RERF Report No. 2-17

A research paper published in Radiation and Environmental Biophysics“Effect of follow-up period on minimal-significant dose in the atomic-bomb survivorstudies”
John Cologne, Dale L Preston, Eric J Grant, Harry M Cullings, Kotaro Ozasa
Radiat Environ Biophys 2018 (March); 57(1):83-8(doi: 10.1007/s00411-017-0720-7)
Study Findings
This study demonstrated that longer follow-up of the Life Span Study (LSS) cohort of atomicbomb survivors provides more reliable estimates of radiation risk. In particular, we refuted a counterintuitive claim recently made by others that earlier RERF reports based on the LSS cohort mightprovide estimates of the risk of radiation at low doses that are better than risk estimates provided in
more recent RERF reports.
Explanation
To obtain estimates of radiation risk that are accurate (unbiased) and precise (estimated with ahigh level of confidence) requires that we be able to estimate well the parameters of statistical models
for the background rates of disease or death (according to attained age, birth cohort, sex, etc.) andmodification of risk by attained age and age at exposure. Continued follow-up of the LSS cohort ofatomic bomb survivors is therefore deemed to be important because it is expected that longer followup—and the resulting accumulation of data—should permit more precise estimation of theseparameters and therefore allow us to obtain better estimates of radiation risk.
1. Study purpose
The notion that longer follow-up should lead to better estimates of radiation risk was challenged
by two researchers in an article published last year in the same journal. We suspected that theanalytical method used by those authors might be flawed, because it ignored the most recent
information about the background-rate and effect-modification parameters that are needed toaccurately and precisely estimate radiation risk. We therefore undertook an analysis to ascertain how
risk estimates depend on length of follow-up by using a method not suffering from this shortcoming.
2. Study methods
We analyzed solid cancer incidence and mortality in the LSS cohort using the most recent datafrom LSS mortality report 14, published in 2014, and the third LSS solid cancer incidence report,
published earlier this year. Complete follow-up data were used to estimate background-rate and effectmodification parameters, but the radiation dose response (the excess relative risk, or ERR*) was
estimated separately for each of the follow-up periods employed in previous mortality and incidence
reports. We also estimated the ERR over shorter and shorter intervals of dose from zero up to prespecified cutpoints and estimated likelihood-based confidence intervals for those dose ranges. By
doing so, we could ascertain the lowest dose level below which estimated ERR is not consistentlysignificant statistically (what we call “minimal-significant dose”).
*excess relative risk is the relative risk minus 1; it reflects the mortality or incidence that can be
attributed to the radiation exposure (as a proportion times the background rate)
3. Study results
The minimal-significant dose tended to be lower with longer follow-up. In other words, longer
follow-up permits substantiation of a significant radiation effect at progressively lower dose levels.
Furthermore, attained age and age at exposure were shown to be highly correlated in the earlier
follow-up periods, so effect modification by these two factors could not be estimated precisely inearlier periods due to their collinearity (lack of independent information about each factor).

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RERF Report No. 2-17

Study SignificanceOur results underscore the need for continued follow-up of the LSS cohort.
The Radiation Effects Research Foundation has studied A-bomb survivors and their offspring in Hiroshima
and Nagasaki for around 70 years. RERF’s research achievements are considered the principal scientific basis
for radiation risk assessment by the United Nations Scientific Committee on the Effects of Atomic Radiation(UNSCEAR) and for recommendations regarding radiation protection standards by the International
Commission on Radiological Protection (ICRP). RERF expresses its profound gratitude to the A-bomb survivors
and survivors’ offspring for their cooperation in our studies.
§Radiation and Environmental Biophysics, is a quarterly peer-reviewed scientific journal, first published in1974, covering research in biophysics and radiation biology. (Impact factor in 2016/2017: 2.398)

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