Huang Xuelin, Yan Fangrong, Ning Jing, Feng Ziding, Choi Sangbum, Cortes Jorge
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, 77230, TX, U.S.A.
Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.
Stat Med. 2016 Jun 15;35(13):2167-82. doi: 10.1002/sim.6860. Epub 2016 Jan 7.
Dynamic prediction uses longitudinal biomarkers for real-time prediction of an individual patient's prognosis. This is critical for patients with an incurable disease such as cancer. Biomarker trajectories are usually not linear, nor even monotone, and vary greatly across individuals. Therefore, it is difficult to fit them with parametric models. With this consideration, we propose an approach for dynamic prediction that does not need to model the biomarker trajectories. Instead, as a trade-off, we assume that the biomarker effects on the risk of disease recurrence are smooth functions over time. This approach turns out to be computationally easier. Simulation studies show that the proposed approach achieves stable estimation of biomarker effects over time, has good predictive performance, and is robust against model misspecification. It is a good compromise between two major approaches, namely, (i) joint modeling of longitudinal and survival data and (ii) landmark analysis. The proposed method is applied to patients with chronic myeloid leukemia. At any time following their treatment with tyrosine kinase inhibitors, longitudinally measured BCR-ABL gene expression levels are used to predict the risk of disease progression. Copyright © 2016 John Wiley & Sons, Ltd.
动态预测使用纵向生物标志物对个体患者的预后进行实时预测。这对于患有诸如癌症等不治之症的患者至关重要。生物标志物轨迹通常不是线性的，甚至也不是单调的，并且个体之间差异很大。因此，用参数模型拟合它们很困难。考虑到这一点，我们提出了一种动态预测方法，该方法无需对生物标志物轨迹进行建模。相反，作为一种权衡，我们假设生物标志物对疾病复发风险的影响是随时间变化的平滑函数。事实证明，这种方法在计算上更简便。模拟研究表明，所提出的方法随着时间推移能够实现对生物标志物效应的稳定估计，具有良好的预测性能，并且对模型误设具有鲁棒性。它是两种主要方法之间的良好折衷，这两种主要方法分别是：（i）纵向数据和生存数据的联合建模，以及（ii）标志性分析。所提出的方法应用于慢性髓性白血病患者。在他们接受酪氨酸激酶抑制剂治疗后的任何时间，纵向测量的BCR-ABL基因表达水平用于预测疾病进展的风险。版权所有© 2016约翰威立父子有限公司。
