Hamilton Glaucoma Center, Shiley Eye Institute, Viterbi Family Department of Ophthalmology, University of California, San Diego, La Jolla.
Duke Eye Center, Department of Ophthalmology, Duke University, Durham, North Carolina.
JAMA Ophthalmol. 2021 Aug 1;139(8):839-846. doi: 10.1001/jamaophthalmol.2021.1812.
Clinical trials of glaucoma therapies focused on protecting the optic nerve have required large sample sizes and lengthy follow-up to detect clinically relevant change due to its slow rate of progression. Whether shorter trials may be possible with more frequent testing and use of rate of change as the end point warrants further investigation.
To describe the design for the Short-term Assessment of Glaucoma Progression (STAGE) model and provide guidance on sample size and power calculations for shorter clinical trials.
DESIGN, SETTING, AND PARTICIPANTS: A cohort study of patients with mild, moderate, or advanced open-angle glaucoma recruited from the Diagnostic Innovations in Glaucoma Study at the University of California, San Diego. Enrollment began in May 2012 with follow-up for every 3 months for 2 years after baseline examination. Follow-up was concluded in September 2016. Data were analyzed from July 2019 to January 2021. Visual fields (VF) and optic coherence tomography (OCT) scans were obtained at baseline and for 2 years with visits every 3 months.
Glaucoma was defined as glaucomatous appearing optic discs classified by disc photographs in at least 1 eye and/or repeatable VF damage at baseline.
Longitudinal rates of change in retinal nerve fiber layer (RNFL) thickness and VF mean deviation (MD) are estimated in study designs of varying length and observation frequency. Power calculations as functions of study length, observation frequency, and sample size were performed.
In a total referred sample of 97 patients with mild, moderate, or advanced glaucoma (mean [SD] age, 69 [11.4] years; 50 [51.5%] were female; 19 [19.6%]), over the 2-year follow-up, the mean VF 24-2 MD slope was -0.32 dB/y (95% CI, -0.43 to -0.21 dB/y) and the mean RNFL thickness slope was -0.54 μm/y (95% CI, -0.75 to -0.32 μm/y). Sufficient power (80%) to detect similar group differences in the rate of change in both outcomes was attained with total follow-up between 18 months and 2 years and fewer than 300 total participants.
In this cohort study, results from the STAGE model with reduction of the rate of progression as the end point, frequent testing, and a moderate effect size, suggest that clinical trials to test efficacy of glaucoma therapy can be completed within 18 months of follow-up and with fewer than 300 participants.
由于青光眼视神经病变的进展速度缓慢，旨在保护视神经的青光眼治疗的临床试验需要较大的样本量和较长的随访时间，才能检测到具有临床意义的变化。更频繁的检测和使用变化率作为终点是否可以使较短的临床试验成为可能，这值得进一步研究。
描述短期青光眼进展评估（STAGE）模型的设计，并提供有关更短临床试验的样本量和功效计算的指导。
设计、设置和参与者：这是一项来自加利福尼亚大学圣地亚哥分校诊断性青光眼创新研究的轻度、中度或晚期开角型青光眼患者的队列研究。招募工作于 2012 年 5 月开始，基线检查后每 3 个月随访 2 年。随访于 2016 年 9 月结束。数据分析于 2019 年 7 月至 2021 年 1 月进行。基线和 2 年时获得视野（VF）和光学相干断层扫描（OCT）扫描，每 3 个月就诊一次。
青光眼定义为至少一只眼存在盘照片显示的青光眼性视盘改变和/或基线时存在可重复的视野损害。
根据不同长度和观察频率的研究设计，估计视网膜神经纤维层（RNFL）厚度和 VF 平均偏差（MD）的纵向变化率。作为研究长度、观察频率和样本量函数的功效计算。
在总共 97 名轻度、中度或晚期青光眼患者的全转诊样本中（平均[标准差]年龄 69[11.4]岁；50[51.5%]为女性；19[19.6%]），在 2 年的随访中，VF 24-2 MD 斜率为-0.32 dB/y（95%CI，-0.43 至-0.21 dB/y），RNFL 厚度斜率为-0.54 μm/y（95%CI，-0.75 至-0.32 μm/y）。在总随访时间为 18 个月至 2 年且总参与者少于 300 名的情况下，达到了以变化率为终点、更频繁的检测和中等效果量来检测青光眼治疗效果的临床试验具有相似的组间差异的足够功效（80%）。
在这项队列研究中，以 STAGE 模型为基础的结果显示，当以降低进展率为终点、更频繁的检测和中等效果量时，提示以进展率为终点的临床试验可以在 18 个月的随访时间内完成，且总参与者少于 300 名。
