A simulation-based assessment of the ability to detect thresholds in chronic risk concentration-response functions in the presence of exposure measurement error.

An important question when setting appropriate air quality standards for fine particulate matter (PM2.5) is whether there exists a "threshold" in the concentration-response (C-R) function, such that PM2.5 levels below this threshold are not expected to produce adverse health effects. We hypothesize that measurement error may affect the recognition of a threshold in long-term cohort epidemiological studies. This study conducts what is, to the best of our knowledge, the first simulation of the effects of measurement error on the statistical models commonly employed in long-term cohort studies. We test the degree to which classical-type measurement error, such as differences between the true population-weighted exposure level to a pollutant and the observed measures of that pollutant, affects the ability to statistically detect a C-R threshold. The results demonstrate that measurement error can obscure the existence of a threshold in a cohort study's C-R function for health risks from chronic exposures. With increased measurement error the ability to statistically detect a C-R threshold decreases, and both the estimated location of the C-R threshold and the estimated hazard ratio associated with PM2.5 are attenuated. This result has clear implications for determining appropriate air quality standards for pollutants.

Integrated Uncertainty Analysis for Ambient Pollutant Health Risk Assessment: A Case Study of Ozone Mortality Risk.

The U.S. Environmental Protection Agency (EPA) uses health risk assessment to help inform its decisions in setting national ambient air quality standards (NAAQS). EPA's standard approach is to make epidemiologically-based risk estimates based on a single statistical model selected from the scientific literature, called the "core" model. The uncertainty presented for "core" risk estimates reflects only the statistical uncertainty associated with that one model's concentration-response function parameter estimate(s). However, epidemiologically-based risk estimates are also subject to "model uncertainty," which is a lack of knowledge about which of many plausible model specifications and data sets best reflects the true relationship between health and ambient pollutant concentrations. In 2002, a National Academies of Sciences (NAS) committee recommended that model uncertainty be integrated into EPA's standard risk analysis approach. This article discusses how model uncertainty can be taken into account with an integrated uncertainty analysis (IUA) of health risk estimates. It provides an illustrative numerical example based on risk of premature death from respiratory mortality due to long-term exposures to ambient ozone, which is a health risk considered in the 2015 ozone NAAQS decision. This example demonstrates that use of IUA to quantitatively incorporate key model uncertainties into risk estimates produces a substantially altered understanding of the potential public health gain of a NAAQS policy decision, and that IUA can also produce more helpful insights to guide that decision, such as evidence of decreasing incremental health gains from progressive tightening of a NAAQS.