Contextualising Single-Arm Ophthalmology Trials With Real-World Data: An Emulated Target Trial Comparing The Efficacy of Interventions For Neovascular Age-Related Macular Degeneration

ABSTRACT Methods: of causal inference have shown promise in replicating randomised trials using real-world data recorded by Electronic Health Records (EHRs). We herein emulated a target trial on the intention-to-treat efficacy of off-label bevacizumab (q6w) pro re nata relative to fixed-interval aflibercept (q8w) for improving week-54 visual acuity of eyes affected by neovascular age-related macular degeneration. The bevacizumab arm (n 65) was taken from the ABC randomised controlled trial. A total of 4,471 aflibercept-treated eyes aligning with the ABC trial eligibility were identified from EHRs and synthetic control arms were created by emulating randomisation conditional on age, sex, and baseline visual read via exact matching and propensity score methods. We undertook an inferiority analysis on mean difference at 54 weeks; outcomes regression on achieving a change in visual acuity of ≥ 15, ≥ 10, and ≤ −15 Early Treatment Diabetic Retinopathy Letters (ETDRS) letters at week 54; and a time-to-event analysis on achieving a change in visual acuity of ≥ 15, ≥ 10, and ≤ −15 ETDRS letters by week 54. Our findings suggest off-label bevacizumab to be neither non-inferior nor superior to licensed aflibercept. While being no substitute for randomised controlled trials, emulated target trials could aid the interpretation of single-armed trials.