Local differential privacy is a differential privacy paradigm in which individuals first apply a privacy mechanism to their data (often by adding noise) before transmitting the result to a curator. The noise for privacy results in additional bias and variance in their analyses. Thus it is of great importance for analysts to incorporate the privacy noise into valid inference. In this article, we develop methodologies to infer causal effects from locally privatized data under randomized experiments. First, we present frequentist estimators under various privacy scenarios with their variance estimators and plug-in confidence intervals. We show a naïve debiased estimator results in inferior mean-squared error (MSE) compared to minimax lower bounds. In contrast, we show that using a customized privacy mechanism, we can match the lower bound, giving minimax optimal inference. We also develop a Bayesian nonparametric methodology along with a blocked Gibbs sampling algorithm, which can be applied to any of our proposed privacy mechanisms, and which performs especially well in terms of MSE for tight privacy budgets. Finally, we present simulation studies to evaluate the performance of our proposed frequentist and Bayesian methodologies for various privacy budgets, resulting in useful suggestions for performing causal inference for privatized data.
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 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.
We consider methods for causal inference in randomized trials nested within cohorts of trial-eligible individuals, including those who are not randomized. We show how baseline covariate data from the entire cohort, and treatment and outcome data only from randomized individuals, can be used to identify potential (counterfactual) outcome means and average treatment effects in the target population of all eligible individuals. We review identifiability conditions, propose estimators, and assess the estimators' finite-sample performance in simulation studies. As an illustration, we apply the esti…
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…
Pragmatic randomized trials are designed to provide evidence for clinical decision-making rather than regulatory approval. Common features of these trials include the inclusion of heterogeneous or diverse patient populations in a wide range of care settings, the use of active treatment strategies as comparators, unblinded treatment assignment, and the study of long-term, clinically relevant outcomes. These features can greatly increase the usefulness of the trial results for patients, clinicians, and other stakeholders. However, these features also introduce an increased risk of non-adherence,…
Evaluating the incremental return on ad spend (iROAS) of a prospective online marketing strategy (i.e., the ratio of the strategy's causal effect on some response metric of interest relative to its causal effect on the ad spend) has become increasingly more important. Although randomized ``geo experiments'' are frequently employed for this evaluation, obtaining reliable estimates of iROAS can be challenging as oftentimes only a small number of highly heterogeneous units are used. Moreover, advertisers frequently impose budget constraints on their ad spends, which further complicates causal inf…
Causal mediation in cluster-randomized trials with multiple mediators: spillover-aware decomposition, identification, and semiparametric efficient inference
We examine study designs for extending (generalizing or transporting) causal inferences from a randomized trial to a target population. Specifically, we consider nested trial designs, where randomized individuals are nested within a sample from the target population, and non-nested trial designs, including composite dataset designs, where a randomized trial is combined with a separately obtained sample of non-randomized individuals from the target population. We show that the causal quantities that can be identified in each study design depend on what is known about the probability of sampling…
With increasing data availability, causal effects can be evaluated across different data sets, both randomized controlled trials (RCTs) and observational studies. RCTs isolate the effect of the treatment from that of unwanted (confounding) co-occurring effects but they may suffer from unrepresentativeness, and thus lack external validity. On the other hand, large observational samples are often more representative of the target population but can conflate confounding effects with the treatment of interest. In this paper, we review the growing literature on methods for causal inference on combi…
The purpose of this work is to improve the efficiency in estimating the average causal effect (ACE) on the survival scale where right-censoring exists and high-dimensional covariate information is available. We propose new estimators using regularized survival regression and survival random forests (SRF) to make the adjustment for the high dimensional covariates to improve efficiency. We study the behavior of the adjusted estimator under mild assumptions and show theoretical guarantees that the proposed estimators are more efficient than the unadjusted ones asymptotically when using SRF for ad…
Nonignorable missingness and noncompliance can occur even in well-designed randomized experiments making the intervention effect that the experiment was designed to estimate nonidentifiable. Nonparametric causal bounds provide a way to narrow the range of possible values for a nonidentifiable causal effect with minimal assumptions. We derive novel bounds for the causal risk difference for a binary outcome and intervention in randomized experiments with nonignorable missingness caused by a variety of mechanisms and with or without noncompliance. We illustrate the use of the proposed bounds in o…
Cluster randomized trials (CRTs) are popular in public health and in the social sciences to evaluate a new treatment or policy where the new policy is randomly allocated to clusters of units rather than individual units. CRTs often feature both noncompliance, when individuals within a cluster are not exposed to the intervention, and individuals within a cluster may influence each other through treatment spillovers where those who comply with the new policy may affect the outcomes of those who do not. Here, we study the identification of causal effects in CRTs when both noncompliance and treatm…
For non-randomized studies, the regression discontinuity design (RDD) can be used to identify and estimate causal effects from a "locally-randomized" subgroup of subjects, under relatively mild conditions. However, current models focus causal inferences on the impact of the treatment (versus non-treatment) variable on the mean of the dependent variable, via linear regression. For RDDs, we propose a flexible Bayesian nonparametric regression model that can provide accurate estimates of causal effects, in terms of the predictive mean, variance, quantile, probability density, distribution functio…
Randomized control trials (RCTs) have been the gold standard to evaluate the effectiveness of a program, policy, or treatment on an outcome of interest. However, many RCTs assume that study participants are willing to share their (potentially sensitive) data, specifically their response to treatment. This assumption, while trivial at first, is becoming difficult to satisfy in the modern era, especially in online settings where there are more regulations to protect individuals' data. The paper presents a new, simple experimental design that is differentially private, one of the strongest notion…
Estimating Causal Treatment Effects in Placebo-Controlled Randomized Clinical Trials When High Placebo Response is Anticipated
Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center（贝斯以色列女医生医疗中心心脏结局研究史密斯中心）；Department of Statistics, SungKyunKwan University（成均馆大学统计系）；Biostatistics Department, Boston University（波士顿大学生物统计学系）
In medical research, a scenario often entertained is randomized controlled $2^2$ factorial design with a binary outcome. By utilizing the concept of potential outcomes, Dasgupta et al. (2015) proposed a randomization-based causal inference framework, allowing flexible and simultaneous estimations and inferences of the factorial effects. However, a fundamental challenge that Dasgupta et al. (2015)'s proposed methodology faces is that the sampling variance of the randomization-based factorial effect estimator is unidentifiable, rendering the corresponding classic "Neymanian" variance estimator s…
When engagement with a randomized trial is driven by factors that affect the outcome or when trial engagement directly affects the outcome independent of treatment, the average treatment effect among trial participants is unlikely to generalize to a target population. In this paper, we use counterfactual and graphical causal models to examine under what conditions we can generalize causal inferences from a randomized trial to the target population of trial-eligible individuals. We offer an interpretation of generalizability analyses using the notion of a hypothetical intervention to "scale-up"…
The Hazard Ratio (HR) is often reported as the main causal effect when studying survival data. Despite its popularity, the HR suffers from an unclear causal interpretation. As already pointed out in the literature, there is a built-in selection bias in the HR, because similarly to the truncation by death problem, the HR conditions on post-treatment survival. A recently proposed alternative, inspired by the Survivor Average Causal Effect (SACE), is the causal HR, defined as the ratio between hazards across treatment groups among the study participants that would have survived regardless of thei…
We present methods for causally interpretable meta-analyses that combine information from multiple randomized trials to estimate potential (counterfactual) outcome means and average treatment effects in a target population. We consider identifiability conditions, derive implications of the conditions for the law of the observed data, and obtain identification results for transporting causal inferences from a collection of independent randomized trials to a new target population in which experimental data may not be available. We propose an estimator for the potential (counterfactual) outcome m…
Estimating within-cluster and between-cluster spillover effects in randomized saturation designs
Department of Statistics, University of California, Berkeley（加州大学伯克利分校统计学系）；Division of Biostatistics, University of California, Berkeley（加州大学伯克利分校生物统计学区）
In a comprehensive cohort study of two competing treatments (say, A and B), clinically eligible individuals are first asked to enroll in a randomized trial and, if they refuse, are then asked to enroll in a parallel observational study in which they can choose treatment according to their own preference. We consider estimation of two estimands: (1) comprehensive cohort causal effect -- the difference in mean potential outcomes had all patients in the comprehensive cohort received treatment A vs. treatment B and (2) randomized trial causal effect -- the difference in mean potential outcomes had…
A Bayesian approach to the survivor average causal effect in cluster-randomized crossover trials
University of Pennsylvania（宾夕法尼亚大学）；Monash University（蒙纳士大学）；Australian and New Zealand Intensive Care Research Centre（澳大利亚和新西兰重症监护研究中心）；Medical Research Institute of New Zealand（新西兰医学研究所）；Wellington Regional Hospital（惠灵顿地区医院）；University of Melbourne（墨尔本大学）；Yale School of Public Health（耶鲁公共卫生学院）
Causal mediation analysis aims to estimate the natural direct and indirect effects under clearly specified assumptions. Traditional mediation analysis based on Ordinary Least Squares (OLS) relies on the absence of unmeasured causes of the putative mediator and outcome. When this assumption cannot be justified, Instrumental Variables (IV) estimators can be used in order to produce an asymptotically unbiased estimator of the mediator-outcome link. However, provided that valid instruments exist, bias removal comes at the cost of variance inflation for standard IV procedures such as Two-Stage Leas…
The micro-randomized trial (MRT) is a sequential randomized experimental design to empirically evaluate the effectiveness of mobile health (mHealth) intervention components that may be delivered at hundreds or thousands of decision points. MRTs have motivated a new class of causal estimands, termed "causal excursion effects", for which semiparametric inference can be conducted via a weighted, centered least squares criterion (Boruvka et al., 2018). Existing methods assume between-subject independence and non-interference. Deviations from these assumptions often occur. In this paper, causal exc…
Causal inference from observational data can be viewed as a missing data problem arising from a hypothetical population-scale randomized trial matched to the observational study. This links a target trial protocol with a corresponding generative predictive model for inference, providing a complete framework for transparent communication of causal assumptions and statistical uncertainty on treatment effects, without the need for counterfactuals. The intuitive foundation for the work is that a whole population randomized trial would provide answers to any observable causal question with certaint…
Mediation analysis is a strategy for understanding the mechanisms by which treatments or interventions affect later outcomes. Mediation analysis is frequently applied in randomized trial settings, but typically assumes: a) that randomized assignment is the exposure of interest as opposed to actual take-up of the intervention, and b) no unobserved confounding of the mediator-outcome relationship. In contrast to the rich literature on instrumental variable (IV) methods to estimate a total effect of a non-randomized exposure, there has been almost no research into using IV as an identification st…
Purdue University（普渡大学）；University of Maryland, Baltimore County（马里兰大学巴尔的摩县分校）
Randomized experiments are often performed to study the causal effects of interest. Blocking is a technique to precisely estimate the causal effects when the experimental material is not homogeneous. It involves stratifying the available experimental material based on the covariates causing non-homogeneity and then randomizing the treatment within those strata (known as blocks). This eliminates the unwanted effect of the covariates on the causal effects of interest. We investigate the problem of finding a stable set of covariates to be used to form blocks, that minimizes the variance of the ca…
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…
Regression adjustments are often considered by investigators to improve the estimation efficiency of causal effect in randomized experiments when there exists many pre-experiment covariates. In this paper, we provide conditions that guarantee the penalized regression including the Ridge, Elastic Net and Adapive Lasso adjusted causal effect estimators are asymptotic normal and we show that their asymptotic variances are no greater than that of the simple difference-in-means estimator, as long as the penalized estimators are risk consistent. We also provide conservative estimators for the asympt…
Causal identification of treatment effects for infectious disease outcomes in interconnected populations is challenging because infection outcomes may be transmissible to others, and treatment given to one individual may affect others' outcomes. Contagion, or transmissibility of outcomes, complicates standard conceptions of treatment interference in which an intervention delivered to one individual can affect outcomes of others. Several statistical frameworks have been proposed to measure causal treatment effects in this setting, including structural transmission models, mediation-based partne…
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…
Causal inference deals with identifying which random variables "cause" or control other random variables. Recent advances on the topic of causal inference based on tools from statistical estimation and machine learning have resulted in practical algorithms for causal inference. Causal inference has the potential to have significant impact on medical research, prevention and control of diseases, and identifying factors that impact economic changes to name just a few. However, these promising applications for causal inference are often ones that involve sensitive or personal data of users that n…
The usual development cycles are too slow for the development of vaccines, diagnostics and treatments in pandemics such as the ongoing SARS-CoV-2 pandemic. Given the pressure in such a situation, there is a risk that findings of early clinical trials are overinterpreted despite their limitations in terms of size and design. Motivated by a non-randomized open-label study investigating the efficacy of hydroxychloroquine in patients with COVID-19, we describe in a unified fashion various alternative approaches to the analysis of non-randomized studies. A widely used tool to reduce the impact of t…
