VA Center for Medication Safety, Veterans Health Administration, Pittsburgh, Pennsylvania.
Department of Pharmacy and Therapeutics, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania.
JAMA Netw Open. 2019 Sep 4;2(9):e1910626. doi: 10.1001/jamanetworkopen.2019.10626.
Drug safety communications released by the US Food and Drug Administration (FDA) are often based on limited evidence on safety signals after approval. Varenicline may serve as a relevant case study because it was the target of several FDA communications in 2008 and 2009; ultimately, the Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) dismissed safety concerns on increased suicidal thoughts and aggressive and erratic behavior on December 16, 2016.
To examine the association between FDA drug safety communications and the use of varenicline.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective, longitudinal, cross-sectional study of Veterans Health Administration (VHA) outpatient data from October 1, 2001, through December 31, 2018, and Medicaid drug state use data from July 1, 2006, through September 30, 2018, on varenicline prescribing.
Prescribing records for varenicline and nicotine replacement therapy (NRT) in the VHA were extracted, and the number of unique varenicline and NRT users in the VHA per quarter was measured. An interrupted time series analysis was performed to describe the association between FDA safety warnings and the use of varenicline and NRT. To test the generalizability of the findings, similar analyses were conducted using the number of prescriptions reimbursed for varenicline by Medicaid every quarter in 2006-2018.
After its addition to the VHA national drug formulary in January 2007, varenicline use presented a steady increase, reaching a peak of 32 581 quarterly unique users in the first quarter of 2008. Within 12 months of the February 1, 2008, public health advisory, quarterly varenicline use in VHA patients decreased by 68.7% (from 32 581 to 10 182 patients; P < .001 for slope change), and NRT use increased by 32.1% (from 55 728 to 73 629 patients; P < .001 for slope change). In Medicaid prescriptions, varenicline use decreased by 38.0% (from 109 308 to 67 761 prescriptions; P < .001 for slope change) within 12 months of the 2008 public health advisory. Twelve months after the publication of the EAGLES trial, which showed no significant increase in psychiatric/behavioral effects with varenicline relative to NRT, use of varenicline increased by 42.7% in VHA patients (from 9251 to 13 199 patients; P = .01 for slope change) and by 26.0% in Medicaid prescriptions (112 063 to 141 122; P = .26 for slope change ).
With use of varenicline as a case study, early communications from the FDA and VHA followed by a labeling change appeared to be associated with a considerable decrease in drug use, which may have been associated with negative public health consequences.
美国食品和药物管理局（FDA）发布的药物安全通讯通常基于批准后安全性信号的有限证据。伐伦克林可能是一个相关的案例研究，因为它是 2008 年和 2009 年 FDA 通讯的目标；最终，全球戒烟研究（EAGLES）评估不良事件于 2016 年 12 月 16 日驳回了对自杀意念增加以及攻击性和不稳定行为的安全担忧。
研究 FDA 药物安全通讯与伐伦克林使用之间的关系。
设计、设置和参与者：对退伍军人健康管理局（VHA）门诊数据（2001 年 10 月 1 日至 2018 年 12 月 31 日）和 2006 年 7 月 1 日至 2018 年 9 月 30 日 Medicaid 药物州使用数据的回顾性、纵向、横断面研究，研究伐伦克林的处方情况。
提取了 VHA 中伐伦克林和尼古丁替代疗法（NRT）的处方记录，并测量了 VHA 中每季度伐伦克林和 NRT 的独特使用者数量。进行了中断时间序列分析，以描述 FDA 安全警告与伐伦克林和 NRT 使用之间的关系。为了检验研究结果的普遍性，还使用了 2006-2018 年 Medicaid 每季度报销的伐伦克林处方数量进行了类似的分析。
伐伦克林于 2007 年 1 月被添加到 VHA 国家药物配方中后，其使用量呈现稳步增加，在 2008 年第一季度达到了 32581 名季度独特使用者的峰值。在 2008 年 2 月 1 日发布公共卫生咨询后的 12 个月内，VHA 患者的伐伦克林季度使用量下降了 68.7%（从 32581 人降至 10182 人；斜率变化的 P <.001），而 NRT 使用量增加了 32.1%（从 55728 人增至 73629 人；斜率变化的 P <.001）。在 Medicaid 处方中，在 2008 年公共卫生咨询后的 12 个月内，伐伦克林的使用量下降了 38.0%（从 109308 张处方降至 67761 张处方；斜率变化的 P <.001）。在 EAGLES 试验公布后的 12 个月内，该试验显示伐伦克林与 NRT 相比没有显著增加精神/行为影响，VHA 患者使用伐伦克林增加了 42.7%（从 9251 人增至 13199 人；斜率变化的 P =.01），而 Medicaid 处方增加了 26.0%（从 112063 人增至 141122 人；斜率变化的 P =.26）。
以伐伦克林为例，FDA 和 VHA 的早期通讯随后进行了标签更改，这似乎与药物使用量的大幅减少有关，而这种减少可能与负面的公共卫生后果有关。
