Cancer Research UK, London, UK.
Early Cancer Detection Consultant, Bethesda, MD, USA.
Lancet Oncol. 2024 May;25(5):e183-e192. doi: 10.1016/S1470-2045(24)00015-9.
The requirement of large-scale expensive cancer screening trials spanning decades creates considerable barriers to the development, commercialisation, and implementation of novel screening tests. One way to address these problems is to use surrogate endpoints for the ultimate endpoint of interest, cancer mortality, at an earlier timepoint. This Review aims to highlight the issues underlying the choice and use of surrogate endpoints for cancer screening trials, to propose criteria for when and how we might use such endpoints, and to suggest possible candidates. We present the current landscape and challenges, and discuss lessons and shortcomings from the therapeutic trial setting. It is hugely challenging to validate a surrogate endpoint, even with carefully designed clinical studies. Nevertheless, we consider whether there are candidates that might satisfy the requirements defined by research and regulatory bodies.
大规模昂贵的癌症筛查试验需要跨越数十年，这给新的筛查试验的开发、商业化和实施带来了相当大的障碍。解决这些问题的一种方法是在更早的时间点使用替代终点来替代最终的感兴趣终点，即癌症死亡率。本综述旨在强调选择和使用癌症筛查试验替代终点所涉及的问题，提出何时以及如何使用此类终点的标准，并提出可能的候选者。我们介绍了当前的格局和挑战，并讨论了从治疗试验设定中获得的经验和不足之处。即使进行了精心设计的临床研究，验证替代终点也极具挑战性。尽管如此，我们仍在考虑是否有符合研究和监管机构定义的要求的候选者。
