Decision curve analysis can be used to determine whether a personalized model for treatment benefit would lead to better clinical decisions. Decision curve analysis methods have been described to estimate treatment benefit using data from a single RCT. Our main objective is to extend the decision curve analysis methodology to the scenario where several treatment options exist and evidence about their effects comes from a set of trials, synthesized using network meta-analysis (NMA). We describe the steps needed to estimate the net benefit of a prediction model using evidence from studies synthesized in an NMA. We show how to compare personalized versus one-size-fit-all treatment decision-making strategies, like "treat none" or "treat all patients with a specific treatment" strategies. The net benefit per strategy can then be plotted for a plausible range of threshold probabilities to reveal the most clinically useful strategy. We applied our methodology to an NMA prediction model for relapsing-remitting multiple sclerosis, which can be used to choose between Natalizumab, Dimethyl Fumarate, Glatiramer Acetate, and placebo. We illustrated the extended decision curve analysis methodology using several threshold values combinations for each available treatment. For the examined threshold values, the "treat patients according to the prediction model" strategy performs either better than or close to the one-size-fit-all treatment strategies. However, even small differences may be important in clinical decision-making. As the advantage of the personalized model was not consistent across all thresholds, an improved model may be needed before advocating its applicability for decision-making. This novel extension of decision curve analysis can be applied to NMA based prediction models to evaluate their use to aid treatment decision-making.
We propose a novel personalized concept for the optimal treatment selection for a situation where the response is a multivariate vector, that could contain right-censored variables such as survival time. The proposed method can be applied with any number of treatments and outcome variables, under a broad set of models. Following a working semiparametric Single Index Model that relates covariates and responses, we first define a patient-specific composite score, constructed from individual covariates. We then estimate conditional means of each response, given the patient score, correspond to ea…
Accurate models of clinical actions and their impacts on disease progression are critical for estimating personalized optimal dynamic treatment regimes (DTRs) in medical/health research, especially in managing chronic conditions. Traditional statistical methods for DTRs usually focus on estimating the optimal treatment or dosage at each given medical intervention, but overlook the important question of "when this intervention should happen." We fill this gap by developing a two-step Bayesian approach to optimize clinical decisions with timing. In the first step, we build a generative model for…
Randomized experimentation (also known as A/B testing or bucket testing) is widely used in the internet industry to measure the metric impact obtained by different treatment variants. A/B tests identify the treatment variant showing the best performance, which then becomes the chosen or selected treatment for the entire population. However, the effect of a given treatment can differ across experimental units and a personalized approach for treatment selection can greatly improve upon the usual global selection strategy. In this work, we develop a framework for personalization through (i) estim…
Dynamic treatment regimens (DTRs) are sequential decision rules tailored at each stage by potentially time-varying patient features and intermediate outcomes observed in previous stages. The complexity, patient heterogeneity and chronicity of many diseases and disorders call for learning optimal DTRs which best dynamically tailor treatment to each individual's response over time. Proliferation of personalized data (e.g., genetic and imaging data) provides opportunities for deep tailoring as well as new challenges for statistical methodology. In this work, we propose a robust hybrid approach re…
The development of high-throughput sequencing and targeted therapies has led to the emergence of personalized medicine: a patient's molecular profile or the presence of a specific biomarker of drug response will correspond to a treatment recommendation made either by a physician or by a treatment assignment algorithm. The growing number of such algorithms raises the question of how to quantify their clinical impact knowing that a personalized medicine strategy will inherently include different versions of treatment. We thus specify an appropriate causal framework with multiple versions of trea…
We present methodological advances in understanding the effectiveness of personalized medicine models and supply easy-to-use open-source software. Personalized medicine involves the systematic use of individual patient characteristics to determine which treatment option is most likely to result in a better outcome for the patient on average. Why is personalized medicine not done more in practice? One of many reasons is because practitioners do not have any easy way to holistically evaluate whether their personalization procedure does better than the standard of care. Our software, "Personalize…
Individualized treatment rules (ITRs) tailor treatments according to individual patient characteristics. They can significantly improve patient care and are thus becoming increasingly popular. The data collected during randomized clinical trials are often used to estimate the optimal ITRs. However, these trials are generally expensive to run, and, moreover, they are not designed to efficiently estimate ITRs. In this paper, we propose a cost-effective estimation method from an active learning perspective. In particular, our method recruits only the "most informative" patients (in terms of learn…
The multilevel model (MLM) is the popular approach to describe dependences of hierarchically clustered observations. A main feature is the capability to estimate (cluster-specific) random effect parameters, while their distribution describes the variation across clusters. However, the MLM can only model positive associations among clustered observations, and it is not suitable for small sample sizes. The limitation of the MLM becomes apparent when estimation methods produce negative estimates for random effect variances, which can be seen as an indication that observations are negatively corre…
Treatment effects vary across different patients and estimation of this variability is important for clinical decisions. The aim is to develop a model to estimate the benefit of alternative treatment options for individual patients. Hence, we developed a two-stage prediction model for heterogeneous treatment effects, by combining prognosis research and network meta-analysis methods when individual patient data is available. In a first stage, we develop a prognostic model and we predict the baseline risk of the outcome. In the second stage, we use this baseline risk score from the first stage a…
University of Pittsburgh（匹兹堡大学）；Southwestern University of Finance and Economics（西南财经大学）
Accurately estimating personalized treatment effects within a study site (e.g., a hospital) has been challenging due to limited sample size. Furthermore, privacy considerations and lack of resources prevent a site from leveraging subject-level data from other sites. We propose a tree-based model averaging approach to improve the estimation accuracy of conditional average treatment effects (CATE) at a target site by leveraging models derived from other potentially heterogeneous sites, without them sharing subject-level data. To our best knowledge, there is no established model averaging approac…
Randomized trials typically estimate average relative treatment effects, but decisions on the benefit of a treatment are possibly better informed by more individualized predictions of the absolute treatment effect. In case of a binary outcome, these predictions of absolute individualized treatment effect require knowledge of the individual's risk without treatment and incorporation of a possibly differential treatment effect (i.e. varying with patient characteristics). In this paper we lay out the causal structure of individualized treatment effect in terms of potential outcomes and describe t…
Southeast University（东南大学）；University of South Australia（南澳大学）
A central question in many fields of scientific research is to determine how an outcome would be affected by an action, or to measure the effect of an action (a.k.a treatment effect). In recent years, a need for estimating the heterogeneous treatment effects conditioning on the different characteristics of individuals has emerged from research fields such as personalized healthcare, social science, and online marketing. To meet the need, researchers and practitioners from different communities have developed algorithms by taking the treatment effect heterogeneity modeling approach and the upli…
Personalized medicine has gained much popularity recently as a way of providing better healthcare by tailoring treatments to suit individuals. Our research, motivated by the UK INTERVAL blood donation trial, focuses on estimating the optimal individualized treatment rule (ITR) in the ordinal treatment-arms setting. Restrictions on minimum lengths between whole blood donations exist to safeguard donor health and quality of blood received. However, the evidence-base for these limits is lacking. Moreover, in England, the blood service is interested in making blood donation both safe and sustainab…
A Doubly Robust Machine Learning Approach for Disentangling Treatment Effect Heterogeneity with Functional Outcomes
Sant’Anna School of Advanced Studies（圣安娜高等研究学院）；School of Pharmaceutical Science, University of Geneva（日内瓦大学药学院）；Department of Statistics & Data Science, Carnegie Mellon University（卡内基梅隆大学统计与数据科学系）；Department of Statistics, Penn State University（宾夕法尼亚州立大学统计系）
A Causal Inference Approach for Evaluating Diagnostic Tests and AI-Enabled Medical Devices: From Effect Modification to Information-Augmented Decision-Making
Division of Biostatistics, University of California, Berkeley（加州大学伯克利分校生物统计系）
We consider a problem of ranking and selection via simulation in the context of personalized decision making, where the best alternative is not universal but varies as a function of some observable covariates. The goal of ranking and selection with covariates (R&S-C) is to use simulation samples to obtain a selection policy that specifies the best alternative with certain statistical guarantee for subsequent individuals upon observing their covariates. A linear model is proposed to capture the relationship between the mean performance of an alternative and the covariates. Under the indifferenc…
University of Cambridge（剑桥大学）；University of Oxford（牛津大学）；UCLA（加州大学洛杉矶分校）
Estimating personalized effects of treatments is a complex, yet pervasive problem. To tackle it, recent developments in the machine learning (ML) literature on heterogeneous treatment effect estimation gave rise to many sophisticated, but opaque, tools: due to their flexibility, modularity and ability to learn constrained representations, neural networks in particular have become central to this literature. Unfortunately, the assets of such black boxes come at a cost: models typically involve countless nontrivial operations, making it difficult to understand what they have learned. Yet, unders…
Recent years have seen a swell in methods that focus on estimating "individual treatment effects". These methods are often focused on the estimation of heterogeneous treatment effects under ignorability assumptions. This paper hopes to draw attention to the fact that there is nothing necessarily "individual" about such effects under ignorability assumptions and isolating individual effects may require additional assumptions. Such individual effects, more often than not, are more precisely described as "conditional average treatment effects" and confusion between the two has the potential to hi…
