Thyroid cancer following scalp irradiation: a reanalysis accounting for uncertainty in dosimetry |
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Authors: | Schafer D W Lubin J H Ron E Stovall M Carroll R J |
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Institution: | Department of Statistics, Oregon State University, Corvallis 97331-4606, USA. schafer@stat.orst.edu |
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Abstract: | In the 1940s and 1950s, over 20,000 children in Israel were treated for tinea capitis (scalp ringworm) by irradiation to induce epilation. Follow-up studies showed that the radiation exposure was associated with the development of malignant thyroid neoplasms. Despite this clear evidence of an effect, the magnitude of the dose-response relationship is much less clear because of probable errors in individual estimates of dose to the thyroid gland. Such errors have the potential to bias dose-response estimation, a potential that was not widely appreciated at the time of the original analyses. We revisit this issue, describing in detail how errors in dosimetry might occur, and we develop a new dose-response model that takes the uncertainties of the dosimetry into account. Our model for the uncertainty in dosimetry is a complex and new variant of the classical multiplicative Berkson error model, having components of classical multiplicative measurement error as well as missing data. Analysis of the tinea capitis data suggests that measurement error in the dosimetry has only a negligible effect on dose-response estimation and inference as well as on the modifying effect of age at exposure. |
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Keywords: | Berkson measurement error Dose uncertainty Dosimetry Errors-in-variables Likelihood Measurement error Missing data Person-year tables Poisson regression Regression calibration Survival analysis |
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