Stratification and rerandomization are two well-known methods used in randomized experiments for balancing the baseline covariates. Renowned scholars in experimental design have recommended combining these two methods; however, limited studies have addressed the statistical properties of this combination. This paper proposes two rerandomization methods to be used in stratified randomized experiments, based on the overall and stratum-specific Mahalanobis distances. The first method is applicable for nearly arbitrary numbers of strata, strata sizes, and stratum-specific proportions of the treated units. The second method, which is generally more efficient than the first method, is suitable for situations in which the number of strata is fixed with their sizes tending to infinity. Under the randomization inference framework, we obtain the asymptotic distributions of estimators used in these methods and the formulas of variance reduction when compared to stratified randomization. Our analysis does not require any modeling assumption regarding the potential outcomes. Moreover, we provide asymptotically conservative variance estimators and confidence intervals for the average treatment effect. The advantages of the proposed methods are exhibited through an extensive simulation study and a real-data example.
Power analyses are an important aspect of experimental design, because they help determine how experiments are implemented in practice. It is common to specify a desired level of power and compute the sample size necessary to obtain that power. Such calculations are well-known for completely randomized experiments, but there can be many benefits to using other experimental designs. For example, it has recently been established that rerandomization, where subjects are randomized until covariate balance is obtained, increases the precision of causal effect estimators. This work establishes the p…
Completely randomized experiments have been the gold standard for drawing causal inference because they can balance all potential confounding on average. However, they may suffer from unbalanced covariates for realized treatment assignments. Rerandomization, a design that rerandomizes the treatment assignment until a prespecified covariate balance criterion is met, has recently got attention due to its easy implementation, improved covariate balance and more efficient inference. Researchers have then suggested to use the treatment assignments that minimize the covariate imbalance, namely the o…
The split-plot design arises from agricultural sciences with experimental units, also known as subplots, nested within groups known as whole plots. It assigns the whole-plot intervention by a cluster randomization at the whole-plot level and assigns the subplot intervention by a stratified randomization at the subplot level. The randomization mechanism guarantees covariate balance on average at both the whole-plot and subplot levels, and ensures consistent inference of the average treatment effects by the Horvitz--Thompson and Hajek estimators. However, covariate imbalance often occurs in fini…
Randomization is a basis for the statistical inference of treatment effects without strong assumptions on the outcome-generating process. Appropriately using covariates further yields more precise estimators in randomized experiments. R. A. Fisher suggested blocking on discrete covariates in the design stage or conducting analysis of covariance (ANCOVA) in the analysis stage. We can embed blocking into a wider class of experimental design called rerandomization, and extend the classical ANCOVA to more general regression adjustment. Rerandomization trumps complete randomization in the design st…
Classical randomized experiments, equipped with randomization-based inference, provide assumption-free inference for treatment effects. They have been the gold standard for drawing causal inference and provide excellent internal validity. However, they have also been criticized for questionable external validity, in the sense that the conclusion may not generalize well to a larger population. The randomized survey experiment is a design tool that can help mitigate this concern, by randomly selecting the experimental units from the target population of interest. However, as pointed out by Morga…
Rerandomization is a strategy of increasing efficiency as compared to complete randomization. The idea with rerandomization is that of removing allocations with imbalance in the observed covariates and then randomizing within the set of allocations with balance in these covariates. Standard asymptotic inference based on mean difference estimator is however conservative after rerandomization. Given a Mahalanobis distance criterion for removing imbalanced allocations, Li et al. (2018) derived the asymptotic distribution of the mean difference estimator and suggested a consistent estimator of its…
Randomized experiments are the "gold standard" for estimating causal effects, yet often in practice, chance imbalances exist in covariate distributions between treatment groups. If covariate data are available before units are exposed to treatments, these chance imbalances can be mitigated by first checking covariate balance before the physical experiment takes place. Provided a precise definition of imbalance has been specified in advance, unbalanced randomizations can be discarded, followed by a rerandomization, and this process can continue until a randomization yielding balance according t…
We present an optimized rerandomization design procedure for a non-sequential treatment-control experiment. Randomized experiments are the gold standard for finding causal effects in nature. But sometimes random assignments result in unequal partitions of the treatment and control group visibly seen as imbalance in observed covariates. There can additionally be imbalance on unobserved covariates. Imbalance in either observed or unobserved covariates increases treatment effect estimator error inflating the width of confidence regions and reducing experimental power. "Rerandomization" is a strat…
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…
Inference of Sample Complier Average Causal Effects under Experiments with Completely Randomized Design and Computer Assisted Balance-Improving Designs
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…
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…
This paper proposes an adaptive randomization procedure for two-stage randomized controlled trials. The method uses data from a first-wave experiment in order to determine how to stratify in a second wave of the experiment, where the objective is to minimize the variance of an estimator for the average treatment effect (ATE). We consider selection from a class of stratified randomization procedures which we call stratification trees: these are procedures whose strata can be represented as decision trees, with differing treatment assignment probabilities across strata. By using the first wave t…
Regression adjustment is widely used for the analysis of randomized experiments to improve the estimation efficiency of the treatment effect. This paper reexamines a weighted regression adjustment method termed as tyranny-of-the-minority (ToM), wherein units in the minority group are given greater weights. We demonstrate that the ToM regression adjustment is more robust than Lin 2013's regression adjustment with treatment-covariate interactions, even though these two regression adjustment methods are asymptotically equivalent in completely randomized experiments. Moreover, we extend ToM regres…
The injunction to `analyze the way you randomize' is well-known to statisticians since Fisher advocated for randomization as the basis of inference. Yet even those convinced by the merits of randomization-based inference seldom follow this injunction to the letter. Bernoulli randomized experiments are often analyzed as completely randomized experiments, and completely randomized experiments are analyzed as if they had been stratified; more generally, it is not uncommon to analyze an experiment as if it had been randomized differently. This paper examines the theoretical foundation behind this …
We consider the problem of estimating and inferring treatment effects in randomized experiments. In practice, stratified randomization, or more generally, covariate-adaptive randomization, is routinely used in the design stage to balance the treatment allocations with respect to a few variables that are most relevant to the outcomes. Then, regression is performed in the analysis stage to adjust the remaining imbalances to yield more efficient treatment effect estimators. Building upon and unifying the recent results obtained for ordinary least squares adjusted estimators under covariate-adapti…
While attractive from a theoretical perspective, finely stratified experiments such as paired designs suffer from certain analytical limitations not present in block-randomized experiments with multiple treated and control individuals in each block. In short, when using an appropriately weighted difference-in-means to estimated the sample average treatment effect, the traditional variance estimator in a paired experiment is conservative unless the pairwise average treatment effects are constant across pairs; however, in more coarsely stratified experiments, the corresponding variance estimator…
In randomized experiments, treatment and control groups should be roughly the same--balanced--in their distributions of pretreatment variables. But how nearly so? Can descriptive comparisons meaningfully be paired with significance tests? If so, should there be several such tests, one for each pretreatment variable, or should there be a single, omnibus test? Could such a test be engineered to give easily computed $p$-values that are reliable in samples of moderate size, or would simulation be needed for reliable calibration? What new concerns are introduced by random assignment of clusters? Wh…
Linear regression is arguably the most fundamental statistical model; however, the validity of its use in randomized clinical trials, despite being common practice, has never been crystal clear, particularly when stratified or covariate-adaptive randomization is used. In this paper, we investigate several of the most intuitive and commonly used regression models for estimating and inferring the treatment effect in randomized clinical trials. By allowing the regression model to be arbitrarily misspecified, we demonstrate that all these regression-based estimators robustly estimate the treatment…
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…
In a cluster-randomized experiment, treatment is assigned to clusters of individual units of interest--households, classrooms, villages, etc.--instead of the units themselves. The number of clusters sampled and the number of units sampled within each cluster is typically restricted by a budget constraint. Previous analysis of cluster randomized experiments under the Neyman-Rubin potential outcomes model of response have assumed a simple random sample of clusters. Estimators of the population average treatment effect (PATE) under this assumption are often either biased or not invariant to locat…
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…
The Fisher randomization test (FRT) is appropriate for any test statistic, under a sharp null hypothesis that can recover all missing potential outcomes. However, it is often sought after to test a weak null hypothesis that the treatment does not affect the units on average. To use the FRT for a weak null hypothesis, we must address two issues. First, we need to impute the missing potential outcomes although the weak null hypothesis cannot determine all of them. Second, we need to choose a proper test statistic. For a general weak null hypothesis, we propose an approach to imputing missing pot…
Two-sample tests with censored outcomes are a classical topic in statistics with wide use even in cutting edge applications. There are at least two modes of inference used to justify two-sample tests. One is usual superpopulation inference assuming that units are independent and identically distributed (i.i.d.) samples from some superpopulation; the other is finite population inference that relies on the random assignments of units into different groups. When randomization is actually implemented, the latter has the advantage of avoiding distributional assumptions on the outcomes. In this pape…
Data-Adaptive and Model-Robust Covariate Adjustment for Time-to-Event Outcomes in Stratified Randomized Trials
Cornell Tech, Cornell University（康奈尔科技校区，康奈尔大学）；Department of Biostatistics, Department of Population Health, New York University School of Medicine（纽约大学医学院生物统计学系、人口健康系）
Randomized clinical trials are often designed to assess whether a test treatment prolongs survival relative to a control treatment. Increased patient heterogeneity, while desirable for generalizability of results, can weaken the ability of common statistical approaches to detect treatment differences, potentially hampering the regulatory approval of safe and efficacious therapies. A novel solution to this problem is proposed. A list of baseline covariates that have the potential to be prognostic for survival under either treatment is pre-specified in the analysis plan. At the analysis stage, u…
Randomized block factorial experiments are widely used in industrial engineering, clinical trials, and social science. Researchers often use a linear model and analysis of covariance to analyze experimental results; however, limited studies have addressed the validity and robustness of the resulting inferences because assumptions for a linear model might not be justified by randomization in randomized block factorial experiments. In this paper, we establish a new finite population joint central limit theorem for usual (unadjusted) factorial effect estimators in randomized block $2^K$ factorial…
Two commonly used methods for improving precision and power in clinical trials are stratified randomization and covariate adjustment. However, many trials do not fully capitalize on the combined precision gains from these two methods, which can lead to wasted resources in terms of sample size and trial duration. We derive consistency and asymptotic normality of model-robust estimators that combine these two methods, and show that these estimators can lead to substantial gains in precision and power. Our theorems cover a class of estimators that handle continuous, binary, and time-to-event outc…
