2. National Drug Abuse Treatment Clinical Trials Network February 13, 2003 Betty Tai, Ph.D. Director, Center for the Clinical Trials Network, NIDA/NIH February 13, 2003 Betty Tai, Ph.D. Director, Center for the Clinical Trials Network, NIDA/NIH

3. Who could want a more lovely way To spend Valentine’s Day Than talking about how we may Implement protocols the CTN way Who could want a more lovely way To spend Valentine’s Day Than talking about how we may Implement protocols the CTN way

4. CTN’s Mission To Improve Drug Abuse Treatment Throughout the Nation… Using SCIENCE as the Vehicle To Improve Drug Abuse Treatment Throughout the Nation… Using SCIENCE as the Vehicle

5. Uniqueness of CTN Blending Research and Practice Bi-directional Collaboration Multi-node, Multi-site RCTs Rigorous Scientific Standards Real World Approach Dissemination End-products Targeted Blending Research and Practice Bi-directional Collaboration Multi-node, Multi-site RCTs Rigorous Scientific Standards Real World Approach Dissemination End-products Targeted

6. CTN Where the Rubber Meets the Road A Paradigm Shift: Transferability, Acceptability, Sustainability

7. CTN Development Update FY 2000 FY 2001 FY 2003 FY 2002 7 Protocol Projects………12………21………26……… Dissemination New Research Agenda (HIV, CJS, etc.) New Concepts & Protocols (Ongoing) Build & Maintain Infrastructure……5…….11………14……….17 Establish Policies and SOPs

8. National Drug Abuse Treatment Clinical Trials Network Node RRTC – Regional Research and Training Center CTP – Community-Based Treatment Program RRTC – Regional Research and Training Center CTP – Community-Based Treatment Program CTP RRTC

9. National Drug Abuse Treatment Clinical Trials Network National Drug Abuse Treatment Clinical Trials Network Oregon Node OHSU Washington Node U. Washington Pacific Node UCLA Rocky Mountain Node U. Colorado Florida Node U. Miami Great Lakes Node Wayne State U. Ohio Valley Node U. Cincinnati South Carolina Node MUSC North Carolina Node Duke California/Arizona Node UCSF/U. Arizona Southwest Node U. New Mexico Northern NE Node McLean/Harvard New England Node Yale New York Node NYU Long Island Node NY State Psych. Inst. Delaware Valley Node U. Pennsylvania Mid-Atlantic Node JHU/MCV 17 Regional Research and Training Centers working in partnership with 115 Community-Based Treatment Programs across 27 States

10. Infrastructure

11. CTN Administrative Overview NIDA Grants Management Branch Ad Hoc Oversight PRB DSMB CCTN Contract Support CTN Nodes Repository Steering Committee NIDA Director New EnglandNew York Delaware Valley Mid-Atlantic OregonPacific South Carolina Florida Great LakesOhio Valley Rocky Mountain Long Island Washington North Carolina California/ Arizona New Mexico Northern New England

12. Steering Committee Research PortfolioOperationsExternal Affairs Executive Committee

13. Administration OD ScienceOperationsDissemination Center for the Clinical Trials Network Steering Committee Research PortfolioOperationsExternal Affairs Executive Committee Review Data Informatics

14. CTN Rules CTN Bylaws CTN Node Performance Index CTN Operations Guidebook CTN Study Integrity Monitoring Standards –Medication Trials –Behavioral Trials CTN Study Safety Monitoring System CTN Bylaws CTN Node Performance Index CTN Operations Guidebook CTN Study Integrity Monitoring Standards –Medication Trials –Behavioral Trials CTN Study Safety Monitoring System

15. Research Concept Generation NIDA CTN CTN Steering Committee Network Oversight Board NIDA Director Concepts CTN Nodes CTPs Protocol Development

16. CTN Protocol Portfolio – 2002 Project #Protocol TitleLI CTN 0001Bup/Nal vs Clonidine for Inpatient Opiate DetoxLing CTN 0002Bup/Nal vs Clonidine for Outpatient Opiate DetoxLing CTN 0003Bup/Nal: Comparison of Three Taper Schedules for Opiate DetoxAmass CTN 0004 MET (Motivational Enhancement Treatment) To Improve Treatment Engagement and Outcome in Subjects Seeking Treatment for Substance Abuse Carroll CTN 0005 MI (Motivational Interviewing) To Improve Treatment Engagement and Outcome in Subjects Seeking Treatment for Substance Abuse Carroll CTN 0006Motivational Incentives for Enhanced Drug Abuse Recovery: Methadone ClinicsStitzer CTN 0007Motivational Incentives for Enhanced Drug Abuse Recovery: Drug Free ClinicsStitzer CTN 0008Baseline SurveyGreenlick CTN 0009 Smoking Cessation Treatment With Transdermal Nicotine Replacement Therapy in Substance Abuse Rehabilitation Program Reid CTN 0010Bup/Nal in the Treatment of Adolescent and Young Adult Heroin AddictsWoody CTN 0011Telephone Enhancement of Long-Term EngagementHubbard CTN 0012Infections Screening in Substance Abuse Treatment ProgramsBrown CTN 0013Motivational Interviewing for Pregnant Women Seeking Substance Abuse TreatmentWinhusen CTN 0014Brief Strategic Family Therapy for Adolescent Drug AbusersSzapocznik CTN 0015 Women’s Treatment for Substance Use Disorders and Trauma in Inpatient Rehabilitation and Intensive Outpatient Settings Hien CTN 0016Patient Feedback: A Performance Improvement StudyForman CTN 0017HIV/HCV Intervention in Drug Treatment SettingsBooth CTN 0018HIV/STD Safer Sex Skills Groups for MenCalsyn CTN 0019HIV/STD Safer Sex Skills Groups for WomenTross CTN 0020Job Seekers Training for Clients with Drug DependenceSvikis CTN 0021MET or MI: Spanish versionCarroll

17. Current CTN Portfolio (21 Protocols) By Intervention Type

18. Current CTN Portfolio (21 Protocols) Total Projected Enrollment by Intervention Type

19. Current CTN Portfolio (21 Protocols) Protocols Involving Special Populations

20. Status of Current Trials: > 1,900 Patients Enrolled Protocol NIDA-CTN- Short Title Number Randomized Enrollment Target 0001Bup/Nx Inpatient113Closed 0002Bup/Nx Outpatient233Closed 0004MET349600 0005MI400Closed 0006Incentives Drug-Free410400 0007Incentives Methadone391400 0011TELE13360

21. CTN Special Interest Groups 1.HIV/AIDS 2.Adolescent 3.Women and Gender 4.Co-morbidity 5.Court-involved Patients 6.Ethnic Minority 7.Behavioral Therapy 8.Buprenorphine 9.Treatment match 10.Smoking 11.Homelessness 12.Spirituality 1.HIV/AIDS 2.Adolescent 3.Women and Gender 4.Co-morbidity 5.Court-involved Patients 6.Ethnic Minority 7.Behavioral Therapy 8.Buprenorphine 9.Treatment match 10.Smoking 11.Homelessness 12.Spirituality

22. 1.Generate snapshots of current practice 2.Identify empirically supported interventions 3.Develop high quality research concepts  4 AIDS concepts  3 Women concepts  2 Adolescent concepts  3 Co-morbidity concepts 4.Identify and develop special research tools 5.Develop long range research plan 6.Serve as expert resources 1.Generate snapshots of current practice 2.Identify empirically supported interventions 3.Develop high quality research concepts  4 AIDS concepts  3 Women concepts  2 Adolescent concepts  3 Co-morbidity concepts 4.Identify and develop special research tools 5.Develop long range research plan 6.Serve as expert resources CTN Special Interest Group

23. CTN as Research Platform Currently 4 RO1s from Services Research Branch –Managed by CTN Research Liaison Sub-C A new PA released from SRB Bup/NX Post Marketing Survey from Pharmaceutical Co. Other collaborations welcome Currently 4 RO1s from Services Research Branch –Managed by CTN Research Liaison Sub-C A new PA released from SRB Bup/NX Post Marketing Survey from Pharmaceutical Co. Other collaborations welcome

24. National CTN Symposia: 2003 4/03 – AATOD 5/03 – ASAM, NCDEU 6/03 – NASADAD, CPDD, RSA 7/03 – SCT 8/03 – APsychologicalA 9/03 – ICTAB-10, Blending Meeting 4/03 – AATOD 5/03 – ASAM, NCDEU 6/03 – NASADAD, CPDD, RSA 7/03 – SCT 8/03 – APsychologicalA 9/03 – ICTAB-10, Blending Meeting

25. CTN By-Products Appreciation of Research/Science in the CTPs Change of Practice Attitudes –Buprenorphine detox for patients in drug-free clinics –TAU has been greatly modified Training –GCP/CAB training on regular basis –80 therapists trained/certified for MI –LIs training in leading complex clinical trials NIDA’s presence in Community Treatment Programs Appreciation of Research/Science in the CTPs Change of Practice Attitudes –Buprenorphine detox for patients in drug-free clinics –TAU has been greatly modified Training –GCP/CAB training on regular basis –80 therapists trained/certified for MI –LIs training in leading complex clinical trials NIDA’s presence in Community Treatment Programs

26. CTN Challenges Gaps Between Researchers and Practitioners –Culture –Interests Clinical Trials in Real-World Settings –Protocol Design & Analysis –Protocol Implementation Gaps Between Researchers and Practitioners –Culture –Interests Clinical Trials in Real-World Settings –Protocol Design & Analysis –Protocol Implementation

27. Concept Selection Criteria Researchers’ perspectives Need scientific evidence Need pilot data Need dose response Need sample size/power considerations Need adequate data analysis Need data to focus future studies Need assurance of data integrity Need scientific evidence Need pilot data Need dose response Need sample size/power considerations Need adequate data analysis Need data to focus future studies Need assurance of data integrity

28. Evidence Criteria Researchers –Published in JAMA –Replicated –Large sample with good power Researchers –Published in JAMA –Replicated –Large sample with good power Practitioners –Everyone is doing it –State mandated –It worked for my patients Practitioners –Everyone is doing it –State mandated –It worked for my patients How to address bi-directionality issues? How to develop “science-based” practice?

29. Concept Selection Criteria Practitioners’ perspectives Need relevance in real life settings 1.How much internal/external validity? 2.How representative are the samples? 3.How does this deviate from practice? 4.How expensive? Who pays for this? 5.Any impact on long-term outcome? 6.Do my patients accept it? Need relevance in real life settings 1.How much internal/external validity? 2.How representative are the samples? 3.How does this deviate from practice? 4.How expensive? Who pays for this? 5.Any impact on long-term outcome? 6.Do my patients accept it?

30. Challenges: Research Design and Analysis Determining Control Treatment Placebo control Ethics Feasibility Bup/Nx vs. clonidine detox trial Open trial for feasibility Patients’/clinicians’ bias uncontrolled Placebo control Ethics Feasibility Bup/Nx vs. clonidine detox trial Open trial for feasibility Patients’/clinicians’ bias uncontrolled Pharmacotherapies

31. Challenges: Research Design and Analysis Determining Control Treatment Standardized control Relevance for individual sites Treatment-as-usual (TAU) control Wide variability of TAU between and within sites and over time Difficulty of analyzing multi-site, multi-TAU data Many trials need to describe and monitor TAUs Standardized control Relevance for individual sites Treatment-as-usual (TAU) control Wide variability of TAU between and within sites and over time Difficulty of analyzing multi-site, multi-TAU data Many trials need to describe and monitor TAUs Behavioral Therapies

32. Implementation Challenges: Accommodating the Real World User friendly Transferable KISS Protocol language Standardized procedures across sites –Quality data output –Quality Assurance User friendly Transferable KISS Protocol language Standardized procedures across sites –Quality data output –Quality Assurance

33. Training –Research experience varies –Fidelity and monitoring –Staff turnover Assessment batteries –Which instruments? Validated? –How much time? –Redundancy? Open vs. blinded –Bleeding or contamination Training –Research experience varies –Fidelity and monitoring –Staff turnover Assessment batteries –Which instruments? Validated? –How much time? –Redundancy? Open vs. blinded –Bleeding or contamination Implementation Challenges: Accommodating the Real World

34. Opportunities A Frontier of Research Researchers and Practitioners are Fully aware of the challenges Determined to conquer them Willing to cooperate

35. CTN trials completed in 2002: Buprenorphine/Naloxone Detoxification Change in programs’ attitudes Change in medical management of opiate addiction Adolescent, Dose Tapering trials Motivational Enhancement Therapy/Motivational Interviewing (MET/MI) 80 therapists trained/certified Complement to usual practice Spanish MET trial Buprenorphine/Naloxone Detoxification Change in programs’ attitudes Change in medical management of opiate addiction Adolescent, Dose Tapering trials Motivational Enhancement Therapy/Motivational Interviewing (MET/MI) 80 therapists trained/certified Complement to usual practice Spanish MET trial Clinical Trials Network

36. Completed and Ongoing Studies Medication Therapies Buprenorphine/Naloxone Detoxification –Inpatient/Outpatient Behavioral Therapies Motivational Enhancement Therapy (MET)/Motivational Interviewing (MI) Motivational Incentives Therapy –Drug-Free Clinics/Methadone Clinics TELE Engagement Procedure Surveys Baseline Survey of CTPs Medication Therapies Buprenorphine/Naloxone Detoxification –Inpatient/Outpatient Behavioral Therapies Motivational Enhancement Therapy (MET)/Motivational Interviewing (MI) Motivational Incentives Therapy –Drug-Free Clinics/Methadone Clinics TELE Engagement Procedure Surveys Baseline Survey of CTPs

37. Studies to Begin Enrollment in 2003 Bup/Nx Tapering Schedules Smoking Cessation Treatment in Substance Rehabilitation Programs Bup/Nx for Adolescents Infections and Substance Abuse Survey MET for Pregnant Substance Users Brief Strategic Family Therapy Women’s Treatment for Trauma and Substance Use Disorders Bup/Nx Tapering Schedules Smoking Cessation Treatment in Substance Rehabilitation Programs Bup/Nx for Adolescents Infections and Substance Abuse Survey MET for Pregnant Substance Users Brief Strategic Family Therapy Women’s Treatment for Trauma and Substance Use Disorders

38. Studies Under Development Patient Feedback HIV/HCV Risk Reduction Intervention in Drug Treatment Settings HIV/STD Safer Sex Skills for Men/Women Job Seekers Training MET for Spanish Speaking Individuals HIV Risk Reduction Intervention for Adolescents Family Management Skills Community Reinforcement and Family Training SSRI Treatment of Comorbid Depression and Substance Dependence Individual 12-Step Facilitation Patient Feedback HIV/HCV Risk Reduction Intervention in Drug Treatment Settings HIV/STD Safer Sex Skills for Men/Women Job Seekers Training MET for Spanish Speaking Individuals HIV Risk Reduction Intervention for Adolescents Family Management Skills Community Reinforcement and Family Training SSRI Treatment of Comorbid Depression and Substance Dependence Individual 12-Step Facilitation