Division of Headache, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Headache Division, Department of Neurology, State University of New York, Buffalo, NY, USA.
Headache. 2018 Nov;58(10):1639-1657. doi: 10.1111/head.13424. Epub 2018 Oct 27.
We sought to analyze publicly available information about patient harm associated with an iontophoretic sumatriptan patch, to identify what went wrong and to suggest ways in which similar problems might be prevented in the future.
The Zecuity® sumatriptan iontophoretic transdermal system was marketed for acute treatment of migraine. The patch was withdrawn less than 10 months after its introduction because of multiple reports of scarring and burning. As of 2018, the FDA Adverse Event Reporting System public dashboard lists a total of 2889 reports of safety problems with the patch, 904 of which were classified as serious.
For this narrative review, we examined US Food and Drug Administration documents related to the new drug application for this product and its approval. We searched Clinicaltrials.gov, PubMed, Google, Facebook, Twitter, and Instagram public posts for relevant information relating to the patch, its approval, marketing, and complications.
The FDA knew about problems with burns and scarring prior to approval of the product, and turned down the initial new drug application for this reason and because of other quality problems with the patch. The reapplication was approved despite continued concerns of several FDA reviewers about safety. The approval required the manufacturer to comply with enhanced postmarketing safety reporting. However, product information and labeling did not mention the possibility of burns or scarring. Approval was based on 1 clinical trial and 2 open label studies in which reporting of adverse events was suboptimal. The clinical trials had been prospectively registered but outcomes had been changed around the time the trial concluded. Aggressive marketing efforts and social media activity may have contributed to inaccurate perceptions of safety and efficacy, but social media also provided a written and photographic record of burns and other harm suffered by patients who used the patch.
Our review identified several problems with the development, testing, approval, and marketing of the Zecuity patch. To improve the process of developing headache treatments, it is important to consider the lessons that can be drawn from an examination of this high-profile failure of the drug development and regulatory system.
我们旨在分析与离子导入型舒马曲坦贴片相关的患者伤害的公开信息，以确定问题所在，并提出未来如何预防类似问题的建议。
Zecuity®舒马曲坦离子导入透皮系统用于偏头痛的急性治疗。在推出不到 10 个月后，由于多份关于疤痕和灼伤的报告，该贴片被撤回。截至 2018 年，美国食品和药物管理局（FDA）不良事件报告系统公共仪表板共列出了 2889 份与该贴片有关的安全问题报告，其中 904 份被归类为严重。
对于本次叙述性综述，我们审查了与该产品新药申请及其批准相关的美国食品和药物管理局文件。我们在 Clinicaltrials.gov、PubMed、Google、Facebook、Twitter 和 Instagram 上搜索了与贴片、其批准、营销和并发症相关的相关信息。
FDA 在批准该产品之前就已经了解到灼伤和疤痕的问题，并因该原因以及贴片的其他质量问题拒绝了最初的新药申请。尽管 FDA 的几位审查员对安全性仍有持续担忧，但重新申请仍获得批准。批准要求制造商遵守强化上市后安全报告要求。然而，产品信息和标签并未提及灼伤或疤痕的可能性。批准基于 1 项临床试验和 2 项开放标签研究，其中不良事件报告并不完善。临床试验已预先注册，但在试验结束时，结果已发生变化。积极的营销努力和社交媒体活动可能导致对安全性和疗效的不准确看法，但社交媒体也提供了患者使用贴片后遭受灼伤和其他伤害的书面和照片记录。
我们的审查发现了 Zecuity 贴片在开发、测试、批准和营销方面存在的几个问题。为了改善头痛治疗的开发过程，重要的是要从药物开发和监管系统这一备受瞩目的失败中吸取教训。
