Making valid causal inferences from observational data.

The ability to make strong causal inferences, based on data derived from outside of the laboratory, is largely restricted to data arising from well-designed randomized control trials. Nonetheless, a number of methods have been developed to improve our ability to make valid causal inferences from data arising from observational studies. In this paper, I review concepts of causation as a background to counterfactual causal ideas; the latter ideas are central to much of current causal theory. Confounding greatly constrains causal inferences in all observational studies. Confounding is a biased measure of effect that results when one or more variables, that are both antecedent to the exposure and associated with the outcome, are differentially distributed between the exposed and non-exposed groups. Historically, the most common approach to control confounding has been multivariable modeling; however, the limitations of this approach are discussed. My suggestions for improving causal inferences include asking better questions (relates to counterfactual ideas and "thought" trials); improving study design through the use of forward projection; and using propensity scores to identify potential confounders and enhance exchangeability, prior to seeing the outcome data. If time-dependent confounders are present (as they are in many longitudinal studies), more-advanced methods such as marginal structural models need to be implemented. Tutorials and examples are cited where possible.