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2015 ; 34
(12
): 2035-47
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Detecting treatment-covariate interactions using permutation methods
#MMPMID25736915
Wang R
; Schoenfeld DA
; Hoeppner B
; Evins AE
Stat Med
2015[May]; 34
(12
): 2035-47
PMID25736915
show ga
The primary objective of a Randomized Clinical Trial usually is to investigate
whether one treatment is better than its alternatives on average. However,
treatment effects may vary across different patient subpopulations. In contrast
to demonstrating one treatment is superior to another on the average sense, one
is often more concerned with the question that, for a particular patient, or a
group of patients with similar characteristics, which treatment strategy is most
appropriate to achieve a desired outcome. Various interaction tests have been
proposed to detect treatment effect heterogeneity; however, they typically
examine covariates one at a time, do not offer an integrated approach that
incorporates all available information, and can greatly increase the chance of a
false positive finding when the number of covariates is large. We propose a new
permutation test for the null hypothesis of no interaction effects for any
covariate. The proposed test allows us to consider the interaction effects of
many covariates simultaneously without having to group subjects into subsets
based on pre-specified criteria and applies generally to randomized clinical
trials of multiple treatments. The test provides an attractive alternative to the
standard likelihood ratio test, especially when the number of covariates is
large. We illustrate the proposed methods using a dataset from the Treatment of
Adolescents with Depression Study.
|*Cognitive Behavioral Therapy
[MESH]
|Adolescent
[MESH]
|Analysis of Variance
[MESH]
|Antidepressive Agents, Second-Generation/adverse effects/therapeutic use
[MESH]
|Bias
[MESH]
|Clinical Decision-Making/*methods
[MESH]
|Combined Modality Therapy
[MESH]
|Computer Simulation
[MESH]
|Confounding Factors, Epidemiologic
[MESH]
|Data Interpretation, Statistical
[MESH]
|Depressive Disorder, Major/*therapy
[MESH]
|Fluoxetine/*adverse effects/therapeutic use
[MESH]
|Humans
[MESH]
|Linear Models
[MESH]
|Precision Medicine/*methods
[MESH]
|Randomized Controlled Trials as Topic/methods/*statistics & numerical data
[MESH]