Downs Jenny, Pichard Dominique C, Kaufmann Walter E, Horrigan Joseph P, Raspa Melissa, Townend Gillian, Marsh Eric D, Leonard Helen, Motil Kathleen, Dietz Andrew C, Garg Nupur, Ananth Amitha, Byiers Breanne, Peters Sarika, Beatty Christopher, Symons Frank, Jacobs Aleksandra, Youakim James, Suter Bernhard, Santosh Paramola, Neul Jeffrey L, Benke Tim A
The Kids Research Institute Australia, Centre for Child Health Research, University of Western Australia, 15 Hospital Avenue, Nedlands, Perth, WA, 6009, Australia.
Curtin School of Allied Health, Curtin University, GPO Box U1987, Perth, WA, 6845, Australia.
Trials. 2024 Dec 21;25(1):845. doi: 10.1186/s13063-024-08678-6.
The clinical, research and advocacy communities for Rett syndrome are striving to achieve clinical trial readiness, including having fit-for-purpose clinical outcome assessments. This study aimed to (1) describe psychometric properties of clinical outcome assessment for Rett syndrome and (2) identify what is needed to ensure that fit-for-purpose clinical outcome assessments are available for clinical trials.
Clinical outcome assessments for the top 10 priority domains identified in the Voice of the Patient Report for Rett syndrome were compiled and available psychometric data were extracted. The clinical outcome assessments measured clinical severity, functional abilities, comorbidities and quality of life, and electrophysiological biomarkers. An international and multidisciplinary panel of 29 experts with clinical, research, psychometric, biostatistical, industry and lived experience was identified through International Rett Syndrome Foundation networks, to discuss validation of the clinical outcome assessments, gaps and next steps, during a workshop and in a follow-up questionnaire. The identified gaps and limitations were coded using inductive content analysis.
Variable validation profiles across 26 clinical outcome assessments of clinical severity, functional abilities, and comorbidities were discussed. Reliability, validity, and responsiveness profiles were mostly incomplete; there were limited content validation data, particularly parent-informed relevance, comprehensiveness and comprehensibility of items; and no data on meaningful change or cross-cultural validity. The panel identified needs for standardised administration protocols and systematic validation programmes.
A pipeline of collaborative clinical outcome assessment development and validation research in Rett syndrome can now be designed, aiming to have fit-for-purpose measures that can evaluate meaningful change, to serve future clinical trials and clinical practice.
雷特综合征的临床、研究和倡导团体正在努力实现临床试验准备就绪，包括具备适用的临床结局评估。本研究旨在：（1）描述雷特综合征临床结局评估的心理测量特性；（2）确定需要采取哪些措施以确保为临床试验提供适用的临床结局评估。
汇总雷特综合征患者报告中确定的前10个优先领域的临床结局评估，并提取现有的心理测量数据。临床结局评估测量临床严重程度、功能能力、合并症和生活质量以及电生理生物标志物。通过国际雷特综合征基金会网络确定了一个由29名具有临床、研究、心理测量、生物统计学、行业和实际经验的专家组成的国际多学科小组，在一次研讨会和后续问卷中讨论临床结局评估的验证、差距和下一步措施。使用归纳性内容分析法对确定的差距和局限性进行编码。
讨论了26项关于临床严重程度、功能能力和合并症的临床结局评估的不同验证概况。信度、效度和反应度概况大多不完整；内容验证数据有限，特别是家长告知的项目相关性、全面性和可理解性；且没有关于有意义变化或跨文化效度的数据。该小组确定了对标准化管理方案和系统验证计划的需求。
现在可以设计雷特综合征协作性临床结局评估开发和验证研究的流程，目标是制定能够评估有意义变化的适用措施，以服务于未来的临床试验和临床实践。
