Noncompliance in Prospective Retina Clinical Trials: Analysis of factors predicting loss to follow up

Abstract Purpose Noncompliance during prospective studies can bias results and limit conclusions. The current study retrospectively investigated the relationship between study subject characteristics and rates of noncompliance in interventional trials involving common causes of blindness. Design Retrospective analysis of 10 randomized clinical trials. Methods Subjects were enrolled in investigator-initiated trials studying proliferative diabetic retinopathy, neovascular age-related macular degeneration, diabetic macular edema, and retinal venous occlusive disease. Records were reviewed for hypothesized risk factors of noncompliance and rates of noncompliance which were defined as at least one missed visit or exiting the study early. Demographic information, systemic medical history, and ocular medical history, including visual acuity (VA) and central retinal thicknesses (CRT), were examined retrospectively using Student’s T test, Pearson’s Chi-square test and logistic regression. Results Of 390 subjects included, 212 (54.4%) were compliant with all scheduled study visits and 178 (45.6%) met criteria for noncompliance, with 53 (13.6%) subjects exiting early. Regression models identified 17 variables that were significant in determining subject noncompliance. Among those, distance, comorbidities, diabetic status, concomitant medications, previous clinic visits, length of study, disease under study, and severe adverse events were highly significant risk factors of noncompliance. Conclusion The current research identified a substantial proportion of subjects who met the criteria for noncompliance within the trials analyzed. The factors identified in the current work are consistent with published clinical observations and the results of previous clinical trials. These results highlight the importance of considering study design and medical history when designing prospective clinical trials in an attempt to minimize data loss.