1. Susan Murphy, PI University of Michigan Acknowledgements: MCAT network and NIH The Goal To facilitate methodological collaborations necessary for producing evidence-based adaptive treatment strategies. This network involves engineers, computer scientists, psychologists, physicians and statisticians interested in forming collaborate groups which will conduct the necessary research and pilot studies so as to apply for R03 or R01 funding. Our long term goal is to enhance the adaptive, sequential, clinical decision making necessary in treating/managing chronic, relapsing disorders. Methodology for Adaptive Treatment Strategies R21 DA019800 Innovations  Intervention Trial Design  Sequential, Multiple Assignment, Randomized Trials (SMART)  Intervention Trial Data Analysis  Q-Learning  Exploratory Tailoring Analyses What are Adaptive Treatment Strategies? Adaptive Treatment Strategies are individually tailored sequences of treatments, with treatment type and dosage adapted and readapted to the individual. Generalization from a one-time decision to a sequence of decisions concerning treatment Operationalize clinical practice Q-Learning: A method from Computer Science  Can be used to construct proposals for adaptive treatment strategies that use more than simply response/non-response to adapt treatment to the individual.  Generalization of regression from one stage of treatment to multiple stages of treatment. CATIE (simplified version) SMART  Precursors are STAR*D (depression) and CATIE (schizophrenia) (NIMH funded)  Identify a few critical decisions, randomize individuals at each critical decision among treatment options.  Critical decisions include: Which treatment to use first?, How long to wait for the treatment to work?, Which treatment to provide next? Example of an Adaptive Treatment Strategy (Drug Court Program for drug abusing offenders.) Provide standard drug counseling If high risk, then provide biweekly court hearings. Else provide “as-needed court hearings.” Monitor compliance and symptoms monthly. If the offender becomes noncompliant, then the offender is subject to a court determined disposition. If offender becomes non-responsive, then provide intensive case management along with assessment and referral for adjunctive services. Else maintain on current treatment. Other SMART Studies  Sequencing Pharmacology and Behavioral Interventions in ADHD. Pelham, PI; IES  Sequencing Behavioral Treatments for Nonverbal Autistic Children. Kasari, PI; Autism Speaks  Sequencing Treatments for Prostate Cancer. Millikan, PI  Adaptive Aftercare for Alcoholism. McKay PI, NIAAA SMART Study II (RBT; Jones, PI; NIDA) Analyses of SMART Studies  Compare two adaptive treatment strategies  Compare outcomes from blue and green groups!  Construct more deeply tailored strategies:  Should the level of adherence during 1 st treatment be used to select 2 nd treatment?  Should severity of disorder influence which treatment should be 1 st ? SMART Study (ExTENd; Oslin, PI: NIAAA) Q-Learning--Example of Results using CATIE  Begin with Olanzapine  If non-responder then  If preference is try for efficacy then  If PANSS > 94 then switch to Clozapine  Else switch to either Quetiapine or Risperidone  If preference is to try for tolerability then  If Olanzapine was not tolerable then switch to Risperidone  If Olanzapine was not efficacious then switch to Quetiapine PANSS: Positive and Negative Syndrome Scale