1. CTN Pharmacotherapy Trials and the CTP Allan J. Cohen, MA, MFT Bay Area Addiction, Research and Treatment, Inc (BAART) Pacific Region Node CTN 10 th Anniversary Symposium April 21, 2010

2. Eyjafjallajokull

3. Growth of the CTN CTP Network 2000: 52 CTP - 6 Nodes 2002: 91 CTP - 14 Nodes 2005: 123 CTP – 17 Nodes 2010: 187 CTP -16 Nodes Total - 206 CTP have participated

5. Community Treatment Programs Many ways to classify CTP but one characteristic frequently used: Medication-assisted treatment (methadone/harm reduction) Traditionally do not utilize medications ( psychosocial, “drug free”, abstinence)

6. We address a broad array of addictions with a wide variety of treatment interventions

9. “Wild Things” Group Therapy

11. Some very innovative treatment approaches

12. Staff of earliest recorded CTP

13. Richard Drandoff

14. Pharmacotherapy Trails in CTP Ten Medications Trials Six = Suboxone ( CTN 0001, 0002, 0003, 0010, 0027, 0030) Two = Methlyphenidate (CTN 0028, 0029) One = Nicotine Patches (CTN 0009) One = Buproprion (CTN 0046) * CTN 0048 Cocaine Use Reduction using buprenorphine (CURB)

15. Agonist Replacement for Opioid Dependence Methadone has been around 50+ years Treatment for heroin addiction in specialized treatment programs 1200 licensed OTP in the US with 260,000 MMT CTP and patients struggle with stigma There were few tools in the treatment box for opiate addiction: naltrexone – effective/poor acceptance LAAM - euthanized

16. Cont’d In non-methadone settings clonidine was (and still is) frequently used together with symptomatic specific meds; results were poor Anticipating approval of buprenorphine for treatment of opioid dependence the CTN launched two early, pre-approval, trials comparing suboxone to clonidine for short-term detox in outpatient and inpatient settings Prior to the early CTN 0001,0002, 0003 trials CTP pragmatic knowledge/understanding of buprenorphine was negligible. Early studies and then later 0010, 0027, 0030 helped shape best- practices guidelines for buprenorphine. Help educated staff and community. Help create a viable treatment addition to the options for opiate addiction.

17. “ Detoxification is good for many things, getting off drugs is not one of them” (Walter Ling)

18. Suboxone CTN 0001, 0002, 0003, 0010, 0027, 0030

19. CTN Studies with Suboxone CTN 0001, 0002, 0003: short-term treatment CTN 0010: adolescent and young adult population CTN 0027: hepatic safety study (START) CTN 0030: specific to prescription opiates Really the first opportunity for many CTP to gain some pragmatic experience with buprenorphine, also gave patients a similar benefit First time buprenorphine used in adolescent/young adult population For CTP the value of such opportunities with new treatments/technologies cannot be underestimated

20. CTP Experience with Suboxone Trials Six CTN trials utilizing Suboxone Variety of programs participated Many had little or no experience with suboxone Some had little or no experience with research All had some medical staff Ranged from brief (13 day) to longer (8 months) exposure to buprenorphine

21. Cont’d Early buprenorphine/medications trials helped to confirm the CTN model: it was feasible to conduct medications trials in community-based treatment programs, retain scientific rigor maintaining fidelity Confirmed the value and utility of bi-directionality: pragmatic and hybrid protocols in real world settings Afforded an invaluable opportunity for exposure to a new treatment option and build a skill set to help optimize it’s use Driving change in treatment Developing tension can be seen: specialized treatment providers/private office-based treatment

22. To date there have been 2,946 patients randomized in six medication trials with suboxone Of these 2,404 had opportunity to receive suboxone

24. START at BAART Fairly typical of the programs participating in START Very busy Opioid Treatment Program: – 700+ MMT Well known and established in community (SF) 30 yrs Staffing included: physicians/extenders medical assistants, counselors, dispensary nurses, (research assistants) Began START 6/2006 – completed recruitment 10/09

25. START at BAART We had turnover of research staff including physicians We “relocated” the entire clinic during the study! When START rolled out the majority of study participants were only interested in methadone By the end a significant number of new participants were hoping to receiving suboxone We have learned much and this will be of practical use

26. Smoking High prevalence of smoking behavior in SUD populations Only one completed study on smoking completed thus far (0009) MMT and Psychosocial CTP Difficulty in recruitment/retention No difference at 3 and 6 mo follow-up Use of behavioral and nicotine replacement therapy Nevertheless, this was an important study in my opinion: First CTN trial for smoking Included MMT and Psychosocial programs Pragmatic study which reflected realities of treatment New smoking medication trial (0046 - Winhusen) using buproprion for a specific subset of substance abusers

27. Medication Assisted Treatment is being more widely adopted partially as a result of CTN research CTP who had previously generally not used agonist replacement treatment began slowly incorporating suboxone: Betty Ford Center Maryhaven others

28. CTP Issues CTP are very busy places Not all CTP are staffed to participate in medication research Program “philosophy” may not always embrace the use of medication-assisted treatment Critical to integrate research staff Space Priorities

29. What is important to CTP Treatment accessibility that meets need/demand Treatment retention Acceptance of treatment by patients Reduction of stigma Sustaining treatment programs in tough times Retaining staff including research staff * Dissemination of new treatment/knowledge Funding Regulatory consistency

30. What’s important to patients: Quality of Life

31. Positive Outcomes  Exposure to new knowledge and skills  Possible new treatment interventions/options  Increased Accessibility to Treatment  Funding  Collegial support/Mentoring  Community Education  Bi-directional: invested in the protocol and research

32. Considerations for future medications research The bi-directional opportunity the CTN affords is unique and should continue to shape research: Co-occurring SUD and psychiatric disorders Co-occurring Alcohol Use Disorders* Adaptive/Sequential Models of Care** Stimulant abuse/dependence Chronic Pain and SUD Treatment Optimization Tapering/converting MMT to suboxone -“crossover” Specific Populations – adolescents, aging, gender, prescription opioid dependence Longitudinal studies/longer follow-up

33. Cost-effectiveness and Cost-benefit analyses are useful to inform providers in making decisions regarding adoption of new treatment

34. Adoption requires Sustainability Sustainability incorporates any number factors: Characteristics of medication is important to adoption Cost-benefit Fit into program Consumer acceptance Timing Funding

35. Researchers/Investigators Providers *Provider-researchers (something more than treatment providers who allow researchers to conduct studies within their programs) This is an outcome of CTN bi-directionality, providers who are actively engaged in research work with research mentor/colleagues, who enjoy and are invested in the research as they are in treatment

36. Legacy of pharmacotherapy trials in CTP Medication-assisted treatment options are gaining wider acceptance among treatment providers and funding sources Buprenorphine has gained broader acceptance by providers and patients Benefits of participation easily justify the effort CTP make excellent locations for “pragmatic or hybrid model” clinical trials Combined medication assisted and behavioral treatment models offer powerful tools which can help drive change in treatment

37. Research drives treatment Treatment drives research

38. Pharmacotherapy “Special Interest Group” Comprised largely of investigators and physicians, NIDA representatives and a few of us CTP folks Current Chair – Kathleen Brady, MD Discuss possible pharmacotherapy studies, medications in various stages of development and concept design for CTN protocols I have found participation very satisfying and a great learning experience

39. Just a few personal thoughts…

40. The moment that I realized what I wanted to do in life!

41. 35 years ago I met….

42. Walter Ling

43. What a great ride! Ten years of bi-directional research New Director of NIDA and NIH 8 NIDA Blending Meetings “All Hands Big Hug” and 9/11 Snipers – Pooks Hill Blizzards, Volcanoes Made many friends Lost some friends: Eileen Pencer, Len Handelsman, Patrick McAuliffe

44. Sepulveda VA Hospital Circa 1977

45. It has been a great ten years, we look forward to the future…