Sormani M P, Molyneux P D, Gasperini C, Barkhof F, Yousry T A, Miller D H, Filippi M
Department of Neuroscience, Scientific Institute Ospedale San Raffaele, University of Milan, Italy.
J Neurol Neurosurg Psychiatry. 1999 Apr;66(4):465-9. doi: 10.1136/jnnp.66.4.465.
To evaluate the durations of the follow up and the reference population sizes needed to achieve optimal and stable statistical powers for two period cross over and parallel group design clinical trials in multiple sclerosis, when using the numbers of new enhancing lesions and the numbers of active scans as end point variables.
The statistical power was calculated by means of computer simulations performed using MRI data obtained from 65 untreated relapsing-remitting or secondary progressive patients who were scanned monthly for 9 months. The statistical power was calculated for follow up durations of 2, 3, 6, and 9 months and for sample sizes of 40-100 patients for parallel group and of 20-80 patients for two period cross over design studies. The stability of the estimated powers was evaluated by applying the same procedure on random subsets of the original data.
When using the number of new enhancing lesions as the end point, the statistical power increased for all the simulated treatment effects with the duration of the follow up until 3 months for the parallel group design and until 6 months for the two period cross over design. Using the number of active scans as the end point, the statistical power steadily increased until 6 months for the parallel group design and until 9 months for the two period cross over design. The power estimates in the present sample and the comparisons of these results with those obtained by previous studies with smaller patient cohorts suggest that statistical power is significantly overestimated when the size of the reference data set decreases for parallel group design studies or the duration of the follow up decreases for two period cross over studies.
These results should be used to determine the duration of the follow up and the sample size needed when planning MRI monitored clinical trials in multiple sclerosis.
在以新出现的强化病灶数量和活跃扫描数量作为终点变量时，评估多发性硬化症两阶段交叉设计和平行组设计临床试验实现最佳和稳定统计效能所需的随访时长及对照人群规模。
利用从65例未经治疗的复发缓解型或继发进展型患者获取的MRI数据进行计算机模拟，计算统计效能。这些患者每月接受扫描，为期9个月。计算平行组设计随访时长为2、3、6和9个月、样本量为40 - 100例患者，以及两阶段交叉设计随访时长为2、3、6和9个月、样本量为20 - 80例患者时的统计效能。通过对原始数据的随机子集应用相同程序评估估计效能的稳定性。
以新出现的强化病灶数量作为终点时，对于所有模拟的治疗效果，平行组设计随访至3个月、两阶段交叉设计随访至6个月时，统计效能均有所增加。以活跃扫描数量作为终点时，平行组设计随访至6个月、两阶段交叉设计随访至9个月时，统计效能稳步增加。本样本中的效能估计以及将这些结果与之前较小患者队列研究结果进行比较表明，对于平行组设计研究，当对照数据集规模减小时，或者对于两阶段交叉设计研究，当随访时长缩短时，统计效能会被显著高估。
这些结果应用于确定在规划多发性硬化症MRI监测临床试验时所需的随访时长和样本量。
