Personalized decision-making, aiming to derive optimal treatment regimes based on individual characteristics, has recently attracted increasing attention in many fields, such as medicine, social services, and economics. Current literature mainly focuses on estimating treatment regimes from a single source population. In real-world applications, the distribution of a target population can be different from that of the source population. Therefore, treatment regimes learned by existing methods may not generalize well to the target population. Due to privacy concerns and other practical issues, individual-level data from the target population is often not available, which makes treatment regime learning more challenging. We consider the problem of treatment regime estimation when the source and target populations may be heterogeneous, individual-level data is available from the source population, and only the summary information of covariates, such as moments, is accessible from the target population. We develop a weighting framework that tailors a treatment regime for a given target population by leveraging the available summary statistics. Specifically, we propose a calibrated augmented inverse probability weighted estimator of the value function for the target population and estimate an optimal treatment regime by maximizing this estimator within a class of pre-specified regimes. We show that the proposed calibrated estimator is consistent and asymptotically normal even with flexible semi/nonparametric models for nuisance function approximation, and the variance of the value estimator can be consistently estimated. We demonstrate the empirical performance of the proposed method using simulation studies and a real application to an eICU dataset as the source sample and a MIMIC-III dataset as the target sample.
Individualizing treatment assignment can improve outcomes for diseases with patient-to-patient variability in comparative treatment effects. When a clinical trial demonstrates that some patients improve on treatment while others do not, it is tempting to assume that treatment effect heterogeneity exists. However, if variability in response is mainly driven by factors other than treatment, investigating the extent to which covariate data can predict differential treatment response is a potential waste of resources. Motivated by recent meta-analyses assessing the potential of individualizing tre…
In biomedical science, analyzing treatment effect heterogeneity plays an essential role in assisting personalized medicine. The main goals of analyzing treatment effect heterogeneity include estimating treatment effects in clinically relevant subgroups and predicting whether a patient subpopulation might benefit from a particular treatment. Conventional approaches often evaluate the subgroup treatment effects via parametric modeling and can thus be susceptible to model mis-specifications. In this manuscript, we take a model-free semiparametric perspective and aim to efficiently evaluate the he…
The Doubly Robust (DR) estimation of ATE can be carried out in 2 steps, where in the first step, the treatment and outcome are modeled, and in the second step the predictions are inserted into the DR estimator. The model misspecification in the first step has led researchers to utilize Machine Learning algorithms instead of parametric algorithms. However, existence of strong confounders and/or Instrumental Variables (IVs) can lead the complex ML algorithms to provide perfect predictions for the treatment model which can violate the positivity assumption and elevate the variance of DR estimator…
When data on treatment assignment, outcomes, and covariates from a randomized trial are available, a question of interest is to what extent covariates can be used to optimize treatment decisions. Statistical hypothesis testing of covariate-by-treatment interaction is ill-suited for this purpose. The application of decision theory results in treatment rules that compare the expected benefit of treatment given the patient's covariates against a treatment threshold. However, determining treatment threshold is often context-specific, and any given threshold might seem arbitrary when the overall ca…
The aim of clinical effectiveness research using repositories of electronic health records is to identify what health interventions 'work best' in real-world settings. Since there are several reasons why the net benefit of intervention may differ across patients, current comparative effectiveness literature focuses on investigating heterogeneous treatment effect and predicting whether an individual might benefit from an intervention. The majority of this literature has concentrated on the estimation of the effect of treatment on binary outcomes. However, many medical interventions are evaluate…
Predicting risks of chronic diseases has become increasingly important in clinical practice. When a prediction model is developed in a given source cohort, there is often a great interest to apply the model to other cohorts. However, due to potential discrepancy in baseline disease incidences between different cohorts and shifts in patient composition, the risk predicted by the original model often under- or over-estimates the risk in the new cohort. The remedy of such a poorly calibrated prediction is needed for proper medical decision-making. In this article, we assume the relative risks of …
Transporting summary measures of relative effects from randomised trials to the treated patient population: an application to breast cancer endocrine therapy
University of Oxford（牛津大学）；University of North Carolina at Chapel Hill（北卡罗来纳大学教堂山分校）
In this paper, we focus on estimating the average treatment effect (ATE) of a target population when individual-level data from a source population and summary-level data (e.g., first or second moments of certain covariates) from the target population are available. In the presence of heterogeneous treatment effect, the ATE of the target population can be different from that of the source population when distributions of treatment effect modifiers are dissimilar in these two populations, a phenomenon also known as covariate shift. Many methods have been developed to adjust for covariate shift,…
Targeted Active Learning for Preference-Based Treatment Effects on Multivariate Outcomes
Theremia；Paris Brain Institute (ICM)（巴黎脑科学研究所（ICM））；Sorbonne Université（索邦大学）；Inserm（法国国家健康与医学研究院）；CNRS（法国国家科学研究中心）；AP-HP（巴黎公共援助医院）；Inria（法国国家信息与自动化研究所）；Université de Montpellier（蒙彼利埃大学）；Université Paris Cité（巴黎西岱大学）；Centre for Research in Epidemiology and Statistics (CRESS)（流行病学与统计学研究中心（CRESS））
We consider estimation of an optimal individualized treatment rule from observational and randomized studies when a high-dimensional vector of baseline variables is available. Our optimality criterion is with respect to delaying expected time to occurrence of an event of interest (e.g., death or relapse of cancer). We leverage semiparametric efficiency theory to construct estimators with desirable properties such as double robustness. We propose two estimators of the optimal rule, which arise from considering two loss functions aimed at (i) directly estimating the conditional treatment effect …
An important objective in the development of targeted therapies is to identify the populations where the treatment under consideration has positive benefit risk balance. We consider pivotal clinical trials, where the efficacy of a treatment is tested in an overall population and/or in a pre-specified subpopulation. Based on a decision theoretic framework we derive optimized trial designs by maximizing utility functions. Features to be optimized include the sample size and the population in which the trial is performed (the full population or the targeted subgroup only) as well as the underlyin…
In this paper we present a new measure for the overlap of two density functions which provides motivation and interpretation currently lacking with benchmark measures based on the proportion of similar response, also known as the overlap coefficient. We use this new measure to present an alternative to the $p$--value as a guide to the choice of treatment in a comparative trial; where a current treatment and a new treatment are undergoing investigation. We show that it is possible to reject the null hypothesis; i.e. the new treatment is significantly different in response to the old treatment, …
Cardio/cerebrovascular diseases (CVD) have become one of the major health issue in our societies. But recent studies show that the present pathology tests to detect CVD are ineffectual as they do not consider different stages of platelet activation or the molecular dynamics involved in platelet interactions and are incapable to consider inter-individual variability. Here we propose a stochastic platelet deposition model and an inferential scheme to estimate the biologically meaningful model parameters using approximate Bayesian computation with a summary statistic that maximally discriminates …
An Online Meta-Level Adaptive Design Framework with Targeted Learning Inference: Applications to Evaluating and Utilizing Surrogate Outcomes in Adaptive Designs
Targeted Learning is a subfield of statistics that unifies advances in causal inference, machine learning and statistical theory to help answer scientifically impactful questions with statistical confidence. Targeted Learning is driven by complex problems in data science and has been implemented in a diversity of real-world scenarios: observational studies with missing treatments and outcomes, personalized interventions, longitudinal settings with time-varying treatment regimes, survival analysis, adaptive randomized trials, mediation analysis, and networks of connected subjects. In contrast t…
Longitudinal targeted maximum likelihood estimation (LTMLE) has very rarely been used to estimate dynamic treatment effects in the context of time-dependent confounding affected by prior treatment when faced with long follow-up times, multiple time-varying confounders, and complex associational relationships simultaneously. Reasons for this include the potential computational burden, technical challenges, restricted modeling options for long follow-up times, and limited practical guidance in the literature. However, LTMLE has desirable asymptotic properties, i.e. it is doubly robust, and can y…
The ability to generalize experimental results from randomized control trials (RCTs) across locations is crucial for informing policy decisions in targeted regions. Such generalization is often hindered by the lack of identifiability due to unmeasured effect modifiers that compromise direct transport of treatment effect estimates from one location to another. We build upon sensitivity analysis in observational studies and propose an optimization procedure that allows us to get bounds on the treatment effects in targeted regions. Furthermore, we construct more informative bounds by balancing on…
Targeted Data Fusion for Region-Specific Survival Effects in the AMP HIV Prevention Trials
North Carolina State University（北卡罗来纳州立大学）；Duke Clinical Research Institute（杜克临床研究所）；University of Pennsylvania（宾夕法尼亚大学）；Duke University School of Medicine（杜克大学医学院）；Fred Hutch Cancer Center（弗雷德·哈钦癌症中心）；Brown University（布朗大学）
Several recently developed methods have the potential to harness machine learning in the pursuit of target quantities inspired by causal inference, including inverse weighting, doubly robust estimating equations and substitution estimators like targeted maximum likelihood estimation. There are even more recent augmentations of these procedures that can increase robustness, by adding a layer of cross-validation (cross-validated targeted maximum likelihood estimation and double machine learning, as applied to substitution and estimating equation approaches, respectively). While these methods hav…
A dynamic treatment regime is a sequence of decision rules in which each decision rule recommends treatment based on features of patient medical history such as past treatments and outcomes. Existing methods for estimating optimal dynamic treatment regimes from data optimize the mean of a response variable. However, the mean may not always be the most appropriate summary of performance. We derive estimators of decision rules for optimizing probabilities and quantiles computed with respect to the response distribution for two-stage, binary treatment settings. This enables estimation of dynamic …
Improving the Estimation of Lifetime Effects in A/B Testing via Treatment Locality
Graduate School of Business, Columbia University（哥伦比亚大学研究生商学院）；Institute for Data, Systems, and Society, Department of Civil and Environmental Engineering, and Operations Research Center, Massachusetts Institute of Technology（麻省理工学院数据、系统与社会研究所）；Naveen Jindal School of Management, University of Texas at Dallas（德克萨斯大学达拉斯分校纳文·金达管理学院）
Inverse probability weights are commonly used in epidemiology to estimate causal effects in observational studies. Researchers can typically focus on either the average treatment effect or the average treatment effect on the treated with inverse probability weighting estimators. However, when overlap between the treated and control groups is poor, this can produce extreme weights that can result in biased estimates and large variances. One alternative to inverse probability weights are overlap weights, which target the population with the most overlap on observed characteristics. While estimat…
Our motivation stems from current medical research aiming at personalized treatment using a molecular-based approach. The broad goal is to develop a more precise and targeted decision making process, relative to traditional treatments based primarily on clinical diagnoses. Specifically, we consider patients affected by Acute Myeloid Leukemia (AML), an hematological cancer characterized by uncontrolled proliferation of hematopoietic stem cells in the bone marrow. Because AML responds poorly to chemoterapeutic treatments, the development of targeted therapies is essential to improve patients' pr…
Information from various data sources is increasingly available nowadays. However, some of the data sources may produce biased estimation due to commonly encountered biased sampling, population heterogeneity, or model misspecification. This calls for statistical methods to combine information in the presence of biased sources. In this paper, a robust data fusion-extraction method is proposed. The method can produce a consistent estimator of the parameter of interest even if many of the data sources are biased. The proposed estimator is easy to compute and only employs summary statistics, and h…
One of the main tasks of causal inference is estimating well-defined causal parameters. One of the main causal parameters is the average causal effect (ACE) - the expected value of the individual level causal effects in the target population. For binary treatments, the individual level causal effect is defined as contrast between potential outcomes. For continuous outcomes, however, there are many such contrasts in finite samples, thus hampering their use as a useful summary of the causal relationship. Here, we proposed a generalized version of the ACE, where individual level causal effects ar…
We wish to infer the value of a parameter at a law from which we sample independent observations. The parameter is smooth and we can define two variation-independent features of the law, its $Q$- and $G$-components, such that estimating them consistently at a fast enough product of rates allows to build a confidence interval (CI) with a given asymptotic level from a plain targeted minimum loss estimator (TMLE). Say that the above product is not fast enough and the algorithm for the $G$-component is fine-tuned by a real-valued $h$. A plain TMLE with an $h$ chosen by cross-validation would typic…
RCTs sometimes test interventions that aim to improve existing services targeted to a subset of individuals identified after randomization. Accordingly, the treatment could affect the composition of service recipients and the offered services. With such bias, intention-to-treat estimates using data on service recipients and nonrecipients may be difficult to interpret. This article develops causal estimands and inverse probability weighting (IPW) estimators for complier populations in these settings, using a generalized estimating equation approach that adjusts the standard errors for estimatio…
The Highly-Adaptive-LASSO Targeted Minimum Loss Estimator (HAL-TMLE) is an efficient plug-in estimator of a pathwise differentiable parameter in a statistical model that at minimal (and possibly only) assumes that the sectional variation norm of the true nuisance functional parameters (i.e., the relevant part of data distribution) are finite. It relies on an initial estimator (HAL-MLE) of the nuisance functional parameters by minimizing the empirical risk over the parameter space under the constraint that the sectional variation norm of the candidate functions are bounded by a constant, where …
Nonparametric efficient causal estimation of the intervention-specific expected number of recurrent events with continuous-time targeted maximum likelihood and highly adaptive lasso estimation
Effect modification occurs while the effect of the treatment is not homogeneous across the different strata of patient characteristics. When the effect of treatment may vary from individual to individual, precision medicine can be improved by identifying patient covariates to estimate the size and direction of the effect at the individual level. However, this task is statistically challenging and typically requires large amounts of data. Investigators may be interested in using the individual patient data (IPD) from multiple studies to estimate these treatment effect models. Our data arise fro…
In randomized experiments, interactions between units might generate a treatment diffusion process. This is common when the treatment of interest is an actual object or product that can be shared among peers (e.g., flyers, booklets, videos). For instance, if the intervention of interest is an information campaign realized through the distribution of a video to targeted individuals, some of these treated individuals might share the video they received with their friends. Such a phenomenon is usually unobserved, causing a misallocation of individuals in the two treatment arms: some of the initia…
Recent work has made important contributions in the development of causally-interpretable meta-analysis. These methods transport treatment effects estimated in a collection of randomized trials to a target population of interest. Ideally, estimates targeted toward a specific population are more interpretable and relevant to policy-makers and clinicians. However, between-study heterogeneity not arising from differences in the distribution of treatment effect modifiers can raise difficulties in synthesizing estimates across trials. The existence of such heterogeneity, including variations in tre…
Federated Causal Inference in Heterogeneous Observational Data
Emory University（埃默里大学）；Cornell University（康奈尔大学）；United States Military Academy（美国军事学院）；Harvard University（哈佛大学）；Johns Hopkins University（约翰斯·霍普金斯大学）；Stanford University（斯坦福大学）
