The individualized treatment rule (ITR), which recommends an optimal treatment based on individual characteristics, has drawn considerable interest from many areas such as precision medicine, personalized education, and personalized marketing. Existing ITR estimation methods mainly adopt 1 of 2 or more treatments. However, a combination of multiple treatments could be more powerful in various areas. In this paper, we propose a novel double encoder model (DEM) to estimate the ITR for combination treatments. The proposed double encoder model is a nonparametric model which not only flexibly incorporates complex treatment effects and interaction effects among treatments but also improves estimation efficiency via the parameter-sharing feature. In addition, we tailor the estimated ITR to budget constraints through a multi-choice knapsack formulation, which enhances our proposed method under restricted-resource scenarios. In theory, we provide the value reduction bound with or without budget constraints, and an improved convergence rate with respect to the number of treatments under the DEM. Our simulation studies show that the proposed method outperforms the existing ITR estimation in various settings. We also demonstrate the superior performance of the proposed method in patient-derived xenograft data that recommends optimal combination treatments to shrink the tumour size of the colorectal cancer.
Individuals may respond to treatments with significant heterogeneity. To optimize the treatment effect, it is necessary to recommend treatments based on individual characteristics. Existing methods in the literature for learning individualized treatment regimes are usually designed for randomized studies with binary treatments. In this study, we propose an algorithm to extend random forest of interaction trees (Su et al., 2009) to accommodate multiple treatments. By integrating the generalized propensity score into the interaction tree growing process, the proposed method can handle both randomized and observational study data with multiple treatments. The performance of the proposed method, relative to existing approaches in the literature, is evaluated through simulation studies. The proposed method is applied to an assessment of multiple voluntary educational programmes at a large public university.
more » « less- Award ID(s):
- 1633130
- NSF-PAR ID:
- 10368595
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Stat
- Volume:
- 11
- Issue:
- 1
- ISSN:
- 2049-1573
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Summary There is a large literature on methods of analysis for randomized trials with noncompliance which focuses on the effect of treatment on the average outcome. The paper considers evaluating the effect of treatment on the entire distribution and general functions of this effect. For distributional treatment effects, fully non-parametric and fully parametric approaches have been proposed. The fully non-parametric approach could be inefficient but the fully parametric approach is not robust to the violation of distribution assumptions. We develop a semiparametric instrumental variable method based on the empirical likelihood approach. Our method can be applied to general outcomes and general functions of outcome distributions and allows us to predict a subject’s latent compliance class on the basis of an observed outcome value in observed assignment and treatment received groups. Asymptotic results for the estimators and likelihood ratio statistic are derived. A simulation study shows that our estimators of various treatment effects are substantially more efficient than the currently used fully non-parametric estimators. The method is illustrated by an analysis of data from a randomized trial of an encouragement intervention to improve adherence to prescribed depression treatments among depressed elderly patients in primary care practices.
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For large observational studies lacking a control group (unlike randomized controlled trials, RCT), propensity scores (PS) are often the method of choice to account for pre-treatment confounding in baseline characteristics, and thereby avoid substantial bias in treatment estimation. A vast majority of PS techniques focus on average treatment effect estimation, without any clear consensus on how to account for confounders, especially in a multiple treatment setting. Furthermore, for time-to event outcomes, the analytical framework is further complicated in presence of high censoring rates (sometimes, due to non-susceptibility of study units to a disease), imbalance between treatment groups, and clustered nature of the data (where, survival outcomes appear in groups). Motivated by a right-censored kidney transplantation dataset derived from the United Network of Organ Sharing (UNOS), we investigate and compare two recent promising PS procedures, (a) the generalized boosted model (GBM), and (b) the covariate-balancing propensity score (CBPS), in an attempt to decouple the causal effects of treatments (here, study subgroups, such as hepatitis C virus (HCV) positive/negative donors, and positive/negative recipients) on time to death of kidney recipients due to kidney failure, post transplantation. For estimation, we employ a 2-step procedure which addresses various complexities observed in the UNOS database within a unified paradigm. First, to adjust for the large number of confounders on the multiple sub-groups, we fit multinomial PS models via procedures (a) and (b). In the next stage, the estimated PS is incorporated into the likelihood of a semi-parametric cure rate Cox proportional hazard frailty model via inverse probability of treatment weighting, adjusted for multi-center clustering and excess censoring, Our data analysis reveals a more informative and superior performance of the full model in terms of treatment effect estimation, over sub-models that relaxes the various features of the event time dataset.more » « less
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Learning optimal individualized treatment rules (ITRs) has become increasingly important in the modern era of precision medicine. Many statistical and machine learning methods for learning optimal ITRs have been developed in the literature. However, most existing methods are based on data collected from traditional randomized controlled trials and thus cannot take advantage of the accumulative evidence when patients enter the trials sequentially. It is also ethically important that future patients should have a high probability to be treated optimally based on the updated knowledge so far. In this work, we propose a new design called sequentially rule-adaptive trials to learn optimal ITRs based on the contextual bandit framework, in contrast to the response-adaptive design in traditional adaptive trials. In our design, each entering patient will be allocated with a high probability to the current best treatment for this patient, which is estimated using the past data based on some machine learning algorithm (for example, outcome weighted learning in our implementation). We explore the tradeoff between training and test values of the estimated ITR in single-stage problems by proving theoretically that for a higher probability of following the estimated ITR, the training value converges to the optimal value at a faster rate, while the test value converges at a slower rate. This problem is different from traditional decision problems in the sense that the training data are generated sequentially and are dependent. We also develop a tool that combines martingale with empirical process to tackle the problem that cannot be solved by previous techniques for i.i.d. data. We show by numerical examples that without much loss of the test value, our proposed algorithm can improve the training value significantly as compared to existing methods. Finally, we use a real data study to illustrate the performance of the proposed method.more » « less
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