West Virginia University Cancer Institute, Morgantown, WV, USA.
Cardiff University and Velindre UNHS Trust, UK.
J Natl Cancer Inst. 2022 Jun 13;114(6):819-828. doi: 10.1093/jnci/djab218.
Meta-analysis based on individual participant data (IPD) is a powerful methodology for synthesizing evidence by combining information drawn from multiple trials. Hitherto, its principal application has been in questions of clinical management, but an increasingly important use is in clarifying trials methodology, for instance in the selection of endpoints, as discussed in this review. In oncology, the Aide et Recherche en Cancérologie Digestive (ARCAD) Metastatic Colorectal Cancer Database is a leader in the use of IPD-based meta-analysis in methodological research. The ARCAD database contains IPD from more than 38 000 patients enrolled in 46 studies and continues to collect phase III trial data. Here, we review the principal findings of the ARCAD project in respect of endpoint selection and examine their implications for cancer trials. Analysis of the database has confirmed that progression-free survival (PFS) is no longer a valid surrogate endpoint predictive of overall survival in the first-line treatment of colorectal cancer. Nonetheless, PFS remains an endpoint of choice for most first-line trials in metastatic colorectal cancer and other solid tumors. Only substantial PFS effects are likely to translate into clinically meaningful benefits, and accordingly, we advocate an oncology research model designed to identify highly effective treatments in carefully defined patient groups. We also review the use of the ARCAD database in assessing clinical response including novel response metrics and prognostic markers. These studies demonstrate the value of IPD as a tool for methodological studies and provide a reference point for the expansion of this approach within clinical cancer research.
基于个体参与者数据（IPD）的荟萃分析是一种通过合并来自多个试验的信息来综合证据的强大方法。迄今为止，其主要应用一直是在临床管理方面，但越来越重要的用途是在澄清试验方法学方面，例如在本综述中讨论的终点选择。在肿瘤学中，Aide et Recherche en Cancérologie Digestive（ARCAD）转移性结直肠癌数据库在使用基于 IPD 的荟萃分析进行方法学研究方面处于领先地位。ARCAD 数据库包含来自 46 项研究中超过 38000 名患者的 IPD，并继续收集 III 期试验数据。在这里，我们回顾了 ARCAD 项目在终点选择方面的主要发现，并研究了它们对癌症试验的影响。对数据库的分析证实，无进展生存期（PFS）不再是预测结直肠癌一线治疗总生存期的有效替代终点。尽管如此，PFS 仍然是转移性结直肠癌和其他实体瘤的大多数一线试验的首选终点。只有实质性的 PFS 效应才有可能转化为具有临床意义的获益，因此，我们提倡一种肿瘤学研究模式，旨在在精心定义的患者群体中确定高度有效的治疗方法。我们还回顾了 ARCAD 数据库在评估临床反应中的应用，包括新的反应指标和预后标志物。这些研究证明了 IPD 作为方法学研究工具的价值，并为在临床癌症研究中扩展这种方法提供了参考点。
