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UBC Theses and Dissertations

Time-varying exposure subject to misclassification : bias characterization and adjustment Cormier, Eric


Measurement error occurs frequently in observational studies investigating the relationship between exposure variables and a clinical outcome. Error-prone observations on the explanatory variable may lead to biased estimation and loss of power in detecting the impact of an exposure variable. When the exposure variable is time-varying, the impact of misclassification is complicated and significant. This increases uncertainty in assessing the consequences of ignoring measurement error associated with observed data, and brings difficulties to adjustment for misclassification. In this study we considered situations in which the exposure is time-varying and nondifferential misclassification occurs independently over time. We determined how misclassification biases the exposure outcome relationship through probabilistic arguments and then characterized the effect of misclassification as the model parameters vary. We show that misclassification of time-varying exposure measurements has a complicated effect when estimating the exposure-disease relationship. In particular the bias toward the null seen in the static case is not observed. After misclassification had been characterized we developed a means to adjust for misclassification by recreating, with greatest likelihood, the exposure path of each subject. Our adjustment uses hidden Markov chain theory to quickly and efficiently reduce the number of misclassified states and reduce the effect of misclassification on estimating the disease-exposure relationship. The method we propose makes use of only the observed misclassified exposure data and no validation data needs to be obtained. This is achieved by estimated switching probabilities and misclassification probabilities from the observed data. When these estimates are obtained the effect of misclassification can be determined through the characterization of the effect of misclassification presented previously. We can also directly adjust for misclassification by recreating the most likely exposure path using the Viterbi algorithm. The methods developed in this dissertation allow the effect of misclassification, on estimating the exposure-disease relationship, to be determined. It accounts for misclassification by reducing the number of misclassified states and allows the exposure-disease relationship to be estimated significantly more accurately. It does this without the use of validation data and is easy to implement in existing statistical software.

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