Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: spontaneous recovery after spinal cord injury and statistical power needed for therapeutic clinical trials
Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: spontaneous recovery after spinal cord injury and statistical power needed for therapeutic clinical trials
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DOI：
10.1038/sj.sc.3102007
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发表时间：
2007-03-01
期刊：
影响因子：
2.2
通讯作者：
Short, D.
中科院分区：
文献类型：
--
作者：
Fawcett, J. W.;Curt, A.;Short, D.
国际脊髓损伤麻痹治疗运动（ICCP）支持一个国际小组，该小组负责审查脊髓损伤（SCI）临床试验的方法，并就未来试验的开展提出建议。这是四篇论文中的第一篇。在这里，我们研究了SCI后的自发恢复率和临床试验中取得统计学显著结果的结果。我们重新分析了Sygen试验的数据，以提供一些信息。几乎所有的SCI患者在最初的脊髓损伤水平以下都表现出一定的运动功能恢复。虽然运动完全性SCI患者的运动功能自发恢复是相当有限和可预测的，但不完全性SCI患者的恢复（美国脊髓损伤协会损伤量表（AIS）C和AIS D）更为实质性和高度可变。对于运动完全性损伤（AIS A/AIS B），大多数功能恢复在部分保留区内，可能足以将损伤节段重新分类为较低的脊柱节段。绝大多数恢复发生在前3个月，但少量恢复可持续长达18个月或更长时间。一些感觉恢复发生在SCI后，与运动恢复大致相同的时间过程。根据之前SCI后自发恢复幅度的数据（通过ASIA运动评分的变化来衡量），把握度计算表明，随着研究开始时间的推迟，从试验中获得显着结果所需的受试者数量大幅下降SCI。因此，在受伤后不久给予最有效的治疗试验将需要比在较晚时间点有效的治疗试验更多的患者数量。由于AIS B组患者的自发恢复率高于AIS A组患者，因此需要入组试验的AIS A组患者数量较少。这一因素必须与某些治疗对不完全患者更有效的可能性相平衡。涉及运动不完全性SCI患者的试验，或在试验开始前无法准确评估AIS等级的试验，将需要大量受试者和/或更好的客观评估方法。
The International Campaign for Cures of Spinal Cord Injury Paralysis (ICCP) supported an international panel tasked with reviewing the methodology for clinical trials in spinal cord injury (SCI), and making recommendations on the conduct of future trials. This is the first of four papers. Here, we examine the spontaneous rate of recovery after SCI and resulting consequences for achieving statistically significant results in clinical trials. We have reanalysed data from the Sygen trial to provide some of this information. Almost all people living with SCI show some recovery of motor function below the initial spinal injury level. While the spontaneous recovery of motor function in patients with motor-complete SCI is fairly limited and predictable, recovery in incomplete SCI patients ( American spinal injury Association impairment scale (AIS) C and AIS D) is both more substantial and highly variable. With motor complete lesions ( AIS A/AIS B) the majority of functional return is within the zone of partial preservation, and may be sufficient to reclassify the injury level to a lower spinal level. The vast majority of recovery occurs in the first 3 months, but a small amount can persist for up to 18 months or longer. Some sensory recovery occurs after SCI, on roughly the same time course as motor recovery. Based on previous data of the magnitude of spontaneous recovery after SCI, as measured by changes in ASIA motor scores, power calculations suggest that the number of subjects required to achieve a significant result from a trial declines considerably as the start of the study is delayed after SCI. Trials of treatments that are most efficacious when given soon after injury will therefore, require larger patient numbers than trials of treatments that are effective at later time points. As AIS B patients show greater spontaneous recovery than AIS A patients, the number of AIS A patients requiring to be enrolled into a trial is lower. This factor will have to be balanced against the possibility that some treatments will be more effective in incomplete patients. Trials involving motor incomplete SCI patients, or trials where an accurate assessment of AIS grade cannot be made before the start of the trial, will require large subject numbers and/or better objective assessment methods.