Sample Size Requirements of Glaucoma Clinical Trials When Using Combined Optical Coherence Tomography and Visual Field Endpoints

Zhichao Wu,Felipe A Medeiros

doi:10.1038/s41598-019-55345-x

Abstract

Glaucoma clinical trials using visual field (VF) endpoints currently require large sample sizes because of the slowly-progressive nature of this disease. We sought to examine whether the combined use of VF testing and non-invasive optical coherence tomography (OCT) imaging of the neuroretinal tissue could improve the feasibility of such trials. To examine this, we included 192 eyes of 121 glaucoma participants seen at ≥5 visits over a 2-year period to extract real-world estimates of the rates of change and variability of VF and OCT imaging measurements for computer simulations to obtain sample size estimates. We observed that the combined use of VF and OCT endpoints led to a 31–33% reduction in sample size requirements compared to using VF endpoints alone for various treatment effect sizes. For example, 189 participants would be required per group to detect a 30% treatment effect with 90% power with combined VF and OCT endpoints, whilst 276 and 285 participants would be required when using VF and OCT endpoints alone respectively. The combined use of OCT and VF endpoints thus has the potential to effectively improve the feasibility of future glaucoma clinical trials.

Highlights

We have previously observed two methodological aspects that could reduce sample size requirements in glaucoma trials
Using both outcome measures together reduced the sample size requirements by 31–33% compared to using visual fields alone, and by 33–35% compared to using optical coherence tomography (OCT) alone
We demonstrated that the combined use of visual field and OCT imaging endpoints reduced sample size requirements by 31–33% compared to the conventional use of visual field endpoints alone in a short-term glaucoma clinical trial scenario

Summary

Introduction

We have previously observed two methodological aspects that could reduce sample size requirements in glaucoma trials. We showed that using a between-group trend-based analysis of the outcome measures instead of the conventional individual-based event-based analysis, resulted in major reductions in the required sample size[17]. We used a testing paradigm that clustered visits at the bookends of the trial period (as originally suggested by Crabb et al.18), as opposed to evenly-spacing the tests, and these changes in the analytical methods and trial design further reduced sample size requirements[19]. This study sought to determine whether the combined used of visual field and OCT imaging endpoints could improve the feasibility of future glaucoma clinical trials by reducing the sample size requirements. OCT Only VF and OCT compared to using conventional visual field endpoints alone, when incorporating the two abovementioned methodological aspects

Methods

Results

Conclusion