Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Department of Public Health Sciences, Canadian Cancer Trials Group, Queen's University, Kingston, ON, Canada.
Value Health. 2022 Jul;25(7):1157-1164. doi: 10.1016/j.jval.2021.12.004. Epub 2022 Jan 29.
The development of novel cancer therapies, including immuno-oncology agents, has increased interest in reconstructed individual patient data (IPD) based restricted mean survival time (RMST) analyses. Additionally, reconstructed IPD-based RMST is recommended in cost-effectiveness analyses when original trial IPD are not available. Nevertheless, recently concerns regarding potential bias of reconstructed-IPD RMST have been presented, because reconstructed-IPD RMSTs have not been validated and previous validation endpoints may not capture the entire Kaplan-Meier (KM) curve, especially the "tail." Our study aims to validate the recommended method of IPD reconstruction by comparing reconstructed IPD- and original trial IPD-based RMST.
Canadian Cancer Trials Group trials from 1990 to 2017 were included. Overall survival and progression-free survival IPD were reconstructed based on published KM curves using the Guyot method. Analysts were blinded to original trial IPD. RMST was calculated at 1 year and over the entire KM curve. Reconstructed-IPD and original trial-IPD (gold-standard) RMSTs were compared for accuracy and predictive error via mean deviation, mean absolute error (MAE), mean percentage bias, and Bland-Altman plots and across KM curve quality (vector traced or bitmapped).
We identified 39 trials. The mean deviation, MAE, and mean percentage bias of RMST between the reconstructed IPD and original trial IPD were small. In particular, the mean deviation was -0.01 months and -0.04 months, MAE was 0.19 months and 0.24 months, and mean percentage bias was 0.82% and 0.84% in overall survival KM curves in control and experimental arms, respectively. Accuracy was generally not associated with KM curve quality.
RMST derived from reconstructed IPD displayed excellent accuracy and predictive error compared with the gold standard. Reconstructed IPD could be used to calculate RMST in lieu of original trial IPD, to facilitate decision making for clinicians, researchers, and policy makers.
新型癌症疗法的发展，包括免疫肿瘤学药物，增加了对基于重建个体患者数据（IPD）的受限平均生存时间（RMST）分析的兴趣。此外，当原始试验 IPD 不可用时，建议在成本效益分析中使用基于重建 IPD 的 RMST。然而，最近人们对重建 IPD-RMST 可能存在的偏差表示担忧，因为重建 IPD-RMST 尚未得到验证，并且之前的验证终点可能无法捕获整个 Kaplan-Meier（KM）曲线，尤其是“尾部”。我们的研究旨在通过比较基于重建 IPD 和原始试验 IPD 的 RMST，验证 IPD 重建的推荐方法。
纳入了 1990 年至 2017 年期间的加拿大癌症试验组试验。使用 Guyot 方法，根据已发表的 KM 曲线，重建总生存和无进展生存 IPD。分析人员对原始试验 IPD 不知情。计算了 1 年和整个 KM 曲线的 RMST。比较了重建 IPD 和原始试验 IPD（金标准）RMST 的准确性和预测误差，通过均方误差、平均绝对误差（MAE）、平均百分比偏差以及 Bland-Altman 图，以及整个 KM 曲线质量（矢量追踪或位图）。
我们确定了 39 项试验。RMST 之间的重建 IPD 和原始试验 IPD 的均方误差、MAE 和平均百分比偏差均较小。特别是，在对照组和实验组的总生存 KM 曲线中，均方误差分别为-0.01 个月和-0.04 个月，MAE 分别为 0.19 个月和 0.24 个月，平均百分比偏差分别为 0.82%和 0.84%。准确性通常与 KM 曲线质量无关。
与金标准相比，重建 IPD 得出的 RMST 具有出色的准确性和预测误差。可以使用重建 IPD 来计算 RMST，以替代原始试验 IPD，为临床医生、研究人员和决策者提供决策依据。
