TL;DR: In this paper, the authors introduce marginal structural models, a new class of causal models that allow for improved adjustment of confounding in observational studies with exposures or treatments that vary over time, when there exist time-dependent confounders that are also affected by previous treatment.
Abstract: In observational studies with exposures or treatments that vary over time, standard approaches for adjustment of confounding are biased when there exist time-dependent confounders that are also affected by previous treatment. This paper introduces marginal structural models, a new class of causal models that allow for improved adjustment of confounding in those situations. The parameters of a marginal structural model can be consistently estimated using a new class of estimators, the inverse-probability-of-treatment weighted estimators.
TL;DR: Several different correlation coefficients reported in medical manuscripts are familiarize medical readers with, clarify confounding aspects and summarize the naming practices for the strength of correlation coefficients are summarized.
Abstract: When writing a manuscript, we often use words such as perfect, strong, good or weak to name the strength of the relationship between variables. However, it is unclear where a good relationship turns into a strong one. The same strength of r is named differently by several researchers. Therefore, there is an absolute necessity to explicitly report the strength and direction of r while reporting correlation coefficients in manuscripts. This article aims to familiarize medical readers with several different correlation coefficients reported in medical manuscripts, clarify confounding aspects and summarize the naming practices for the strength of correlation coefficients.
TL;DR: An important approach to evaluating evidence for causation in the face of unmeasured confounding is sensitivity analysis (or bias analysis), and it is proposed that observational studies start reporting the E-value, a new measure related to evidence for causality.
Abstract: Sensitivity analysis is useful in assessing how robust an association is to potential unmeasured or uncontrolled confounding. This article introduces a new measure called the "E-value," which is related to the evidence for causality in observational studies that are potentially subject to confounding. The E-value is defined as the minimum strength of association, on the risk ratio scale, that an unmeasured confounder would need to have with both the treatment and the outcome to fully explain away a specific treatment-outcome association, conditional on the measured covariates. A large E-value implies that considerable unmeasured confounding would be needed to explain away an effect estimate. A small E-value implies little unmeasured confounding would be needed to explain away an effect estimate. The authors propose that in all observational studies intended to produce evidence for causality, the E-value be reported or some other sensitivity analysis be used. They suggest calculating the E-value for both the observed association estimate (after adjustments for measured confounders) and the limit of the confidence interval closest to the null. If this were to become standard practice, the ability of the scientific community to assess evidence from observational studies would improve considerably, and ultimately, science would be strengthened.
TL;DR: The statistical similarities among mediation, confounding, and suppression are described and methods to determine the confidence intervals for confounding and suppression effects are proposed based on methods developed for mediated effects.
Abstract: This paper describes the statistical similarities among mediation, confounding, and suppression. Each is quantified by measuring the change in the relationship between an independent and a dependent variable after adding a third variable to the analysis. Mediation and confounding are identical statistically and can be distinguished only on conceptual grounds. Methods to determine the confidence intervals for confounding and suppression effects are proposed based on methods developed for mediated effects. Although the statistical estimation of effects and standard errors is the same, there are important conceptual differences among the three types of effects.
TL;DR: A large simulation study of other influences on confidence interval coverage, type I error, relative bias, and other model performance measures found a range of circumstances in which coverage and bias were within acceptable levels despite less than 10 EPV.
Abstract: The rule of thumb that logistic and Cox models should be used with a minimum of 10 outcome events per predictor variable (EPV), based on two simulation studies, may be too conservative. The authors conducted a large simulation study of other influences on confidence interval coverage, type I error, relative bias, and other model performance measures. They found a range of circumstances in which coverage and bias were within acceptable levels despite less than 10 EPV, as well as other factors that were as influential as or more influential than EPV. They conclude that this rule can be relaxed, in particular for sensitivity analyses undertaken to demonstrate adequate control of confounding.