Temporal analysis of a dose-response relationship: leukemia mortality in atomic bomb survivors

A data analysis that incorporates time dependencies is demonstrated for the dose response of leukemia mortality in the atomic bomb survivors. The time dependencies are initially left unspecified and the data on leukemia mortality, up to the end of 1978, are used to infer them. Several findings based on T65 revised doses (T65DR) are obtained. First, it is shown that the fits to the data of time-independent L (linear in γ dose)-Q (quadratic in γ dose)-L (linear in nuetron dose, L-L, and Q-L dose-response models are significantly improved by using the corresponding time-dependent dose-response models. Second, it is shown that the increased risk of leukemia mortality due to γ irradiation decreases in time while the increased risk due to neutron exposure decreases more slowly, if at all, in time. Consequently, relative biological effectiveness (RBE) of neutrons is shown to increase in time and the current definition of RBE as a time-dependent quantity is therefore challenged. It is demonstrated with time-dependent models that the L-L model has a poor fit to the data for the first 7 years of study, but has an adequate fit for the remaining 21 years. In contrast the Q-L model has an adequate fit for the entire follow-up period