Ambient ozone concentrations and cardiac mortality in Southern California 1983-2000: application of a new marginal structural model approach.

The authors evaluated the association between ambient ozone levels and cardiac mortality in California's South Coast Air Basin during the period 1983-2000 and compared inferences from several types of marginal structural model (MSM) estimators. The authors undertook an ecologic study during the high-ozone seasons among persons over age 55 years. In contrast to conditional regression analysis and MSMs based on G-computation and simple inverse probability-of-treatment weighting (IPTW), an MSM that protected against violation of the experimental treatment assignment (ETA) assumption and considered only those areas that could have experienced both high and low ozone concentrations during 1983-2000 found no consistent evidence that reductions in quarterly 1-hour maximum ozone concentrations from levels above any of the regulatory standards to levels below those standards led to decreases in cardiac mortality; however, it did find evidence of decreases related to a decrease in 8-hour maximum concentrations. The G-computation estimator and simple IPTW estimators were biased because of serious violation of the ETA assumption. These analyses highlight the importance of nonviolation of the ETA assumption for valid inference and the failure of conditional regression to provide marginal estimates in the presence of interactions. Noncausal models also consistently inferred larger associations, which may have been due to bias violation of the ETA assumption on which these models rely.