Additional safety risk to exceptionally approved drugs in Europe?
Additional safety risk to exceptionally approved drugs in Europe?
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DOI：
10.1111/j.1365-2125.2011.03995.x
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发表时间：
2011-09-01
影响因子：
3.4
通讯作者：
Mol, Peter G. M.
中科院分区：
文献类型：
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作者：
Arnardottir, Arna H.;Haaijer-Ruskamp, Flora M.;Mol, Peter G. M.
目的新药的监管要求有所增加。对于有明确“未满足医疗需求”的药物，可以采取特殊审批程序，并进行优先评估。我们质疑这些例外情况（EC）或有条件批准（CA）程序是否导致了更高的概率严重safety issues.METHODSA回顾性队列研究在欧洲批准的新药在1999年和2009年之间。决定因素是EC/CA与标准程序批准。结果变量是第一次直接医疗保健专业人士沟通（DHPC）的频率和时间。采用Kaplan-Meyer生存分析和Cox回归分析评估批准程序与从上市批准到DHPC的时间之间的关联，以校正协变量。46个（16.4%）获得EC或CA批准，其中7个（15%）获得DHPC。这与标准批准药物（243）相似，其中33种接受了一种或多种DHPC（14%，P = 0.77）。在11年随访期间，标准批准药物与EC/CA药物获得DHPC的概率分别为22%（95% CI 14%，29%）和26%（95% CI 8%，44%）（对数秩P = 0.726）。在Cox回归模型中，该差异仍然不显著：风险比0.94（95% CI 0.40，2.20）。只有药物类型被确定为一个混杂协variable.CONCLUSIONThe EC/CA程序是不相关的DHPC的概率较高，尽管有限的临床开发数据。这些数据并不支持早期药物批准会增加上市批准后出现严重安全性问题的风险的观点。
AIMSRegulatory requirements for new drugs have increased. Special approval procedures with priority assessment are possible for drugs with clear 'unmet medical need'. We question whether these Exceptional Circumstances (EC) or Conditional Approval (CA) procedures have led to a higher probability of serious safety issues.METHODSA retrospective cohort study was performed of new drugs approved in Europe between 1999 and 2009. The determinant was EC/CA vs. standard procedure approval. Outcome variables were frequency and timing of a first Direct Healthcare Professional Communication (DHPC). An association between approval procedure and the time from market approval to DHPC was assessed using Kaplan-Meyer survival analysis and Cox-regression to correct for covariates.RESULTSIn total 289 new drugs were approved. Forty-six (16.4%) were approved under EC or CA, of which seven received a DHPC (15%). This was similar to the standard approval drugs (243), of which 33 received one or more DHPC (14%, P = 0.77). The probability of acquiring a DHPC for standard approval drugs vs. EC/CA drugs during 11-year follow-up is 22% (95% CI 14%, 29%) and 26% (95% CI 8%, 44%), respectively (log-rank P = 0.726). This difference remained not significant in the Cox-regression model: hazard ratio 0.94 (95% CI 0.40, 2.20). Only drug type was identified as a confounding covariate.CONCLUSIONThe EC/CA procedure is not associated with a higher probability of DHPCs despite limited clinical development data. These data do not support the view that early drug approval increases the risk of serious safety issues emerging after market approval.