Bayesian model of disease progression in GNE myopathy
Bayesian model of disease progression in GNE myopathy
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DOI：
10.1002/sim.8050
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发表时间：
2019-04-15
影响因子：
2
通讯作者：
Carrillo, N.
中科院分区：
文献类型：
--
作者：
Quintana, M.;Shrader, J.;Carrillo, N.
一句话总结：基于前瞻性自然史研究的定量肌肉力量数据，开发了贝叶斯重复测量模型，以确定疾病进展并设计GNE肌病（一种罕见且缓慢进展的肌肉疾病）的临床试验。GNE肌病是一种罕见的肌肉疾病，其特征是骨骼肌缓慢进行性无力和萎缩。为了解决定义GNE肌病的自然史和设计临床试验的重大挑战，我们开发了贝叶斯潜变量重复测量模型来确定疾病进展。该模型是基于纵向定量肌肉力量数据收集的一部分，前瞻性自然史研究。GNE肌病进展模型提供了对疾病进展的理解，否则需要不可行的持续时间的自然史。“疾病年龄”是模型生成的疾病进展指标，与各种临床、功能和患者报告的结局高度相关。通过将治疗效果参数纳入GNE疾病进展模型，我们描述了一种新的GNE肌病疾病修饰分析，与更传统的分析方法相比，该分析显著增加了功效并减少了测试新疗法有效性所需的受试者数量。GNE肌病疾病进展模型和疾病修饰分析可应用于具有前瞻性收集的肌肉力量数据的肌肉疾病，以及各种罕见和缓慢进展的疾病。
One Sentence Summary: A Bayesian repeated measures model based on quantitative muscle strength data from a prospective Natural History Study was developed to determine disease progression and design clinical trials for GNE myopathy, a rare and slowly progressive muscle disease. GNE myopathy is a rare muscle disease characterized by slowly progressive weakness and atrophy of skeletal muscles. To address the significant challenges of defining the natural history and designing clinical trials for GNE myopathy, we developed a Bayesian latent variable repeated measures model to determine disease progression. The model is based on longitudinal quantitative muscle strength data collected as part of a prospective Natural History Study. The GNE Myopathy Progression Model provides an understanding of disease progression that would have otherwise required a natural history of unfeasible duration. "Disease age," the model-generated measure of disease progression, highly correlates with a variety of clinical, functional and patient-reported outcomes. With the incorporation of a treatment effect parameter to the GNE Disease Progression Model, we describe a novel GNE Myopathy Disease Modification Analysis that significantly increases power and reduces the number of subjects required to test the effectiveness of novel therapies when compared to more traditional analysis methods. The GNE Myopathy Disease Progression Model and Disease Modification Analysis can be applied to muscle diseases with prospectively collected muscle strength data, and a variety of rare and slowly progressive diseases.