Sherry Alexander D, Liu Yufei, Msaouel Pavlos, Lin Timothy A, Koong Alex, Lin Christine, Abi Jaoude Joseph, Patel Roshal R, Kouzy Ramez, El-Alam Molly B, Miller Avital M, Owiwi Mohannad, Ofer Jonathan, Bomze David, McCaw Zachary R, Meirson Tomer, Ludmir Ethan B
Division of Radiation Oncology, Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.
NPJ Precis Oncol. 2025 Jul 24;9(1):256. doi: 10.1038/s41698-025-01024-2.
In phase III oncology trials, superiority is defined by statistical significance using P thresholds. However, this approach has been criticized because P is continuous. Here, we reconstruct patient-level data for 230 phase III oncology trials to model the robustness of statistical significance by estimating the survival-inferred fragility index (SIFI), defined as the smallest number of patients changing arms that alters the statistical significance interpretation. The median SIFI was 8 patients (IQR 4-19), representing 1.4% of enrollments (IQR 0.7%-3%). As a continuous statistic, P-but not the significance interpretation-was correlated with SIFI. Moreover, overall survival endpoints were more fragile than surrogate endpoints. Taken together, while phase III oncology trials are intended to robustly inform patient care, shifting the assignment of a few patients is often sufficient to upend the statistical significance interpretation. This vulnerability underscores the need for more robust strategies to identify superiority in oncology.
在III期肿瘤学试验中，优越性是通过使用P值阈值的统计学显著性来定义的。然而，这种方法受到了批评，因为P值是连续的。在这里，我们重建了230项III期肿瘤学试验的患者水平数据，通过估计生存推断脆弱性指数（SIFI）来模拟统计学显著性的稳健性，SIFI定义为改变治疗组会改变统计学显著性解释的最少患者数量。SIFI的中位数为8名患者（四分位间距4-19），占入组人数的1.4%（四分位间距0.7%-3%）。作为一个连续统计量，P值（而非显著性解释）与SIFI相关。此外，总生存终点比替代终点更脆弱。综上所述，虽然III期肿瘤学试验旨在为患者护理提供有力依据，但改变少数患者的治疗分配往往足以颠覆统计学显著性解释。这种脆弱性凸显了在肿瘤学中需要更稳健的策略来确定优越性。
