在阿尔茨海默病或认知障碍治疗中报告罗费可克西布试验中的死亡率发现:基于罗费可克西布诉讼文件的案例研究
Bruce M Psaty1, Richard A Kronmal
1Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington and Center for Health Studies, Group Health, Seattle, WA 98101, USA. psaty@u.washington.edu
JAMA
|April 17, 2008
概括
赞助商对罗菲可西布 (一种COX-2抑制剂) 试验的报告选择性地呈现了安全数据,淡化了死亡风险. 内部分析显示,死亡率明显高于最初公布的,需要加强对行业赞助的临床研究的监督.
科学领域:
- 临床试验方法和报告标准.
- 制药行业对科学传播的影响.
- 对药物安全数据的监管监督.
背景情况:
- 赞助商有营销动机,以有利的方式呈现产品,这可能与科学报告标准相冲突.
- 对临床试验结果的选择性报告可能会扭曲药物的风险益处概况.
- 本研究检查了阿尔茨海默病和认知障碍试验中rofecoxib死亡率发现的报告.
研究的目的:
- 分析rofecoxib的赞助商在临床试验中如何表示死亡率数据.
- 将赞助商提供的数据与内部分析和已公布的结果进行比较.
- 突出报告中的差异及其对患者安全的影响.
主要方法:
- 审查了诉讼文件,包括公司内部分析和FDA提交的文件.
- 评估了发表的文章,报告了两项rofecoxib试验的结果 (协议091和078).
- 将内部治疗意图 (ITT) 分析与已公布的治疗分析和赞助商提交给FDA进行了比较.
主要成果:
- 发表的文章报告了较低的死亡率,并得出结论,罗菲可克西布耐受性良好,但遗漏了统计分析.
- 内部ITT分析显示,罗菲可西布的总死亡风险显著增加 (HR 2.99;95% CI,1.55-5.77).
- 赞助人的FDA提交使用了治疗分析,最大限度地降低了明显的死亡风险;没有及时披露ITT发现.
结论:
- 选择性报告和使用不合适的分析方法 (在治疗期间与ITT) 误导了罗菲可西布的安全性.
- 赞助商未能及时向FDA提供关键的死亡率分析,也没有公开披露.
- 迫切需要加强对人类研究参与者的保护,并改善对行业赞助的试验的监督.
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