基于临床和替代指标结果经加拿大卫生部批准的药物上市后安全性：一项队列研究。
Postmarket safety of drugs approved by Health Canada on the basis of clinical and surrogate outcomes: a cohort study.
作者信息
Lexchin Joel, Ahmed Tareq
机构信息
School of Health Policy and Management, York University, Toronto, Ont. ; Emergency Department, University Health Network, Toronto, Ont. ; Department of Family and Community Medicine, University of Toronto, Toronto, Ont.
Faculty of Health Sciences, Simon Fraser University, Burnaby, BC ; Drug Assessment Working Group, Therapeutics Initiative, University of British Columbia, Vancouver, BC.
出版信息
CMAJ Open. 2015 Jul 17;3(3):E286-91. doi: 10.9778/cmajo.20150023. eCollection 2015 Jul-Sep.
BACKGROUND
Health Canada approves drugs on the basis of evidence from clinical trials using clinical or surrogate outcomes. This study compares the postmarket safety of these 2 groups of drugs.
METHODS
Information about whether clinical or surrogate outcomes were used and the date of market approval were obtained from Health Canada's Summary Basis of Decision documents issued from Jan. 1, 2005, to Dec. 31, 2014. Safety warnings and the dates they were issued were identified through advisories on the MedEffect Canada website. Kaplan-Meier survival curves were calculated to determine the likelihood that drugs in the clinical and surrogate outcome groups would receive a serious safety warning. The time from market authorization to first serious safety warning was compared for the 2 groups of drugs.
RESULTS
A total of 124 drugs were approved by Health Canada using clinical outcomes and 114 using surrogate outcomes. Kaplan-Meier curves did not differ between the 2 groups (p < 0.9). The median time from market authorization to first serious safety warning was 722 days in the clinical outcome group and 818 days in the surrogate outcome group (difference 96 days, 95% confidence interval -295 to 425).
INTERPRETATION
We found no statistically significant difference in postmarket safety between drugs approved using clinical outcomes and those approved using surrogate outcomes. Because drugs in the surrogate outcome group are approved before their benefit:harm ratio is fully established, these drugs should be used with caution until their clinical benefits are better understood.
背景
加拿大卫生部基于使用临床结局或替代结局的临床试验证据来批准药物。本研究比较了这两组药物的上市后安全性。
方法
从加拿大卫生部2005年1月1日至2014年12月31日发布的决策摘要文件中获取有关是否使用临床或替代结局以及上市批准日期的信息。通过加拿大药品不良反应监测网站上的公告确定安全警告及其发布日期。计算Kaplan-Meier生存曲线以确定临床结局组和替代结局组中的药物收到严重安全警告的可能性。比较两组药物从上市授权到首次严重安全警告的时间。
结果
加拿大卫生部使用临床结局批准了124种药物，使用替代结局批准了114种药物。两组之间的Kaplan-Meier曲线无差异（p<0.9）。临床结局组从上市授权到首次严重安全警告的中位时间为722天，替代结局组为818天（差异96天，95%置信区间-295至425）。
解读
我们发现使用临床结局批准的药物与使用替代结局批准的药物在上市后安全性方面没有统计学上的显著差异。由于替代结局组中的药物在其利弊比完全确定之前就已获批，因此在更好地了解其临床益处之前，应谨慎使用这些药物。
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