Methodological Appraisal of Phase 3 Clinical Trials in Geographic Atrophy

Area of Science:

• Ophthalmology
• Clinical Trial Methodology
• Retinal Diseases

Background:

• Geographic atrophy (GA) is a significant cause of vision loss globally.
• The recent approval of pegcetacoplan marks a milestone in GA treatment.
• Critical evaluation of clinical trial methodology is essential for understanding treatment efficacy.

Purpose of the Study:

• To critically appraise the methodological aspects of phase 3 clinical trials for geographic atrophy.
• To analyze the design, analysis, and interpretation of these trials.
• To enhance the understanding and interpretation of clinical trial results in GA.

Main Methods:

• Systematic review of phase 3 clinical trials for GA registered in public databases as of May 2023.
• Analysis of key trial attributes including endpoints, eligibility, statistical methods, and reporting.
• Comparison of methodological similarities and differences across five major trials (GATHER1, DERBY/OAKS, CHROMA/SPECTRI, SEATTLE, GATE).

Main Results:

• Five phase 3 trials (GATHER1, DERBY/OAKS, CHROMA/SPECTRI, SEATTLE, GATE) have reported results.
• Trials share similarities in endpoints and eligibility but differ in key aspects like primary endpoint metrics and sample size.
• Methodological variations can influence trial outcomes and their interpretation.

Conclusions:

• Understanding clinical trial methodology is crucial for accurate interpretation of GA treatment data.
• Authors should follow reporting guidelines for transparent communication of trial conduct and findings.
• Standardized reporting and methodological considerations are vital for advancing GA research and treatment.