Department of Management, Health System Management Program, Bar Ilan University, Ramat Gan, Israel.
Coller School of Management, Tel Aviv University, Tel Aviv, Israel.
Oncologist. 2019 Nov;24(11):1469-1478. doi: 10.1634/theoncologist.2019-0175. Epub 2019 Jul 18.
Understanding the efficacy of treatments is crucial for patients, physicians, and policymakers. Median survival, the most common measure used in the outcome reporting of oncology clinical trials, is easy to understand; however, it describes only a single time point. The interpretation of the hazard ratio is difficult, and its underlying statistical assumptions are not always met. The objective of this study was to evaluate alternative measures based on the mean benefit of novel oncology treatments.
We reviewed all U.S. Food and Drug Administration (FDA) approvals for oncology agents between 2013 and 2017. We digitized survival curves as reported in the clinical trials used for the FDA approvals and implemented statistical transformations to calculate for each trial the restricted mean survival time (RMST), as well as the mean survival using Weibull distribution. We compared the mean survival with the median survival benefit in each clinical trial.
The FDA approved 83 solid tumor indications for oncology agents between 2013 and 2017, of which 27 approvals based on response rates, whereas 49 approvals were based on survival endpoints (progression-free survival and overall survival). The average improvement in median overall survival or progression-free survival was 4.6 months versus 3.6 months improvement in the average RMST and 6.1 months improvement in mean survival using Weibull distribution.
Mean survival may supply valuable information for different stakeholders. Its inclusion should be considered in the reporting of prospective clinical trials.
Mean survival may supply valuable information for different stakeholders. Its inclusion should be considered in the reporting of clinical trials.
了解治疗效果对患者、医生和政策制定者至关重要。中位生存期是肿瘤临床试验结果报告中最常用的指标，易于理解；然而，它仅描述了一个时间点。风险比的解释较为困难，且其潜在的统计假设并不总是成立。本研究旨在评估基于新型肿瘤治疗获益均值的替代指标。
我们回顾了 2013 年至 2017 年间美国食品和药物管理局（FDA）批准的所有肿瘤学药物。我们对用于 FDA 批准的临床试验中报告的生存曲线进行了数字化，并实施了统计变换，以计算每个试验的受限平均生存时间（RMST）和 Weibull 分布下的平均生存时间。我们比较了每个临床试验中平均生存时间与中位生存获益的差异。
2013 年至 2017 年间，FDA 批准了 83 种实体瘤肿瘤药物适应证，其中 27 种适应证基于缓解率，49 种适应证基于生存终点（无进展生存期和总生存期）。中位总生存期或无进展生存期的平均改善为 4.6 个月，而 RMST 的平均改善为 3.6 个月， Weibull 分布下的平均生存时间改善为 6.1 个月。
平均生存时间可为不同利益相关者提供有价值的信息。在报告前瞻性临床试验时，应考虑纳入平均生存时间。
平均生存时间可为不同利益相关者提供有价值的信息。在报告临床试验时，应考虑纳入平均生存时间。
