Hughes Sarah E, Khatsuria Foram, McMullan Christel, Shaw Karen L, Walker Anita, Kinsella Francesca, Burns David, Aiyegbusi Olalekan L, Davies Elin Haf, Ansell John, Chakera Evelyn, Craddock Charles, Denniston Alastair, Lloyd Rebecca, Ferguson Paul, Chakraverty Ronjon, Calvert Melanie
Centre for Patient Reported Outcome Research, University of Birmingham, Birmingham, UK.
National Institute of Health and Care Research (NIHR) Blood and Transplant Research Unit (BTRU) in Precision Cellular Therapeutics, University of Birmingham, Birmingham, UK.
EClinicalMedicine. 2025 May 28;84:103256. doi: 10.1016/j.eclinm.2025.103256. eCollection 2025 Jun.
BACKGROUND: Chimeric Antigen Receptor (CAR) T-cell therapies are effective for treating haematological cancers but carry risks of toxicity and substantial symptom burden. Patient-reported outcomes (PROs) could significantly enhance clinical management for patients undergoing these treatments. However, guidance on selection of PRO measures for monitoring adverse event and quality of life after CAR T-cell therapy is limited. This study aimed to achieve consensus among patients and healthcare professionals on the selection of PRO measures for an electronic PRO (ePRO) system for CAR T-cell therapy clinical settings. METHODS: Two-round modified Delphi study (online survey and consensus meeting) conducted from December 2023 to January 2024 to select PRO measures for the ePRO system, guided by a conceptual framework with four measurement domains: symptom burden, impacts of cancer and CAR T-cell therapy, treatment tolerability, and health-related quality of life (HRQoL). Database searches (PubMed, ePROVIDE, COSMIN, and COMET) and licensing websites of cancer-specific PRO measures identified 113 PRO measures. Measures were pre-specified for treatment tolerability and HRQoL domains and concept mapping established conceptual coverage for the remaining domains. Seven PRO measures were shortlisted and prespecified inclusion thresholds and stopping criteria guided Delphi panel selection. Registration: ISRCTN11232653. FINDINGS: Nineteen participants (5 CAR T-cell patients, 14 healthcare professionals/researchers) recruited from a UK National Health Service (NHS) cellular therapy centre and professional networks took part in Round One (Delphi online survey). Shortlisted measures were rated for relevance, comprehensiveness, and ease of understanding for the symptom burden and impacts of cancer and CAR T-cell treatment domains. Consensus was achieved after Round One, precluding the requirement for Round 2 (consensus meeting). The Symptom Burden Questionnaire™ (SBQ™) and the Quality of Life in Adult Cancer Survivors (QLACS) were selected to represent the Symptom Burden and Impacts domains, respectively. These measures, EQ5D-5L, measuring HRQoL, and Functional Assessment of Chronic Illness Therapy-Item GP5 (FACT-GP5), single-item global indicator of cancer treatment tolerability, will be included in the ePRO system. INTERPRETATION: In the absence of guidance on PRO measure selection for CAR T-cell therapies, consensus-based methods represent an important step towards use of PROs with this clinical population. Modest sample size and representativeness of the patient subgroup are limitations of this study. FUNDING: This study is funded by the National Institute for Health and Care Research (NIHR) Blood and Transplant Research Unit in Precision Cellular Therapeutics (NIHR203339). The views expressed are those of the authors and not necessarily those of the NIHR, NHS Blood and Transplant, or the Department of Health and Social Care.
背景:嵌合抗原受体(CAR)T细胞疗法对治疗血液系统癌症有效,但存在毒性风险和严重的症状负担。患者报告结局(PRO)可显著改善接受这些治疗的患者的临床管理。然而,关于选择PRO措施以监测CAR T细胞治疗后的不良事件和生活质量的指导有限。本研究旨在就CAR T细胞治疗临床环境中电子PRO(ePRO)系统的PRO措施选择,在患者和医疗保健专业人员之间达成共识。 方法:2023年12月至2024年1月进行了两轮改良德尔菲研究(在线调查和共识会议),以选择ePRO系统的PRO措施,以一个具有四个测量领域的概念框架为指导:症状负担、癌症和CAR T细胞治疗的影响、治疗耐受性以及健康相关生活质量(HRQoL)。数据库搜索(PubMed、ePROVIDE、COSMIN和COMET)以及癌症特异性PRO措施的许可网站识别出113项PRO措施。为治疗耐受性和HRQoL领域预先指定了措施,概念映射为其余领域建立了概念覆盖范围。七项PRO措施入围,预先指定的纳入阈值和停止标准指导德尔菲小组选择。注册:ISRCTN11232653。 结果:从英国国家医疗服务体系(NHS)细胞治疗中心和专业网络招募的19名参与者(5名CAR T细胞患者、14名医疗保健专业人员/研究人员)参加了第一轮(德尔菲在线调查)。对入围措施在症状负担以及癌症和CAR T细胞治疗影响领域的相关性、全面性和易理解性进行了评分。第一轮后达成了共识,无需第二轮(共识会议)。分别选择了症状负担问卷™(SBQ™)和成年癌症幸存者生活质量(QLACS)来代表症状负担和影响领域。这些措施,测量HRQoL的EQ5D-5L,以及癌症治疗耐受性的单项总体指标慢性病治疗功能评估-项目GP5(FACT-GP5),将纳入ePRO系统。 解读:在缺乏CAR T细胞疗法PRO措施选择指导的情况下,基于共识的方法是朝着在这一临床人群中使用PRO迈出的重要一步。样本量较小和患者亚组的代表性是本研究的局限性。 资金:本研究由国家卫生与保健研究机构(NIHR)精准细胞治疗血液与移植研究单位(NIHR203339)资助。所表达的观点是作者的观点,不一定是NIHR、NHS血液与移植或卫生与社会保健部的观点。
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