3,077 research outputs found

    Subgroup Analysis via Recursive Partitioning

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    Subgroup analysis is an integral part of comparative analysis where assessing the treatment effect on a response is of central interest. Its goal is to determine the heterogeneity of the treatment effect across subpopulations. In this paper, we adapt the idea of recursive partitioning and introduce an interaction tree (IT) procedure to conduct subgroup analysis. The IT procedure automatically facilitates a number of objectively defined subgroups, in some of which the treatment effect is found prominent while in others the treatment has a negligible or even negative effect. The standard CART (Breiman et al., 1984) methodology is inherited to construct the tree structure. Also, in order to extract factors that contribute to the heterogeneity of the treatment effect, variable importance measure is made available via random forests of the interaction trees. Both simulated experiments and analysis of census wage data are presented for illustration

    Subgroup identification in dose-finding trials via model-based recursive partitioning

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    An important task in early phase drug development is to identify patients, which respond better or worse to an experimental treatment. While a variety of different subgroup identification methods have been developed for the situation of trials that study an experimental treatment and control, much less work has been done in the situation when patients are randomized to different dose groups. In this article we propose new strategies to perform subgroup analyses in dose-finding trials and discuss the challenges, which arise in this new setting. We consider model-based recursive partitioning, which has recently been applied to subgroup identification in two arm trials, as a promising method to tackle these challenges and assess its viability using a real trial example and simulations. Our results show that model-based recursive partitioning can be used to identify subgroups of patients with different dose-response curves and improves estimation of treatment effects and minimum effective doses, when heterogeneity among patients is present.Comment: 23 pages, 6 figure

    Model-based Recursive Partitioning for Subgroup Analyses

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    The identification of patient subgroups with differential treatment effects is the first step towards individualised treatments. A current draft guideline by the EMA discusses potentials and problems in subgroup analyses and formulated challenges to the development of appropriate statistical procedures for the data-driven identification of patient subgroups. We introduce model-based recursive partitioning as a procedure for the automated detection of patient subgroups that are identifiable by predictive factors. The method starts with a model for the overall treatment effect as defined for the primary analysis in the study protocol and uses measures for detecting parameter instabilities in this treatment effect. The procedure produces a segmented model with differential treatment parameters corresponding to each patient subgroup. The subgroups are linked to predictive factors by means of a decision tree. The method is applied to the search for subgroups of patients suffering from amyotrophic lateral sclerosis that differ with respect to their Riluzole treatment effect, the only currently approved drug for this disease.Comment: 26 pages, 6 figure

    A model-based multithreshold method for subgroup identification

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    Thresholding variable plays a crucial role in subgroup identification for personalizedmedicine. Most existing partitioning methods split the sample basedon one predictor variable. In this paper, we consider setting the splitting rulefrom a combination of multivariate predictors, such as the latent factors, principlecomponents, and weighted sum of predictors. Such a subgrouping methodmay lead to more meaningful partitioning of the population than using a singlevariable. In addition, our method is based on a change point regression modeland thus yields straight forward model-based prediction results. After choosinga particular thresholding variable form, we apply a two-stage multiple changepoint detection method to determine the subgroups and estimate the regressionparameters. We show that our approach can produce two or more subgroupsfrom the multiple change points and identify the true grouping with high probability.In addition, our estimation results enjoy oracle properties. We design asimulation study to compare performances of our proposed and existing methodsand apply them to analyze data sets from a Scleroderma trial and a breastcancer study
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