Improving the Power of Glaucoma Neuroprotection Trials Using Existing Visual Field Data.

PURPOSE

Selecting reliable visual field (VF) test takers could improve the power of randomized clinical trials in glaucoma. We test this hypothesis via simulations using a large real world data set.

DESIGN

Methodology analysis: assessment of how improving reliability affects sample size estimates.

METHODS

A variability index (VI) estimating intertest variability was calculated for each subject using the residuals of the regression of the mean deviation over time for the first 6 tests in a series of at least 10 examinations for 2,804 patients. Using data from the rest of the series, we simulate VFs at regular intervals for 2 years. To simulate the neuroprotective effect (NE), we reduced the observed progression rate by 20%, 30%, or 50%. The main outcome measure was the sample size to detect a significant difference (P < .05) at 80% power.

RESULTS

In the first experiment, we simulated a trial including one eye per subject, either selecting randomly from the database or prioritizing patients with low VI. We could not reach 80% power for the low NE with the available patients, but the sample size was reduced by 38% and 49% for the 30% and 50% NE, respectively. In the second experiment, we simulated 2 eyes per subject, one of which was the control eye. The sample size (smaller overall) was reduced by 26% and 38% for the 30% and 50% NE by prioritizing patients with low VI.

CONCLUSIONS

Selecting patients with low intertest variability can significantly improve the power and reduce the sample size needed in a trial.