Dancey J E, Dodd L E, Ford R, Kaplan R, Mooney M, Rubinstein L, Schwartz L H, Shankar L, Therasse P
National Cancer Institute of Canada-Clinical Trials Group, 10 Stuart Street, Queen's University, Kingston, Ontario, Canada.
Eur J Cancer. 2009 Jan;45(2):281-9. doi: 10.1016/j.ejca.2008.10.042.
Progression-free survival (PFS) is an increasingly important end-point in cancer drug development. However, several concerns exist regarding the use of PFS as a basis to compare treatments. Unlike survival, the exact time of progression is unknown, so progression times might be over-estimated (or under-estimated) and, consequently, bias may be introduced when comparing treatments. In addition, the assessment of progression is subject to measurement variability which may introduce error or bias. Ideally trials with PFS as the primary end-point should be randomised and, when feasible, double-blinded. All patients eligible for study should be evaluable for the primary end-point and thus, in general, have measurable disease at baseline. Appropriate definitions should be provided in the protocol and data collected on the case-report forms, if patients with only non-measurable disease are eligible and/or clinical, or symptomatic progression are to be considered progression events for analysis. Protocol defined assessments of disease burden should be obtained at intervals that are symmetrical between arms. Independent review of imaging may be of value in randomised phase II trials and phase III trials as an auditing tool to detect possible bias.
无进展生存期（PFS）在癌症药物研发中日益成为重要的终点指标。然而，将PFS用作比较治疗方法的依据存在一些问题。与总生存期不同，进展的确切时间未知，因此进展时间可能被高估（或低估），进而在比较治疗方法时可能引入偏差。此外，进展的评估存在测量变异性，这可能导致误差或偏差。理想情况下，以PFS作为主要终点指标的试验应进行随机分组，并且在可行时采用双盲设计。所有符合研究条件的患者均应能对主要终点指标进行评估，因此一般来说，患者在基线时应具有可测量的疾病。如果仅患有不可测量疾病的患者符合条件和/或临床或症状性进展将被视为分析的进展事件，则应在方案中提供适当的定义，并在病例报告表上收集数据。应在各治疗组之间对称的时间间隔获取方案定义的疾病负担评估。在随机II期试验和III期试验中，影像的独立审查作为检测可能偏差的审核工具可能具有价值。
