Abstrak: Outcome misclassification is widespread in epidemiology, but methods to account for it are rarely used. We describe the use of multiple imputation to reduce bias when validation data are available for a subgroup of study participants. This approach is illustrated using data from 308 participants in the multicenter Herpetic Eye Disease Study between 1992 and 1998 (48% female; 85% white; median age, 49 years). The odds ratio comparing the acyclovir group with the placebo group on the gold-standard outcome (physician-diagnosed herpes simplex virus recurrence) was 0.62 (95% confidence interval (CI): 0.35, 1.09). We masked ourselves to physician diagnosis except for a 30% validation subgroup used to compare methods. Multiple imputation (odds ratio (OR) = 0.60; 95% CI: 0.24, 1.51) was compared with naive analysis using self-reported outcomes (OR = 0.90; 95% CI: 0.47, 1.73), analysis restricted to the validation subgroup (OR = 0.57; 95% CI: 0.20, 1.59), and direct maximum likelihood (OR = 0.62; 95% CI: 0.26, 1.53). In simulations, multiple imputation and direct maximum likelihood had greater statistical power than did analysis restricted to the validation subgroup, yet all 3 provided unbiased estimates of the odds ratio. The multiple-imputation approach was extended to estimate risk ratios using log-binomial regression. Multiple imputation has advantages regarding flexibility and ease of implementation for epidemiologists familiar with missing data methods.

Abstrak: We employed the parametric G formula to analyze lung cancer mortality in a cohort of textile manufacturing workers who were occupationally exposed to asbestos in South Carolina. A total of 3,002 adults with a median age of 24 years at enrollment (58% male, 81% Caucasian) were followed for 117,471 person-years between 1940 and 2001, and 195 lung cancer deaths were observed. Chrysotile asbestos exposure was measured in fiber-years per milliliter of air, and annual occupational exposures were estimated on the basis of detailed work histories. Sixteen percent of person-years involved exposure to asbestos, with a median exposure of 3.30 fiber-years/mL among those exposed. Lung cancer mortality by age 90 years under the observed asbestos exposure was 9.44%. In comparison with observed asbestos exposure, if the facility had operated under the current Occupational Safety and Health Administration asbestos exposure standard of < 0.1 fibers/mL, we estimate that the cohort would have experienced 24% less lung cancer mortality by age 90 years (mortality ratio = 0.76, 95% confidence interval: 0.62, 0.94). A further reduction in asbestos exposure to a standard of < 0.05 fibers/mL was estimated to have resulted in a minimal additional reduction in lung cancer mortality by age 90 years (mortality ratio = 0.75, 95% confidence interval: 0.61, 0.92).