1. Adaptive Treatment Strategies in the Addictions: Current Examples and Future Directions James R. McKay, Ph.D. Professor of Psychology in Psychiatry University of Pennsylvania CTN Meeting 3.22.07

2. Overview of Presentation Major problems in providing addiction treatment and how we’ve tried to address them Adaptive treatment models and how they are developed Examples of adaptive treatment in specialty care Examples of adaptive treatment in other treatment settings Challenges in designing and implementing adaptive treatment protocols

3. Problems in Addiction Treatment High rates of dropout and continued alcohol and drug use –In community-based programs –In research protocols Even with evidence-based treatments, considerable response heterogeneity

4. Attempts to Address Nonresponse? Improve existing treatments Develop new treatments Tailoring, or “matching” treatments to subgroups of patients Results???

5. Still left with variable response….. Even when treatment delivery is standardized and high adherence to manual is achieved, some patients do well and others do not. Very hard to predict who will do well in a particular treatment Some patients do well at first, but then deteriorate Nonresponse often blamed on the patient, but that is likely not the whole story.

6. Another Possible Approach? Adaptive Treatment

7. In Adaptive Treatment Protocols… Treatment is tailored or modified on the basis of measures of response (e.g., symptoms, status, or functioning) obtained at regular intervals during treatment Goal is to deliver the treatment that is most effective for a particular patient at a particular time. Rules for changing treatment are clearly operationalized and described….. “ If……..Then” Temporal issues important– when has sufficient time elapsed to indicate “non-response”?

8. How Do You Put Together an Adaptive Protocol?

9. Experimental Design for Developing Adaptive Protocols Use randomization to develop optimal adaptive treatment strategies –Example: What to do with early non-responders? Switch treatment? Augment treatment? Determine the set of decision rules and interventions that produce the highest percentage of responders THEN……. Compare the optimal adaptive protocol to TAU or other treatments in standard RCT

10. The alternative approach…. Devise adaptive protocol on the basis of: –Expert clinical judgment –Feedback from patients –Prior research findings –Face validity Compare that adaptive protocol to TAU or other treatment in standard RCT Pros and Cons: Faster than experimental approach, but protocol may be flawed

11. Examples of Adaptive Protocols from Addiction Specialty Care

12. Recovery Management Checkups Protocol developed by Dennis, Scott et al. –Interview patients every quarter for 2 years –If patient reports any of the following…… Use of alcohol or drugs on > 2 weeks Being drunk or high all day on any days Alcohol/drug use led to not meeting responsibilities Alcohol/drug use caused other problems Withdrawal symptoms ….. ….Patient transferred to linkage manager

13. RMC Linkage Manager provides the following: –Personalized feedback –Explore possibility of returning to treatment –Address barriers to returning to treatment –Schedule an intake assessment –Reminder cards, transportation, and escort to intake appointment

14. Results: RMC vs. TAU Time to return to treatment 376 vs. 600 days (p<.05) Total days of treatment 62 vs. 40 days (p<.05) In need of treatment at 24 months 43% vs. 56% (p<.01) In need of treatment in at least 5 quarters 23% vs. 32% (p<.05) Dennis et al. (2003) Evaluation and Program Planning, 26, 339-352

15. Adaptive Methadone Treatment Brooner & Kidorf (2002) protocol –Methadone patients start in low intensity psychosocial condition –Missed session or dirty/missing urine leads to increases in psychosocial counseling –Providing additional contingencies for participation further improves outcomes More/less convenient dosing times Methdone taper and possible discharge

16. Penn Telephone Continuing Care Study Patients: –359 graduates of 4-week IOP programs –Cocaine (75%) and/or alcohol (75%) dependent Continuing care treatment conditions (12 weeks): –Standard group counseling (STND) –Individualized relapse prevention (RP) –brief telephone-based counseling (TEL) McKay et al., 2004, Journal of Consulting and Clinical Psychology

17. Continuing Care Conditions Telephone Monitoring and Counseling –Weeks 1-4, patients make a 15 minute call and attend a “transition” group (1x/week @) –Weeks 5-12, patients have telephone contact only (1x/week) –During calls, patients report results of self-monitoring and progress toward 1-2 goals, and plan goals for next week –Patients use a workbook that structures intervention for each week. –Total minutes of contact with therapist 50% of minutes in other conditions

18. Total Abstinence Rates Tx Main Effect TEL > STND p<.05 McKay et al., 2005, Archives of General Psychiatry

19. Adaptive Treatment Strategy: Using Progress in Initial Phase of Treatment to Select Optimal Continuing Care Models

20. 7-Item Composite Risk Indicator Failure to achieve key goals while in IOP: –Any alcohol use in prior 30 days –Any cocaine use in prior 30 days –Attendance at < 12 self-help meetings in prior 30 days –Social support < median for the sample –Does not have goal of absolute abstinence –Self-efficacy < 80% Current dependence on both alcohol and cocaine (each item: yes=1, no=0) McKay et al., 2005, Addiction, Archives of General Psychiatry

21. Distribution of Scores on the Composite Risk Indicator Mean score= 2.50

22. TEL vs. STND contrast X Risk Index Score: p <.05

24. Extended Telephone-Based Adaptive Protocol for the Management of Cocaine Dependence

25. Design Patients: Cocaine dependent IOP participants recruited after achieving early engagement Treatment conditions: –Treatment as usual (TAU) –TAU plus adaptive protocol (24 mo.) –TAU plus adaptive protocol (24 mo.), plus incentives for participation and cocaine-free urines (12 mo) Outcomes assessed over 24 months

26. The Telephone Calls Frequency: weekly at first, titrated to bimonthly Each call starts with a brief “risk assessment” that assesses negative and positive factors and yields overall risk score (low, moderate, high) Similar protocol to prior study for telephone counseling: 1.Provide feedback on risk level 2.Review progress/goals from last call 3. Identify upcoming high-risk situations 4. Select target for remainder of call 5. Brief problem-solving regarding target concern(s) 6. Set goal(s) for interval before next call 7. Suggest change in level of care if warranted

27. Adaptive Protocol Increases in services triggered when risk reaches moderate level –First: increase frequency of phone calls –Second: bring patient in for 1-2 face-to-face evaluation and motivational interviewing (MI) sessions –Third: provide 8 CBT relapse prevention sessions –Fourth: refer back to IOP

28. Examples of Adaptive Protocols from Non-Specialty Addiction Care

29. Adaptive Primary Care Protocols for Heavy Drinkers Kristenson et al. (1983, 2003) –Patients randomized to visits with a nurse (every month) and physician (every 3 months), vs. TAU –Both provided for up to 4 years –GGT levels monitored, and treatment/drinking goals modified on basis of scores –Results: fewer sick days, fewer hospital days, lower mortality over 6 and 16 years than TAU

30. Adaptive Continuing Care Naltrexone Protocol O’Malley et al. (2003) study of NTX treatment comparing primary care (PC) and specialty care (CBT) approaches First, pts given NTX and randomized to PC or CBT for 10 weeks Responders (57%) further randomized: –PC plus extended NTX vs. placebo (24 wks) –CBT plus extended NTX vs. placebo (24 wks)

31. Alcohol Use Results and Interpretations Findings: –Initiation phase: PC=CBT –Extended PC phase: NTX > placebo –Extended CBT phase: NTX= placebo Resulting treatment algorithm –If patient responds to PC and NTX in first 10 weeks, continue both for at least 24 more weeks –If patient responds to CBT and NTX in first 10 weeks, continue CBT but stop NTX Note: no guidance regarding nonresponders

32. Adaptive Naltrexone Study (David Oslin, PI) Experimental design to determine optimal algorithms for naltrexone responders and nonresponders All patients begin with 8 week trial of open label naltrexone, plus weekly medication management session During the 8 week trial, patients self-select into Responder and Non-responder groups First randomization: Different definitions of “non- response” –More than 1 heavy drinking day –More than 4 heavy drinking days

33. Adaptive Naltrexone, cont. Second Randomization Nonresponders: –Add CBI and drop NAL (i.e., “switch”) –Add CBI and continue NAL (i.e., augment”) Responders: –NAL script plus no further care –NAL script plus telephone disease management

34. Adaptive Intervention Strategies Embedded in Oslin Trial Adaptive intervention Definition of nonresponder Decision rules for responders Decision rules for nonresponders 1 > 1 heavy drinking day Stay with NTX aloneNTX with CBI 2 > 1 heavy drinking day Stay with NTX aloneChange to CBI alone 3 > 1 heavy drinking day NTX with TDMNTX with CBI 4 > 1 heavy drinking day NTX with TDMChange to CBI alone 5 > 4 heavy drinking day Stay with NTX aloneNTX with CBI 6 > 4 heavy drinking day Stay with NTX aloneChange to CBI alone 7 > 4 heavy drinking day NTX with TDMNTX with CBI 8 > 4 heavy drinking day NTX with TDMChange to CBI alone

35. Comparing Definitions of Response Adaptive intervention Definition of nonresponder Decision rules for responders Decision rules for nonresponders 1 > 1 heavy drinking day Stay with NTX aloneNTX with CBI 2 > 1 heavy drinking day Stay with NTX aloneChange to CBI alone 3 > 1 heavy drinking day NTX with TDMNTX with CBI 4 > 1 heavy drinking day NTX with TDMChange to CBI alone 5 > 4 heavy drinking day Stay with NTX aloneNTX with CBI 6 > 4 heavy drinking day Stay with NTX aloneChange to CBI alone 7 > 4 heavy drinking day NTX with TDMNTX with CBI 8 > 4 heavy drinking day NTX with TDMChange to CBI alone

36. Comparing Augment vs. Switch for NonResponders Adaptive intervention Definition of nonresponder Decision rules for responders Decision rules for nonresponders 1 > 1 heavy drinking day Stay with NTX aloneNTX with CBI 2 > 1 heavy drinking day Stay with NTX aloneChange to CBI alone 3 > 1 heavy drinking day NTX with TDMNTX with CBI 4 > 1 heavy drinking day NTX with TDMChange to CBI alone 5 > 4 heavy drinking day Stay with NTX aloneNTX with CBI 6 > 4 heavy drinking day Stay with NTX aloneChange to CBI alone 7 > 4 heavy drinking day NTX with TDMNTX with CBI 8 > 4 heavy drinking day NTX with TDMChange to CBI alone

37. Summary of Possible Adaptations Non-responders –Step up (e.g., OP to IOP or residential) –Lateral move (e.g., CBT to TSF) –Modality change (e.g., CBT to medication) –Step down (e.g., IOP to telephone monitoring) Responders –Reduce frequency of intervention (e.g., IOP to OP) –Change to lower burden intervention (e.g., OP to periodic check-ups, or e-treatment)

38. Adaptive Treatment and the CTN: Difficult Problems………….. But Big Opportunities and Potential Benefits

39. Challenges in Adaptive Treatment Clinical Keeping patients engaged, especially when deterioration occurs Increasing compliance with adaptive changes, especially “step ups” Identifying alternative treatments for non- responders –Lack of a variety of effective medications –Are different types of “talk” therapy really different enough? –How important is patient preference/choice?

40. Challenges, cont. Research Incorporating choice in algorithms –Comparing heterogeneous condition to other interventions Sequential randomization designs –Randomizing patients 2+ times –Analytic issues (first decision) Power –Primary vs. secondary comparisons –New methods under development

41. Focus of Efforts in Treatment Development Emphasis in field has been on improving efficacy and adherence to manuals, and coming up with more cost-effective approaches. Shift emphasis to making participation more attractive to the patients to improve retention: –Greater weight to patient choice– at intake, and for non- responders –Use of more convenient forms of care whenever possible –Incentives for participation?

42. Possible Research Designs Adaptive strategies to address early dropout –Test providing a menu of treatment options vs. efforts to re-engage in standard care “So you don’t like IOP. How about…….?” Adaptive medication algorithms –Start with promising med– augment with or switch to additional medication for nonresponders

43. Research Designs, cont. Adaptive studies that combine behavioral and pharmacological interventions: –Start with medication and low intensity behavioral treatment, step up to more intensive treatment if no response –Offer non-responders sequential package that first involves switching meds, but then includes augmentation with stepped up behavioral treatment if response still not achieved.

44. Acknowledgments Colleagues: –NIDA CTN algorithms group –Dave Oslin, Kevin Lynch, Tom TenHave –Susan Murphy, Linda Collins Grant support: –NIDA: K02-DA00361, R01-DA14059, R01- DA20623 –NIAAA: R01AA14850