INSERM U1219 (Biostatistic), Université Bordeaux Segalen, Bordeaux, France.
Graduate Institute of Statistics, National Central University, Taoyuan, Taiwan.
Stat Med. 2019 Jul 20;38(16):2928-2942. doi: 10.1002/sim.8162. Epub 2019 Apr 17.
A surrogate endpoint can be used instead of the most relevant clinical endpoint to assess the efficiency of a new treatment. Before being used, a surrogate endpoint must be validated based on appropriate methods. Numerous validation approaches have been proposed with the most popular used in a context of meta-analysis, based on a two-step analysis strategy. For two failure-time endpoints, two association measurements are usually used, Kendall's τ at the individual level and the adjusted coefficient of determination ( ) at the trial level. However, is not always available due to model estimation constraints. We propose a one-step validation approach based on a joint frailty model, including both individual-level and trial-level random effects. Parameters have been estimated using a semiparametric penalized marginal log-likelihood method, and various numerical integration approaches were considered. Both individual- and trial-level surrogacy were evaluated using a new definition of Kendall's τ and the coefficient of determination. Estimators' performances were evaluated using simulation studies and satisfactory results were found. The model was applied to individual patient data meta-analyses in gastric cancer to assess disease-free survival as a surrogate for overall survival, as part of the evaluation of adjuvant therapy.
替代终点可用于替代最相关的临床终点，以评估新治疗方法的疗效。在使用替代终点之前，必须基于适当的方法对其进行验证。已经提出了许多验证方法，其中最流行的方法是在荟萃分析的背景下使用，基于两步分析策略。对于两个失效时间终点，通常使用两种关联测量，个体水平的 Kendall's τ 和试验水平的调整决定系数（ ）。然而，由于模型估计的限制， 并不总是可用的。我们提出了一种基于联合脆弱性模型的一步验证方法，该模型包括个体水平和试验水平的随机效应。使用半参数惩罚边际对数似然方法估计参数，并考虑了各种数值积分方法。使用 Kendall's τ 和决定系数的新定义评估个体和试验水平的替代情况。通过模拟研究评估了估计器的性能，结果令人满意。该模型应用于胃癌的个体患者数据荟萃分析，以无病生存率作为总生存率的替代指标，作为辅助治疗评估的一部分。
