Design and analysis of studies of the health effects of ozone.

The design and analysis of studies that investigate the effect of exposure to ozone on health outcomes need to define carefully the methods for the assessment of the exposure and to determine precisely which is the outcome of biological relevance. The estimation of sample size for longitudinal studies requires the expected rates of change among the exposed and unexposed, the variance of the outcome, and the correlation of measurements taken within an individual. Methods of analysis whose primary interest is in the combination of cross-sectional studies for the determination of the marginal distribution of the outcome are particularly appropriate for biological processes where the effect of exposure is acute. Conditional models are particularly useful for investigating the effect of changes in exposure on changes in outcome at the individual level. In addition, conditional models incorporate a dampening effect of exposure that may provide a reasonable agreement with several biological mechanisms. The identification of susceptible individuals and the description of the behavior of their outcomes over time may be better accomplished by using the within-individual variance as the outcome of interest. Discrepancies of the within- and between-individual regressions may be suggestive of chronic effects, and methodological research in this area is needed. Studies of the health effects of ozone exposure need to address the incorporation of missing data, measurement error, and the combination of complementary studies.