Indolent cancers are characterized by long overall survival (OS) times. Therefore, powering a clinical trial to provide definitive assessment of the effects of an experimental intervention on OS in a reasonable timeframe is generally infeasible. Instead, the primary outcome in many pivotal trials is an intermediate clinical response such as progression-free survival (PFS). In several recently reported pivotal trials of interventions for indolent cancers that yielded promising results on an intermediate outcome, however, more mature data or post-approval trials showed concerning OS trends. These problematic results have prompted a keen interest in quantitative approaches for monitoring OS that can support regulatory decision-making related to the risk of an unacceptably large detrimental effect on OS. For example, the US Food and Drug Administration, the American Association for Cancer Research, and the American Statistical Association recently organized a one-day multi-stakeholder workshop entitled 'Overall Survival in Oncology Clinical Trials'. In this paper, we propose OS monitoring guidelines tailored for the setting of indolent cancers. Our pragmatic approach is modeled, in part, on the monitoring guidelines the FDA has used in cardiovascular safety trials conducted in Type 2 Diabetes Mellitus. We illustrate proposals through application to several examples informed by actual case studies.

翻译：惰性癌症以长期总生存期（OS）为特征。因此，在合理时间范围内为临床试验提供充分依据以评估实验性干预对OS的确定效应通常不可行。相反，许多关键试验的主要终点是中间临床反应，例如无进展生存期（PFS）。然而，在近期报道的若干惰性癌症干预措施关键试验中，尽管中间结局取得了令人鼓舞的结果，但更成熟的数据或批准后试验却显示出令人担忧的OS趋势。这些有问题的结果促使人们强烈关注用于监测OS的定量方法，这些方法可以为与OS不可接受的大幅不利效应风险相关的监管决策提供支持。例如，美国食品药品监督管理局、美国癌症研究协会和美国统计协会最近组织了一场为期一天的多方利益相关者研讨会，题为"肿瘤临床试验中的总生存期"。在本文中，我们提出了针对惰性癌症场景量身定制的OS监测指南。我们的实用方法部分借鉴了FDA在2型糖尿病心血管安全性试验中使用的监测指南。我们通过基于实际案例研究的多个示例来说明这些建议。