Marginal structural model

Summary

Marginal structural models are a class of statistical models used for causal inference in epidemiology. Such models handle the issue of time-dependent confounding in evaluation of the efficacy of interventions by inverse probability weighting for receipt of treatment, they allow us to estimate the average causal effects. For instance, in the study of the effect of zidovudine in AIDS-related mortality, CD4 lymphocyte is used both for treatment indication, is influenced by treatment, and affects survival. Time-dependent confounders are typically highly prognostic of health outcomes and applied in dosing or indication for certain therapies, such as body weight or lab values such as alanine aminotransferase or bilirubin. The first marginal structural models were introduced in 2000. The works of James Robins, Babette Brumback, and Miguel Hernán provided an intuitive theory and an easy-to-implement software which made them popular for the analysis of longitudinal data.

Official source

https://en.wikipedia.org/wiki/Marginal_structural_model

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This course covers formal frameworks for causal inference. We focus on experimental designs, definitions of causal models, interpretation of causal parameters and estimation of causal effects.

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Causal inference in continuous time: an example on prostate cancer therapy

Pal Christie Ryalen, Mats Julius Stensrud

In marginal structural models (MSMs), time is traditionally treated as a discrete parameter. In survival analysis on the other hand, we study processes that develop in continuous time. Therefore, Røysland (2011. A martingale approach to continuous-time marginal structural models. Bernoulli 17, 895–915) developed the continuous-time MSMs, along with continuous-time weights. The continuous-time weights are conceptually similar to the inverse probability weights that are used in discrete time MSMs. Here, we demonstrate that continuous-time MSMs may be used in practice. First, we briefly describe the causal model assumptions using counting process notation, and we suggest how causal effect estimates can be derived by calculating continuous-time weights. Then, we describe how additive hazard models can be used to find such effect estimates. Finally, we apply this strategy to compare medium to long-term differences between the two prostate cancer treatments radical prostatectomy and radiation therapy, using data from the Norwegian Cancer Registry. In contrast to the results of a naive analysis, we find that the marginal cumulative incidence of treatment failure is similar between the strategies, accounting for the competing risk of other death.

2020

Marginal structural models (MSMs) allow for causal analysis of longitudinal data. The standard MSM is based on discrete time models, but the continuous-time MSM is a conceptually appealing alternative for survival analysis. In applied analyses, it is often assumed that the theoretical treatment weights are known, but these weights are usually unknown and must be estimated from the data. Here we provide a sufficient condition for continuous-time MSM to be consistent even when the weights are estimated, and we show how additive hazard models can be used to estimate such weights. Our results suggest that continuous-time weights perform better than IPTW when the underlying process is continuous. Furthermore, we may wish to transform effect estimates of hazards to other scales that are easier to interpret causally. We show that a general transformation strategy can be used on weighted cumulative hazard estimates to obtain a range of other parameters in survival analysis, and explain how this strategy can be applied on data using our R packages ahw and transform.hazards.

2019

Sufficient Cause Interaction for Time-to-event Outcomes

Pal Christie Ryalen, Mats Julius Stensrud

Methods to assess sufficient cause interactions are well developed for binary outcomes. We extend these methods to handle time-to-event outcomes, which occur frequently in medicine and epidemiology. Based on theory for marginal structural models in continuous time, we show how to assess sufficient cause interaction nonparametrically, allowing for censoring and competing risks. We apply the method to study interaction between intensive blood pressure therapy and statin treatment on all-cause mortality.

2019