A new approach to causal inference in mortality studies with a sustained exposure period—application to control of the healthy worker survivor effect

AbstractIn observational cohort mortality studies with prolonged periods of exposure to the agent under study, it is not uncommon for risk factors for death to be determinants of subsequent exposure. For instance, in occupational mortality studies date of termination of employment is both a determinant of future exposure (since terminated individuals receive no further exposure) and an independent risk factor for death (since disabled individuals tend to leave employment). When current risk factor status determines subsequent exposure and is determined by previous exposure, standard analyses that estimate age-specific mortality rates as a function of cumulative exposure may underestimate the true effect of exposure on mortality whether or not one adjusts for the risk factor in the analysis. This observation raises the question, which if any population parameters can be given a causal interpretation in observational mortality studies?In answer, we offer a graphical approach to the identification and computation of causal parameters in mortality studies with sustained exposure periods. This approach is shown to be equivalent to an approach in which the observational study is identified with a hypothetical double-blind randomized trial in which data on each subject's assigned treatment protocol has been erased from the data file. Causal inferences can then be made by comparing mortality as a function of treatment protocol, since, in a double-blind randomized trial missing data on treatment protocol, the association of mortality with treatment protocol can still be estimated.We reanalyze the mortality experience of a cohort of arsenic-exposed copper smelter workers with our method and compare our results with those obtained using standard methods. We find an adverse effect of arsenic exposure on all-cause and lung cancer mortality which standard methods fail to detect