Advances in anticancer therapies have provided crucial benefits for millions of patients who are living long and fulfilling lives. While these successes should be celebrated, there is certainly room to continue improving cancer care. Increased long-term survival presents additional challenges for determining whether new therapies further extend patients’ lives through clinical trials, commonly known as the gold standard endpoint of overall survival (OS). As a result, there is an increasing reliance on earlier efficacy endpoints , which may or may not correlate with OS, to continue the timely pace of translating innovation into novel therapies available for patients. Even when not powered as an efficacy endpoint, OS remains a critical indication of safety for regulatory decisions and is a key aspect of the U.S. Food and Drug Administration’s Project Endpoint. Unfortunately, in the pursuit of earlier endpoints, many registrational clinical trials lack adequate planning, collection, and analysis of OS data, which complicates interpretation of a net clinical benefit or harm. This article shares best practices, proposes novel statistical methodologies, and provides detailed recommendations to improve the rigor of using OS data to inform benefit-risk assessments, including incorporating the following in clinical trials intending to demonstrate the safety and effectiveness of a cancer therapy: prospective collection of OS data, establishment of fit-for-purpose definitions of OS detriment, and prespecification of analysis plans for using OS data to evaluate for potential harm. These improvements hold promise to help regulators, patients and providers better understand the benefits and risks of novel therapies.

中文翻译：

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改进总体生存数据的收集和分析


抗癌疗法的进步为数百万长寿且充实的生活的患者提供了重要的益处。虽然这些成功值得庆祝，但癌症治疗肯定还有继续改善的空间。长期生存率的提高给确定新疗法是否通过临床试验进一步延长患者的生命带来了额外的挑战，这通常被称为总生存期 (OS) 的金标准终点。因此，人们越来越依赖早期疗效终点（可能与 OS 相关，也可能不相关），以继续及时将创新转化为患者可用的新疗法。即使不作为功效终点，OS 仍然是监管决策安全性的关键指标，也是美国食品和药物管理局终点项目的一个关键方面。不幸的是，为了追求更早的终点，许多注册临床试验缺乏对 OS 数据的充分规划、收集和分析，这使得净临床获益或危害的解释变得复杂。本文分享了最佳实践，提出了新颖的统​​计方法，并提供了详细的建议，以提高使用 OS 数据为获益风险评估提供信息的严谨性，包括将以下内容纳入旨在证明癌症治疗的安全性和有效性的临床试验中：收集操作系统数据，建立适合目的的操作系统损害定义，以及预先制定使用操作系统数据评估潜在危害的分析计划。这些改进有望帮助监管机构、患者和提供者更好地了解新疗法的益处和风险。