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Abstract

PURPOSE: The purpose of this study was to evaluate the power of trend-based visual field (VF) progression end points against long-term development of event-based end points accepted by the US Food and Drug Administration (FDA). METHODS: One eye from 3352 patients with ≥10 24-2 VFs (median = 11 years) follow-up were analyzed. Two FDA-compatible criteria were applied to these series to label "true-progressed" eyes: ≥5 locations changing from baseline by more than 7 dB (FDA-7) or by more than the expected test-retest variability (GPA-like) in 2 consecutive tests. Observed rates of progression (RoP) were used to simulate trial-like series (2 years) randomly assigned (1000 times) to a "placebo" or a "treatment" arm. We simulated neuroprotective "treatment" effects by changing the proportion of "true progressed" eyes in the two arms. Two trend-based methods for mean deviation (MD) were assessed: (1) linear mixed model (LMM), testing average difference in RoP between the two arms, and (2) time-to-progression (TTP), calculated by linear regression as time needed for MD to decline by predefined cutoffs from baseline. Power curves with 95% confidence intervals were calculated for trend and event-based methods on the simulated series. RESULTS: The FDA-7 and GPA-like progression was achieved by 45% and 55% of the eyes in the clinical database. LMM and TTP had similar power, significantly superior to the event-based methods, none of which reached 80% power. All methods had a 5% false-positive rate. CONCLUSIONS: The trend-based methods can efficiently detect treatment effects defined by long-term FDA-compatible progression. TRANSLATIONAL RELEVANCE: The assessment of the power of trend-based methods to detect clinically relevant progression end points.

Publication Type:	Article
Additional Information:	This work is licensed under a Creative Commons Attribution 4.0 International License.
Publisher Keywords:	visual field (VF); glaucoma; neuroprotection; clinical trials
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry R Medicine > RE Ophthalmology
Departments:	School of Health & Psychological Sciences > Optometry & Visual Sciences
SWORD Depositor:	Symplectic Administrator

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