Short-term Assessment of Glaucoma Progression in Clinical Trials Using Trend-based Visual Field Progression Analysis

To evaluate the effect of disease stage, frequency and clustering of visual field (VF) tests, inclusion of 1 or both eyes, and 1 (1 arm; before and after a treatment) or 2 groups (2 arms; treatment and control arm) on sample size calculation in clinical trials.

Clinical cohort study.

A series of VFs were simulated based on test-retest VF data in the early, moderate, and advanced stages of glaucoma with 231, 204, and 226 eyes, respectively.

The mean of mean deviation (MD) slope was -0.75 decibels (dB)/year before treatment initiation in the 1-arm trial, and in the control group in the 2-arm trial. Visual field measurements were scheduled as 8 times in 2 years.

Sample size calculation in clinical trials.

In the 1-arm trial, when only 1 eye was used in each patient, the 80% probability of significance in the moderate stage was observed with sample size = 70 eyes. Disease in the early stage and inclusion of both eyes decreased this number to 30 eyes; these decreasing effects were significantly larger than performing 1 or 2 additional VFs at the beginning and end of the observation. Conversely, a greater number of eyes was necessary in advanced stage than in moderate stage. In the 2-arm trial (80% probability of significance, and 1 eye per patient), the 80% probability of significance was observed with sample size = 80 eyes in each arm, a tendency that was similar to what observed for the 1-arm trial. Similar tendency was observed in the simulations with much slower VF progression (mean MD slope = -0.25 dB/year).

The present study highlights the importance of considering disease stage when planning a clinical trial.

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.