Radiation Epidemiology Branch, National Cancer Institute, 9609 Medical Center Drive, Bethesda, MD, 20892-9778, USA.
Office of Radiation and Indoor Air, Environmental Protection Agency, 1200 Pennsylvania Avenue, Washington, DC 20460, USA.
Radiat Environ Biophys. 2021 Aug;60(3):485-491. doi: 10.1007/s00411-021-00921-x. Epub 2021 Jul 4.
Epidemiological studies of cancer rates associated with external and internal exposure to ionizing radiation have been subject to extensive reviews by various scientific bodies. It has long been assumed that radiation-induced cancer risks at low doses or low-dose rates are lower (per unit dose) than those at higher doses and dose rates. Based on a mixture of experimental and epidemiologic evidence the International Commission on Radiological Protection recommended the use of a dose and dose-rate effectiveness factor for purposes of radiological protection to reduce solid cancer risks obtained from moderate-to-high acute dose studies (e.g. those derived from the Japanese atomic bomb survivors) when applied to low dose or low-dose rate exposures. In the last few years there have been a number of attempts at assessing the effect of extrapolation of dose rate via direct comparison of observed risks in low-dose rate occupational studies and appropriately age/sex-adjusted analyses of the Japanese atomic bomb survivors. The usual approach is to consider the ratio of the excess relative risks in the two studies, a measure of the inverse of the dose rate effectiveness factor. This can be estimated using standard meta-analysis with inverse weighting of ratios of relative risks using variances derived via the delta method. In this paper certain potential statistical problems in the ratio of estimated excess relative risks for low-dose rate studies to the excess relative risk in the Japanese atomic bomb survivors are discussed, specifically the absence of a well-defined mean and the theoretically unbounded variance of this ratio. A slightly different method of meta-analysis for estimating uncertainties of these ratios is proposed, motivated by Fieller's theorem, which leads to slightly different central estimates and confidence intervals for the dose rate effectiveness factor. However, given the uncertainties in the data, the differences in mean values and uncertainties from the dose rate effectiveness factor estimated using delta-method-based meta-analysis are not substantial, generally less than 70%.
有关电离辐射内外暴露与癌症发病率的流行病学研究已被多个科学机构进行了广泛审查。长期以来，人们一直认为低剂量或低剂量率辐射引起的癌症风险（每单位剂量）低于高剂量和高剂量率。基于实验和流行病学证据的混合，国际辐射防护委员会建议使用剂量和剂量率效应因子，用于放射防护，以降低从中等到高急性剂量研究（例如，来自日本原子弹幸存者）获得的固体癌症风险，当应用于低剂量或低剂量率暴露时。在过去几年中，已经有许多尝试通过直接比较低剂量率职业研究中观察到的风险和对日本原子弹幸存者进行适当年龄/性别调整的分析，评估剂量率外推的效果。通常的方法是考虑两项研究中过量相对风险的比值，这是剂量率效应因子的倒数的度量。这可以使用标准荟萃分析来估计，使用方差通过 delta 方法得出的相对风险比的倒数进行逆加权。本文讨论了低剂量率研究中估计的过量相对风险与日本原子弹幸存者中过量相对风险的比值的某些潜在统计问题，特别是该比值的平均值未明确定义和理论上无界方差。提出了一种稍微不同的荟萃分析方法来估计这些比值的不确定性，这是受 Fieller 定理的启发，该定理导致剂量率效应因子的中心估计值和置信区间略有不同。然而，考虑到数据的不确定性，基于 delta 方法的荟萃分析估计的剂量率效应因子的平均值和不确定性的差异并不显著，通常小于 70%。
