Designing An Adaptive Treatment

Susan A. MurphyUniv. of MichiganJoint with Linda Collins & Karen BiermanPennsylvania State Univ.

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

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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

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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

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Why Use? Subjects are heterogeneous in their

need for treatment Increase salience To devote additional resources to

higher-risk individuals

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Why Use? Variations of treatment may

enhance compliance Excessive treatment leads to non-

compliance or other side effects Treatment is costly

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When to Use? Use if you expect that there will be

significant variation in treatment effects across subjects in comparisons of fixed treatments.

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Design Goals: Maximize strength of treatment

By well chosen moderators, well measured moderators, & well conceived dosage assignment rules

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Design Goals: Maximize replicability in future

experimental and real-world implementation conditions

By fidelity of implementation & by clearly defining the treatment.

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Parts of the Treatment: Choice of dosage moderator Measurement of dosage moderator Rules linking dosage moderator to

dosage assignment Implementation of the rules

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Dosage Moderators:

Significant differences in effect sizes in a comparison of fixed treatments as a function of characteristics.

Dosage moderator=individual, family, contextual characteristics.

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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.

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Technical Interlude!Technical Interlude!s=dosage moderatort=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.

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S Interacts with Treatment but is NOT a Dosage Moderator

0 1

Dose

Y

s=1

s=0

S is a Dosage Moderator

0 1

Dose

Y

s=1

s=0

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Measurement of Dosage Moderators

Reliability -- high signal to noise ratio

Validity -- unbiased

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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?”

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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.

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Implementation Try to implement rules universally,

applying them consistently across subjects, time, site & staff members.

Document values of dosage moderator!

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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.

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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

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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.

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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.

Extra slides follow

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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

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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.

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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

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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.

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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.

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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!

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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.