German Cancer Research Center (DKFZ)
Office of Health Economics.
Int J Technol Assess Health Care. 2018 Jan;34(3):300-316. doi: 10.1017/S0266462318000338.
A primary outcome in oncology trials is overall survival (OS). However, to estimate OS accurately requires a sufficient number of patients to have died, which may take a long time. If an alternative end point is sufficiently highly correlated with OS, it can be used as a surrogate. Progression-free survival (PFS) is the surrogate most often used in oncology, but does not always satisfy the correlation conditions for surrogacy. We analyze the methodologies used when extrapolating from PFS to OS.
Davis et al. previously reviewed the use of surrogate end points in oncology, using papers published between 2001 and 2011. We extend this, reviewing papers published between 2012 and 2016. We also examine the reporting of statistical methods to assess the strength of surrogacy.
The findings from 2012 to 2016 do not differ substantially from those of 2001 to 2011: the same factors are shown to affect the relationship between PFS and OS. The proportion of papers reporting individual patient data (IPD), strongly recommended for full assessment of surrogacy, remains low: 33 percent. A wide range of methods has been used to determine the appropriateness of surrogates. While usually adhering to reporting standards, the standard of scholarship appears sometimes to be questionable and the reporting of results often haphazard.
Standards of analysis and reporting PFS to OS surrogate studies should be improved by increasing the rigor of statistical reporting and by agreeing to a minimum set of reporting guidelines. Moreover, the use of IPD to assess surrogacy should increase.
肿瘤临床试验的主要结局指标是总生存期（OS）。然而，要准确估计 OS 需要有足够数量的患者死亡，这可能需要很长时间。如果替代终点与 OS 具有足够高的相关性，则可以将其用作替代指标。无进展生存期（PFS）是肿瘤学中最常用的替代指标，但并不总是满足替代条件。我们分析了从 PFS 外推到 OS 时使用的方法。
Davis 等人此前回顾了 2001 年至 2011 年间发表的关于肿瘤学替代终点的使用情况。我们在此基础上进行了扩展，回顾了 2012 年至 2016 年间发表的论文。我们还检查了用于评估替代指标强度的统计方法的报告。
2012 年至 2016 年的研究结果与 2001 年至 2011 年的研究结果没有显著差异：同样的因素被证明会影响 PFS 和 OS 之间的关系。报告个体患者数据（IPD）的论文比例仍然很低，强烈建议对替代指标进行全面评估，这一比例仅为 33%。已使用各种方法来确定替代指标的适当性。虽然通常遵守报告标准，但学术标准有时似乎值得怀疑，并且结果的报告往往很随意。
应通过提高统计报告的严格性并同意一套最低的报告指南来改进分析和报告 PFS 替代 OS 研究的标准。此外，应该增加使用 IPD 来评估替代指标的使用。
