Das Snigdha, Chae Minwoo, Pati Debdeep, Bandyopadhyay Dipankar
Department of Statistics, Texas A&M University, College Station, Texas, 77843, United States.
Department of Industrial and Management Engineering, Pohang University of Science & Technology, Pohang, 37673, South Korea.
Biometrics. 2025 Jul 3;81(3). doi: 10.1093/biomtc/ujaf105.
Assessment of multistate disease progression is commonplace in biomedical research, such as in periodontal disease (PD). However, the presence of multistate current status endpoints, where only a single snapshot of each subject's progression through disease states is available at a random inspection time after a known starting state, complicates the inferential framework. In addition, these endpoints can be clustered, and spatially associated, where a group of proximally located teeth (within subjects) may experience similar PD status, compared to those distally located. Motivated by a clinical study recording PD progression, we propose a Bayesian semiparametric accelerated failure time model with an inverse-Wishart proposal for accommodating (spatial) random effects, and flexible errors that follow a Dirichlet process mixture of Gaussians. For clinical interpretability, the systematic component of the event times is modeled using a monotone single index model, with the (unknown) link function estimated via a novel integrated basis expansion and basis coefficients endowed with constrained Gaussian process priors. In addition to establishing parameter identifiability, we present scalable computing via a combination of elliptical slice sampling, fast circulant embedding techniques, and smoothing of hard constraints, leading to straightforward estimation of parameters, and state occupation and transition probabilities. Using synthetic data, we study the finite sample properties of our Bayesian estimates and their performance under model misspecification. We also illustrate our method via application to the real clinical PD dataset.
多状态疾病进展评估在生物医学研究中很常见,例如在牙周病(PD)研究中。然而,多状态当前状态终点的存在使推理框架变得复杂,在已知起始状态后的随机检查时间,每个受试者通过疾病状态的进展只有一个快照。此外,这些终点可能会聚类且在空间上相关,与远端牙齿相比,一组近端牙齿(在受试者体内)可能会经历相似的牙周病状态。受一项记录牙周病进展的临床研究的启发,我们提出了一种贝叶斯半参数加速失效时间模型,该模型采用逆 Wishart 提议来适应(空间)随机效应,以及遵循高斯狄利克雷过程混合的灵活误差。为了便于临床解释,事件时间的系统成分使用单调单指标模型进行建模,通过新颖的积分基展开估计(未知的)链接函数,并赋予基系数受约束的高斯过程先验。除了建立参数可识别性之外,我们还通过椭圆切片采样、快速循环嵌入技术和硬约束平滑的组合,提出了可扩展计算方法,从而能够直接估计参数、状态占据和转移概率。我们使用合成数据研究了贝叶斯估计的有限样本性质及其在模型误设下的性能。我们还通过将我们的方法应用于实际临床牙周病数据集来说明该方法。