Clinical Research Department, Centre Léon Bérard, Lyon, France; UMR CNRS 5558 LBBE, Claude Bernard Lyon 1 University, Villeurbanne, France.
Clinical Research Department, Centre Léon Bérard, Lyon, France.
Eur J Cancer. 2024 Dec;213:115072. doi: 10.1016/j.ejca.2024.115072. Epub 2024 Oct 22.
Demonstration of trial emulation ability to benchmark randomised controlled trials (RCTs) from real-world data (RWD) is required to increase confidence in the use of routinely collected data for decision making in oncology.
To assess the frequency with which emulation findings align with RCTs regarding effect size on overall survival (OS) in metastatic breast cancer (MBC), 8 of 13 pre-selected pivotal RCTs in MBC were emulated using data from 32,598 patients enrolled in the French ESME-MBC cohort between January 1, 2008 and December 31, 2021. Adjustment methods and confounders were selected a priori for each emulation; stabilized weight was the reference method to mitigate confounding. Concordance in OS hazard ratios with associated 95 % confidence intervals between RCTs and emulations were assessed used predefined metrics based on statistical significance, estimates, and standardized differences.
The effect sizes were consistent with RCT results in 7 out of the 8 emulations; 4 emulations achieved full statistical significance agreement; 5 emulations had a point estimate included in the RCT CI (estimate agreement); 6 emulations reported no significant differences between RCT and emulation (standardized difference agreement). Discrepancies related to residual confounders and significant shifts in prescription practices post-drug approval may arise in some cases.
Target trial emulation from RWD combined with appropriate adjustment can provide conclusions similar to RCTs in MBC. In oncology, this methodology offers opportunities for confirming the impact on long-term survival, for expanding indications in patients excluded from RCTs and for comparative effectiveness in single-arm trials using external control arms.
为了提高在肿瘤学中使用常规收集数据进行决策的信心，需要证明从真实世界数据（RWD）中模拟试验的能力，以与随机对照试验（RCT）相匹配。
为了评估在转移性乳腺癌（MBC）中，模拟试验结果在总生存（OS）方面与 RCT 之间的一致性频率，使用了 2008 年 1 月 1 日至 2021 年 12 月 31 日期间纳入法国 ESME-MBC 队列的 32598 名患者的数据，对 13 项预先选择的 MBC 关键 RCT 中的 8 项进行了模拟。为每个模拟预先选择了调整方法和混杂因素；稳定权重是减轻混杂的参考方法。使用基于统计学意义、估计值和标准化差异的预定指标，评估了 RCT 和模拟之间 OS 风险比及其相关 95%置信区间的一致性。
在 8 次模拟中有 7 次的效果大小与 RCT 结果一致；4 次模拟达到了完全统计学意义的一致性；5 次模拟的点估计值包含在 RCT CI 内（估计一致性）；6 次模拟报告了 RCT 和模拟之间没有显著差异（标准化差异一致性）。在某些情况下，可能会出现与残留混杂因素和药物批准后处方实践的显著变化相关的差异。
从 RWD 进行目标试验模拟，结合适当的调整，可以提供与 RCT 在 MBC 中类似的结论。在肿瘤学中，这种方法为确认对长期生存的影响、为 RCT 排除的患者扩大适应证以及在使用外部对照臂的单臂试验中进行比较有效性提供了机会。
