Improved doubly robust estimation in learning optimal individualized treatment rules.
Ontology highlight
ABSTRACT:
SUBMITTER: Pan Y
PROVIDER: S-EPMC8132732 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Individualized treatment rules recommend treatments based on individual patient characteristics in order to maximize clinical benefit. When the clinical outcome of interest is survival time, estimation is often complicated by censoring. We develop nonparametric methods for estimating an optimal individualized treatment rule in the presence of censored data. To adjust for censoring, we propose a doubly robust estimator which requires correct specification of either the censoring model or survival model, but not both; the method is shown to be Fisher consistent when either model is correct. Furthermore, we establish the convergence rate of the expected survival under the estimated optimal individualized treatment rule to the expected survival under the optimal individualized treatment rule. We illustrate the proposed methods using simulation study and data from a Phase III clinical trial on non-small cell lung cancer.
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Project description:Personalized medicine aims to tailor medical decisions based on patient-specific characteristics. Advances in data capturing techniques such as electronic health records dramatically increase the availability of comprehensive patient profiles, promoting the rapid development of optimal treatment rule (OTR) estimation methods. An archetypal OTR estimation approach is the outcome weighted learning, where OTR is determined under a weighted classification framework with clinical outcomes as the weights. Although outcome weighted learning has been extensively studied and extended, existing methods are susceptible to irregularities of outcome distributions such as outliers and heavy tails. Methods that involve modeling of the outcome are also sensitive to model misspecification. We propose a contrast weighted learning (CWL) framework that exploits the flexibility and robustness of contrast functions to enable robust OTR estimation for a wide range of clinical outcomes. The novel value function in CWL only depends on the pairwise contrast of clinical outcomes between patients irrespective of their distributional features and supports. The Fisher consistency and convergence rate of the estimated decision rule via CWL are established. We illustrate the superiority of the proposed method under finite samples using comprehensive simulation studies with ill-distributed continuous outcomes and ordinal outcomes. We apply the CWL method to two datasets from clinical trials on idiopathic pulmonary fibrosis and COVID-19 to demonstrate its real-world application.
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Project description:Estimating an optimal individualized treatment rule (ITR) based on patients' information is an important problem in precision medicine. An optimal ITR is a decision function that optimizes patients' expected clinical outcomes. Many existing methods in the literature are designed for binary treatment settings with the interest of a continuous outcome. Much less work has been done on estimating optimal ITRs in multiple treatment settings with good interpretations. In this article, we propose angle-based direct learning (AD-learning) to efficiently estimate optimal ITRs with multiple treatments. Our proposed method can be applied to various types of outcomes, such as continuous, survival, or binary outcomes. Moreover, it has an interesting geometric interpretation on the effect of different treatments for each individual patient, which can help doctors and patients make better decisions. Finite sample error bounds have been established to provide a theoretical guarantee for AD-learning. Finally, we demonstrate the superior performance of our method via an extensive simulation study and real data applications. Supplementary materials for this article are available online.
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Project description:In many biomedical settings, assigning every patient the same treatment may not be optimal due to patient heterogeneity. Individualized treatment regimes have the potential to dramatically improve clinical outcomes. When the primary outcome is censored survival time, a main interest is to find optimal treatment regimes that maximize the survival probability of patients. Since the survival curve is a function of time, it is important to balance short-term and long-term benefit when assigning treatments. In this paper, we propose a doubly robust approach to estimate optimal treatment regimes that optimize a user specified function of the survival curve, including the restricted mean survival time and the median survival time. The empirical and asymptotic properties of the proposed method are investigated. The proposed method is applied to a data set from an ongoing HIV/AIDS clinical observational study conducted by the University of North Carolina (UNC) Center of AIDS Research (CFAR), and shows the proposed methods significantly improve the restricted mean time of the initial treatment duration. Finally, the proposed methods are extended to multi-stage studies.
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