No Arabic abstract
When interested in a time-to-event outcome, competing events that prevent the occurrence of the event of interest may be present. In the presence of competing events, various statistical estimands have been suggested for defining the causal effect of treatment on the event of interest. Depending on the estimand, the competing events are either accommodated or eliminated, resulting in causal effects with different interpretation. The former approach captures the total effect of treatment on the event of interest while the latter approach captures the direct effect of treatment on the event of interest that is not mediated by the competing event. Separable effects have also been defined for settings where the treatment effect can be partitioned into its effect on the event of interest and its effect on the competing event through different causal pathways. We outline various causal effects that may be of interest in the presence of competing events, including total, direct and separable effects, and describe how to obtain estimates using regression standardisation with the Stata command standsurv. Regression standardisation is applied by obtaining the average of individual estimates across all individuals in a study population after fitting a survival model. With standsurv several contrasts of interest can be calculated including differences, ratios and other user-defined functions. Confidence intervals can also be obtained using the delta method. Throughout we use an example analysing a publicly available dataset on prostate cancer to allow the reader to replicate the analysis and further explore the different effects of interest.
In time-to-event settings, the presence of competing events complicates the definition of causal effects. Here we propose the new separable effects to study the causal effect of a treatment on an event of interest. The separable direct effect is the treatment effect on the event of interest not mediated by its effect on the competing event. The separable indirect effect is the treatment effect on the event of interest only through its effect on the competing event. Similar to Robins and Richardsons extended graphical approach for mediation analysis, the separable effects can only be identified under the assumption that the treatment can be decomposed into two distinct components that exert their effects through distinct causal pathways. Unlike existing definitions of causal effects in the presence of competing events, our estimands do not require cross-world contrasts or hypothetical interventions to prevent death. As an illustration, we apply our approach to a randomized clinical trial on estrogen therapy in individuals with prostate cancer.
Estimation of causal effects is fundamental in situations were the underlying system will be subject to active interventions. Part of building a causal inference engine is defining how variables relate to each other, that is, defining the functional relationship between variables given conditional dependencies. In this paper, we deviate from the common assumption of linear relationships in causal models by making use of neural autoregressive density estimators and use them to estimate causal effects within the Pearls do-calculus framework. Using synthetic data, we show that the approach can retrieve causal effects from non-linear systems without explicitly modeling the interactions between the variables.
The functional linear model is a popular tool to investigate the relationship between a scalar/functional response variable and a scalar/functional covariate. We generalize this model to a functional linear mixed-effects model when repeated measurements are available on multiple subjects. Each subject has an individual intercept and slope function, while shares common population intercept and slope function. This model is flexible in the sense of allowing the slope random effects to change with the time. We propose a penalized spline smoothing method to estimate the population and random slope functions. A REML-based EM algorithm is developed to estimate the variance parameters for the random effects and the data noise. Simulation studies show that our estimation method provides an accurate estimate for the functional linear mixed-effects model with the finite samples. The functional linear mixed-effects model is demonstrated by investigating the effect of the 24-hour nitrogen dioxide on the daily maximum ozone concentrations and also studying the effect of the daily temperature on the annual precipitation.
Forest-based methods have recently gained in popularity for non-parametric treatment effect estimation. Building on this line of work, we introduce causal survival forests, which can be used to estimate heterogeneous treatment effects in a survival and observational setting where outcomes may be right-censored. Our approach relies on orthogonal estimating equations to robustly adjust for both censoring and selection effects. In our experiments, we find our approach to perform well relative to a number of baselines.
Standard estimators of the global average treatment effect can be biased in the presence of interference. This paper proposes regression adjustment estimators for removing bias due to interference in Bernoulli randomized experiments. We use a fitted model to predict the counterfactual outcomes of global control and global treatment. Our work differs from standard regression adjustments in that the adjustment variables are constructed from functions of the treatment assignment vector, and that we allow the researcher to use a collection of any functions correlated with the response, turning the problem of detecting interference into a feature engineering problem. We characterize the distribution of the proposed estimator in a linear model setting and connect the results to the standard theory of regression adjustments under SUTVA. We then propose an estimator that allows for flexible machine learning estimators to be used for fitting a nonlinear interference functional form. We propose conducting statistical inference via bootstrap and resampling methods, which allow us to sidestep the complicated dependences implied by interference and instead rely on empirical covariance structures. Such variance estimation relies on an exogeneity assumption akin to the standard unconfoundedness assumption invoked in observational studies. In simulation experiments, our methods are better at debiasing estimates than existing inverse propensity weighted estimators based on neighborhood exposure modeling. We use our method to reanalyze an experiment concerning weather insurance adoption conducted on a collection of villages in rural China.