A critical appraisal of the reporting of the National Acute Spinal Cord Injury Studies (II and III) of methylprednisolone in acute spinal cord injury
A critical appraisal of the reporting of the National Acute Spinal Cord Injury Studies (II and III) of methylprednisolone in acute spinal cord injury
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DOI：
10.1097/00002517-200006000-00001
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发表时间：
2000-06-01
期刊：
影响因子：
--
通讯作者：
Zeidman, S
中科院分区：
文献类型：
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作者：
Coleman, WP;Benzel, E;Zeidman, S
从一开始，国家急性脊髓损伤研究（NASCIS）II和III的结果报告就不完整，使得脊髓损伤（SCI）社区的临床医生在急性SCI中使用或避免使用甲基强的松龙，而不是基于信仰，而不是公开发展的科学共识。NASCIS II最初由美国国立卫生研究院公告、美国国立卫生研究院传真给急诊室医生和新闻媒体报道。随后发表在《新英格兰医学杂志》上的报告暗示，对整个487例患者样本进行的主要疗效分析结果为阳性。然而，该分析实际上是阴性的，仅在8小时内接受治疗的患者亚组的二次分析中发现阳性结果。此外，该亚组显然只有62名患者服用甲基强的松龙，67名患者服用安慰剂。NASCIS II和III报告体现了统计方法的具体选择，这些方法对结果报告产生了重大影响，但没有受到充分质疑，甚至没有得到解释。这些研究显示出的统计假象使他们的结果受到质疑。在NASCIS II中，8小时前治疗的安慰剂组表现不佳，不仅与8小时前治疗的甲基强的松龙组相比，甚至与8小时后治疗的安慰剂组相比。因此，阳性结果可能是由于对照组的虚弱而不是甲泼尼龙的任何强度引起的。在NASCIS III中，发生了随机化失衡，将不成比例数量的无运动功能障碍（因此无恢复机会）的患者分配至较低剂量对照组。当这种不平衡得到控制时，高剂量组的大部分优势似乎消失了。NASCIS小组决定接纳患有轻微SCI的人，这些人具有最小或没有运动缺陷，这不仅使统计伪像成为可能，而且使对实际抽样人群结果的解释复杂化。也许有一半的NASCIS III样本可能最多有一个轻微的赤字。因此，我们不知道这些研究的结果是否反映了它们所适用的严重受伤人群。发表的报告中的数字、表格和数字很少，定义也不一致，即使是专业统计人员也无法重复分析，无法猜测假设变化的影响，也无法提供图片中缺失的部分。然而，即使在NASCIS II之后9年，原始数据也没有公布。NASCIS研究的报告远远低于ICH/FDA和循证医学组的指南。尽管SCI中甲基强的松龙的“标签外”市场利润丰厚，但尚未获得食品和药物协会的适应症。没有公开的验证过程。这些缺点使医生们没有机会自信地使用一种许多人都热衷的药物，并使他们在治疗选择、法律的暴露以及进行进一步研究以帮助患者的能力方面处于令人难以忍受的模棱两可的地位。
From the beginning, the reporting of the results of National Acute Spinal Cord Injury Studies (NASCIS) II and III has been incomplete, leaving clinicians in the spinal cord injury (SCI) community to use or avoid using methylprednisolone in acute SCI on the basis of faith rather than a publicly developed scientific consensus. NASCIS II was initially reported by National Institutes of Health announcements, National Institutes of Health facsimiles to emergency room physicians, and the news media. The subsequent report in the New England Journal of Medicine implied that there was a positive result in the primary efficacy analysis for the entire 487 patient sample. However, this analysis was in fact negative, and the positive result was found only in a secondary analysis of the subgroup of patients who received treatment within 8 hours. In addition, that subgroup apparently had only 62 patients taking methylprednisolone and 67 receiving placebo. The NASCIS II and III reports embody specific choices of statistical methods that have strongly shaped the reporting of results but have not been adequately challenged or or even explained. These studies show statistical artifacts that call their results into question. In NASCIS II, the placebo group treated before 8 hours did poorly, not only when compared with the methylprednisolone group treated before 8 hours but even when compared with the placebo group treated after 8 hours. Thus, the positive result may have been caused by a weakness in the control group rather than any strength of methylprednisolone. In NASCIS III, a randomization imbalance occurred that allocated a disproportionate number of patients with no motor deficit (and therefore no chance for recovery) to the lower dose control group. When this imbalance is controlled for, much of the superiority of the higher dose group seems to disappear. The NASCIS group's decision to admit persons with minor SCIs with minimal or no motor deficit not only enables statistical artifacts it complicates the interpretation of results from the population actually sampled. Perhaps one half of the NASCIS III sample may have had at most a minor deficit. Thus, we do not know whether the results of these studies reflect the severely injured population to which they have been applied. The numbers, tables, and figures in the published reports are scant and are inconsistently defined, making it impossible even for professional statisticians to duplicate the analyses, to guess the effect of changes in assumptions, or to supply the missing parts of the picture. Nonetheless, even 9 years after NASCIS II, the primary data have not been made public. The reporting of the NASCIS studies has fallen far short of the guidelines of the ICH/FDA and of the Evidence-based Medicine Group. Despite the lucrative "off label" markets for methylprednisolone in SCI, no Food and Drug Association indication has been obtained. There has been no public process of validation. These shortcomings have denied physicians the chance to use confidently a drug that many were enthusiastic about and has left them in an intolerably ambiguous position in their therapeutic choices, in their legal exposure, and in their ability to perform further research to help their patients.