Clarke Andrea, Deeks Jonathan J, Shakir Saad A W
Drug Safety Research Unit, Southampton, UK.
Drug Saf. 2006;29(2):175-81. doi: 10.2165/00002018-200629020-00008.
The objective of this study was to assess the publicly disseminated evidence used to support decisions to withdraw medicinal products for safety reasons, and related implications for the conduct of systematic reviews of harm.
Medicinal products withdrawn from the UK and US markets for safety reasons were identified from websites of the UK Medicines Control Agency (now known as the Medicines and Healthcare products Regulatory Agency) and the US FDA. Related scientific evidence was identified from communications made to the public and healthcare professionals at the time of each product withdrawal. Evidence for each product withdrawal decision was classified according to study design and outcome.
Eleven products were withdrawn during 1999-2001. Randomised trial evidence was cited for two products (18%) and comparative observational studies for two products (18%). Evidence from spontaneous reports supported the withdrawal of eight products (73%), with four products (36%) apparently withdrawn on the basis of spontaneous reports alone. Only two products (18%) were withdrawn on evidence for a patient relevant outcome from comparative studies.
It is rare that evidence other than spontaneous reports is cited in support of drug withdrawals. The serious implications of product withdrawal mandate the elevation of the level of evidence that supports such public health decisions. Once suspicions of important safety hazards have emerged, prospective studies may be unfeasible and may be seen as unethical. Prospective studies can strengthen the evidence base and should be planned to commence when every drug is first marketed. Systematic reviews are unlikely to elicit evidence of harm associated with a drug unless they include spontaneous reports and surrogate outcomes.
本研究的目的是评估用于支持因安全原因撤市药品决策的公开传播证据，以及对危害系统评价实施的相关影响。
从英国药品控制局（现称为药品和医疗产品监管局）和美国食品药品监督管理局的网站上识别出因安全原因从英国和美国市场撤市的药品。从每种药品撤市时向公众和医疗专业人员发布的信息中识别相关科学证据。根据研究设计和结果对每种药品撤市决策的证据进行分类。
在1999年至2001年期间有11种药品撤市。两种药品（18%）的撤市引用了随机试验证据，两种药品（18%）引用了比较观察性研究证据。自发报告的证据支持8种药品（73%）撤市，其中4种药品（36%）显然仅基于自发报告撤市。只有两种药品（18%）因比较研究中与患者相关的结果证据而撤市。
除自发报告外，很少有其他证据被引用来支持药品撤市。药品撤市的严重影响要求提高支持此类公共卫生决策的证据水平。一旦出现对重大安全危害的怀疑，前瞻性研究可能不可行，也可能被视为不道德。前瞻性研究可以加强证据基础，应在每种药品首次上市时就计划开展。系统评价不太可能得出与药物相关的危害证据，除非纳入自发报告和替代结局。
