Double blind randomized controlled trials are traditionally seen as the gold standard for causal inferences as the difference-in-means estimator is an unbiased estimator of the average treatment effect in the experiment. The fact that this estimator is unbiased over all possible randomizations does not, however, mean that any given estimate is close to the true treatment effect. Similarly, while pre-determined covariates will be balanced between treatment and control groups on average, large imbalances may be observed in a given experiment and the researcher may therefore want to condition on such covariates using linear regression. This paper studies the theoretical properties of both the difference-in-means and OLS estimators \emph{conditional} on observed differences in covariates. By deriving the statistical properties of the conditional estimators, we can establish guidance for how to deal with covariate imbalances. We study both inference with OLS, as well as with a new version of Fisher's exact test, where the randomization distribution comes from a small subset of all possible assignment vectors.
We consider the conditional randomization test as a way to account for covariate imbalance in randomized experiments. The test accounts for covariate imbalance by comparing the observed test statistic to the null distribution of the test statistic conditional on the observed covariate imbalance. We prove that the conditional randomization test has the correct significance level and introduce original notation to describe covariate balance more formally. Through simulation, we verify that conditional randomization tests behave like more traditional forms of covariate adjustmet but have the adde…
We address estimation of intervention effects in experimental designs in which (a) interventions are assigned at the cluster level; (b) clusters are selected to form pairs, matched on observed characteristics; and (c) intervention is assigned to one cluster at random within each pair. One goal of policy interest is to estimate the average outcome if all clusters in all pairs are assigned control versus if all clusters in all pairs are assigned to intervention. In such designs, inference that ignores individual level covariates can be imprecise because cluster-level assignment can leave substan…
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…
A benefit of randomized experiments is that covariate distributions of treatment and control groups are balanced on average, resulting in simple unbiased estimators for treatment effects. However, it is possible that a particular randomization yields covariate imbalances that researchers want to address in the analysis stage through adjustment or other methods. Here we present a randomization test that conditions on covariate balance by only considering treatment assignments that are similar to the observed one in terms of covariate balance. Previous conditional randomization tests have only a…
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…
In comparative studies, such as in causal inference and clinical trials, balancing important covariates is often one of the most important concerns for both efficient and credible comparison. However, chance imbalance still exists in many randomized experiments. This phenomenon of covariate imbalance becomes much more serious as the number of covariates $p$ increases. To address this issue, we introduce a new randomization procedure, called pairwise sequential randomization (PSR). The proposed method allocates the units sequentially and adaptively, using information on the current level of imb…
We present a new experimental design procedure that divides a set of experimental units into two groups in order to minimize error in estimating an additive treatment effect. One concern is minimizing error at the experimental design stage is large covariate imbalance between the two groups. Another concern is robustness of design to misspecification in response models. We address both concerns in our proposed design: we first place subjects into pairs using optimal nonbipartite matching, making our estimator robust to complicated non-linear response models. Our innovation is to keep the match…
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…
Bias in causal comparisons has a direct correspondence with distributional imbalance of covariates between treatment groups. Weighting strategies such as inverse propensity score weighting attempt to mitigate bias by either modeling the treatment assignment mechanism or balancing specified covariate moments. This paper introduces a new weighting method, called energy balancing, which instead aims to balance weighted covariate distributions. By directly targeting distributional imbalance, the proposed weighting strategy can be flexibly utilized in a wide variety of causal analyses, including th…
We study nonparametric estimation for the partially conditional average treatment effect, defined as the treatment effect function over an interested subset of confounders. We propose a hybrid kernel weighting estimator where the weights aim to control the balancing error of any function of the confounders from a reproducing kernel Hilbert space after kernel smoothing over the subset of interested variables. In addition, we present an augmented version of our estimator which can incorporate estimations of outcome mean functions. Based on the representer theorem, gradient-based algorithms can b…
Chance imbalance in baseline characteristics is common in randomized clinical trials. Regression adjustment such as the analysis of covariance (ANCOVA) is often used to account for imbalance and increase precision of the treatment effect estimate. An objective alternative is through inverse probability weighting (IPW) of the propensity scores. Although IPW and ANCOVA are asymptotically equivalent, the former may demonstrate inferior performance in finite samples. In this article, we point out that IPW is a special case of the general class of balancing weights, and advocate to use overlap weig…
Background: Subgroup analyses are frequently conducted in randomized clinical trials to assess evidence of heterogeneous treatment effect across patient subpopulations. Although randomization balances covariates within subgroups in expectation, chance imbalance may be amplified in small subgroups and harm the precision. Covariate adjustment in overall analysis of RCT is often conducted, via either ANCOVA or propensity score weighting, but for subgroup analysis has been rarely discussed. In this article, we develop propensity score weighting methodology for covariate adjustment to improve the p…
Causal analyses for observational studies are often complicated by covariate imbalances among treatment groups, and matching methodologies alleviate this complication by finding subsets of treatment groups that exhibit covariate balance. It is widely agreed upon that covariate balance can serve as evidence that a matched dataset approximates a randomized experiment, but what kind of experiment does a matched dataset approximate? In this work, we develop a randomization test for the hypothesis that a matched dataset approximates a particular experimental design, such as complete randomization, …
Estimating the average treatment causal effect in clustered data often involves dealing with unmeasured cluster-specific confounding variables. Such variables may be correlated with the measured unit covariates and outcome. When the correlations are ignored, the causal effect estimation can be biased. By utilizing sufficient statistics, we propose an inverse conditional probability weighting (ICPW) method, which is robust to both (i) the correlation between the unmeasured cluster-specific confounding variable and the covariates and (ii) the correlation between the unmeasured cluster-specific c…
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…
Conditional power calculations are frequently used to guide the decision whether or not to stop a trial for futility or to modify planned sample size. These ignore the information in short-term endpoints and baseline covariates, and thereby do not make fully efficient use of the information in the data. We therefore propose an interim decision procedure based on the conditional power approach which exploits the information contained in baseline covariates and short-term outcomes. We will realise this by considering the estimation of the treatment effect at the interim analysis as a missing dat…
On regression with estimated covariates and conditional effects given the propensity score
Rutgers, The State University of New Jersey（新泽西州立罗格斯大学）；Carnegie Mellon University（卡内基梅隆大学）；University of California, Los Angeles（加州大学洛杉矶分校）；Princeton University（普林斯顿大学）
A surrogate endpoint S in a clinical trial is an outcome that may be measured earlier or more easily than the true outcome of interest T. In this work, we extend causal inference approaches to validate such a surrogate using potential outcomes. The causal association paradigm assesses the relationship of the treatment effect on the surrogate with the treatment effect on the true endpoint. Using the principal surrogacy criteria, we utilize the joint conditional distribution of the potential outcomes T, given the potential outcomes S. In particular, our setting of interest allows us to assume th…
In this paper, we propose a doubly robust method to present the heterogeneity of the average treatment effect with respect to observed covariates of interest. We consider a situation where a large number of covariates are needed for identifying the average treatment effect but the covariates of interest for analyzing heterogeneity are of much lower dimension. Our proposed estimator is doubly robust and avoids the curse of dimensionality. We propose a uniform confidence band that is easy to compute, and we illustrate its usefulness via Monte Carlo experiments and an application to the effects o…
Multi-CATE: Multi-Accurate Conditional Average Treatment Effect Estimation Robust to Unknown Covariate Shifts
Ludwig-Maximilians-University of Munich（慕尼黑大学）；Munich Center for Machine Learning (MCML)（慕尼黑机器学习中心）；Cornell University（康奈尔大学）；University of Southern California（南加州大学）
Randomized controlled trials are the gold standard for measuring causal effects. However, they are often not always feasible, and causal treatment effects must be estimated from observational data. Observational studies do not allow robust conclusions about causal relationships unless statistical techniques account for the imbalance of pretreatment confounders across groups while key assumptions hold. Propensity score and balance weighting (PSBW) are useful techniques that aim to reduce the imbalances between treatment groups by weighting the groups to look alike on the observed confounders. T…
When a strict subset of covariates are given, we propose conditional quantile treatment effect to capture the heterogeneity of treatment effects via the quantile sheet that is the function of the given covariates and quantile. We focus on deriving the asymptotic normality of probability score-based estimators under parametric, nonparametric and semiparametric structure. We make a systematic study on the estimation efficiency to check the importance of propensity score structure and the essential differences from the unconditional counterparts. The derived unique properties can answer: what is …
In paired experiments, participants are grouped into pairs with similar characteristics, and one observation from each pair is randomly assigned to treatment. Because of both the pairing and the randomization, the treatment and control groups should be well balanced; however, there may still be small chance imbalances. It may be possible to improve the precision of the treatment effect estimate by adjusting for these imbalances. Building on related work for completely randomized experiments, we propose the P-LOOP (paired leave-one-out potential outcomes) estimator for paired experiments. We le…
Randomization ensures that observed and unobserved covariates are balanced, on average. However, randomizing units to treatment and control often leads to covariate imbalances in realization, and such imbalances can inflate the variance of estimators of the treatment effect. One solution to this problem is rerandomization---an experimental design strategy that randomizes units until some balance criterion is fulfilled---which yields more precise estimators of the treatment effect if covariates are correlated with the outcome. Most rerandomization schemes in the literature utilize the Mahalanob…
The difference in restricted mean survival times between two groups is a clinically relevant summary measure. With observational data, there may be imbalances in confounding variables between the two groups. One approach to account for such imbalances is to estimate a covariate-adjusted restricted mean difference by modeling the covariate-adjusted survival distribution and then marginalizing over the covariate distribution. We demonstrate that the mean-squared error of the restricted mean difference is bounded by the mean-squared error of the covariate-adjusted survival distribution estimators…
Estimating causal effects under exogeneity hinges on two key assumptions: unconfoundedness and overlap. Researchers often argue that unconfoundedness is more plausible when more covariates are included in the analysis. Less discussed is the fact that covariate overlap is more difficult to satisfy in this setting. In this paper, we explore the implications of overlap in observational studies with high-dimensional covariates and formalize curse-of-dimensionality argument, suggesting that these assumptions are stronger than investigators likely realize. Our key innovation is to explore how strict…
In this study, we consider the problem of selecting explanatory variables of fixed effects in linear mixed models under covariate shift, which is when the values of covariates in the model for prediction differ from those in the model for observed data. We construct a variable selection criterion based on the conditional Akaike information introduced by Vaida and Blanchard (2005). We focus especially on covariate shift in small area estimation and demonstrate the usefulness of the proposed criterion. In addition, numerical performance is investigated through simulations, one of which is a desi…
Missing covariate data commonly occur in epidemiological and clinical research, and are often dealt with using multiple imputation (MI). Imputation of partially observed covariates is complicated if the substantive model is non-linear (e.g. Cox proportional hazards model), or contains non-linear (e.g. squared) or interaction terms, and standard software implementations of MI may impute covariates from models that are incompatible with such substantive models. We show how imputation by fully conditional specification, a popular approach for performing MI, can be modified so that covariates are …
The comparison of Receiver Operating Characteristic (ROC) curves is frequently used in the literature to compare the discriminatory capability of different classification procedures based on diagnostic variables. The performance of these variables can be sometimes influenced by the presence of other covariates, and thus they should be taken into account when making the comparison. A new non-parametric test is proposed here for testing the equality of two or more dependent ROC curves conditioned to the value of a multidimensional covariate. Projections are used for transforming the problem into…
We consider estimating the density of a response conditioning on an error-prone covariate. Motivated by two existing kernel density estimators in the absence of covariate measurement error, we propose a method to correct the existing estimators for measurement error. Asymptotic properties of the resultant estimators under different types of measurement error distributions are derived. Moreover, we adjust bandwidths readily available from existing bandwidth selection methods developed for error-free data to obtain bandwidths for the new estimators. Extensive simulation studies are carried out t…
