Designing An Adaptive Treatment

1. Designing An Adaptive Treatment Susan A. Murphy Univ. of Michigan Joint with Linda Collins & Karen Bierman Pennsylvania State Univ.

2. Outline • Adaptive Treatments • Why Use? • When to Use? • Design Goals • What Does the Treatment Include? • Summary & Discussion

3. Adaptive Treatments • Individualized tailoring of dosage type and amount to the subject across time. • dosage moderators: variables expected to moderate the effect of treatment component • link values on the dosage moderator with specific dosage via a priori rules

4. Example : Aftercare for Alcohol Dependency • Overall Goal: deter heavy drinking • Adaptive Treatment Condition: Naltrexone, and CBI • Dosage Moderator: # days heavy drinking • Frequency of Decisions: weekly

5. Why Use? • Subjects are heterogeneous in their need for treatment • Increase salience • To devote additional resources to higher-risk individuals

6. Why Use? • Variations of treatment may enhance compliance • Excessive treatment leads to non-compliance or other side effects • Treatment is costly

7. When to Use? • Use if you expect that there will be significant variation in treatment effects across subjects in comparisons of fixed treatments.

8. Design Goals: • Maximize strength of treatment By well chosen moderators, well measured moderators, & well conceived dosage assignment rules

9. Design Goals: • Maximize replicability in future experimental and real-world implementation conditions By fidelity of implementation & by clearly defining the treatment.

10. Parts of the Treatment: • Choice of dosage moderator • Measurement of dosage moderator • Rules linking dosage moderator to dosage assignment • Implementation of the rules

11. Dosage Moderators: • Significant differences in effect sizes in a comparison of fixed treatments as a function of characteristics. • Dosage moderator=individual, family, contextual characteristics.

12. Aftercare for Alcohol Dependency • Individuals who return to heavy drinking while on Naltrexone need additional help to maintain a non-drinking lifestyle. • Dosage Moderator is heavy drinking • Providing CBI to individuals who are maintaining a non-drinking lifestyle is costly.

13. Technical Interlude! s=dosage moderator t=treatment type (0 or 1) Y=response Y = 0 + 1s + 2t + 3st + error = 0 + 1s + (2 + 3s)t + error If (2 + 3s) is zero or negative for some s and positive for others then s is a dosage moderator.

15. Measurement of Dosage Moderators • Reliability -- high signal to noise ratio • Validity -- unbiased

16. Derivation of Rules • Articulate a theoretical model for how treatment effect on key outcomes should differ across values of the moderator. • Use scientific theory and prior clinical experience. • Use prior experimental and observational studies. • Discuss with research team and clinical staff, “What dosage would be best for people with this value on the moderator?”

17. Derivation of Rules • Good dosage assignment rules are objective, are operationalized. • Strive for comprehensive rules (this is hard!) –cover situations that can occur in practice, including when the dosage moderator is unavailable.

18. Implementation • Try to implement rules universally, applying them consistently across subjects, time, site & staff members. • Document values of dosage moderator!

19. Implementation • Exceptions to the rules should be made only after group discussions and with group agreement. • If it is necessary to make an exception, document this so you can describe the implemented treatment.

20. Summary & Discussion • Research is needed to build a theoretical literature that can provide guidance: • in identifying dosage moderators, • in the development of reliable and valid indices of the moderators that can be used in the course of repeated clinical assessments

21. Summary & Discussion • Research is needed on how we might use existing experimental and observational studies to • identify useful dosage moderators • Formulate best rules. • Research is needed on how we might design experiments that find good moderators and rules.

22. Summary & Discussion • In comparison to fixed treatments, adaptive treatments hold much promise in terms of increasing potency, improving compliance, reducing side effects and reducing waste. • As treatment and prevention programs move in the direction of more comprehensive, multi-layered systems, adaptive components should become more common, particularly for chronic problems.

23. Extra slides follow

24. Example : Fast Track • Overall Goal: reduce incidence of conduct disorder • Adaptive Treatment Component: family counseling via home visits • Dosage Moderator: level of family functioning • Frequency of Decisions: 3 x year for 10 years

25. Fast Track: • Multiple pathways to conduct disorder • Use family functioning as a dosage moderator • It was expected that less frequent home visits would be sufficient to promote positive child behavior in families with few family functioning problems.

26. Fast Track: • Researchers anticipated that higher levels of home visiting to families with few family functioning problems would have a negative impact on child behavior • By stigmatizing the family • By burdening the family and inducing noncompliance

27. Fast Track • Family Functioning is a latent construct and can not be measured with the same precision as a biological measurement. • Frequent assessment via standardized interviews, family observations, teacher and staff ratings was untenable. • Fast Track used a rating of family functioning completed by home visiting staff.

28. Fast Track & Home Visiting • Formulated a 6 item assessment, each item results in a 0,1,2,3,4. They summed the items. • Assign weekly home visits if sum is less than 9. • Assign biweekly home visits if sum is between 9 and 16. • Assign monthly home visits if sum is greater than 16. • Deviations were permitted in exceptional(!!!!) circumstances.

29. Statistical Evaluation • Standard comparisons between adaptive treatments proceed as in fixed treatments comparison. • No dose response analyses unless dose is assigned by randomization. • Assessing planned treatment effect rather than the intention to treat effect when the rules are not followed is an immature area of statistics!

30. Summary & Discussion • In order to develop innovative statistical analyses examining how adaptive treatments work, we need to think about the dosage moderator – outcome relationship within an effective treatment condition.