2 research outputs found

    Controlling Cumulative Adverse Risk in Learning Optimal Dynamic Treatment Regimens

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    Dynamic treatment regimen (DTR) is one of the most important tools to tailor treatment in personalized medicine. For many diseases such as cancer and type 2 diabetes mellitus (T2D), more aggressive treatments can lead to a higher efficacy but may also increase risk. However, few methods for estimating DTRs can take into account both cumulative benefit and risk. In this work, we propose a general statistical learning framework to learn optimal DTRs that maximize the reward outcome while controlling the cumulative adverse risk to be below a pre-specified threshold. We convert this constrained optimization problem into an unconstrained optimization using a Lagrange function. We then solve the latter using either backward learning algorithms or simultaneously over all stages based on constructing a novel multistage ramp loss. Theoretically, we establish Fisher consistency of the proposed method and further obtain non-asymptotic convergence rates for both reward and risk outcomes under the estimated DTRs. The finite sample performance of the proposed method is demonstrated via simulation studies and through an application to a two-stage clinical trial for T2D patients.</p

    An Algorithm for Generating Individualized Treatment Decision Trees and Random Forests

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    <p>With new treatments and novel technology available, precision medicine has become a key topic in the new era of healthcare. Traditional statistical methods for precision medicine focus on subgroup discovery through identifying interactions between a few markers and treatment regimes. However, given the large scale and high dimensionality of modern datasets, it is difficult to detect the interactions between treatment and high-dimensional covariates. Recently, novel approaches have emerged that seek to directly estimate individualized treatment rules (ITR) via maximizing the expected clinical reward by using, for example, support vector machines (SVM) or decision trees. The latter enjoys great popularity in clinical practice due to its interpretability. In this article, we propose a new reward function and a novel decision tree algorithm to directly maximize rewards. We further improve a single tree decision rule by an ensemble decision tree algorithm, ITR random forests. Our final decision rule is an average over single decision trees and it is a soft probability rather than a hard choice.   Depending on how strong the treatment recommendation is, physicians can make decisions based on our model along with their own judgment and experience.  Performance of ITR forest and tree methods is assessed through simulations along with applications to a randomized controlled trial (RCT) of 1385 patients with diabetes and an EMR cohort of 5177 patients with diabetes. ITR forest and tree methods are implemented using statistical software R (<i><a href="https://github.com/kdoub5ha/ITR.Forest" target="_blank">https://github.com/kdoub5ha/ITR.Forest</a></i>). Supplementary materials for this article are available online.</p