Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA.
Division of Hematology and Oncology, H. Moffitt Cancer Center, University of South Florida, Tampa, FL, USA.
Hematol Oncol Stem Cell Ther. 2024 Mar 22;17(2):88-94. doi: 10.56875/2589-0646.1118.
This systematic review aimed to evaluate the proportion of primary and secondary endpoints in hematopoietic stem cell transplant (HSCT) phase III randomized clinical trials (RCTs) and analyze their trends in time and study sponsorship status. The Chi-square test and logistic regression analyses were performed using SPSS version 28. A total of 147 HSCT phase III RCTs from 2006 to 2021 reported 197 primary and 600 secondary endpoints. Overall survival (OS, 17 %), progression-free survival (PFS, 15 %), graft versus host disease (GVHD, 8 %), event-free survival (EFS, 8 %), and organ function (8 %) were the most common primary endpoints. GVHD (12.3 %, n = 74), safety/toxicity/adverse events (11.8 %, n = 71), OS (11.5 %, n = 69), PFS (9.3 %, n = 56), and relapse rate (RR; 7.5 %, n = 45) were the most common secondary endpoints during 2006-2021. After 2013, an increase was noted in the use of PFS as a primary endpoint (12 %-18 %, p = 0.196), while the use of OS as a primary endpoint declined (20 %-13 %, p = 0.170). An increase was observed in using the secondary endpoints RR (5 %-10 %, p = 0.047) and NRM (3 %-6 %, p = 0.047). EFS was used more (14 % vs. 4 %, p = 0.012) than ORR (11 % vs. 2 %, p = 0.003) as a primary endpoint in pharmaceutical-compared to non-pharmaceutical-sponsored studies. As secondary endpoints, the use of EFS (4 % vs. 1 %, p = 0.013) and ORR (4 % vs. 1 %, p = 0.028) was higher, whereas that of organ systems/functions (1.5 % vs. 5.5 %, p = 0.022) and GVHD (6.5 % vs. 15 %, p = 0.002) was lower in pharmaceutical-compared to non-pharmaceutical sponsored studies. GVHD-free relapse-free survival was reported as a primary endpoint in 2 % of studies, while only 5 % reported quality of life as a secondary endpoint. We described commonly used endpoints in HSCT phase III RCTs and patterns in their use over time by funding source and study intervention category.
本系统评价旨在评估造血干细胞移植（HSCT）III 期随机临床试验（RCT）中主要和次要终点的比例，并分析其随时间和研究资助状况的趋势。使用 SPSS 版本 28 进行卡方检验和逻辑回归分析。共有 147 项 2006 年至 2021 年报道的 HSCT III 期 RCT 报告了 197 项主要终点和 600 项次要终点。总生存（OS，17%）、无进展生存（PFS，15%）、移植物抗宿主病（GVHD，8%）、无事件生存（EFS，8%）和器官功能（8%）是最常见的主要终点。GVHD（12.3%，n=74）、安全性/毒性/不良事件（11.8%，n=71）、OS（11.5%，n=69）、PFS（9.3%，n=56）和复发率（RR；7.5%，n=45）是 2006-2021 年期间最常见的次要终点。2013 年后，PFS 作为主要终点的使用有所增加（12%-18%，p=0.196），而 OS 作为主要终点的使用有所下降（20%-13%，p=0.170）。RR（5%-10%，p=0.047）和非复发死亡率（NRM；3%-6%，p=0.047）作为次要终点的使用有所增加。与非制药赞助研究相比，制药赞助研究中 EFS（14%对 4%，p=0.012）比 ORR（11%对 2%，p=0.003）更常用于作为主要终点。作为次要终点，EFS（4%对 1%，p=0.013）和 ORR（4%对 1%，p=0.028）的使用更高，而器官系统/功能（1.5%对 5.5%，p=0.022）和 GVHD（6.5%对 15%，p=0.002）的使用则更低。GVHD 无复发无事件生存被报告为 2%的研究的主要终点，而只有 5%的研究报告了生活质量作为次要终点。我们描述了 HSCT III 期 RCT 中常用的终点，并按资金来源和研究干预类别分析了其随时间的使用模式。
