Department of Medical Oncology, University Hospital of Nîmes, Rue du Pr Henri Pujol, 30029, Nîmes Cedex 9, France.
Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, Montpellier, France.
BMC Cancer. 2019 Apr 16;19(1):361. doi: 10.1186/s12885-019-5579-3.
Phase I trials aim to identify the recommended dose for further development. Health-related quality of life (HRQoL) could be a complement to the usual National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) scale to detect adverse events and define the doses. The objective of this study is to review the phase I in oncology which used HRQoL as endpoint.
A search in PubMed database identified phase I trials in oncology with HRQoL as endpoint, published between January 2012 to May 2016. Hematological and pediatric phase I were excluded.
A total of 1333 phase I were identified and 15 trials were identified with HRQoL as endpoint (1.1%). The European Organisation for Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) was the most frequently used instrument: 5 studies (33.3%). The targeted dimensions of HRQoL and the minimal clinically important difference were prespecified in 1 study (6.7%) and 2 studies (13.3%), respectively. Twelve studies (80%) described the statistical approach to analyze HRQoL data. Eight studies used the mean change from baseline (60%) to analyse longitudinal HRQoL data, two the mean score at certain times (13.3%), one the linear mixed model for repeated measures (6.7%), one the time to HRQoL score deterioration (6.7%), one percentage of patient-reported symptoms (6.7%). None of the studies used HRQoL to determine the recommended doses.
Few phase I studies used HRQoL as endpoint and among studies with HRQoL as endpoint, the methodology of HRQoL measurement and statistical analysis was heterogeneous. HRQoL. endpoint not used for assessing the recommended phase II doses.
I 期临床试验旨在确定进一步开发的推荐剂量。健康相关生活质量（HRQoL）可以作为常用的国立癌症研究所不良事件通用术语标准（NCI-CTCAE）的补充，以检测不良事件并确定剂量。本研究旨在回顾使用 HRQoL 作为终点的肿瘤学 I 期临床试验。
在 PubMed 数据库中搜索以 HRQoL 为终点的肿瘤学 I 期临床试验，发表时间为 2012 年 1 月至 2016 年 5 月。排除血液学和儿科 I 期临床试验。
共确定了 1333 项 I 期临床试验，其中 15 项以 HRQoL 为终点（1.1%）。欧洲癌症研究与治疗组织生活质量问卷 C30（EORTC QLQ-C30）是最常用的工具：5 项研究（33.3%）。HRQoL 的目标维度和最小临床重要差异分别在 1 项研究（6.7%）和 2 项研究（13.3%）中预先指定。12 项研究（80%）描述了分析 HRQoL 数据的统计方法。8 项研究使用从基线的平均变化（60%）来分析纵向 HRQoL 数据，2 项研究使用特定时间的平均评分（13.3%），1 项研究使用线性混合模型进行重复测量（6.7%），1 项研究使用 HRQoL 评分恶化的时间（6.7%），1 项研究使用患者报告症状的百分比（6.7%）。没有一项研究使用 HRQoL 来确定推荐剂量。
少数 I 期研究将 HRQoL 作为终点，在以 HRQoL 作为终点的研究中，HRQoL 测量和统计分析的方法学存在异质性。HRQoL 终点未用于评估推荐的 II 期剂量。
