A sensitivity analysis to separate bias due to confounding from bias due to predicting misclassification by a variable that does both.
Variables that predict misclassification of exposure, outcome, or a confounder cannot be controlled by techniques that adjust for predictors of risk. They must be controlled by external adjustments. We confronted an analysis in which a variable predicted misclassification of the exposure and of a confounder. The same variable confounded the exposure-outcome relation. The analysis focused on the relation between less-than-definitive therapy and breast cancer mortality in the 5 years after diagnosis. Receipt of less-than-definitive prognostic evaluation predicted misclassification of definitive therapy (the exposure) and stage (a confounder). Prognostic evaluation also confounded the therapy-breast cancer mortality relation. We used a sensitivity analysis to separate the misclassification biases from the confounding bias. The relative hazard associated with less-than-definitive therapy in the original multivariable model equaled 1.75 (95% confidence interval = 1.02-3.00). The median estimate in 2,500 repetitions of the sensitivity analysis was a relative hazard of 1.64, and 90% of the estimates fell between 1.47 and 1.83. The sensitivity analysis suggests that less-than-definitive therapy confers an excess relative hazard of breast cancer mortality in the 5 years after diagnosis. The original analysis, which adjusted for confounding by prognostic evaluation but not its misclassification biases, overestimated the relative hazard.
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Department of Epidemiology and Biostatistics, Boston University School of Public Health, MA, USA.
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D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015982:Bias; D001943:Breast Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D002965:Classification; D015986:Confounding Factors, Epidemiologic; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012237:Rhode Island / Q000453:epidemiology; D012680:Sensitivity and Specificity; D016019:Survival Analysis