Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Center for Science in the Public Interest, Washington, DC.
JAMA. 2019 Feb 19;321(7):676-685. doi: 10.1001/jama.2019.0235.
Transmucosal immediate-release fentanyls (TIRFs), indicated solely for breakthrough cancer pain in opioid-tolerant patients, are subject to a US Food and Drug Administration (FDA) Risk Evaluation and Mitigation Strategy (REMS) to prevent them from being prescribed inappropriately.
To evaluate knowledge assessments of pharmacists, prescribers, and patients regarding appropriate TIRF use; to describe sponsor assessments, based on claims data, of whether the REMS program was meeting its goals; and to characterize how the FDA responded to REMS assessments.
DESIGN, SETTING, AND PARTICIPANTS: Qualitative analysis of 4877 pages of FDA documents obtained through a Freedom of Information Act request, including 6 annual REMS assessment reports (2012-2017), FDA evaluations of these reports, and FDA-sponsor correspondence about safety issues.
A REMS program to reduce the risk of adverse outcomes, including misuse, abuse, addiction, and overdose, arising from use of TIRFs.
(1) Knowledge assessments of pharmacists, prescribers, and patients; (2) survey and claims-based prescribing assessments; (3) FDA and TIRF sponsor communications; (4) modifications to the REMS program; and (5) disenrollment of noncompliant prescribers.
Twelve months after initiation of the program, 24 of 302 pharmacists (7.9%), 35 of 302 prescribers (11.6%), and 5 of 192 patients (2.6%) incorrectly reported that TIRFs can be prescribed to opioid-nontolerant patients, with similar levels of misunderstanding maintained in the subsequent reports. At 60 months, product-specific analyses of claims data indicated that between 34.6% and 55.4% of patients prescribed TIRFs were opioid-nontolerant. In the 48-month survey, 106 of 310 prescribers (34.2%) reported prescribing TIRFs for opioid-tolerant patients with chronic, noncancer pain; at 60 months, 54 of 302 prescribers (18.4%) and 148 of 310 patients (47.7%) erroneously reported that TIRFs were FDA-approved for such use. Over the 60-month period examined, there were few substantive changes made to the REMS to address evidence of high rates of off-label TIRF use, and, although the REMS program had a noncompliance plan, there was no report of prescribers being disenrolled for inappropriate prescribing.
In this review of FDA documents pertaining to the TIRF REMS, surveys of pharmacists, prescribers, and patients reflected generally high levels of knowledge regarding proper TIRF prescribing, yet some survey items as well as claims-based analyses indicated substantial rates of inappropriate TIRF use. Despite these findings, the FDA did not require substantive changes to the program.
仅用于缓解阿片类药物耐受患者爆发性癌痛的经黏膜快速释放芬太尼（TIRFs）受到美国食品和药物管理局（FDA）风险评估和缓解策略（REMS）的限制，以防止不当处方。
评估药剂师、处方者和患者对 TIRF 合理使用的知识评估；根据索赔数据描述赞助商评估，以确定 REMS 计划是否达到其目标；并描述 FDA 对 REMS 评估的反应。
设计、地点和参与者：通过信息自由法案请求获得的 4877 页 FDA 文件的定性分析，包括 6 份年度 REMS 评估报告（2012-2017 年）、FDA 对这些报告的评估以及 FDA-赞助商关于安全问题的通信。
REMS 计划旨在降低因使用 TIRFs 而产生的不良后果的风险，包括误用、滥用、成瘾和过量。
（1）药剂师、处方者和患者的知识评估；（2）调查和基于索赔的处方评估；（3）FDA 和 TIRF 赞助商的沟通；（4）REMS 计划的修改；（5）不遵守规定的处方者被除名。
计划启动后 12 个月，302 名药剂师中的 24 名（7.9%）、302 名处方者中的 35 名（11.6%）和 192 名患者中的 5 名（2.6%）错误地报告 TIRFs 可用于非阿片类药物耐受患者，随后的报告中也保持了类似的误解水平。在 60 个月时，对索赔数据的特定产品分析表明，接受 TIRF 处方的患者中有 34.6%至 55.4%为非阿片类药物耐受。在 48 个月的调查中，310 名处方者中的 106 名（34.2%）报告为阿片类药物耐受的慢性非癌痛患者开 TIRF；在 60 个月时，302 名处方者中的 54 名（18.4%）和 310 名患者中的 148 名（47.7%）错误地报告 TIRF 已获得此类用途的 FDA 批准。在检查的 60 个月期间，针对高比例的 TIRF 标签外使用证据，对 REMS 进行了很少的实质性更改，尽管 REMS 计划有不合规计划，但没有报告处方者因不当处方而被除名。
在对 FDA 与 TIRF REMS 相关文件的审查中，药剂师、处方者和患者的调查反映了对 TIRF 正确处方的普遍较高水平的知识，但一些调查项目和基于索赔的分析表明，TIRF 的使用存在大量不适当的情况。尽管有这些发现，FDA 并未要求对该计划进行实质性更改。
