Powers Sonya, Anderson Katherine N, Tan Wen-Hann, Gwaltney Angela, Potter Sarah Nelson, Tillmann Julian, Daniel Mark, Thum Audrey, Farmer Cristan, Clinch Susanne, Squassante Lisa, Tjeertes Jorrit, Vincenzi Brenda, Buzasi Katalin, Wheeler Anne C, Sadhwani Anjali
medRxiv. 2025 Apr 7:2025.04.05.25325305. doi: 10.1101/2025.04.05.25325305.
To develop within-patient meaningful score differences (MSDs) on the Bayley Scales of Infant Development, Fourth Edition (Bayley-4), and the Vineland Adaptive Behavior Scales, Third Edition (Vineland-3), for individuals with Angelman syndrome (AS).
A Delphi method, involving a panel of 19 caregivers of individuals with AS, was used to establish MSDs for Bayley-4 and Vineland-3 Growth Scale Values. MSD was defined as the smallest change that would noticeably impact the daily functioning of an individual with AS or family quality of life in a way that was important to the individual with AS or their family. For each subscale of the Bayley-4 and Vineland-3, the panel was presented with 2 to 4 vignettes describing varying levels of baseline functioning and asked to select a MSD from a range of potential values. An iterative process involving three rounds of ratings and two rounds of discussion was used to build consensus. The median caregiver rating from round 3 was retained as the final recommended MSD value for each vignette.
Final MSD ratings for the five subscales of Bayley-4 and 10 subscales of the Vineland-3 had an agreement rate of 70% or higher. MSD thresholds for each subscale were not single cut-offs, but rather reflected a range of MSD values dependent on level of baseline functioning.
The Delphi Panel method incorporates the caregiver perspective to provide preliminary estimates of what constitutes meaningful within person change on the Bayley-4 and Vineland-3 in individuals with AS with various levels of baseline functioning.
⍰ To acquire regulatory approval in drug development, sponsors must demonstrate both statistical significance and clinical meaningfulness of a treatment effect.While several clinical trials are underway in AS, within person meaningful score difference thresholds are not yet established for the most commonly used outcome measures, namely the Bayley and Vineland.⍰ Aligning with FDA guidance, we have developed an innovative qualitative approach using a Delphi panel to incorporate caregiver perspectives in defining meaningful change and generated preliminary patient-informed meaningful score differences (MSDs) for individuals with Angelman Syndrome.⍰ What caregivers of individuals with AS consider to be a MSD on the measures depends primarily on the baseline severity of their child's presentation.
为患有天使综合征（AS）的个体制定贝利婴儿发展量表第四版（Bayley - 4）和文兰适应行为量表第三版（Vineland - 3）的患者内有意义得分差异（MSD）。
采用德尔菲法，由19名AS个体的照料者组成的小组参与，为Bayley - 4和Vineland - 3生长量表值确定MSD。MSD被定义为最小变化，该变化会以对AS个体或其家庭重要的方式显著影响AS个体的日常功能或家庭生活质量。对于Bayley - 4和Vineland - 3的每个子量表，向小组展示2至4个描述不同基线功能水平的 vignette，并要求从一系列潜在值中选择一个MSD。采用三轮评分和两轮讨论的迭代过程来达成共识。第3轮照料者评分的中位数被保留为每个vignette的最终推荐MSD值。
Bayley - 4的五个子量表和Vineland - 3的十个子量表的最终MSD评分一致率达到70%或更高。每个子量表的MSD阈值不是单一的临界值，而是反映了一系列取决于基线功能水平的MSD值。
德尔菲小组法纳入了照料者的观点，以初步估计对于不同基线功能水平的AS个体，Bayley - 4和Vineland - 3中构成有意义的个体内变化的因素。
⍰ 在药物开发中获得监管批准时，申办者必须证明治疗效果的统计学显著性和临床意义。虽然针对AS正在进行多项临床试验，但对于最常用的结局指标，即贝利量表和文兰量表，尚未确定个体内有意义得分差异阈值。⍰ 遵循美国食品药品监督管理局（FDA）的指导方针，我们开发了一种创新的定性方法，使用德尔菲小组纳入照料者观点来定义有意义的变化，并为患有天使综合征的个体生成了初步的患者知情有意义得分差异（MSD）。⍰ AS个体的照料者认为这些测量指标上的MSD主要取决于其孩子表现的基线严重程度。
