Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences Research, Triangle Park, NC, USA.
The Netherlands Organization, Utrechtseweg, Zeist, 3704 HE, The Netherlands.
Risk Anal. 2021 Jan;41(1):56-66. doi: 10.1111/risa.13585. Epub 2020 Oct 16.
To better understand the risk of exposure to food allergens, food challenge studies are designed to slowly increase the dose of an allergen delivered to allergic individuals until an objective reaction occurs. These dose-to-failure studies are used to determine acceptable intake levels and are analyzed using parametric failure time models. Though these models can provide estimates of the survival curve and risk, their parametric form may misrepresent the survival function for doses of interest. Different models that describe the data similarly may produce different dose-to-failure estimates. Motivated by predictive inference, we developed a Bayesian approach to combine survival estimates based on posterior predictive stacking, where the weights are formed to maximize posterior predictive accuracy. The approach defines a model space that is much larger than traditional parametric failure time modeling approaches. In our case, we use the approach to include random effects accounting for frailty components. The methodology is investigated in simulation, and is used to estimate allergic population eliciting doses for multiple food allergens.
为了更好地了解接触食物过敏原的风险,食物挑战研究旨在逐渐增加过敏原的剂量,直到过敏个体出现客观反应。这些剂量失败研究用于确定可接受的摄入量水平,并使用参数失效时间模型进行分析。尽管这些模型可以提供生存曲线和风险的估计,但它们的参数形式可能会对感兴趣的剂量的生存函数产生误导。描述数据的不同模型可能会产生不同的剂量失败估计。受预测推理的启发,我们开发了一种贝叶斯方法,基于后验预测堆叠来组合生存估计,其中权重的形成旨在最大化后验预测准确性。该方法定义了一个比传统参数失效时间建模方法大得多的模型空间。在我们的案例中,我们使用该方法包含随机效应,以考虑脆弱性成分。该方法在模拟中进行了研究,并用于估计多种食物过敏原的过敏人群引发剂量。