Purchase this article with an account.
Giovanni Montesano, David F. Garway-Heath, Alessandro Rabiolo, Carlos Gustavo De Moraes, Giovanni Ometto, David P. Crabb; Validating Trend-Based End Points for Neuroprotection Trials in Glaucoma. Trans. Vis. Sci. Tech. 2023;12(10):20. https://doi.org/10.1167/tvst.12.10.20.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
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).
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.
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.
The trend-based methods can efficiently detect treatment effects defined by long-term FDA-compatible progression.
The assessment of the power of trend-based methods to detect clinically relevant progression end points.
This PDF is available to Subscribers Only