Background: In age-related macular degeneration (ARMD) trials, the FDA-approved endpoint is the loss (or gain) of at least three lines of vision as compared to baseline. The use of such a response endpoint entails a potentially severe loss of information. A more efficient strategy could be obtained by using longitudinal measures of the change in visual acuity. In this paper we investigate, by using data from two randomized clinical trials, the mean and variance-covariance structures of the longitudinal measurements of the change in visual acuity.
Methods: Individual patient data were collected in 234 patients in a randomized trial comparing interferon-α with placebo and in 1181 patients in a randomized trial comparing three active doses of pegaptanib with sham. A linear model for longitudinal data was used to analyze the repeated measurements of the change in visual acuity.
Results: For both trials, the data were adequately summarized by a model that assumed a quadratic trend for the mean change in visual acuity over time, a power variance function, and an antedependence correlation structure. The power variance function was remarkably similar for the two datasets and involved the square root of the measurement time.
Conclusions: The similarity of the estimated variance functions and correlation structures for both datasets indicates that these aspects may be a genuine feature of the measurements of changes in visual acuity in patients with ARMD. The feature can be used in the planning and analysis of trials that use visual acuity as the clinical endpoint of interest.
Copyright © 2010 John Wiley & Sons, Ltd.