Duchenne muscular dystrophy (DMD) is a rare X-linked genetic pediatric disease characterized by a lack of functional dystrophin production in the body, resulting in muscle deterioration. Lower body muscle weakness progresses to non-ambulation typically by early teenage years, followed by upper body muscle deterioration and ultimately death by the late twenties. The objective of this study was to enhance the quantitative understanding of DMD disease progression through nonlinear mixed effects modeling of the population mean and variability of the 6-min walk test (6MWT) clinical endpoint. An indirect response model with a latent process was fit to digitized literature data using full Bayesian estimation. The modeling data set consisted of 22 healthy controls and 218 DMD patients from one interventional and four observational trials. The model reasonably described the central tendency and population variability of the 6MWT in healthy subjects and DMD patients. An exploratory categorical covariate analysis indicated that there was no apparent effect of corticosteroid administration on DMD disease progression. The population predicted 6MWT began to rise at 1.32 years of age, plateauing at 654 meters (m) at 17.2 years of age for the healthy population. The DMD trajectory reached a maximum of 411 m at 8.90 years before declining and falling below 1 m at age 18.0. The model has potential to be used as a Bayesian estimation and posterior simulation tool to make informed model-based drug development decisions that incorporate prior knowledge with new data.

中文翻译：

---

Duchenne肌营养不良症6分钟步行测试的潜在过程模型：量化罕见疾病进展的贝叶斯方法。

Duchenne肌营养不良症（DMD）是一种罕见的X连锁遗传性儿科疾病，其特征是体内缺乏功能性肌营养不良蛋白的产生，导致肌肉退化。下半身肌无力通常在十几岁的早期发展为非轻ulation，然后是上半身肌的恶化，最终在二十年代末期死亡。这项研究的目的是通过对人群均值的非线性混合效应建模和6分钟步行测试（6MWT）临床终点的变异性，增强对DMD疾病进展的定量理解。使用完全贝叶斯估计，将具有潜在过程的间接响应模型拟合到数字化文献数据。建模数据集由一项干预和四项观察性试验的22名健康对照和218名DMD患者组成。该模型合理地描述了健康受试者和DMD患者中6MWT的集中趋势和人群变异性。探索性的分类协变量分析表明，皮质类固醇给药对DMD疾病的进展没有明显影响。人口预测6MWT在1.32岁时开始上升，健康人群在17.2岁时达到654米（m）时达到平稳状态。DMD轨迹在8.90年时达到最大411 m，然后在18.0岁时下降并降至1 m以下。该模型有可能用作贝叶斯估计和后验模拟工具，以做出基于先验知识的基于模型的药物开发决策，将先验知识与新数据相结合。探索性的分类协变量分析表明，皮质类固醇给药对DMD疾病的进展没有明显影响。人口预测6MWT在1.32岁时开始上升，健康人群在17.2岁时达到654米（m）时达到平稳状态。DMD轨迹在8.90年时达到最大411 m，然后在18.0岁时下降并降至1 m以下。该模型有可能用作贝叶斯估计和后验仿真工具，以做出基于先验模型的药物开发决策，将先验知识与新数据结合在一起。探索性分类协变量分析表明，皮质类固醇给药对DMD疾病进展没有明显影响。人口预测6MWT在1.32岁时开始上升，健康人群在17.2岁时达到654米（m）时达到平稳状态。DMD轨迹在8.90年时达到最大411 m，然后在18.0岁时下降并降至1 m以下。该模型有可能用作贝叶斯估计和后验模拟工具，以做出基于先验知识的基于模型的药物开发决策，将先验知识与新数据相结合。健康人群的年龄为2岁。DMD轨迹在8.90年时达到最大411 m，然后在18.0岁时下降并降至1 m以下。该模型有可能用作贝叶斯估计和后验仿真工具，以做出基于先验模型的药物开发决策，将先验知识与新数据结合在一起。健康人群的年龄为2岁。DMD轨迹在8.90年时达到最大411 m，然后在18.0岁时下降并降至1 m以下。该模型有可能用作贝叶斯估计和后验仿真工具，以做出基于先验模型的药物开发决策，将先验知识与新数据结合在一起。