Abstract
Purpose :
The investigation of screening failures (SF) in dry eye studies is crucial for the advancement of dry eye drug development and the optimization of clinical trial designs. Numerous factors can contribute to subjects failing the screening process. The commonly used endpoint measurements for assessing signs and symptoms of Dry Eye Disease (DED) exhibit poor correlation, with the possibility for age-related variations. This study investigates the causes of screen failures in dry eye studies and explores demographic factors as well as clinical endpoints that contribute to screening failures.
Methods :
Screening and pre-randomization data from two identically designed clinical trials (Phase 2 and Phase 3) were combined into one dataset. In both trials, exposure to a controlled adverse environment (CAE) occurred at visits 1 and 2, each lasting 90 minutes. Schirmer’s values and Lissamine values were compared to symptom scores across different age groups in order to evaluate significant correlations or trends. Symptoms were graded using the multi-symptom Visual Analog Scale (VAS), SANDE symptom assessment, Ora Calibra® Ocular Discomfort scale and 4-Symptom Questionnaire.
Results :
494 subjects met the screening criteria. For subjects less than age 50 primary cause of SF was due to Schirmer test (48.1%) with only (3.8%) failure due to symptoms and (1.5%) due to lissamine. For subjects over age 50, SF were due to Schirmer test (42.2%) with only 18.2% of SF due to symptoms and 1.9% from lissamine. Significant correlations between lissamine green staining and symptoms were found across all subject age groups (p<0.05). Schirmer scores did not show evidence of correlation with any symptoms across all subjects.
Conclusions :
Overall, lissamine provides a higher probability of being enrolled into a dry eye clinical trial than the Schirmer’s test.. Lissamine also correlates better with symptoms due in part to the reproducibility of Lissamine testing. While a proper tear film is essential in protecting the ocular surface, the variation in Schirmer’s Testing, make this a problematic factor for inclusion into clinical trials and requires further evaluation.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.