A Look Under the Hood of SMART Designs for Developing Adaptive - PowerPoint PPT Presentation

A Look Under the Hood of SMART Designs for Developing Adaptive Interventions Daniel Almirall, PhD Survey Research Center, Institute for Social Research University of Michigan April 11, 2016 Center for Drug Use and HIV Research New York, NY Almirall and many friends Adaptive Interventions April 2016 1 / 66

I don’t do any of this research by myself. Students Xi Lu , Penn State Colleagues Billie Nahum-Shani , Univ Mich Susan A. Murphy , Univ Mich Connie Kasari , UCLA (autism) Amy Kilbourne , Univ Mich (implementation science) Kevin Lynch , Univ Penn And many others... Almirall and many friends Adaptive Interventions April 2016 2 / 66

Outline Adaptive Interventions Sequential Multiple Assignment Randomized Trials (SMART) Longitudinal Analysis of a (first) SMART in Autism 5 SMART Case Studies (all in the field or in data analysis mode) ◮ Adaptive Interventions for Minimally Verbal Children (AIM-ASD) ◮ Adaptive Implementation of Effective Programs (ADEPT, mood dx) ◮ Extending Treatment Effectiveness in Adult Alcoholism (ExTEnD) ◮ Treatment for Pregnant Women with Heroine Dependence (RBT) ◮ Getting SMART about Social & Academic Engagement (ASD Schools) Myths or Misconceptions about Adaptive Interventions and SMARTs Almirall and many friends Adaptive Interventions April 2016 3 / 66

Sequential, Individualized Treatment Often Needed in Mental Health Intervention often entails a sequential, individualized approach whereby treatment is adapted and re-adapted over time in response to the specific needs and evolving status of the individual. This type of sequential decision-making is necessary when there is high level of individual heterogeneity in response to treatment. ◮ e.g., what works for one individual may not work for another ◮ e.g., what works now may not work later ◮ e.g., for some, what appears not to work in the short-run has positive long-term consequences Adaptive interventions help guide this type of individualized, sequential, treatment decision making Almirall and many friends Adaptive Interventions April 2016 4 / 66

Adaptive Interventions Almirall and many friends Adaptive Interventions April 2016 5 / 66

Definition of an Adaptive Intervention Adaptive Interventions (AI) provide one way to operationalize the strategies (e.g., continue, augment, switch, step-down) leading to individualized sequences of treatment. A sequence of decision rules that specify whether, how, when (timing), and based on which measures, to alter the dosage (duration, frequency or amount), type, or delivery of treatment(s) at decision stages in the course of care. Almirall and many friends Adaptive Interventions April 2016 6 / 66

Example of an Adaptive Intervention in Alcoholism Stage One NTX + MM + Monitor weekly for 2+ HDD/week; Stage Two IF patient trigger’s a non-response in weeks 2-8 ◮ THEN Augment with Cognitive Behavioral Intervention (CBI); ◮ ELSE IF continued responder until week 8 ⋆ THEN NTX + Phone Counseling to maintain response; Almirall and many friends Adaptive Interventions April 2016 7 / 66

Example of an Adaptive Intervention in Alcoholism Stage One NTX + MM + Monitor weekly for 2+ HDD/week; Stage Two IF patient trigger’s a non-response in weeks 2-8 ◮ THEN Augment with Cognitive Behavioral Intervention (CBI); ◮ ELSE IF continued responder until week 8 ⋆ THEN NTX + Phone Counseling to maintain response; Almirall and many friends Adaptive Interventions April 2016 7 / 66

Many Unanswered Questions when Building a High-Quality Adaptive Intervention. Why 2+ HDDs per week? Why not, instead, 5+ HDDs per week? Why should responders transition at week 8 to maintenance treatment? For continued responders at week 8, what is the effect of providing Phone Counseling? Do we really need it? Insufficient empirical evidence or theory to address such questions. In the past: relied on expert opinion, clinical expertise, or piecing together an AI with separate RCTs (e.g., practice parameters) Sequential Multiple Assignment Randomized Trials (SMARTs) address such questions empirically, using experimental design principles. Almirall and many friends Adaptive Interventions April 2016 8 / 66

‐ ‐ ‐ ‐ Example of an Adaptive Intervention in Autism For minimally verbal children with autism spectrum disorder Stage One JASP for 12 weeks; Stage Two At the end of week 12, determine early sign of response: ◮ IF slow responder: Augment JASP with AAC for 12 weeks; ◮ ELSE IF responder: Maintain JASP for 12 weeks. Almirall and many friends Adaptive Interventions April 2016 9 / 66

Example of an Adaptive Intervention in Autism For minimally verbal children with autism spectrum disorder Stage One JASP for 12 weeks; Stage Two At the end of week 12, determine early sign of response: ◮ IF slow responder: Augment JASP with AAC for 12 weeks; ◮ ELSE IF responder: Maintain JASP for 12 weeks. Continue: Responders JASP JASP Augment: Slow Responders JASP + AAC First ‐ stage Second ‐ stage End of Week 12 Treatment Treatment Responder Status (Weeks 1 ‐ 12) (Weeks 13 ‐ 24) Almirall and many friends Adaptive Interventions April 2016 9 / 66

How was response/slow-response defined? Percent change from baseline to week 12 was calculated for 7 variables: 7 variables: socially communicative utterances (SCU), percent SCU, mean length utterance, total word roots, words per minute, total comments, unique word combinations Fast Responder: if ≥ 25% change on 7 measures; Slower Responder: otherwise (includes kids with no improvement) Almirall and many friends Adaptive Interventions April 2016 10 / 66

Many Unanswered Questions when Building a High-Quality Adaptive Intervention. Is it better to provide AAC from the start? Who benefits from initial AAC versus who benefits from delayed AAC? For slow responders, what is the effect of providing the AAC vs intensifying JASP (not providing AAC)? Insufficient empirical evidence or theory to address such questions. In the past: relied on expert opinion, clinical expertise, or piecing together an AI with separate RCTs (e.g., practice parameters) Sequential Multiple Assignment Randomized Trials (SMARTs) address such questions empirically, using experimental design principles. Almirall and many friends Adaptive Interventions April 2016 11 / 66

Sequential Multiple Assignment Randomized Trials (SMART) Almirall and many friends Adaptive Interventions April 2016 12 / 66

What is a Sequential Multiple Assignment Randomized Trial (SMART)? A type of multi-stage randomized trial design. At each stage, subjects randomized to a set of feasible/ethical treatment options. Treatment options at latter stages may be restricted by response to earlier treatments. Almirall and many friends Adaptive Interventions April 2016 13 / 66

What is a Sequential Multiple Assignment Randomized Trial (SMART)? A type of multi-stage randomized trial design. At each stage, subjects randomized to a set of feasible/ethical treatment options. Treatment options at latter stages may be restricted by response to earlier treatments. SMARTs were developed explicitly for the purpose of building a high-quality Adaptive Intervention. Almirall and many friends Adaptive Interventions April 2016 13 / 66

Example of a SMART in Autism Research The population of interest: Children with autism spectrum disorder Age: 5-8 Minimally verbal: < 20 spontaneous words in a 20-min. language test History of treatment: ≥ 2 years of prior intervention Functioning: ≥ 2 year-old on non-verbal intelligence tests Almirall and many friends Adaptive Interventions April 2016 14 / 66

Example of a SMART in Autism Research ( N = 61) PI: Kasari (UCLA). Almirall and many friends Adaptive Interventions April 2016 15 / 66

There are 3 AIs Embedded in this Example Autism SMART (JASP,JASP+) Subgroups A+C (JASP,AAC) Subgroups A+B (AAC,AAC+) Subgroups D+E Almirall and many friends Adaptive Interventions April 2016 16 / 66

SMARTs permit scientists to answer many interesting questions for building a high-quality adaptive intervention. Primary Aim: What is the best first-stage treatment in terms of spoken communication at week 24: JASP alone vs JASP+AAC? Almirall and many friends Adaptive Interventions April 2016 17 / 66

SMARTs permit scientists to answer many interesting questions for building a high-quality adaptive intervention. Primary Aim: What is the best first-stage treatment in terms of spoken communication at week 24: JASP alone vs JASP+AAC? Secondary Aim: Which is the best of the three adaptive interventions embedded in this SMART? I will show you results for the Secondary Aim: Compare 3 adaptive interventions based on a longitudinal outcome. Almirall and many friends Adaptive Interventions April 2016 17 / 66

There are 3 AIs Embedded in this Example Autism SMART (JASP,JASP+) Subgroups A+C (JASP,AAC) Subgroups A+B (AAC,AAC+) Subgroups D+E Almirall and many friends Adaptive Interventions April 2016 18 / 66

Longitudinal Analyses Almirall and many friends Adaptive Interventions April 2016 19 / 66

Longitudinal Outcomes in the Autism SMART Outcomes collected at baseline, and weeks 12, 24 and 36 Primary outcome (verbal): from 20-minute “natural language sample”: Total spontaneous communicative utterances (TSCU) Secondary outcome (non-linguistic): Initiating joint attention (IJA; e.g., pointing; JASP mechanism) Almirall and many friends Adaptive Interventions April 2016 20 / 66