Meera S Ramakrishnan1, Yinxi Yu2, Brian L VanderBeek1,3,4. 1. Scheie Eye Institute, Perelman School of Medicine, Department of Ophthalmology, University of Pennsylvania, Philadelphia. 2. Center for Preventative Ophthalmology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia. 3. Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, University of Pennsylvania, Philadelphia. 4. Leonard Davis Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Abstract
Importance: Visit adherence has been shown to play a significant role in patient health outcomes. The effect of missing visits on visual acuity (VA) in individuals with neovascular age-related macular degeneration has yet to be characterized. Objective: To quantify the association between patients' adherence to randomized clinical trial visits and VA in individuals with neovascular age-related macular degeneration based on 4 visit adherence metrics. Design, Setting, and Participants: This is a secondary analysis of the Comparison of Age-Related Macular Degeneration Treatment Trial randomized clinical trial. Individuals with age-related macular degeneration were recruited from 44 clinical centers in the United States between February 2008 and December 2009. The 2-year study protocol required 1 visit every 4 weeks (every 21-35 days for a total of 26 visits) for monthly vs pro re nata treatments of bevacizumab vs ranibizumab. Analysis took place from November 2018 through May 2019. Exposures: Visit adherence was measured in 4 ways: total number of missed visits, average number of days (avg days) between each visit, longest duration in days (max days) between visits, and visit constancy (the tally of 3-month periods with at least 1 visit attended). Average and max days were also categorized as on time (28-35 days), late (36-60 days), and very late (>60 days). Main Outcomes and Measures: Change in Early Treatment Diabetic Retinopathy Study VA between the baseline and the last visit. Linear multivariate regression models were applied to analyze the association between visit adherence and change in VA, controlling for age, sex, baseline VA, anti-vascular endothelial growth factor drug, number of injections, and dosing regimen. Results:Of 1178 patients, the mean (SD) age was 79.1 (7.3) years, and 727 (61.7%) were women. The mean (SD) number of missed visits was 2.4 (3.1). Overall, 1091 patients (92.6%) had complete visit constancy during the entire study period. Average days were categorized with 1060 patients (90.0%) classified as on time, 108 (9.2%) were late, and 10 (0.8%) were very late. For max days between visits, 197 patients (16.7%) were on time, 773 (65.6%) were late, and 208 (17.7%) were very late. After controlling for covariates, the late (avg days = -6.1; max days = -2.0) and very late (avg days = -12.5; max days = -5.9) groups saw fewer letters in both the avg and max days categories than patients in the on-time group (P < .001). Conclusions and Relevance: These results provide evidence to support the concept that visit adherence contributes to VA outcomes in neovascular age-related macular degeneration. The magnitude of the association of visit adherence with VA outcomes in this clinical scenario suggests that substantial effort should be expended to strive for visit adherence or therapeutic strategies that reduce the visit burden without compromising VA outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT00593450.
RCT Entities:
Importance: Visit adherence has been shown to play a significant role in patient health outcomes. The effect of missing visits on visual acuity (VA) in individuals with neovascular age-related macular degeneration has yet to be characterized. Objective: To quantify the association between patients' adherence to randomized clinical trial visits and VA in individuals with neovascular age-related macular degeneration based on 4 visit adherence metrics. Design, Setting, and Participants: This is a secondary analysis of the Comparison of Age-Related Macular Degeneration Treatment Trial randomized clinical trial. Individuals with age-related macular degeneration were recruited from 44 clinical centers in the United States between February 2008 and December 2009. The 2-year study protocol required 1 visit every 4 weeks (every 21-35 days for a total of 26 visits) for monthly vs pro re nata treatments of bevacizumab vs ranibizumab. Analysis took place from November 2018 through May 2019. Exposures: Visit adherence was measured in 4 ways: total number of missed visits, average number of days (avg days) between each visit, longest duration in days (max days) between visits, and visit constancy (the tally of 3-month periods with at least 1 visit attended). Average and max days were also categorized as on time (28-35 days), late (36-60 days), and very late (>60 days). Main Outcomes and Measures: Change in Early Treatment Diabetic Retinopathy Study VA between the baseline and the last visit. Linear multivariate regression models were applied to analyze the association between visit adherence and change in VA, controlling for age, sex, baseline VA, anti-vascular endothelial growth factor drug, number of injections, and dosing regimen. Results: Of 1178 patients, the mean (SD) age was 79.1 (7.3) years, and 727 (61.7%) were women. The mean (SD) number of missed visits was 2.4 (3.1). Overall, 1091 patients (92.6%) had complete visit constancy during the entire study period. Average days were categorized with 1060 patients (90.0%) classified as on time, 108 (9.2%) were late, and 10 (0.8%) were very late. For max days between visits, 197 patients (16.7%) were on time, 773 (65.6%) were late, and 208 (17.7%) were very late. After controlling for covariates, the late (avg days = -6.1; max days = -2.0) and very late (avg days = -12.5; max days = -5.9) groups saw fewer letters in both the avg and max days categories than patients in the on-time group (P < .001). Conclusions and Relevance: These results provide evidence to support the concept that visit adherence contributes to VA outcomes in neovascular age-related macular degeneration. The magnitude of the association of visit adherence with VA outcomes in this clinical scenario suggests that substantial effort should be expended to strive for visit adherence or therapeutic strategies that reduce the visit burden without compromising VA outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT00593450.