When devising a course of treatment for a patient, doctors often have little quantitative evidence on which to base their decisions, beyond their medical education and published clinical trials. Stanford Health Care alone has millions of electronic medical records (EMRs) that are only just recently being leveraged to inform better treatment recommendations. These data present a unique challenge because they are high-dimensional and observational. Our goal is to make personalized treatment recommendations based on the outcomes for past patients similar to a new patient. We propose and analyze three methods for estimating heterogeneous treatment effects using observational data. Our methods perform well in simulations using a wide variety of treatment effect functions, and we present results of applying the two most promising methods to data from The SPRINT Data Analysis Challenge, from a large randomized trial of a treatment for high blood pressure.
Identifying subgroups within the patient population is becoming especially challenging in high-dimensional data, as in EMRs. In recent years, a great amount of work has been done to apply methods from machine learning to enable the data to inform what are the important subgroups in terms of treatment effect. @cite_7 proposed interaction trees for adaptively defining subgroups based on treatment effect. @cite_15 proposed causal trees, which are similar, and constructed valid confidence intervals.
@cite_15 @cite_7
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Providing personalized treatments designed to maximize benefits and minimizing harms is of tremendous current medical interest. One problem in this area is the evaluation of the interaction between the treatment and other predictor variables. Treatment effects in subgroups having the same direction but different magnitudes are called quantitative interactions, whereas those having opposite directions in subgroups are called qualitative interactions (QIs). Identifying QIs is challenging because they are rare and usually unknown among many potential biomarkers. Meanwhile, subgroup analysis reduces the power of hypothesis testing and multiple subgroup analyses inflate the type I error rate. We propose a new Bayesian approach to search for QI in a multiple regression setting with adaptive decision rules. We consider various regression models for the outcome. We illustrate this method in two examples of phase III clinical trials. The algorithm is straightforward and easy to implement using existing software packages. We provide a sample code in Appendix A. Copyright © 2012 John Wiley & Sons, Ltd. 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 (, 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. Two challenging problems in the clinical study of cancer are the characterization of cancer subtypes and the classification of individual patients according to those subtypes. Statistical approaches addressing these problems are hampered by population heterogeneity and challenges inherent in data integration across high-dimensional, diverse covariates. We have developed a survival-supervised latent Dirichlet allocation (survLDA) modeling framework to address these concerns. LDA models have proven extremely effective at identifying themes common across large collections of text, but applications to genomics have been limited. Our framework extends LDA to the genome by considering each patient as a document' with text' constructed from clinical and high-dimensional genomic measurements. We then further extend the framework to allow for supervision by a time-to-event response. The model enables the efficient identification of collections of clinical and genomic features that co-occur within patient subgroups, and then characterizes each patient by those features. An application of survLDA to The Cancer Genome Atlas (TCGA) ovarian project identifies informative patient subgroups that are characterized by different propensities for exhibiting abnormal mRNA expression and methylations, corresponding to differential rates of survival from primary therapy. Recently, there has been increasing interest in making causal inference when interference is possible. In the presence of interference, treatment may have several types of effects. In this article, we consider inference about such effects when the population consists of groups of individuals where interference is possible within groups but not between groups. A two-stage randomization design is assumed where in the first stage groups are randomized to different treatment allocation strategies and in the second stage individuals are randomized to treatment or control conditional on the strategy assigned to their group in the first stage. For this design, the asymptotic distributions of estimators of the causal effects are derived when either the number of individuals per group or the number of groups grows large. Under certain homogeneity assumptions, the asymptotic distributions provide justification for Wald-type confidence intervals (CIs) and tests. Empirical results demonstrate that the Wald CIs have good coverage in finite samples and are narrower than CIs based on either the Chebyshev or Hoeffding inequalities provided the number of groups is not too small. The methods are illustrated by two examples which consider the effects of cholera vaccination and an intervention to encourage voting.