Condon Carolyn, Parkerson Kimberly A, Dandurand Ann, Wang Fei, Howse Chloe, Mayhew Megan, Whyman Sophie, Ventola Pamela, Anne Meskis Mary, Sullivan Joseph, Knupp Kelly G, Gater Adam, Mahon-Smith Aoife
Stoke Therapeutics, MA, USA.
Adelphi Values, Patient-Centered Outcomes, Bollington, United Kingdom.
Epilepsy Behav. 2025 Jun;167:110381. doi: 10.1016/j.yebeh.2025.110381. Epub 2025 Apr 9.
The Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) is used to assess non-seizure outcomes in developmental and epileptic encephalopathies, including Dravet syndrome (DS); meaningful change thresholds (MCTs) have not been established. This qualitative study examined MCTs for the Vineland-3 and associated life impacts. Semi-structured interviews with 18 caregivers of children/adolescents with DS, including concept elicitation then completion and qualitative exploration of meaningful change for eight Vineland-3 subdomains considered most relevant to DS were conducted. Findings were used in clinical expert discussions. Caregivers spontaneously reported 35 signs/symptoms; most frequent were seizures (n = 16). Disruptive behavior, delays in adaptive behavior, and impaired communication were considered important to change with treatment. Raw score improvements ranging from 1 to 3 points (2 to 3 growth scale values) across subdomains were considered meaningful to ≥50 % of caregivers. These meaningful changes were associated with greater patient independence and safety. Caregivers ranked expressive and receptive communication as most important for improvement. Clinical experts' feedback regarding clinically meaningful changes aligned with caregivers' feedback. Clinical experts highlighted multiple factors for determining Vineland-3 MCTs in DS, including age, underlying intellectual and developmental ability, and presence of autism spectrum disorder. Overall, small changes on the Vineland-3 were considered meaningful to caregivers and clinical experts and were associated with important impacts for patients and families. This study provides novel insights supporting Vineland-3 MCT selection in DS, supporting the Vineland-3's use to explore non-seizure treatment-related benefit in clinical trial settings. Further evaluation of MCTs via in-trial interviews and quantitative anchor-based methods may be considered.
《文兰适应性行为量表》第三版（Vineland - 3）用于评估发育性和癫痫性脑病（包括德雷维特综合征（DS））的非癫痫发作结局；尚未确定有意义的变化阈值（MCT）。这项定性研究考察了Vineland - 3的MCT及其相关的生活影响。对18名患有DS的儿童/青少年的照料者进行了半结构化访谈，包括概念引出，然后完成并对8个被认为与DS最相关的Vineland - 3子领域的有意义变化进行定性探索。研究结果用于临床专家讨论。照料者自发报告了35种体征/症状；最常见的是癫痫发作（n = 16）。破坏性行为、适应性行为延迟和沟通障碍被认为对治疗改变很重要。各子领域原始分数提高1至3分（2至3个增长量表值）被≥50%的照料者认为是有意义的。这些有意义的变化与患者更大的独立性和安全性相关。照料者将表达性和接受性沟通列为改善最重要的方面。临床专家关于临床有意义变化的反馈与照料者的反馈一致。临床专家强调了确定DS中Vineland - 3 MCT的多个因素，包括年龄、潜在的智力和发育能力以及自闭症谱系障碍的存在。总体而言，Vineland - 3上的小变化被照料者和临床专家认为是有意义的，并且对患者和家庭有重要影响。本研究提供了新的见解，支持在DS中选择Vineland - 3 MCT，支持Vineland - 3在临床试验环境中用于探索与非癫痫发作治疗相关的益处。可考虑通过试验中的访谈和基于定量锚定的方法对MCT进行进一步评估。
