CERobs Consulting, LLC, Wrightsville Beach, NC, USA.
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Ther Innov Regul Sci. 2023 Nov;57(6):1304-1313. doi: 10.1007/s43441-023-00568-4. Epub 2023 Aug 17.
Neurodegenerative diseases cause developmental delays and loss of milestones in infants and children. However, scalable outcome measures that quantify features meaningful to parents/caregivers (P/CGs) and have regulatory precedence are lacking for assessing the effectiveness of treatments in clinical trials of neurodegenerative disorders. To address this gap, we developed an innovative, blinded strategy for single-arm trials with external controls using expert panel review of home video.
We identified meaningful, observable, and objective developmental milestones from iterative interviews with P/CGs and clinical experts. Subsequently, we standardized video recording procedures and instructions to ensure consistency in how P/CGs solicited each activity. In practice, videos would be graded by an expert panel blinded to treatment. To ensure blinding and quality control, video recordings from interim time points would be randomly interspersed. We conducted a pilot study and a pretest of grading to test feasibility and improve the final strategy.
The five P/CGs participating in the pilot study found the instructions clear, selected activities important and reflective of their children's abilities, and recordings at-home preferrable to in-clinic assessments. The three grading experts found the videos easy to grade and the milestones clinically meaningful.
Our standardized strategy enables expert panel grading of developmental milestone achievements using at-home recordings, blinded to treatment and post-baseline time points. This rigorous and objective scoring system has broad applicability in various disease contexts, with or without external controls. Moreover, our strategy facilitates flexible, continued data collection and the videos can be archived for future analyses.
神经退行性疾病会导致婴儿和儿童发育迟缓，丧失发育里程碑。然而，在神经退行性疾病临床试验中，缺乏可衡量对父母/照顾者（P/CG）有意义且具有监管优先权的特征的可扩展结果测量方法，以评估治疗效果。为了解决这一差距，我们开发了一种使用外部对照的专家小组对家庭录像进行盲审的单臂试验的创新策略。
我们从与 P/CG 和临床专家的迭代访谈中确定了有意义、可观察和客观的发育里程碑。随后，我们标准化了录像记录程序和说明，以确保 P/CG 以一致的方式征求每个活动。实际上，视频将由对治疗方案盲目的专家小组进行评分。为了确保盲法和质量控制，将在中间时间点随机穿插视频记录。我们进行了一项试点研究和分级预测试，以测试可行性并改进最终策略。
参与试点研究的五名 P/CG 认为说明清晰，选择的活动重要且反映了他们孩子的能力，并且在家中录制比在诊所评估更受欢迎。三位分级专家认为视频易于评分，里程碑具有临床意义。
我们的标准化策略可使用家庭录像记录对专家小组进行发育里程碑成就的盲审，对治疗和基线后时间点均为盲法。这种严格而客观的评分系统具有广泛的适用性，适用于各种疾病环境，无论是否有外部对照。此外，我们的策略便于灵活的持续数据收集，并且可以将视频存档以备将来分析。
