Renfro Lindsay A, Shang Hongwei, Sargent Daniel J
a Division of Biomedical Statistics and Informatics , Mayo Clinic , Rochester , Minnesota , USA.
J Biopharm Stat. 2015;25(4):857-77. doi: 10.1080/10543406.2014.920870.
Evaluation of surrogate end points using patient-level data from multiple trials is the gold standard, where multi-trial copula models are used to quantify both patient-level and trial-level surrogacy. While limited consideration has been given in the literature to copula choice (e.g., Clayton), no prior consideration has been given to direction of implementation (via survival vs. distribution functions). We demonstrate that even with the "correct" copula family, directional misspecification leads to biased estimates of patient-level and trial-level surrogacy. We illustrate with a simulation study and a reanalysis of disease-free survival as a surrogate for overall survival in early stage colon cancer.
使用来自多个试验的患者层面数据评估替代终点是金标准，其中多试验copula模型用于量化患者层面和试验层面的替代指标。虽然文献中对copula选择（如Clayton）的考虑有限，但尚未对实施方向（通过生存函数与分布函数）进行过预先考虑。我们证明，即使使用“正确”的copula族，方向错误指定也会导致患者层面和试验层面替代指标的估计产生偏差。我们通过模拟研究和对早期结肠癌无病生存作为总生存替代指标的重新分析进行说明。
