Estimating Counterfactual Risk Under Hypothetical Interventions in the Presence of Competing Events: Crystalline Silica Exposure and Mortality From two Causes of Death

Abstract

Exposure to silica has been linked to excess risk of lung cancer and non-malignant respiratory disease mortality. In this study we estimated risk for both these outcomes in relation to occupational silica exposure as well as the reduction in risk that would result from hypothetical interventions on exposure in a cohort of exposed workers. Analyses were carried out in an all-male study population consisting of 2342 California diatomaceous earth workers regularly exposed to crystalline silica, followed between 1942 and 2011. We estimated subdistribution risk for each event under the natural course and interventions of interest using the parametric g-formula to adjust for healthy worker survivor bias. The risk ratio for lung cancer mortality comparing an intervention in which a theoretical maximum exposure limit was set at 0.05 mg/m³ (the current U.S. regulatory limit) to the observed exposure concentrations was 0.86 (95% confidence interval: 0.63, 1.22). The corresponding risk ratio for non-malignant respiratory disease mortality was 0.69 (95% confidence interval: 0.52, 0.93). Our findings suggest that risks from both outcomes would have been considerably lower if historical silica exposures in this cohort had not exceeded current regulatory limits.