Safety related label changes for new drugs after approval in the US through expedited regulatory pathways: retrospective cohort study.
Safety related label changes for new drugs after approval in the US through expedited regulatory pathways: retrospective cohort study.
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DOI：
10.1136/bmj.j3837
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发表时间：
2017-09-07
期刊：
影响因子：
--
通讯作者：
Kesselheim AS
中科院分区：
文献类型：
--
作者：
Mostaghim SR;Gagne JJ;Kesselheim AS
目的确定通过美国食品药品监督管理局的快速开发和审查途径批准的药物与通过标准非快速途径批准的药物相比，在批准后是否有不同的安全性相关标签变更率。 设计回顾性队列研究。 设置FDA公共记录，1997年1月至2016年4月。 参与者382种FDA批准的药物。 主要结果测量在药物上市期间，标签的特定安全性部分（黑框警告，禁忌症，警告，注意事项或不良反应）发生变化的次数。通过形成相同治疗类别中相互在3年内获批的药物配对，比较了加速途径和非加速途径药物每年安全性相关标签变更的相对发生率。 在382个符合条件的新药中，135个（35%）与加速开发或审查途径相关，96个（71%）匹配。在研究期间，匹配对共涉及1710项安全性相关标签变更。快速途径药物的特征是每种药物每年发生0.94次安全性相关标签变更，而非快速途径药物每年发生0.68次安全性相关标签变更（率比1.38，95%置信区间1.25 - 1.52）。与非加速途径药物相比，加速途径药物的黑框警告和禁忌症的变更率高出48%，这是两种临床上最重要的安全性警告类别（1.48，95%置信区间1.07至2.06）。对黑框警告章节变更的定性审查显示，不到5%（3/67）的变更描述了患者风险降低。 结论加速开发和监管审查途径可以加速新药的可用性，但通过这些途径批准的药物与批准后增加的安全性相关标签变更相关，特别是代表最高风险警告的变更类型。为了提供适当的政策干预信息，应进行更多的研究，探讨造成这些不同比率的因果因素。
Objective To determine if drugs approved through the Food and Drug Administration’s expedited development and review pathways have different rates of safety related label changes after approval compared with drugs approved through standard non-expedited pathways. Design Retrospective cohort study. Setting FDA public records, January 1997 to April 2016. Participants 382 FDA approved drugs. Main outcome measures The number of times a particular safety section of a label (boxed warning, contraindication, warning, precaution, or adverse reaction) was changed during a drug’s time on the market. The relative rate of safety related label changes per year for expedited pathway and non-expedited pathway drugs was compared by forming matched pairs of drugs in the same therapeutic class that were approved within three years of each other. Results Among the 382 eligible new drugs, 135 (35%) were associated with an expedited development or review pathway, and matches were available for 96 (71%). The matched pairs were associated with a total of 1710 safety related label changes during the study period. Expedited pathway drugs were characterized by a rate of 0.94 safety related label changes for each drug per year, compared with 0.68 safety related label changes per year for non-expedited pathway drugs (rate ratio 1.38, 95% confidence interval 1.25 to 1.52). Compared with non-expedited pathway drugs, expedited pathway drugs had a 48% higher rate of changes to boxed warnings and contraindications, the two most clinically important categories of safety warnings (1.48, 95% confidence interval 1.07 to 2.06). A qualitative review of changes to the boxed warning sections revealed that less than 5% (3/67) were changed to describe reduced risks for patients. Conclusions Expedited development and regulatory review pathways can accelerate the availability of new drugs, but drugs approved through these pathways are associated with increased safety related label changes after approval, particularly for the types of changes representing the highest risk warnings. To inform appropriate policy interventions, additional research should explore the causal factors contributing to these different rates.
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影响因子：
3.5
作者：
Olson, MK
通讯作者：
Olson, MK
影响因子：
2.2
作者：
Olson, MK
通讯作者：
Olson, MK
DOI：
10.1136/bmj.h4633
发表时间：
2015-09-23
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Kesselheim AS;Wang B;Franklin JM;Darrow JJ
通讯作者：
Darrow JJ
影响因子：
120.7
作者：
Downing, Nicholas S.;Shah, Nilay D.;Ross, Joseph S.
通讯作者：
Ross, Joseph S.
影响因子：
3.4
作者：
Arnardottir, Arna H.;Haaijer-Ruskamp, Flora M.;Mol, Peter G. M.
通讯作者：
Mol, Peter G. M.