All models may be wrong---but that is not necessarily a problem for inference. Consider the standard $t$-test for the significance of a variable $X$ for predicting response $Y$ whilst controlling for $p$ other covariates $Z$ in a random design linear model. This yields correct asymptotic type~I error control for the null hypothesis that $X$ is conditionally independent of $Y$ given $Z$ under an \emph{arbitrary} regression model of $Y$ on $(X,Z)$, provided that a linear regression model for $X$ on $Z$ holds. An analogous robustness to misspecification, which we term the ``double-estimation-friendly'' (DEF) property, also holds for Wald tests in generalised linear models, with some small modifications.

In this expository paper we explore this phenomenon, and propose methodology for high-dimensional regression settings that respects the DEF property. We advocate specifying (sparse) generalised linear regression models for both $Y$ and the covariate of interest $X$; our framework gives valid inference for the conditional independence null if either of these hold. In the special case where both specifications are linear, our proposal amounts to a small modification of the popular debiased Lasso test. We also investigate constructing confidence intervals for the regression coefficient of $X$ via inverting our tests; these have coverage guarantees even in partially linear models where the contribution of $Z$ to $Y$ can be arbitrary. Numerical experiments demonstrate the effectiveness of the methodology.