Office of Oncologic Diseases, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
Oncology Center for Excellence, US Food and Drug Administration, Silver Spring, MD, USA.
J Natl Cancer Inst. 2022 Jan 11;114(1):12-19. doi: 10.1093/jnci/djab087.
Pediatric patient-reported outcome (PRO) data can help inform the US Food and Drug Administration's (FDA's) benefit-risk assessment of cancer therapeutics by quantifying symptom and functional outcomes from the patient's perspective. This study assessed use of PROs in commercial pediatric oncology trials submitted to the FDA for regulatory review. FDA databases were searched to identify pediatric oncology product applications approved between 1997 and 2020. Sponsor-submitted documents were reviewed to determine whether PRO data were collected, which instruments were used, and the quality of collected data (ie, sample size, completion rates, and use of fit-for-purpose instruments). The role of PROs in each trial (endpoint hierarchy) was also recorded in addition to whether any PRO endpoints were included in product labeling. We reviewed 17 pediatric oncology applications, 4 of which included PRO data: denosumab, tisagenlecleucel, larotrectinib, and selumetinib. In these 4 instances, PROs served as exploratory endpoints and were not incorporated in product labeling. Trials that collected PRO data were phase II or phase I/II single-arm studies with sample sizes of 28 to 88 patients. Symptomatic adverse events (AEs) were characterized using clinician-reported Common Terminology Criteria for Adverse Events (CTCAE) without additional patient self-report. PROs were infrequently used in pediatric cancer registration trials. When PROs were used, PRO data were limited by lack of a clear research objective and corresponding prospective statistical analysis plan. Contemporary PRO symptom libraries, such as the National Cancer Institute's Pediatric PRO-CTCAE, may provide an opportunity to better evaluate the occurrence and impact of symptomatic AEs, from the patient's perspective, in pediatric oncology trials.
儿科患者报告结局 (PRO) 数据可以帮助量化患者视角下的症状和功能结局，从而为美国食品和药物管理局 (FDA) 的癌症疗法的获益-风险评估提供信息。本研究评估了在向 FDA 提交的用于监管审查的商业儿科肿瘤学试验中 PRO 的使用情况。检索了 FDA 数据库以识别 1997 年至 2020 年期间批准的儿科肿瘤学产品应用。审查了赞助商提交的文件，以确定是否收集了 PRO 数据、使用了哪些工具以及收集数据的质量（即样本量、完成率和使用适合目的的工具）。还记录了 PRO 在每个试验中的作用（终点层次结构），以及是否将任何 PRO 终点纳入产品标签。我们审查了 17 项儿科肿瘤学应用，其中 4 项包含 PRO 数据：地舒单抗、tisagenlecleucel、拉罗替尼和 selumetinib。在这 4 种情况下，PRO 用作探索性终点，并未纳入产品标签。收集 PRO 数据的试验为 II 期或 I/II 期单臂研究，样本量为 28 至 88 例患者。使用临床医生报告的常见不良事件术语标准 (CTCAE) 描述有症状的不良事件 (AE)，而没有额外的患者自我报告。PRO 在儿科癌症注册试验中很少使用。当使用 PRO 时，PRO 数据受到缺乏明确的研究目标和相应的前瞻性统计分析计划的限制。当代 PRO 症状库，如国家癌症研究所的儿科 PRO-CTCAE，可能为更好地从患者的角度评估儿科肿瘤学试验中症状性 AE 的发生和影响提供机会。
