Boudes Pol F
PFB Consulting, 152 E. Delaware Avenue, Pennington, NJ, 08534, USA.
Drugs R D. 2017 Jun;17(2):245-254. doi: 10.1007/s40268-017-0175-y.
Risk Evaluation and Mitigation Strategies (REMSs) with Elements to Assure Safe Use (ETASU) are requested for drugs with significant safety risks. We reviewed REMS programs issued since 2011 to evaluate their rationales, characteristics, and consistencies, and evaluated their impact on improving drug safety. We conducted a literature search and a survey of relevant websites (FDA, manufacturers, and REMSs). ETASU characteristics were summarized. REMS risks were compared with labeled risks, including black box warnings. Forty-two programs were analyzed. Seven incorporated drugs of the same class. Most drugs (57%) were indicated for an orphan disease. A single risk was mentioned in 24 REMSs, and multiple risks in 18. Embryo-fetal toxicity and abuse or misuse were the most frequent risks. All risks were identified during clinical development but some were hypothetical. Thirty-six drugs had a black box warning. REMS risks and black box risks differed for 11 drugs. A drug with multiple indications could have a REMS for one of them but not for another. Most REMSs required prescriber training and certification, half required dispenser certification and patient enrolment. REMSs were revised multiple times and only three (7%) were discontinued. No data were available to establish whether REMSs were effective in improving drug safety. Some REMSs were deemed inefficient. REMSs with ETASU continue to be implemented but their impact on improving drug safety is still not documented. Hence, one of the main requirements of the FDA Amendments Act of 2007 is not being addressed. In addition, REMSs are complex and their logic is inconsistent; we recommend a thorough re-evaluation of the REMS program.
对于具有重大安全风险的药物，需要制定带有确保安全使用要素（ETASU）的风险评估和缓解策略（REMS）。我们回顾了自2011年以来发布的REMS计划，以评估其基本原理、特征和一致性，并评估它们对提高药物安全性的影响。我们进行了文献检索并调查了相关网站（美国食品药品监督管理局、制造商和REMS）。总结了ETASU的特征。将REMS风险与标签风险（包括黑框警告）进行了比较。分析了42个计划。其中7个纳入了同类药物。大多数药物（57%）用于治疗罕见病。24个REMS提到了单一风险，18个提到了多种风险。胚胎-胎儿毒性以及滥用或误用是最常见的风险。所有风险均在临床开发期间识别出，但有些是假设性的。36种药物有黑框警告。11种药物的REMS风险和黑框风险不同。一种具有多种适应症的药物可能针对其中一种适应症有REMS，但针对另一种则没有。大多数REMS要求开处方者培训和认证，一半要求配药者认证和患者登记。REMS多次修订，只有三个（7%）被终止。没有数据可用于确定REMS在提高药物安全性方面是否有效。一些REMS被认为效率低下。带有ETASU的REMS仍在实施，但其对提高药物安全性的影响仍未得到记录。因此，2007年《美国食品药品监督管理局修正案法案》的主要要求之一未得到满足。此外，REMS很复杂且其逻辑不一致；我们建议对REMS计划进行全面重新评估。
