By using frequent testing and monitoring the rate of change in retinal nerve fiber layer thickness (RNFL) and visual field (VF) mean deviation (MD) as an end point, research suggests that clinical trials of glaucoma therapies can be completed within a relatively short time frame. A JAMA Ophthalmology study shows that these trials can be completed within 18 months of follow-up and with fewer than 300 participants.
Researchers conducted a cohort study 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. The study consisted of 97 patients (mean age 69 years) with mild, moderate, or advanced open-angle glaucoma between 2012 and 2016. At baseline, optic coherence tomography (OCT) scans and VF exams were conducted. The main outcome measures included longitudinal rates of change in the RNFL thickness and VF MD.
In the 2-year follow up, mean 24-2 VF slope was -0.32 dB per year y (95% CI, -0.43 to -0.21 dB per year) and the mean RNFL thickness slope was -0.54 μm per year (95% CI, -0.75 to -0.32 μm per year). The researchers successfully attained sufficient power (80%) to detect similar group differences in the rate of change for both outcomes between 18 months and 2 years, and with fewer than 300 total participants.
The researchers explain that prior research also suggests that large sample sizes or follow up durations are not required to detect differences in VF, or RNFL thickness change rates, and that the methods applied in the present study were consistent with them.
“We found that totals of 223, 125, and 80 participants per group were required to obtain 90% power for treatment effects of 30%, 40%, and 50% (0.17 dB per year, 0.23 dB per year, and 0.29 dB per year), respectively,” the study explains.
Limitations include possible selection bias, possible confounding due to missed visits or lack of followup, possible false positives resulting from VF tests, and possible confounding due to 10-2 VF testing, VF index, or pattern standard deviation. Additionally, generalizability to advanced glaucoma trials is limited due to the large number of participants with early glaucoma.
Proudfoot JA, Zangwill LM, Moghimi S, et al. Estimated utility of the short-term assessment of glaucoma progression model in clinical practice. JAMA Ophthalmol. Published online June 10, 2021. doi:10.1001/jamaophthalmol.2021.1812