Hermes Jacques, Steiert Bernhard
Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Institute of Physics, University of Freiburg, Freiburg, Germany.
Transl Vis Sci Technol. 2025 Sep 2;14(9):2. doi: 10.1167/tvst.14.9.2.
Early-stage clinical trials for major retinal diseases face challenges due to substantial interpatient variability, end points with high intrapatient variability, and prolonged follow-up periods required to detect treatment effects. This study explores whether integrating home optical coherence tomography (OCT) monitoring with pharmacokinetic/pharmacodynamic (PK/PD) modeling can reduce clinical trial sample size.
A population PK/PD model was developed using longitudinal central subfield thickness data from a home OCT study. Monte Carlo simulations and bootstrapping were used to evaluate the impact of different monitoring strategies on sample size requirements to detect a simulated effect size of approximately 50-µm central subfield thickness reduction over an active comparator drug.
To reliably detect this effect, traditional biweekly in-clinic monitoring required 41 to 54 patients per arm, whereas home OCT monitoring only required 33 to 35 patients per arm, representing a 20% to 40% sample size reduction.
These findings highlight the potential for home OCT and PK/PD modeling to improve trial efficiency and patient convenience while maintaining statistical power.
By reducing sample size requirements while maintaining statistical power, this approach can streamline clinical trials, expediting the development of new retinal therapies and improving patient access to treatment.
由于患者间存在显著差异、患者内终点存在高变异性以及检测治疗效果需要较长的随访期，主要视网膜疾病的早期临床试验面临挑战。本研究探讨将家庭光学相干断层扫描（OCT）监测与药代动力学/药效学（PK/PD）建模相结合是否可以减少临床试验样本量。
使用来自家庭OCT研究的纵向中心子场厚度数据建立群体PK/PD模型。蒙特卡罗模拟和自抽样法用于评估不同监测策略对检测活性对照药物中心子场厚度减少约50μm模拟效应量所需样本量的影响。
为了可靠地检测到这种效应，传统的每两周一次的门诊监测每组需要41至54名患者，而家庭OCT监测每组仅需要33至35名患者，样本量减少了20%至40%。
这些发现突出了家庭OCT和PK/PD建模在保持统计效力的同时提高试验效率和患者便利性的潜力。
通过在保持统计效力的同时减少样本量要求，这种方法可以简化临床试验，加快新的视网膜治疗方法的开发，并改善患者获得治疗的机会。
