Paper detail

Bayesian dose-response analysis for epidemiological studies with complex uncertainty in dose estimation

Most conventional risk analysis methods rely on a single best estimate of exposure per person which does not allow for adjustment for exposure-related uncertainty. Here, we propose a Bayesian model averaging method to properly quantify the relationship between radiation dose and disease outcomes by accounting for shared and unshared uncertainty in estimated dose. Our Bayesian risk analysis method utilizes multiple realizations of sets (vectors) of doses generated by a two-dimensional Monte Carlo simulation method that properly separates shared and unshared errors in dose estimation. The exposure model used in this work is taken from a study of the risk of thyroid nodules among a cohort of 2,376 subjects following exposure to fallout resulting from nuclear testing in Kazakhstan. We assessed the performance of our method through an extensive series of simulation tests and comparisons against conventional regression risk analysis methods. We conclude that when estimated doses contain relatively small amounts of uncertainty, the Bayesian method using multiple realizations of possibly true dose vectors gave similar results to the conventional regression-based methods of dose-response analysis. However, when large and complex mixtures of shared and unshared uncertainties are present, the Bayesian method using multiple dose vectors had significantly lower relative bias than conventional regression-based risk analysis methods as well as a markedly increased capability to include the pre-established 'true' risk coefficient within the credible interval of the Bayesian-based risk estimate. An evaluation of the dose-response using our method is presented for an epidemiological study of thyroid disease following radiation exposure.