The case-crossover design (Maclure, 1991) is widely used in epidemiology and other fields to study causal effects of transient treatments on acute outcomes. However, its validity and causal interpretation have only been justified under informal conditions. Here, we place the design in a formal counterfactual framework for the first time. Doing so helps to clarify its assumptions and interpretation. In particular, when the treatment effect is non-null, we identify a previously unnoticed bias arising from common causes of the outcome at different person-times. We analytically characterize the direction and size of this bias and demonstrate its potential importance with a simulation. We also use our derivation of the limit of the case-crossover estimator to analyze its sensitivity to treatment effect heterogeneity, a violation of one of the informal criteria for validity. The upshot of this work for practitioners is that, while the case-crossover design can be useful for testing the causal null hypothesis in the presence of baseline confounders, extra caution is warranted when using the case-crossover design for point estimation of causal effects.
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）
Data61；The Australian National University（澳大利亚国立大学）；The University of Sydney（悉尼大学）；Ambiata
It is usual to consider data protection and learnability as conflicting objectives. This is not always the case: we show how to jointly control inference --- seen as the attack --- and learnability by a noise-free process that mixes training examples, the Crossover Process (cp). One key point is that the cp~is typically able to alter joint distributions without touching on marginals, nor altering the sufficient statistic for the class. In other words, it saves (and sometimes improves) generalization for supervised learning, but can alter the relationship between covariates --- and therefore fo…
Causal effects may vary among individuals and can even be of opposite signs. When significant effect heterogeneity exists, the population average causal effect might be uninformative for an individual. Due to the fundamental problem of causality, individual causal effects (ICEs) cannot be retrieved from cross-sectional data. However, in crossover studies, it is accepted that ICEs can be estimated under the assumptions of no carryover effects and time invariance of potential outcomes. A generic potential-outcome formulation with appropriate statistical assumptions to identify ICEs is lacking fo…
We consider basic conceptual questions concerning the relationship between statistical estimation and causal inference. Firstly, we show how to translate causal inference problems into an abstract statistical formalism without requiring any structure beyond an arbitrarily-indexed family of probability models. The formalism is simple but can incorporate a variety of causal modelling frameworks, including 'structural causal models', but also models expressed in terms of, e.g., differential equations. We focus primarily on the structural/graphical causal modelling literature, however. Secondly, w…
It is known that the hazard ratio lacks a useful causal interpretation. Even for data from a randomized controlled trial, the hazard ratio suffers from built-in selection bias as, over time, the individuals at risk in the exposed and unexposed are no longer exchangeable. In this work, we formalize how the observed hazard ratio evolves and deviates from the causal hazard ratio of interest in the presence of heterogeneity of the hazard of unexposed individuals (frailty) and heterogeneity in effect (individual modification). For the case of effect heterogeneity, we define the causal hazard ratio.…
Australian National University（澳大利亚国立大学）；Data61/NICTA（Data61/国家信息与通信技术研究院）；University of Alberta（阿尔伯塔大学）
We study the problem of using causal models to improve the rate at which good interventions can be learned online in a stochastic environment. Our formalism combines multi-arm bandits and causal inference to model a novel type of bandit feedback that is not exploited by existing approaches. We propose a new algorithm that exploits the causal feedback and prove a bound on its simple regret that is strictly better (in all quantities) than algorithms that do not use the additional causal information.
We describe the interface between measure theoretic probability and causal inference by constructing causal models on probability spaces within the potential outcomes framework. We find that measure theory provides a precise and instructive language for causality and that consideration of the probability spaces underlying causal models offers clarity into central concepts of causal inference. By closely studying simple, instructive examples, we demonstrate insights into causal effects, causal interactions, matching procedures, and randomization. Additionally, we introduce a simple technique fo…
Crossover designs are an extremely useful tool to investigators, whilst group sequential methods have proven highly proficient at improving the efficiency of parallel group trials. Yet, group sequential methods and crossover designs have rarely been paired together. One possible explanation for this could be the absence of a formal proof of how to strongly control the familywise error rate in the case when multiple comparisons will be made. Here, we provide this proof, valid for any number of initial experimental treatments and any number of stages, when results are analysed using a linear mix…
