Non-randomized treatment effect models are widely used for the assessment of treatment effects in various fields and in particular social science disciplines like political science, psychometry, psychology. More specifically, these are situations where treatment is assigned to an individual based on some of their characteristics (e.g. scholarship is allocated based on merit or antihypertensive treatments are allocated based on blood pressure level) instead of being allocated randomly, as is the case, for example, in randomized clinical trials. Popular methods that have been largely employed till date for estimation of such treatment effects suffer from slow rates of convergence (i.e. slower than $\sqrt{n}$). In this paper, we present a new model coined SCENTS: Score Explained Non-Randomized Treatment Systems, and a corresponding method that allows estimation of the treatment effect at $\sqrt{n}$ rate in the presence of fairly general forms of confoundedness, when the `score' variable on whose basis treatment is assigned can be explained via certain feature measurements of the individuals under study. We show that our estimator is asymptotically normal in general and semi-parametrically efficient under normal errors. We further extend our analysis to high dimensional covariates and propose a $\sqrt n$ consistent and asymptotically normal estimator based on a de-biasing procedure. Our analysis for the high dimensional incarnation can be readily extended to analyze partial linear models in the presence of noisy variables corresponding to the non-linear part of the model, where the noise can be correlated with the variables corresponding to the linear part. We analyze two real datasets via our method and compare our results with those obtained by using previous approaches. We conclude this paper with a discussion on some possible extensions of our approach.
Researchers often use linear regression to analyse randomized experiments to improve treatment effect estimation by adjusting for imbalances of covariates in the treatment and control groups. Our work offers a randomization-based inference framework for regression adjustment in stratified randomized experiments. Under mild conditions, we re-establish the finite population central limit theorem for a stratified experiment. We prove that both the stratified difference-in-means and the regression-adjusted average treatment effect estimators are consistent and asymptotically normal. The asymptotic…
In a randomized controlled trial, treatment switching (also called contamination or crossover) occurs when a patient initially assigned to one treatment arm changes to another arm during the course of follow-up. Overlooking treatment switching might substantially bias the evaluation of treatment efficacy or safety. To account for treatment switching, instrumental variable (IV) methods by leveraging the initial randomized assignment as an IV serve as natural adjustment methods because they allow dependent treatment switching possibly due to underlying prognoses. However, the ``exclusion restric…
When the difference between treatments in a clinical trial is estimated by a difference in means, then it is well known that randomization ensures unbiassed estimation, even if no account is taken of important baseline covariates. However, when the treatment effect is assessed by other summaries, e.g. by an odds ratio if the outcome is binary, then bias can arise if some covariates are omitted, regardless of the use of randomization for treatment allocation or the size of the trial. We present accurate closed-form approximations for this asymptotic bias when important Normally distributed cova…
We establish the inferential properties of the mean-difference estimator for the average treatment effect in randomized experiments where each unit in a population is randomized to one of two treatments and then units within treatment groups are randomly sampled. The properties of this estimator are well-understood in the experimental design scenario where first units are randomly sampled and then treatment is randomly assigned, but not for the aforementioned scenario where the sampling and treatment assignment stages are reversed. We find that the inferential properties of the mean-difference…
Researchers are often interested in analyzing conditional treatment effects. One variant of this is "causal moderation," which implies that intervention upon a third (moderator) variable would alter the treatment effect. This study considers the conditions under which causal moderation can be identified and presents a generalized framework for estimating causal moderation effects given randomized treatments and non-randomized moderators. As part of the estimation process, it allows researchers to implement their preferred method of covariate adjustment, including parametric and non-parametric …
We provide a principled way for investigators to analyze randomized experiments when the number of covariates is large. Investigators often use linear multivariate regression to analyze randomized experiments instead of simply reporting the difference of means between treatment and control groups. Their aim is to reduce the variance of the estimated treatment effect by adjusting for covariates. If there are a large number of covariates relative to the number of observations, regression may perform poorly because of overfitting. In such cases, the Lasso may be helpful. We study the resulting La…
Some patients benefit from a treatment while others may do so less or do not benefit at all. We have previously developed a two-stage network meta-regression prediction model that synthesized randomized trials and evaluates how treatment effects vary across patient characteristics. In this article, we extended this model to combine different sources of types in different formats: aggregate data (AD) and individual participant data (IPD) from randomized and non-randomized evidence. In the first stage, a prognostic model is developed to predict the baseline risk of the outcome using a large coho…
The first step towards investigating the effectiveness of a treatment via a randomized trial is to split the population into control and treatment groups then compare the average response of the treatment group receiving the treatment to the control group receiving the placebo. In order to ensure that the difference between the two groups is caused only by the treatment, it is crucial that the control and the treatment groups have similar statistics. Indeed, the validity and reliability of a trial are determined by the similarity of two groups' statistics. Covariate balancing methods increase …
Understanding and characterizing treatment effect variation in randomized experiments has become essential for going beyond the "black box" of the average treatment effect. Nonetheless, traditional statistical approaches often ignore or assume away such variation. In the context of randomized experiments, this paper proposes a framework for decomposing overall treatment effect variation into a systematic component explained by observed covariates and a remaining idiosyncratic component. Our framework is fully randomization-based, with estimates of treatment effect variation that are entirely j…
In randomized experiments, the actual treatments received by some experimental units may differ from their treatment assignments. This non-compliance issue often occurs in clinical trials, social experiments, and the applications of randomized experiments in many other fields. Under certain assumptions, the average treatment effect for the compliers is identifiable and equal to the ratio of the intention-to-treat effects of the potential outcomes to that of the potential treatment received. To improve the estimation efficiency, we propose three model-assisted estimators for the complier averag…
Methods for extending -- generalizing or transporting -- inferences from a randomized trial to a target population involve conditioning on a large set of covariates that is sufficient for rendering the randomized and non-randomized groups exchangeable. Yet, decision-makers are often interested in examining treatment effects in subgroups of the target population defined in terms of only a few discrete covariates. Here, we propose methods for estimating subgroup-specific potential outcome means and average treatment effects in generalizability and transportability analyses, using outcome model-b…
We develop a Bayesian nonparametric (BNP) approach to evaluate the causal effect of treatment in a randomized trial where a nonterminal event may be censored by a terminal event, but not vice versa (i.e., semi-competing risks). Based on the idea of principal stratification, we define a novel estimand for the causal effect of treatment on the nonterminal event. We introduce identification assumptions, indexed by a sensitivity parameter, and show how to draw inference using our BNP approach. We conduct simulation studies and illustrate our methodology using data from a brain cancer trial.
Complete randomization allows for consistent estimation of the average treatment effect based on the difference in means of the outcomes without strong modeling assumptions on the outcome-generating process. Appropriate use of the pretreatment covariates can further improve the estimation efficiency. However, missingness in covariates is common in experiments and raises an important question: should we adjust for covariates subject to missingness, and if so, how? The unadjusted difference in means is always unbiased. The complete-covariate analysis adjusts for all completely observed covariate…
Oversubscribed treatments are often allocated using randomized waiting lists. Applicants are ranked randomly, and treatment offers are made following that ranking until all seats are filled. To estimate causal effects, researchers often compare applicants getting and not getting an offer. We show that those two groups are not statistically comparable. Therefore, the estimator arising from that comparison is inconsistent. We propose a new estimator, and show that it is consistent. Finally, we revisit an application, and we show that using our estimator can lead to sizably different results from…
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…
To improve precision of estimation and power of testing hypothesis for an unconditional treatment effect in randomized clinical trials with binary outcomes, researchers and regulatory agencies recommend using g-computation as a reliable method of covariate adjustment. However, the practical application of g-computation is hindered by the lack of an explicit robust variance formula that can be used for different unconditional treatment effects of interest. To fill this gap, we provide explicit and robust variance estimators for g-computation estimators and demonstrate through simulations that t…
In randomized controlled trials (RCTs), treatment is often assigned by stratified randomization. I show that among all stratified randomization schemes which treat all units with probability one half, a certain matched-pair design achieves the maximum statistical precision for estimating the average treatment effect (ATE). In an important special case, the optimal design pairs units according to the baseline outcome. In a simulation study based on datasets from 10 RCTs, this design lowers the standard error for the estimator of the ATE by 10% on average, and by up to 34%, relative to the origi…
The original Finite Selection Model (FSM) was developed in the 1970s to enhance the design of the RAND Health Insurance Experiment (HIE; Newhouse et al. 1993). At the time of its development by Carl Morris (Morris 1979), there were fundamental computational limitations to make the method widely available for practitioners. Today, as randomized experiments increasingly become more common, there is a need for implementing experimental designs that are randomized, balanced, robust, and easily applicable to several treatment groups. To help address this problem, we revisit the original FSM under t…
Cluster-randomized experiments are widely used due to their logistical convenience and policy relevance. To analyze them properly, we must address the fact that the treatment is assigned at the cluster level instead of the individual level. Standard analytic strategies are regressions based on individual data, cluster averages, and cluster totals, which differ when the cluster sizes vary. These methods are often motivated by models with strong and unverifiable assumptions, and the choice among them can be subjective. Without any outcome modeling assumption, we evaluate these regression estimat…
Many policy evaluations occur in settings where treatment is randomized at the cluster level, and there is treatment noncompliance within each cluster. For example, villages might be assigned to treatment and control, but residents in each village may choose to comply or not with their assigned treatment status. When noncompliance is present, the instrumental variables framework can be used to identify and estimate causal effects. While a large literature exists on instrumental variables estimation methods, relatively little work has been focused on settings with clustered treatments. Here, we…
Treatment effect heterogeneity occurs when individual characteristics influence the effect of a treatment. We propose a novel approach that combines prognostic score matching and conditional inference trees to characterize effect heterogeneity of a randomized binary treatment. One key feature that distinguishes our method from alternative approaches is that it controls the Type I error rate, i.e., the probability of identifying effect heterogeneity if none exists and retains the underlying subgroups. This feature makes our technique particularly appealing in the context of clinical trials, whe…
Scientific researchers utilize randomized experiments to draw casual statements. Most early studies as well as current work on experiments with sequential intervention decisions has been focusing on estimating the causal effects among sequential treatments, ignoring the non-compliance issues that experimental units might not be compliant with the treatment assignments that they were originally allocated. A series of methodologies have been developed to address the non-compliance issues in randomized experiments with time-fixed treatment. However, to our best knowledge, there is little literatu…
Treatment switching in a randomized controlled trial is said to occur when a patient randomized to one treatment arm switches to another treatment arm during follow-up. This can occur at the point of disease progression, whereby patients in the control arm may be offered the experimental treatment. It is widely known that failure to account for treatment switching can seriously dilute the estimated effect of treatment on overall survival. In this paper, we aim to account for the potential impact of treatment switching in a re-analysis evaluating the treatment effect of NucleosideReverse Transc…
Budgeted Active Experimentation for Treatment Effect Estimation from Observational and Randomized Data
Didi Chuxing（滴滴出行）；School of Statistics, East China Normal University（华东师范大学统计学院）；School of Mathematics and Statistics, Beijing Jiaotong University（北京交通大学数学与统计学院）；School of Computing and Information Technology, Great Bay University（大湾区大学计算与信息技术学院）；School of Statistics and Data Science, Shanghai University of Finance and Economics（上海财经大学统计与数据科学学院）；Institute of Data Science and Statistics, Shanghai University of Finance and Economics（上海财经大学数据科学与统计研究院）
The primary analysis of randomized screening trials for cancer typically adheres to the intention-to-screen principle, measuring cancer-specific mortality reductions between screening and control arms. These mortality reductions result from a combination of the screening regimen, screening technology and the effect of the early, screening-induced, treatment. This motivates addressing these different aspects separately. Here we are interested in the causal effect of early versus delayed treatments on cancer mortality among the screening-detectable subgroup, which under certain assumptions is es…
The use and development of mobile interventions are experiencing rapid growth. In "just-in-time" mobile interventions, treatments are provided via a mobile device and they are intended to help an individual make healthy decisions "in the moment," and thus have a proximal, near future impact. Currently the development of mobile interventions is proceeding at a much faster pace than that of associated data science methods. A first step toward developing data-based methods is to provide an experimental design for testing the proximal effects of these just-in-time treatments. In this paper, we pro…
We propose new, optimal methods for analyzing randomized trials, when it is suspected that treatment effects may differ in two predefined subpopulations. Such sub-populations could be defined by a biomarker or risk factor measured at baseline. The goal is to simultaneously learn which subpopulations benefit from an experimental treatment, while providing strong control of the familywise Type I error rate. We formalize this as a multiple testing problem and show it is computationally infeasible to solve using existing techniques. Our solution involves a novel approach, in which we first transfo…
Randomized experiments are widely used to estimate the causal effects of a proposed treatment in many areas of science, from medicine and healthcare to the physical and biological sciences, from the social sciences to engineering, to public policy and to the technology industry at large. Here, we consider situations where classical methods for estimating the total treatment effect on a target population are considerably biased due to confounding network effects, i.e., the fact that the treatment of an individual may impact their neighbors' outcomes, an issue referred to as network interference…
In this review, we present econometric and statistical methods for analyzing randomized experiments. For basic experiments we stress randomization-based inference as opposed to sampling-based inference. In randomization-based inference, uncertainty in estimates arises naturally from the random assignment of the treatments, rather than from hypothesized sampling from a large population. We show how this perspective relates to regression analyses for randomized experiments. We discuss the analyses of stratified, paired, and clustered randomized experiments, and we stress the general efficiency g…
Background: Randomized controlled trials are often used to inform policy and practice for broad populations. The average treatment effect (ATE) for a target population, however, may be different from the ATE observed in a trial if there are effect modifiers whose distribution in the target population is different that from that in the trial. Methods exist to use trial data to estimate the target population ATE, provided the distributions of treatment effect modifiers are observed in both the trial and target population -- an assumption that may not hold in practice. Methods: The proposed sensi…
Technological advancements in the field of mobile devices and wearable sensors have helped overcome obstacles in the delivery of care, making it possible to deliver behavioral treatments anytime and anywhere. Increasingly the delivery of these treatments is triggered by predictions of risk or engagement which may have been impacted by prior treatments. Furthermore the treatments are often designed to have an impact on individuals over a span of time during which subsequent treatments may be provided. Here we discuss our work on the design of a mobile health smoking cessation experimental study…
Randomized experiments have become important tools in empirical research. In a completely randomized treatment-control experiment, the simple difference in means of the outcome is unbiased for the average treatment effect, and covariate adjustment can further improve the efficiency without assuming a correctly specified outcome model. In modern applications, experimenters often have access to many covariates, motivating the need for a theory of covariate adjustment under the asymptotic regime with a diverging number of covariates. We study the asymptotic properties of covariate adjustment unde…
Evaluating treatment effect heterogeneity widely informs treatment decision making. At the moment, much emphasis is placed on the estimation of the conditional average treatment effect via flexible machine learning algorithms. While these methods enjoy some theoretical appeal in terms of consistency and convergence rates, they generally perform poorly in terms of uncertainty quantification. This is troubling since assessing risk is crucial for reliable decision-making in sensitive and uncertain environments. In this work, we propose a conformal inference-based approach that can produce reliabl…
ETH Zurich（苏黎世联邦理工学院）；University of Cambridge（剑桥大学）；LMU Munich（慕尼黑大学）；The Alan Turing Institute（阿兰·图灵研究所）；UCLA（加州大学洛杉矶分校）
Estimating heterogeneous treatment effects is an important problem across many domains. In order to accurately estimate such treatment effects, one typically relies on data from observational studies or randomized experiments. Currently, most existing works rely exclusively on observational data, which is often confounded and, hence, yields biased estimates. While observational data is confounded, randomized data is unconfounded, but its sample size is usually too small to learn heterogeneous treatment effects. In this paper, we propose to estimate heterogeneous treatment effects by combining …
