Outcome Assessment in Epidemiological Studies of Low-Dose Radiation Exposure and Cancer Risks: Sources, Level of Ascertainment, and Misclassification.

Abstract

Outcome assessment problems and errors that could lead to biased risk estimates in low-dose radiation epidemiological studies of cancer risks have not been systematically evaluated. Incidence or mortality risks for all cancers or all solid cancers combined and for leukemia were examined in 26 studies published in 2006-2017 involving low-dose (mean dose ≤100 mGy) radiation from environmental, medical, or occupational sources. We evaluated the impact of loss to follow-up, under- or overascertainment, outcome misclassification, and changing classifications occurring similarly or differentially across radiation dose levels. Loss to follow-up was not reported in 62% of studies, but when reported it was generally small. Only one study critically evaluated the completeness of the sources of vital status. Underascertainment of cancers ("false negatives") was a potential shortcoming for cohorts that could not be linked with high-quality population-based registries, particularly during early years of exposure in five studies, in two lacking complete residential history, and in one with substantial emigration. False positives may have occurred as a result of cancer ascertainment from self- or next-of-kin report in three studies or from enhanced medical surveillance of exposed patients that could lead to detection bias (eg, reporting precancer lesions as physician-diagnosed cancer) in one study. Most pediatric but few adult leukemia studies used expert hematopathology review or current classifications. Only a few studies recoded solid cancers to the latest International Classification of Diseases or International Classification of Diseases for Oncology codes. These outcome assessment shortcomings were generally nondifferential in relation to radiation exposure level except possibly in four studies. The majority of studies lacked information to enable comprehensive evaluation of all major sources of outcome assessment errors, although reported data suggested that the outcome assessment limitations generally had little effect on risk or biased estimates towards the null except possibly in four studies.