Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA.
J Natl Cancer Inst. 2021 May 4;113(5):532-542. doi: 10.1093/jnci/djaa174.
Patient-reported outcomes (PROs) promote patient centeredness in clinical trials; however, in the field of rapidly emerging and clinically impressive immunotherapy, data on PROs are limited.
We systematically identified all immunotherapy approvals from 2011 through 2018 and assessed the analytic tools and reporting quality of associated PRO reports. For randomized clinical trials (RCTs), we developed a novel 24-point scoring scale: the PRO Endpoints Analysis Score based on 24 criteria derived from the recommendations of the Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data Consortium.
We assessed 44 trial publications supporting 42 immunotherapy approvals. PROs were published for 21 of the 44 (47.7%) trial publications. Twenty-three trials (52.3%) were RCTs and 21 (47.7%) pertained to single-arm trials. The median time between primary clinical outcomes publications and their corresponding secondary PRO publications was 19 months (interquartile range = 9-29 months). Of the 21 PRO reports, 4 (19.0%) reported a specific hypothesis, and most (85.7%) used descriptive statistics. Three (3 of 21 [14.3%]) studies performed a control for type I error. As for RCTs, 14 of 23 (60.9%) published PRO data, including 13 (56.5%) that published a secondary dedicated manuscript. One-half of these 14 trials scored less than 13 points on the 24-point PRO Endpoints Analysis Score. The mean score was 12.71 (range = 5-17, SD = 3.71), and none met all the recommendations of the Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data Consortium.
Suboptimal reporting of PROs occurs regularly in cancer immunotherapy trials. Increased efforts are needed to maximize the value of these data in cancer immunotherapy development and approval.
患者报告的结局（PROs）促进临床试验以患者为中心；然而，在迅速发展和具有临床吸引力的免疫治疗领域，PROs 的数据有限。
我们系统地确定了 2011 年至 2018 年所有免疫治疗的批准，并评估了相关 PRO 报告的分析工具和报告质量。对于随机临床试验（RCTs），我们开发了一个新的 24 分评分量表：基于从设定分析患者报告的结局和生活质量结局数据国际标准建议中得出的 24 个标准的 PRO 终点分析评分。
我们评估了支持 42 项免疫治疗批准的 44 项试验出版物。在 44 项试验出版物中有 21 项（47.7%）出版了 PROs。23 项试验（52.3%）为 RCT，21 项（47.7%）为单臂试验。主要临床结局出版物和相应的次要 PRO 出版物之间的中位时间为 19 个月（四分位距=9-29 个月）。在 21 份 PRO 报告中，有 4 份（19.0%）报告了具体假设，大多数（85.7%）使用了描述性统计。有 3 项（21 项中的 3 项[14.3%]）研究进行了 I 型错误的控制。对于 RCT，23 项中有 14 项（60.9%）发表了 PRO 数据，其中 13 项（56.5%）发表了专门的二次文献。这 14 项试验中有一半的评分低于 24 分 PRO 终点分析评分的 13 分。平均得分为 12.71（范围=5-17，标准差=3.71），没有一项符合设定分析患者报告的结局和生活质量结局数据国际标准建议的所有建议。
癌症免疫治疗试验中 PROs 的报告通常不充分。需要做出更多努力来最大限度地发挥这些数据在癌症免疫治疗开发和批准中的价值。
