City, University of London Optometry and Visual Sciences (G.M., D.P.C.), London, United Kingdom; NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology (G.M.), London, United Kingdom.
Wilmer Institute, Johns Hopkins School of Medicine (H.A.Q.), Baltimore, MD, USA.
Am J Ophthalmol. 2021 Sep;229:127-136. doi: 10.1016/j.ajo.2021.04.008. Epub 2021 Apr 24.
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.
Methodology analysis: assessment of how improving reliability affects sample size estimates.
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.
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.
Selecting patients with low intertest variability can significantly improve the power and reduce the sample size needed in a trial.
选择可靠的视野（VF）测试者可以提高青光眼随机临床试验的效力。我们通过使用大型真实世界数据集进行模拟来检验这一假设。
方法分析：评估提高可靠性如何影响样本量估计。
使用 2804 名患者至少 10 次系列检查中前 6 次平均偏差随时间的回归残差，为每个受试者计算一个估计测试间变异性的变异指数（VI）。使用该系列其余部分的数据，我们在 2 年内定期模拟 VF。为了模拟神经保护效应（NE），我们将观察到的进展率降低 20%、30%或 50%。主要观察指标是检测到 80%功效的显著差异（P<.05）的样本量。
在第一个实验中，我们模拟了一个包括每个受试者一只眼睛的试验，要么从数据库中随机选择，要么优先选择 VI 较低的患者。对于低 NE，我们无法使用现有的患者达到 80%的效力，但对于 30%和 50%的 NE，样本量分别减少了 38%和 49%。在第二个实验中，我们模拟了每个受试者的两只眼睛，其中一只作为对照眼。通过优先选择 VI 较低的患者，对于 30%和 50%的 NE，样本量（总体较小）分别减少了 26%和 38%。
选择测试间变异性低的患者可以显著提高试验的效力并减少所需的样本量。
