Universal Difference-in-Differences for Causal Inference in Epidemiology

Abstract: Difference-in-differences is undoubtedly one of the most widely used methods for evaluating the causal effect of an intervention in observational (i.e., nonrandomized) settings. The approach is typically used when pre- and post-exposure outcome measurements are available, and one can reasonably assume that the association of the unobserved confounder with the outcome has the same absolute magnitude in the two exposure arms, and is constant over time; a so-called parallel trends assumption. The parallel trends assumption may not be credible in many practical settings, including if the outcome is binary, a count, or polytomous, as well as when an uncontrolled confounder exhibits non-additive effects on the distribution of the outcome, even if such effects are constant over time. We introduce an alternative approach that replaces the parallel trends assumption with an odds ratio equi-confounding assumption under which an association between treatment and the potential outcome under no-treatment is identified with a well-specified generalized linear model relating the pre-exposure outcome and the exposure. Because the proposed method identifies any causal effect that is conceivably identified in the absence of confounding bias, including nonlinear effects such as quantile treatment effects, the approach is aptly called Universal Difference-in-differences (UDiD). Both fully parametric and more robust semiparametric UDiD estimators are described and illustrated in a real-world application concerning the causal effects of a Zika virus outbreak on birth rate in Brazil.