Abstract：
In radiation risk estimation based on the Radiation Effects Research Foundation (RERF) cohort studies, one common analysis is Poisson regression on radiation dose and background and effect modifying variables of an aggregate endpoint such as all solid cancer incidence or all non-cancer mortality. As currently performed, these analyses require selection of a surrogate radiation organ dose, (e.g., colon dose), which could conceptually be problematic since the aggregate endpoint comprises events arising from a variety of organs. We use maximum likelihood theory to compare inference from the usual aggregate endpoint analysis to analyses based on joint analysis. These two approaches are also compared in a re-analysis of RERF Life Span Study all cancer mortality. We show that, except for a trivial difference, these two analytic approaches yield identical inference with respect to radiation dose response and background and effect modification when based on a single surrogate organ radiation dose. When repeating the analysis with organ-specific doses, an interesting issue of bias in intercept parameters arises when dose estimates are undefined for one sex when sex-specific outcomes are included in the aggregate endpoint, but a simple correction will avoid this issue. Lastly, while the joint analysis formulation allows use of organ-specific doses, the interpretation of such an analysis for inference regarding an aggregate endpoint can be problematic. To the extent that analysis of radiation risk for an aggregate endpoint is of interest, the joint-analysis formulation with a single surrogate dose is an appropriate analytic approach, whereas joint analysis with organ-specific doses may only be interpretable if endpoints are considered separately for estimating dose response. However, for neither approach is inference about dose response well defined.
摘要：
在基于辐射效应研究基金会(RERF)队列研究的辐射风险估计中，一种常见的分析是对辐射剂量和背景的泊松回归,以及总终点的影响修正变量,如所有实体癌发病率或所有非癌症死亡率.正如目前所执行的，这些分析需要选择替代放射器官剂量，(例如，结肠剂量)，这在概念上可能是有问题的，因为聚合终点包括由各种器官引起的事件。我们使用最大似然理论将通常的聚合终点分析与基于联合分析的分析进行比较。在对所有癌症死亡率的RERF寿命研究的重新分析中也比较了这两种方法。我们证明,除了微不足道的差异，当基于单个替代器官辐射剂量时，这两种分析方法在辐射剂量响应以及背景和效应修改方面产生相同的推断。当用器官特异性剂量重复分析时，当一个性别的剂量估计未定义时，当总终点中包括性别特异性结果时，截距参数中的一个有趣的偏倚问题就会出现，但一个简单的修正将避免这个问题。最后,虽然联合分析配方允许使用器官特异性剂量，对关于聚合终点的推断的这种分析的解释可能是有问题的。在对总体终点的辐射风险分析感兴趣的范围内，单一替代剂量的联合分析配方是一种适当的分析方法，而器官特异性剂量的联合分析只有在单独考虑终点以估计剂量反应时才能解释.然而,因为这两种方法都不是关于剂量反应的推断。
