In March 2011, a Final Rule for expedited reporting of serious adverse events took effect in the United States for studies conducted under an Investigational New Drug (IND) application. In December 2012, the U.S. Food and Drug Administration (FDA) promulgated a final Guidance describing the operationalization of this Final Rule. The Rule and Guidance clarified that a clinical trial sponsor should have evidence suggesting causality before defining an unexpected serious adverse event as a suspected adverse reaction that would require expedited reporting to the FDA. The Rule's emphasis on the need for evidence suggestive of a causal relation should lead to fewer events being reported but, among those reported, a higher percentage actually being caused by the product being tested. This article reviews the practices that were common before the Final Rule was issued and the approach the New Rule specifies. It then discusses methods for operationalizing the Final Rule with particular focus on relevant statistical considerations. It concludes with a set of recommendations addressed to Sponsors and to the FDA in implementing the Final Rule.

2011年3月，针对严重不良事件的快速报告的最终规则在美国对根据新药研究申请进行的研究生效。2012年12月，美国食品药品监督管理局（FDA）颁布了最终指南，描述了该最终规则的实施情况。规则和指南明确指出，临床试验申办者应有证据表明存在因果关系，然后再将意外的严重不良事件定义为可疑的不良反应，需要迅速向FDA报告。该规则强调需要证据表明存在因果关系，因此应减少所报告的事件，但在所报告的事件中，被测试产品实际造成的百分比较高。本文回顾了最终规则发布之前的常见做法以及新规则指定的方法。然后讨论了最终规则实施的方法，特别侧重于相关的统计考虑。最后，针对实施最终规则的提案国和FDA提出了一系列建议。