Treffer: Statistical and Machine Learning Methods for Precision Medicine

Heterogeneous treatment responses are commonly observed in patients with mental disorders. Thus, a universal treatment strategy may not be adequate, and tailored treatments adapted to individual characteristics could improve treatment responses. The theme of the dissertation is to develop statistical and machine learning methods to address patients heterogeneity and derive robust and generalizable individualized treatment strategies by integrating evidence from multi-domain data and multiple studies to achieve precision medicine. Unique challenges arising from the research of mental disorders need to be addressed in order to facilitate personalized medical decision-making in clinical practice. This dissertation contains four projects to achieve these goals while addressing the challenges: (i) a statistical method to learn dynamic treatment regimes (DTRs) by synthesizing independent trials over different stages when sequential randomization data is not available; (ii) a statistical method to learn optimal individualized treatment rules (ITRs) for mental disorders by modeling patients' latent mental states using probabilistic generative models; (iii) an integrative learning algorithm to incorporate multi-domain and multi-treatment-phase measures for optimizing individualized treatments; (iv) a statistical machine learning method to optimize ITRs that can benefit subjects in a target population for mental disorders with improved learning efficiency and generalizability. DTRs adaptively prescribe treatments based on patients' intermediate responses and evolving health status over multiple treatment stages. Data from sequential multiple assignment randomization trials (SMARTs) are recommended to be used for learning DTRs. However, due to the re-randomization of the same patients over multiple treatment stages and a prolonged follow-up period, SMARTs are often difficult to implement and costly to manage, and patient adherence is always a concern in practice. To lessen such practical challenges, in the first part of ...