Enhancing postmarketing surveillance: continuing challenges.
Enhancing postmarketing surveillance: continuing challenges.
复制标题
加强上市后监督：持续的挑战。
DOI：
10.1111/bcp.12658
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发表时间：
2015
影响因子：
3.4
通讯作者：
Campbell,RobertR
中科院分区：
文献类型：
--
作者：
French,DustinD;Margo,CurtisE;Campbell,RobertR
在本期中，Zeitoun及其同事[1]研究了2001年至2010年期间欧洲药品管理局（EMA）对161种药物的监管审查速度与报告的上市后安全事件之间是否存在任何关系;他们发现没有相关性。快速EMA监管审查或临近最后期限的批准与更多的不良事件报告无关。考虑到监管机构面临的及时审查和确保公共安全的压力，这些发现令人放心。然而，有证据表明，匆忙批准新药可能会危及安全性，至少在美国是这样。自1992年美国食品药品监督管理局（FDA）通过立法成本转移策略（称为《处方药使用者费用法案》）加快批准程序以来，上市后黑盒警告和市场撤回的数量都显着增加[2]。但影响一个监管体系的紧张局势可能不适用于另一个体系。上市前批准的过程也应该被视为药品安全的一个方面。虽然Zeitoun et al. [1]尽管这些措施令人鼓舞，但监管机构和公众都不应自满。严重药物不良事件的迟发性发现并不总是由于临床试验进行不当、制药公司邪恶或监管不力造成的;一些与药物有关的并发症反映了人类生物学的复杂性。即使是最细致的监管审查也无法保证检测到所有的药物不良反应。维持一个强大的上市后监测系统必须补充一个完整的药物审批程序。然而，这些过程也经常受到健康记录数据和相应决策支持工具（例如仪表板、数据立方体等）的限制的阻碍，用于勃起功能障碍（艾德）和非动脉炎性缺血性视神经病变（NAION）的磷酸二酯酶（PDE）-5抑制剂提供了药物安全性的难以捉摸的性质的主要例子。从2002年到2005年，文献中出现了磷酸二酯酶PDE-5抑制剂治疗艾德和非动脉炎性缺血性视神经病变（NAION）的相关报告[3]。建立严重并发症和药物使用之间的因果关系可能是一项艰巨的任务，即使不良事件在临床上与视力丧失一样明显。在上市前临床试验中未报告该并发症。上市后阶段的患者在用药后30分钟至36小时内描述了视力丧失。缺血性视神经损伤的生物学合理解释从一开始就很明显：PDE-5抑制剂能够短暂降低血压。这种短暂的压力下降可能会减少视神经乳头的血管灌注，足以导致局部梗死。到2005年秋天，非营利消费者组织Public Citizen请求FDA在所有PDE-5抑制剂上添加黑框警告，收集了足够的上市后证据，将视力丧失的风险视为公共安全问题[4]。怀疑论者指出，使用PDE-5抑制剂治疗艾德的男性也是NAION风险最高的人群，即患有糖尿病和动脉粥样硬化性血管疾病的男性。2007年，一项涉及4157357名男性退伍军人的大型回顾性队列研究发现，在使用PDE-5抑制剂的男性中，NAION的风险并未增加[比值比1.02（95%置信区间0.92-1.12）][5]。使用行政数据的类似发现继续积累，尽管有关于药物暴露和药物滥用之间密切时间关系的轶事报道。
In this issue, Zeitoun and colleagues [1] examined whether any relationship existed between the speed of European Medicines Agency (EMA) regulatory review of 161 medicines between 2001 and 2010 and reported postmarket safety events; they found no relevant correlation. Neither rapid EMA regulatory review nor approval near the deadline was associated with more reports of adverse events. The findings are reassuring, given the pressure that regulatory agencies face to achieve timely reviews and ensure public safety. There is evidence, however, that the rush to approve new medicines may compromise safety, at least in the United States. Since the approval process at the Food and Drug Administration (FDA) was accelerated through a legislative costshifting strategy known as the Prescription Drug User Fee Act in 1992, the numbers of both postmarketing black-box warning and market withdrawals have significantly increased [2]. But the tensions affecting one regulatory system may not be applicable to another. The process of premarket approval should also be viewed as just one facet of pharmaceutical safety. While the findings of Zeitoun et al.[1] are encouraging, neither regulatory agencies nor the public should become complacent. Belated discovery of serious adverse drug events is not always the result of poorly conducted clinical trials, nefarious drug companies or weak regulatory oversight; some drugrelated complications reflect the complexities of human biology. The most meticulous regulatory review will never guarantee the detection of all adverse drug effects. Maintaining a robust system of postmarketing surveillance must complement a thorough drug approval process. However, these processes too are often thwarted by limitations of health record data and corresponding decision support tools (eg dashboards, data cubes, etc.), and the practice of off-label prescribing.Phosphodiesterase (PDE)-5 inhibitors for erectile dysfunction (ED) and non-arteritic ischemic optic neuropathy (NAION) provides a prime example of the elusive nature of drug safety. From 2002 through 2005, reports linking the use of phosphodiesterase PDE-5 inhibitors for ED and non-arteritic ischaemic optic neuropathy (NAION) appeared in the literature [3]. Establishing the causal association between serious complications and drug use can be an arduous task, even when the adverse event is as clinically evident as vision loss. This complication had not been reported in premarketing clinical trials. Patients in the postmarketing phase described vision loss within 30 min to 36 h after drug use. A biologically plausible explanation for ischaemic injury to the optic nerve was evident from the start: PDE-5 inhibitors are capable of transiently lowering blood pressure. This transient dip in pressure could reduce vascular perfusion of the optic nerve head enough to result in localized infarction. By autumn 2005, Public Citizen, a nonprofit consumer organization, petitioned the FDA to add a black-box warning on all PDE-5 inhibitors, having gathered sufficient postmarketing evidence to consider the risk of vision loss a matter of public safety [4]. Skeptics noted that the men who use PDE-5 inhibitors for ED are also those who are at the highest risk for NAION–ie men who have diabetes and atherosclerotic vascular disease. In 2007, a large retrospective cohort study involving 4157357 male veterans found no increased risk of NAION in men prescribed PDE-5 inhibitors [odds ratio 1.02 (95% confidence interval 0.92–1.12)][5]. Similar findings using administrative data have continued to accumulate, despite anecdotal reports of the close temporal relationships between drug exposure and …
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影响因子：
3.5
作者：
Campbell, Ulka B.;Walker, Alexander M.;Reynolds, Robert F.
通讯作者：
Reynolds, Robert F.
影响因子：
2.9
作者：
Nathoo, Nawaaz A.;Etminan, Mahyar;Mikelberg, Frederick S.
通讯作者：
Mikelberg, Frederick S.
影响因子：
9.7
作者：
Abdus, Salam;Hudson, Julie;Selden, Thomas M.
通讯作者：
Selden, Thomas M.
男性退伍军人的缺血性视神经病变需服用磷酸二酯酶 5 抑制剂。
DOI：
--
发表时间：
2007
期刊：
American journal of ophthalmology-glaucoma
影响因子：
--
作者：
C. Margo;D. French
通讯作者：
D. French
根除机构腐败以管理不适当的超说明书用药
DOI：
10.1111/jlme.12075
发表时间：
2013
期刊：
The Journal of Law, Medicine & Ethics
影响因子：
--
作者：
M. Rodwin
通讯作者：
M. Rodwin