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

Area of Science:

• Ophthalmology
• Clinical Trials
• Biostatistics

Background:

• Glaucoma clinical trials require accurate sample size calculations for statistical validity.
• Factors such as disease severity and testing protocols can influence these calculations.
• Optimizing sample size is crucial for efficient trial design and resource allocation.

Purpose of the Study:

• To evaluate how disease stage, visual field (VF) test frequency and clustering, inclusion of one or both eyes, and trial design (1-arm vs. 2-arm) affect sample size calculations in glaucoma clinical trials.
• To provide data-driven insights for more precise sample size determination in future glaucoma research.

Main Methods:

• Simulated a series of visual field tests using test-retest data from early, moderate, and advanced glaucoma stages.
• Analyzed sample size requirements for 1-arm (before/after treatment) and 2-arm (treatment/control) trial designs.
• Varied parameters including number of eyes per patient and visual field progression rates.

Main Results:

• In a 1-arm trial, moderate-stage glaucoma required 70 eyes; early-stage and bilateral inclusion reduced this to 30 eyes.
• Advanced-stage glaucoma necessitated a larger sample size than moderate-stage.
• In a 2-arm trial, 80 eyes per arm were needed for significance, mirroring trends in the 1-arm design.
• Slower visual field progression rates maintained similar sample size tendencies.

Conclusions:

• Disease stage is a critical factor that must be considered during sample size calculation for glaucoma clinical trials.
• The number of eyes included per patient and the trial design also influence required sample sizes.
• These findings aid in optimizing the design and efficiency of glaucoma clinical trials.