Most patients with neurovascular age-related macular degeneration (nAMD) would not qualify for the trials that inform currents standards of care, according to a study presented at the 39th Annual Scientific Meeting of ASRS 2021 held from October 8-12, in San Antonio, Texas. “Real-world outcomes do mirror outcomes expected from clinical trials when only trial-eligible patients are analyzed,” the study authors write. “The pejorative implications that real-world patients do worse than expected may be due to methodology that does not account for the heterogeneity of real-world patients.”
The study team compared the treatment and clinical outcomes of real-world patients with nAMD, who would have qualified for Phase 3 trials, with those of real -world patients with nAMD, who would have been deemed trial-ineligible.
Accurate knowledge of real-world outcomes is essential to health policy, practice management, and physician reimbursement, the researchers point out. “Conventional wisdom holds that real-world patients achieve outcomes inferior to what is expected from Phase 3 clinical trials,” they write. “But this belief stems largely from registry studies that ignore underlying differences between real-world patients and clinical trial participants.”
Visual Acuity Was Primary Outcome Measure
The researchers reviewed clinical and imaging data of consecutive patients with new active nAMD from a community-based tertiary retina practice. Protocols from the HARBOR, VIEW-1, CATT, and LUCAS trials were applied to determine which patients would have been eligible for any of these trials. Patients not meeting all study inclusion criteria were defined as trial-ineligible. Primary outcome measures were visual acuity (VA) at 24 months following diagnosis and number of anti-VEGF injections received throughout 12 and 24 months. To replicate the methods from published Vestrum analyses, patients receiving three or more injections within 4 months of diagnosis were identified for additional analysis.
They analyzed clinical data and angiograms from 1,239 eyes and found that only 589 eyes (48%) would have been eligible for CATT, 41% for LUCAS, 37% for HARBOR, and only 36% for VIEW-1. The most common reasons for ineligibility were lesion characteristics and prior anti-VEGF therapy. “CATT trial-eligible” eyes gained mean 8.7 ETDRS letters at 12 months, after median 10 injections, and gained mean 7.8 ETDRS letters at 24 months, with median additional seven injections.
These results are comparable to what is expected from the CATT trial, the researchers note. “Trial-ineligible eyes at 24 months, by contrast, showed significantly worse median VA, were less likely to have improved VA, gained fewer ETDRS letters, were less likely to achieve 20/40 or better, were more likely to have 20/200 or worse, and received significantly fewer anti-VEGF injections,” they write. “Even when applying Vestrum-analysis methodology, outcomes consistent with clinical trials were observed when analysis was limited to trial-eligible patients.”
