In causal inference, principal stratification is a framework for dealing with a posttreatment intermediate variable between a treatment and an outcome, in which the principal strata are defined by the joint potential values of the intermediate variable. Because the principal strata are not fully observable, the causal effects within them, also known as the principal causal effects, are not identifiable without additional assumptions. Several previous empirical studies leveraged auxiliary variables to improve the inference of principal causal effects. We establish a general theory for identification and estimation of the principal causal effects with auxiliary variables, which provides a solid foundation for statistical inference and more insights for model building in empirical research. In particular, we consider two commonly-used strategies for principal stratification problems: principal ignorability, and the conditional independence between the auxiliary variable and the outcome given principal strata and covariates. For these two strategies, we give non-parametric and semi-parametric identification results without modeling assumptions on the outcome. When the assumptions for neither strategies are plausible, we propose a large class of flexible parametric and semi-parametric models for identifying principal causal effects. Our theory not only establishes formal identification results of several models that have been used in previous empirical studies but also generalizes them to allow for different types of outcomes and intermediate variables.
The principal stratification has become a popular tool to address a broad class of causal inference questions, particularly in dealing with non-compliance and truncation-by-death problems. The causal effects within principal strata which are determined by joint potential values of the intermediate variable, also known as the principal causal effects, are often of interest in these studies. Analyses of principal causal effects from observed data in the literature mostly rely on ignorability of the treatment assignment, which requires practitioners to accurately measure as many as covariates so …
Causal inference concerns not only the average effect of the treatment on the outcome but also the underlying mechanism through an intermediate variable of interest. Principal stratification characterizes such a mechanism by targeting subgroup causal effects within principal strata, which are defined by the joint potential values of an intermediate variable. Due to the fundamental problem of causal inference, principal strata are inherently latent, rendering it challenging to identify and estimate subgroup effects within them. A line of research leverages the principal ignorability assumption …
This research was motivated by studying anti-drug antibody (ADA) formation and its potential impact on long-term benefit of a biologic treatment in a randomized controlled trial, in which ADA status was not only unobserved in the control arm but also in a subset of patients from the experimental treatment arm. Recent literature considers the principal stratum estimand strategy to estimate treatment effect in groups of patients defined by an intercurrent status, i.e. in groups defined by a post-randomization variable only observed in one arm and potentially associated with the outcome. However,…
Bayesian Nonparametrics for Principal Stratification with Continuous Post-Treatment Variables
Data Science Institute, Brown University（布朗大学数据科学研究所）；Department of Statistics, University of Padova（帕多瓦大学统计系）；Department of Economics, European University Institute（欧洲研究院经济系）；Department of Biostatistics, Harvard School of Public Health（哈佛公共卫生学院生物统计系）；Department of Biostatistics, University of California, Los Angeles（加州大学洛杉矶分校生物统计系）
Practitioners are interested in not only the average causal effect of the treatment on the outcome but also the underlying causal mechanism in the presence of an intermediate variable between the treatment and outcome. However, in many cases we cannot randomize the intermediate variable, resulting in sample selection problems even in randomized experiments. Therefore, we view randomized experiments with intermediate variables as semi-observational studies. In parallel with the analysis of observational studies, we provide a theoretical foundation for conducting objective causal inference with …
In cluster randomized trials, patients are typically recruited after clusters are randomized, and the recruiters and patients may not be blinded to the assignment. This often leads to differential recruitment and consequently systematic differences in baseline characteristics of the recruited patients between intervention and control arms, inducing post-randomization selection bias. We rigorously define causal estimands in the presence of selection bias. We elucidate the conditions under which standard covariate adjustment methods can validly estimate these estimands. We further discuss the ad…
This paper uses a "principal strata" approach to decompose treatment effects and interpret why a schooling intervention that yielded exceptional initial effects yielded substantially smaller effects in a replication years later. The specific application is a set of 2008 and 2015 replications of an intervention aiming to increase primary education for girls in rural Afghanistan. The intervention offers a new schooling option, and as such, its effects depend on how individuals use alternatives that already exist. The principal strata approach accounts variation in use patterns when comparing eff…
Principal stratification is a causal framework to analyze randomized experiments with a post-treatment variable between the treatment and endpoint variables. Because the principal strata defined by the potential outcomes of the post-treatment variable are not observable, we generally cannot identify the causal effects within principal strata. Motivated by a real data set of phase III adjuvant colon clinical trials, we propose approaches to identifying and estimating the principal causal effects via multiple trials. For the identifiability, we remove the commonly-used exclusion restriction assu…
Estimation of treatment effect for principal strata has been studied for more than two decades. Existing research exclusively focuses on the estimation, but there is little research on forming and testing hypotheses for principal stratification-based estimands. In this brief report, we discuss a phenomenon in which the true treatment effect for a principal stratum may not equal zero even if the two treatments have the same effect at patient level which implies an equal average treatment effect for the principal stratum. We explain this phenomenon from the perspective of selection bias. This is…
In vaccine studies, investigators are often interested in studying effect modifiers of clinical treatment efficacy by biomarker-based principal strata, which is useful for selecting biomarker study endpoints for evaluating treatments in new trials, exploring biological mechanisms of clinical treatment efficacy, and studying mediators of clinical treatment efficacy. However, in trials where participants may enter the study with prior exposure therefore with variable baseline biomarker values, clinical treatment efficacy may depend jointly on a biomarker measured at baseline and measured at a fi…
Auxiliary information can increase the efficiency of survey estimators through an assisting model when the model captures some of the relationship between the auxiliary data and the study variables. Despite their superior properties, model-assisted estimators are rarely used in anything but their simplest form by statistical agencies to produce official statistics. This is due to the fact that the more complicated models that have been used in model-assisted estimation are often ill suited to the available auxiliary data. Under a model-assisted framework, we propose a regression tree estimator…
In clinical trials, it is often of interest to understand the principal causal effect (PCE), the average treatment effect for a principal stratum (a subset of patients defined by the potential outcomes of one or more post-baseline variables). Commonly used assumptions include monotonicity, principal ignorability, and cross-world assumptions of principal ignorability and principal strata independence. In this article, we evaluate these assumptions through a 2$\times$2 cross-over study in which the potential outcomes under both treatments can be observed, provided there are no carry-over and stu…
Datasets from field experiments with covariate-adaptive randomizations (CARs) usually contain extra covariates in addition to the strata indicators. We propose to incorporate these additional covariates via auxiliary regressions in the estimation and inference of unconditional quantile treatment effects (QTEs) under CARs. We establish the consistency and limit distribution of the regression-adjusted QTE estimator and prove that the use of multiplier bootstrap inference is non-conservative under CARs. The auxiliary regression may be estimated parametrically, nonparametrically, or via regulariza…
Principal Stratification with Bayesian Additive Regression Trees for Count-Valued Intermediate Variables: Estimating the Effect of Fertility on Women's Employment
Combining BART and Principal Stratification to estimate the effect of intermediate on primary outcomes with application to estimating the effect of family planning on employment in sub-Saharan Africa
Motivated by a potential-outcomes perspective, the idea of principal stratification has been widely recognized for its relevance in settings susceptible to posttreatment selection bias such as randomized clinical trials where treatment received can differ from treatment assigned. In one such setting, we address subtleties involved in inference for causal effects when using a key covariate to predict membership in latent principal strata. We show that when treatment received can differ from treatment assigned in both study arms, incorporating a stratum-predictive covariate can make estimates of…
Participants in longitudinal studies on the effects of drug treatment and criminal justice system interventions are at high risk for institutionalization (e.g., spending time in an environment where their freedom to use drugs, commit crimes, or engage in risky behavior may be circumscribed). Methods used for estimating treatment effects in the presence of institutionalization during follow-up can be highly sensitive to assumptions that are unlikely to be met in applications and thus likely to yield misleading inferences. In this paper we consider the use of principal stratification to control …
It has recently become popular to define treatment effects for subsets of the target population characterized by variables not observable at the time a treatment decision is made. Characterizing and estimating such treatment effects is tricky; the most popular but naive approach inappropriately adjusts for variables affected by treatment and so is biased. We consider several appropriate ways to formalize the effects: principal stratification, stratification on a single potential auxiliary variable, stratification on an observed auxiliary variable and stratification on expected levels of auxili…
In survey sampling, calibration is a very popular tool used to make total estimators consistent with known totals of auxiliary variables and to reduce variance. When the number of auxiliary variables is large, calibration on all the variables may lead to estimators of totals whose mean squared error (MSE) is larger than the MSE of the Horvitz-Thompson estimator even if this simple estimator does not take account of the available auxiliary information. We study in this paper a new technique based on dimension reduction through principal components that can be useful in this large dimension cont…
This paper considers conducting inference about the effect of a treatment (or exposure) on an outcome of interest. In the ideal setting where treatment is assigned randomly, under certain assumptions the treatment effect is identifiable from the observable data and inference is straightforward. However, in other settings such as observational studies or randomized trials with noncompliance, the treatment effect is no longer identifiable without relying on untestable assumptions. Nonetheless, the observable data often do provide some information about the effect of treatment, that is, the param…
In survey statistics, the usual technique for estimating a population total consists in summing appropriately weighted variable values for the units in the sample. Different weighting systems exit: sampling weights, GREG weights or calibration weights for example. In this article, we propose to use the inverse of conditional inclusion probabilities as weighting system. We study examples where an auxiliary information enables to perform an a posteriori stratification of the population. We show that, in these cases, exact computations of the conditional weights are possible. When the auxiliary i…
Estimation of heterogeneous principal effects under principal ignorability
School of Statistics, University of Minnesota（明尼苏达大学统计学院）；Division of Biostatistics and Health Data Science, School of Public Health, University of Minnesota（明尼苏达大学公共卫生学院生物统计与健康数据科学系）
An emerging challenge for time-to-event data is studying semi-competing risks, namely when two event times are of interest: a non-terminal event time (e.g. age at disease diagnosis), and a terminal event time (e.g. age at death). The non-terminal event is observed only if it precedes the terminal event, which may occur before or after the non-terminal event. Studying treatment or intervention effects on the dual event times is complicated because for some units, the non-terminal event may occur under one treatment value but not under the other. Until recently, existing approaches (e.g., the su…
In many medical studies, an ultimate failure event such as death is likely to be affected by the occurrence and timing of other intermediate clinical events. Both event times are subject to censoring by loss-to-follow-up but the nonterminal event may further be censored by the occurrence of the primary outcome, but not vice versa. To study the effect of an intervention on both events, the intermediate event may be viewed as a mediator, but conventional definition of direct and indirect effects is not applicable due to semi-competing risks data structure. We define three principal strata based …
Analysis of sample survey data often requires adjustments to account for missing data in the outcome variables of principal interest. Standard adjustment methods based on item imputation or on propensity weighting factors rely heavily on the availability of auxiliary variables for both responding and non-responding units. Application of these adjustment methods can be especially challenging in cases for which the auxiliary variables are numerous and are themselves subject to substantial incomplete-data problems. This paper shows how classification and regression trees and forests can overcome …
