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1.  Impact of Uncertainties in Exposure Assessment on Estimates of Thyroid Cancer Risk among Ukrainian Children and Adolescents Exposed from the Chernobyl Accident 
PLoS ONE  2014;9(1):e85723.
The 1986 accident at the Chernobyl nuclear power plant remains the most serious nuclear accident in history, and excess thyroid cancers, particularly among those exposed to releases of iodine-131 remain the best-documented sequelae. Failure to take dose-measurement error into account can lead to bias in assessments of dose-response slope. Although risks in the Ukrainian-US thyroid screening study have been previously evaluated, errors in dose assessments have not been addressed hitherto. Dose-response patterns were examined in a thyroid screening prevalence cohort of 13,127 persons aged <18 at the time of the accident who were resident in the most radioactively contaminated regions of Ukraine. We extended earlier analyses in this cohort by adjusting for dose error in the recently developed TD-10 dosimetry. Three methods of statistical correction, via two types of regression calibration, and Monte Carlo maximum-likelihood, were applied to the doses that can be derived from the ratio of thyroid activity to thyroid mass. The two components that make up this ratio have different types of error, Berkson error for thyroid mass and classical error for thyroid activity. The first regression-calibration method yielded estimates of excess odds ratio of 5.78 Gy−1 (95% CI 1.92, 27.04), about 7% higher than estimates unadjusted for dose error. The second regression-calibration method gave an excess odds ratio of 4.78 Gy−1 (95% CI 1.64, 19.69), about 11% lower than unadjusted analysis. The Monte Carlo maximum-likelihood method produced an excess odds ratio of 4.93 Gy−1 (95% CI 1.67, 19.90), about 8% lower than unadjusted analysis. There are borderline-significant (p = 0.101–0.112) indications of downward curvature in the dose response, allowing for which nearly doubled the low-dose linear coefficient. In conclusion, dose-error adjustment has comparatively modest effects on regression parameters, a consequence of the relatively small errors, of a mixture of Berkson and classical form, associated with thyroid dose assessment.
PMCID: PMC3906013  PMID: 24489667
2.  Methods for Estimation of Radiation Risk in Epidemiological Studies Accounting for Classical and Berkson Errors in Doses 
With a binary response Y, the dose-response model under consideration is logistic in flavor with pr(Y=1 | D) = R (1+R)−1, R = λ0 + EAR D, where λ0 is the baseline incidence rate and EAR is the excess absolute risk per gray. The calculated thyroid dose of a person i is expressed as Dimes=fiQimes/Mimes. Here, Qimes is the measured content of radioiodine in the thyroid gland of person i at time tmes, Mimes is the estimate of the thyroid mass, and fi is the normalizing multiplier. The Qi and Mi are measured with multiplicative errors ViQ and ViM, so that Qimes=QitrViQ (this is classical measurement error model) and Mitr=MimesViM (this is Berkson measurement error model). Here, Qitr is the true content of radioactivity in the thyroid gland, and Mitr is the true value of the thyroid mass. The error in fi is much smaller than the errors in ( Qimes, Mimes) and ignored in the analysis.
By means of Parametric Full Maximum Likelihood and Regression Calibration (under the assumption that the data set of true doses has lognormal distribution), Nonparametric Full Maximum Likelihood, Nonparametric Regression Calibration, and by properly tuned SIMEX method we study the influence of measurement errors in thyroid dose on the estimates of λ0 and EAR. The simulation study is presented based on a real sample from the epidemiological studies. The doses were reconstructed in the framework of the Ukrainian-American project on the investigation of Post-Chernobyl thyroid cancers in Ukraine, and the underlying subpolulation was artificially enlarged in order to increase the statistical power. The true risk parameters were given by the values to earlier epidemiological studies, and then the binary response was simulated according to the dose-response model.
PMCID: PMC3058406  PMID: 21423564
Berkson measurement error; Chornobyl accident; classical measurement error; estimation of radiation risk; full maximum likelihood estimating procedure; regression calibration; SIMEX estimator; uncertainties in thyroid dose

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