Synthesis estimators for positivity violations with a continuous covariate

Research intended to estimate the effect of an action, like in randomized trials, often do not have random samples of the intended target population. Instead, estimates can be transported to the desired target population. Methods for transporting between populations are often premised on a positivity assumption, such that all relevant covariate patterns in one population are also present in the other. However, eligibility criteria, particularly in the case of trials, can result in violations of positivity. To address nonpositivity, a synthesis of statistical and mechanistic models was previously proposed in the context of violations by a single binary covariate. Here, we extend the synthesis approach for positivity violations with a continuous covariate. For estimation, two novel augmented inverse probability weighting estimators are proposed, with one based on estimating the parameters of a marginal structural model and the other based on estimating the conditional average causal effect. Both estimators are compared to other common approaches to address nonpositivity via a simulation study. Finally, the competing approaches are illustrated with an example in the context of two-drug versus one-drug antiretroviral therapy on CD4 T cell counts among women with HIV.