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Summary Precision medicine is an emerging scientific topic for disease treatment and prevention that takes into account individual patient characteristics. It is an important direction for clinical research, and many statistical methods have been proposed recently. One of the primary goals of precision medicine is to obtain an optimal individual treatment rule (ITR), which can help make decisions on treatment selection according to each patient's specific characteristics. Recently, outcome weighted learning (OWL) has been proposed to estimate such an optimal ITR in a binary treatment setting by maximizing the expected clinical outcome. However, for ordinal treatment settings, such as individualized dose finding, it is unclear how to use OWL. In this article, we propose a new technique for estimating ITR with ordinal treatments. In particular, we propose a data duplication technique with a piecewise convex loss function. We establish Fisher consistency for the resulting estimated ITR under certain conditions, and obtain the convergence and risk bound properties. Simulated examples and an application to a dataset from a type 2 diabetes mellitus observational study demonstrate the highly competitive performance of the proposed method compared to existing alternatives. 

Summary Cluster analysis has proved to be an invaluable tool for the exploratory and unsupervised analysis of high-dimensional datasets. Among methods for clustering, hierarchical approaches have enjoyed substantial popularity in genomics and other fields for their ability to simultaneously uncover multiple layers of clustering structure. A critical and challenging question in cluster analysis is whether the identified clusters represent important underlying structure or are artifacts of natural sampling variation. Few approaches have been proposed for addressing this problem in the context of hierarchical clustering, for which the problem is further complicated by the natural tree structure of the partition, and the multiplicity of tests required to parse the layers of nested clusters. In this article, we propose a Monte Carlo based approach for testing statistical significance in hierarchical clustering which addresses these issues. The approach is implemented as a sequential testing procedure guaranteeing control of the family-wise error rate. Theoretical justification is provided for our approach, and its power to detect true clustering structure is illustrated through several simulation studies and applications to two cancer gene expression datasets. 

Summary We consider scenarios in which the likelihood function for a semiparametric regression model factors into separate components, with an efficient estimator of the regression parameter available for each component. An optimal weighted combination of the component estimators, named an ensemble estimator, may be employed as an overall estimate of the regression parameter, and may be fully efficient under uncorrelatedness conditions. This approach is useful when the full likelihood function may be difficult to maximize, but the components are easy to maximize. It covers settings where the nuisance parameter may be estimated at different rates in the component likelihoods. As a motivating example we consider proportional hazards regression with prospective doubly censored data, in which the likelihood factors into a current status data likelihood and a left-truncated right-censored data likelihood. Variable selection is important in such regression modelling, but the applicability of existing techniques is unclear in the ensemble approach. We propose ensemble variable selection using the least squares approximation technique on the unpenalized ensemble estimator, followed by ensemble re-estimation under the selected model. The resulting estimator has the oracle property such that the set of nonzero parameters is successfully recovered and the semiparametric efficiency bound is achieved for this parameter set. Simulations show that the proposed method performs well relative to alternative approaches. Analysis of an AIDS cohort study illustrates the practical utility of the method.