The impact of dosimetry uncertainties on dose-response analyses

Radiation dose estimates used in epidemiological studies are subject to many sources of uncertainty, and the error structure may be a complicated mixture of different types of error. Increasingly, efforts are being made to evaluate dosimetry uncertainties and to take account of them in statistical analyses. The impact of these uncertainties on dose-response analyses depends on the magnitude and type of error. Errors that are independent from subject to subject (random errors) reduce statistical power for detecting a dose-response relationship, increase uncertainties in estimated risk coefficients, and may lead to underestimation of risk coefficients. The specific effects of random errors depend on whether the errors are "classical" or "Berkson." Classical error can be thought of as error that arises from an imprecise measuring device, whereas Berkson error occurs when a single dose is used to represent a group of subjects (with varying true doses). Uncertainties in quantities that are common to some or all subjects are "shared" uncertainties. Such uncertainties increase the possibility of bias, and accounting for this possibility increases the length of confidence intervals. In studies that provide a direct evaluation of risk at low doses and dose rates, dosimetry errors are more likely to mask a true effect than to create a spurious one. In addition, classical errors and shared dosimetry uncertainties increase the potential for bias in estimated risks coefficients, but this potential may already be large due to the extreme vulnerability to confounding in studies involving very small relative risk.