Methods for estimating the exposure–response curve to inform the new safety standards for fine particulate matter

Exposure to fine particulate matter (PM_2.5) poses significant health risks and accurately determining the shape of the relationship between PM_2.5 and health outcomes has crucial policy implications. Although various statistical methods exist to estimate this exposure-response curve (ERC), few studies have compared their performance under plausible data-generating scenarios. This study compares seven commonly used ERC estimators across 72 exposure-response and confounding scenarios via simulation. Additionally, we apply these methods to estimate the ERC between long-term PM_2.5 exposure and all-cause mortality using data from over 68 million Medicare beneficiaries in the United States. Our simulation indicates that regression methods not placed within a causal inference framework are unsuitable when anticipating heterogeneous exposure effects. Under the setting of a large sample size and unknown ERC functional form, we recommend utilizing causal inference methods that allow for nonlinear ERCs. In our data application, we observe a nonlinear relationship between annual average PM_2.5 and all-cause mortality in the Medicare population, with a sharp increase in relative mortality at low PM_2.5 concentrations. Our findings suggest that stricter limits on PM_2.5 could avert numerous premature deaths. To facilitate the utilization of our results, we provide publicly available, reproducible code on Github for every step of the analysis.