Real-World Applicability of Anti-VEGF Trial Criteria for Diabetic Macular Edema

OBJECTIVE:To characterize the real-world eligibility based on systemic medical criteria of patients receiving anti-VEGF injections for DME, including potential rates of trial exclusion and associated patient demographics. DESIGN:Cross-sectional study. SUBJECTS:Patients who received at least one anti-VEGF injection for treatment of DME with recorded pre-injection blood pressure (BP) and hemoglobin A1c (A1c) measurements. METHODS:Data was sourced from United States healthcare organizations enrolled in the TriNetX database. Trial selection criteria were sourced from ClinicalTrials.gov. MAIN OUTCOME MEASURES:The primary outcome was the overall rate of trial exclusion across all participants. Secondary outcomes comprised the rate of exclusion based on patient demographics. RESULTS:The most inclusionary ("liberal") criteria allowed for participation with BP ≤180/100, A1c ≤12.0%, no history of myocardial infarction (MI) or cerebrovascular accident (CVA) within 3 months prior to first injection, and no history of end stage renal disease (ESRD). The most exclusionary ("stringent") criteria required BP ≤160/95, A1c ≤10.0%, no history of MI or CVA within 6 months prior to first injection, and no history of ESRD. Application of the liberal and stringent criteria excluded 25.7% and 59.1% of real-world patients, respectively. Compared to White individuals, Black individuals were significantly more likely to be excluded by the liberal criteria (Odds ratio [OR] 1.97; 95% CI, 1.57 to 2.46; Padj < .001) as well as stringent criteria (OR, 2.29; 95% CI, 1.82 to 2.87; Padj < .001). Individuals of Other race(s) were significantly more likely to be excluded by the liberal criteria (OR, 1.94; 95% CI, 1.33 to 2.84; Padj = .004). CONCLUSIONS:Systemic medical selection criteria for clinical trials of anti-VEGF therapy for DME exclude a significant portion of real-world patients, with members of racial minority groups being disproportionately affected.