Visual Field Endpoints for Neuroprotective Trials: A Case for AI-Driven Patient Enrichment

Abstract

PurposeTo evaluate whether an artificial intelligence (AI) model can better select candidates that would demonstrate visual field (VF) progression, in order to shorten the duration or the number of patients needed for a clinical trial.DesignRetrospective cohort study.Methods7428 eyes of 3871 patients from the University of Washington Department of Ophthalmology VF Dataset were included. Progression was defined as at least 5 locations with >7 dB of change compared with baseline on 2 consecutive tests. Progression for all patients, a subgroup of the fastest progressing based on survival curves, and patients selected based on an elastic net Cox regression model were compared. The model was trained on pointwise threshold deviation values of the first VF, age, gender, laterality, and the mean total deviation (MD) at baseline.ResultsA total of 13% of all patients met the criteria for progression at 5 years. Differences in survival were observed when stratified by MD and age (P < .0001). Those at risk of progression included patients aged 60 to 80 years with an initial MD < –5.0. This subgroup decreased the sample size required to detect progression compared with the entire cohort. The AI model-selected patients required the lowest number of patients for all effect sizes and trial lengths. For a trial length of 3 years and effect size of 30%, the number of patients required was 1656 (95% CI, 1638–1674), 903 (95% CI, 884–922), and 636 (95% CI, 625–646) for the entire cohort, the subgroup, and the model-selected patients, respectively.ConclusionAn AI model can identify high-risk patients to substantially reduce the number of patients needed or study duration required to meet clinical trial endpoints. To evaluate whether an artificial intelligence (AI) model can better select candidates that would demonstrate visual field (VF) progression, in order to shorten the duration or the number of patients needed for a clinical trial. Retrospective cohort study. 7428 eyes of 3871 patients from the University of Washington Department of Ophthalmology VF Dataset were included. Progression was defined as at least 5 locations with >7 dB of change compared with baseline on 2 consecutive tests. Progression for all patients, a subgroup of the fastest progressing based on survival curves, and patients selected based on an elastic net Cox regression model were compared. The model was trained on pointwise threshold deviation values of the first VF, age, gender, laterality, and the mean total deviation (MD) at baseline. A total of 13% of all patients met the criteria for progression at 5 years. Differences in survival were observed when stratified by MD and age (P < .0001). Those at risk of progression included patients aged 60 to 80 years with an initial MD < –5.0. This subgroup decreased the sample size required to detect progression compared with the entire cohort. The AI model-selected patients required the lowest number of patients for all effect sizes and trial lengths. For a trial length of 3 years and effect size of 30%, the number of patients required was 1656 (95% CI, 1638–1674), 903 (95% CI, 884–922), and 636 (95% CI, 625–646) for the entire cohort, the subgroup, and the model-selected patients, respectively. An AI model can identify high-risk patients to substantially reduce the number of patients needed or study duration required to meet clinical trial endpoints.

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