Adaptive Treatment Strategies in the Addictions: Current Examples and Future Directions

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Adaptive Treatment Strategies in the
AddictionsCurrent Examples and Future
Directions

• James R. McKay, Ph.D.
• Professor of Psychology in Psychiatry
• University of Pennsylvania
• CTN Meeting
• 3.22.07

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Overview of Presentation

• Major problems in providing addiction treatment
  and how weve 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

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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

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Attempts to Address Nonresponse?

• Improve existing treatments
• Develop new treatments
• Tailoring, or matching treatments to subgroups
  of patients
• Results???

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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.

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Another Possible Approach?Adaptive Treatment
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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?

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How Do You Put Together an Adaptive Protocol?
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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

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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

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Examples of Adaptive Protocols from Addiction
Specialty Care
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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 gt 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

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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

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Results RMC vs. TAU

• Time to return to treatment
• 376 vs. 600 days (plt .05)
• Total days of treatment
• 62 vs. 40 days (plt .05)
• In need of treatment at 24 months
• 43 vs. 56 (plt .01)
• In need of treatment in at least 5 quarters
• 23 vs. 32 (plt .05)

Dennis et al. (2003) Evaluation and Program
Planning, 26, 339-352
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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

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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
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Continuing Care Conditions

• Telephone Monitoring and Counseling
• Weeks 1-4, patients make a 15 minute call and
  attend a transition group (1x/week _at_)
• 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

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Total Abstinence Rates
Tx Main Effect TEL gt STND plt .05
McKay et al., 2005, Archives of General Psychiatry
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Adaptive Treatment Strategy Using Progress in
Initial Phase of Treatment to Select
OptimalContinuing Care Models
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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 lt 12 self-help meetings in prior 30
  days
• Social support lt median for the sample
• Does not have goal of absolute abstinence
• Self-efficacy lt 80
• Current dependence on both alcohol and cocaine
• (each item yes1, no0)

McKay et al., 2005, Addiction, Archives of
General Psychiatry
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Distribution of Scores on the Composite Risk
Indicator
Mean score 2.50
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TEL vs. STND contrast X Risk Index Score p lt .05
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(No Transcript)
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Extended Telephone-Based Adaptive Protocol for
the Management of Cocaine Dependence
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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

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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
• Provide feedback on risk level
• 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

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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

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Examples of Adaptive Protocols from Non-Specialty
Addiction Care
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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

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Adaptive Continuing Care Naltrexone Protocol

• OMalley 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)

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Alcohol Use Results and Interpretations

• Findings
• Initiation phase PCCBT
• Extended PC phase NTX gt 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

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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

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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

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Adaptive Intervention Strategies Embedded in
Oslin Trial
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Comparing Definitions of Response
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Comparing Augment vs. Switch for NonResponders
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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)

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Adaptive Treatment and the CTNDifficult
Problems.. But Big Opportunitiesand
Potential Benefits
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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?

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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

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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?

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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 dont like IOP. How about.?
• Adaptive medication algorithms
• Start with promising med augment with or switch
  to additional medication for nonresponders

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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.

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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