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. 2013 Nov;70(11):1241-7.
doi: 10.1001/jamapsychiatry.2013.1960.

A novel approach for developing and interpreting treatment moderator profiles in randomized clinical trials

Meredith L Wallace  1 , Ellen Frank, Helena C Kraemer
Affiliations

A novel approach for developing and interpreting treatment moderator profiles in randomized clinical trials

Meredith L Wallace et al. JAMA Psychiatry. 2013 Nov.

Abstract

Importance: Identifying treatment moderators may help mental health practitioners arrive at more precise treatment selection for individual patients and can focus clinical research on subpopulations that differ in treatment response.

Objective: To demonstrate a novel exploratory approach to moderation analysis in randomized clinical trials.

Design, setting, and participants: A total of 291 adults from a randomized clinical trial that compared an empirically supported psychotherapy with selective serotonin reuptake inhibitor (SSRI) pharmacotherapy as treatments for depression.

Main outcomes and measures: We selected 8 relatively independent individual moderators out of 32 possible variables. A combined moderator, M*, was developed as a weighted combination of the 8 selected individual moderators. M* was then used to identify individuals for whom psychotherapy may be preferred to SSRI pharmacotherapy or vice versa.

Results: Among individual moderators, psychomotor activation had the largest moderator effect size (0.12; 95% CI, <.01 to 0.24). The combined moderator, M*, had a larger moderator effect size than any individual moderator (0.31; 95% CI, 0.15 to 0.46). Although the original analyses demonstrated no overall difference in treatment response, M* divided the study population into 2 subpopulations, with each showing a clinically significant difference in response to psychotherapy vs SSRI pharmacotherapy.

Conclusions and relevance: Our results suggest that the strongest determinations for personalized treatment selection will likely require simultaneous consideration of multiple moderators, emphasizing the value of the methods presented here. After validation in a randomized clinical trial, a mental health practitioner could input a patient's relevant baseline values into a handheld computer programmed with the weights needed to calculate M*. The device could then output the patient's M* value and suggested treatment, thereby allowing the mental health practitioner to select the treatment that would offer the greatest likelihood of success for each patient.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Frank reported serving as a consultant to Servier and Vanda Pharmaceuticals; receiving grant or research support from the Fine Foundation, the Pittsburgh Foundation, and Forest Research Institute; and receiving royalties from Guilford Press.

Figures

Figure.
Figure.
Predicted Integrated Preference Score (IPS) Outcome for the IPT and SSRI Pharmacotherapy Groups Across the Observed Values of the Combined Moderator, M* The cross point of M* = .01 indicates that individuals with M* > .01 may prefer interpersonal psychotherapy (IPT), while those with M* < .01 may prefer selective serotonin reuptake inhibitor (SSRI) pharmacotherapy.
See this image and copyright information in PMC

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