G.M., and Azrin, N. A community reinforcement approach to alcoholism. Behavior Research and Therapy, 11: 91-104, 1973. Stitzer, M.L., Iguchi, M.Y., Kidors, M., and Bigelow, G.E. "Contingency management in methadone treatment: The case for positive incentives," In Onken, L. Simon, Blaine, J.D., and Boren, J.J. (Eds.) Behavioral Treatments for Drug Abuse and Dependence, NIDA Research Monograph, Department of Health and Human Services, 1993. .
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