The Nordic Cochrane Centre, Rigshospitalet, Copenhagen, Denmark.
Eur J Clin Pharmacol. 2010 Apr;66(4):341-7. doi: 10.1007/s00228-010-0791-8. Epub 2010 Feb 17.
It was predicted from the mechanism of action that, compared to older non-steroidal anti-inflammatory drugs, rofecoxib (Vioxx) would reduce gastrointestinal bleeding, but also that it would increase the occurrence of cardiovascular thrombosis. From the patient's point of view, both effects are important and should be investigated and reported similarly. We studied how they have been reported over time.
We searched PubMed for abstracts on rofecoxib that commented on gastrointestinal bleeding or cardiovascular thrombosis or both. Two researchers, blinded to date of publication and authors, assessed the abstracts independently. We judged the authors' view on rofecoxib and comments on gastrointestinal bleeding and thrombosis as being favourable, neutral or unfavourable towards rofecoxib.
We included 393 abstracts commenting on gastrointestinal bleeding (72%) and cardiovascular thrombosis (54%) or both. Before October 2000, all abstracts (n = 27) mentioned only gastrointestinal bleeding and 89% were positive towards rofecoxib. The year before the withdrawal of rofecoxib (October 2003 to September 2004) (n = 46), 59% of abstracts commented on gastrointestinal bleeding only, 17% on thrombosis only, 24% on both and 67% were still positive. From October 2006 to September 2007 (n = 54), 13% mentioned gastrointestinal bleeding, 54% thrombosis, 33% mentioned both and only 11% were positive.
The reporting of benefits and harms was not balanced and changed markedly over time. Knowledge of increased risk of thrombosis existed early on, but the harms came into focus too late, when the drug was already withdrawn, and when tens of thousands of patients had been harmed unnecessarily.
从作用机制上预测，与较老的非甾体抗炎药相比，罗非昔布（万络）会减少胃肠道出血，但也会增加心血管血栓形成的发生。从患者的角度来看，这两种效果都很重要，应该进行类似的调查和报告。我们研究了它们随时间的变化是如何报告的。
我们在 PubMed 上搜索了有关罗非昔布的摘要，这些摘要评论了胃肠道出血或心血管血栓形成或两者兼有。两名研究人员对摘要进行了独立评估，对出版日期和作者均不知情。我们判断作者对罗非昔布的看法以及对胃肠道出血和血栓形成的评论是对罗非昔布有利、中立还是不利。
我们纳入了 393 篇评论胃肠道出血（72%）和心血管血栓形成（54%）或两者的摘要。在 2000 年 10 月之前，所有的摘要（n=27）都只提到胃肠道出血，89%的摘要对罗非昔布持积极态度。在罗非昔布撤出前一年（2003 年 10 月至 2004 年 9 月）（n=46），59%的摘要仅评论胃肠道出血，17%的仅评论血栓形成，24%的同时评论了两者，而 67%的摘要仍然是积极的。从 2006 年 10 月到 2007 年 9 月（n=54），13%的摘要提到胃肠道出血，54%的提到血栓形成，33%的同时提到了两者，只有 11%的摘要是积极的。
利益和危害的报告是不平衡的，而且随着时间的推移发生了明显的变化。关于血栓形成风险增加的知识很早就存在了，但危害直到药物已经撤出时才引起关注，此时已经有数千名患者不必要地受到了伤害。
