ERRORS IN EXPOSURE ASSESSMENT, STATISTICAL POWER AND THE INTERPRETATION OF RESIDENTIAL RADON STUDIES

To date, epidemiological studies of risk from residential radon have n ot convincingly demonstrated an association with lung cancer. These ca se-control studies, however, have inherent limitations due to errors i n estimates of exposure to indoor radon. These errors take on special significance because the level of residential risk predicted from stud ies of underground miners is relatively low and possibly at the limit detectable by current epidemiological methods. To illustrate the probl em caused by errors in exposure assessment, a series of case-control s tudies were simulated and resulting dose-response relationships evalua ted. For each of four assumed error distributions for exposure to rado n progeny, 10 indoor radon studies of 700 cases and 700 controls were generated randomly from a population with a risk of radon-induced lung cancer based on extrapolations from studies of underground miners. Wh en exposures were assumed as known without error, 6 of 10 studies fail ed to find a significant dose response, in accord with the theoretical power of the study of 0.47. For simulations in which exposures were m easured with error, the situation was worse, as the power of the study was reduced further and it was even less likely that a single study w ould result in a significant finding. For each error scenario, combini ng data from the 10 simulated studies did result in a significant dose response, However, the pooled results are somewhat misleading, becaus e the effects of mobility, missing radon measurements, residential occ upancy and potential confounding variables such as cigarette smoking w ere not taken into account. Empirical estimates of power were computed using 1,000 simulated case-control studies. When mobility and missing radon measurements in prior homes were incorporated into the design, the power of the study decreased, reducing the chance of detecting a s ignificant effect of exposure. Enlarging study size to 2,000 cases and 2,000 controls increased the power of the study to 0.90 when exposure error was absent and subjects lived in one home only, but power was b elow 0.40 under realistic conditions for exposure error and mobility. When studies were generated under an assumption that exposure does not increase risk, up to 15% of simulated studies with 700 cases and 700 controls resulted in an estimated dose-response parameter in excess of the dose response from studies of miners. With increasing mobility an d exposure error, it became virtually impossible to distinguish betwee n the distributions of risk estimates from simulated studies based on an underlying excess relative risk of 0.015/working level month from e stimates based on no risk from exposure. This exercise reveals the sub stantial contribution that errors in exposure assessment and incomplet e measurements must play in explaining the inconsistency of current re sidential radon studies and highlights the intrinsic difficulty with s uch studies. Further, these simulations imply that it is unlikely that case-control studies alone will be able to determine precise estimate s of risk from indoor radon, and that even future efforts at pooling e pidemiological studies may not adequately address issues of risk from residential radon exposure. (C) 1995 by Radiation Research Society