Short-term Assessment of Glaucoma Progression in Clinical Trials Using Trend-based Visual Field Progression Analysis.
Ryo Asaoka, Makoto Nakamura, Masaki Tanito, Yuri Fujino, Akira Obana, Shiro Mizoue, Kazuhiko Mori, Katsuyoshi Suzuki, Takehiro Yamashita, Kazunori Hirasawa, Nobuyuki Shoji, Hiroshi Murata
Summary
Glaucoma clinical trial sample sizes vary significantly with disease stage, test frequency, and eye inclusion. Early-stage disease and bilateral eye inclusion reduce required sample sizes, improving trial efficiency.
Abstract
OBJECTIVE
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.
DESIGN
Clinical cohort study.
PARTICIPANTS
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.
METHODS
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.
MAIN OUTCOME MEASURES
Sample size calculation in clinical trials.
RESULTS
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).
CONCLUSIONS
The present study highlights the importance of considering disease stage when planning a clinical trial.
FINANCIAL DISCLOSURES
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Keywords
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