Department of Hematological Malignancies and Cellular Therapeutics, Kansas University Medical Center, Westwood, Kansas, USA.
Division of Hematology and Hematologic Malignancies, University of Utah, Salt Lake City, Utah, USA.
Am J Hematol. 2021 Jun 1;96(6):690-697. doi: 10.1002/ajh.26166. Epub 2021 Apr 1.
Surrogate endpoints are being used more frequently in randomized controlled trials, even though they do not consistently corelate with patient outcomes. We systemically evaluated the use of surrogate endpoints in multiple myeloma randomized controlled trials over the past 15 years. We searched three databases (Pubmed, Embase, Cochrane) for multiple myeloma randomized controlled trials from January 1, 2005 to December 30, 2019. The primary outcome of our study was the proportion of randomized controlled trials that used overall survival as their primary endpoint. Secondary outcomes included the use of surrogate endpoints, and trends over time, and whether they differed based on study sponsorship. We included 151 randomized controlled trials in our analysis. The primary endpoint was overall survival (OS) in 17 (11.3%) of studies, progression free survival (PFS) or event-defined endpoints in 91 studies (60.3%) and response-based endpoints in 44 studies (29.1%). Quality of life was a primary endpoint in only three studies (2%). The use of OS as a primary endpoint decreased from 28.5% of trials from 2005 to 2009 to 5.5% from 2015 to 2019. There has been a decrease in the clinically meaningful endpoint of OS over the past 15 years in multiple myeloma randomized controlled trials. Use of quality of life as a primary endpoint remains exceedingly low. It remains paramount to recognize that the use of surrogate endpoints is imperfect, and care based upon them requires constant physician and patient re-analysis.
替代终点在随机对照试验中被越来越多地使用，尽管它们并不总是与患者的结果一致。我们系统地评估了过去 15 年来在多发性骨髓瘤随机对照试验中使用替代终点的情况。我们在三个数据库（Pubmed、Embase 和 Cochrane）中搜索了 2005 年 1 月 1 日至 2019 年 12 月 30 日期间的多发性骨髓瘤随机对照试验。我们研究的主要结果是使用总生存期作为主要终点的随机对照试验的比例。次要结果包括替代终点的使用情况以及随时间的趋势，以及它们是否因研究资助而异。我们的分析纳入了 151 项随机对照试验。主要终点是 17 项研究（11.3%）的总生存期（OS），91 项研究（60.3%）的无进展生存期（PFS）或事件定义终点，44 项研究（29.1%）的基于反应的终点。仅有三项研究（2%）将生活质量作为主要终点。OS 作为主要终点的研究比例从 2005 年至 2009 年的 28.5%下降到 2015 年至 2019 年的 5.5%。在过去的 15 年中，多发性骨髓瘤随机对照试验中 OS 这一具有临床意义的终点的使用有所减少。将生活质量作为主要终点的使用仍然非常低。必须认识到，替代终点的使用并不完美，基于它们的治疗需要医生和患者不断重新分析。
