Department of Patient Safety & Quality, Hackensack Meridian Health, Edison, New Jersey.
Centers for Medicare & Medicaid Services, Baltimore, Maryland.
JAMA Netw Open. 2019 Mar 1;2(3):e191340. doi: 10.1001/jamanetworkopen.2019.1340.
Transmucosal immediate-release fentanyl (TIRF) drugs are potent, rapid-acting opioids approved to treat breakthrough pain in patients with cancer who are tolerant to other around-the-clock opioid analgesics. In March 2012, a US Food and Drug Administration-approved Risk Evaluation and Mitigation Strategy (REMS) was implemented, mandating prescribers, distributors, pharmacies, and patients to enroll in the REMS to prescribe, dispense, or receive TIRF drugs.
To evaluate the association of the TIRF-REMS Access Program with TIRF prescribing.
DESIGN, SETTING, AND PARTICIPANTS: Cohort study using an interrupted time series analysis of TIRF prescriptions to Medicare Part D beneficiaries nationwide from 2010 to 2014. Data were analyzed from August 2017 through July 2018.
Prescribing of TIRF per 100 000 Medicare Part D beneficiaries, overall and stratified by cancer status; percentage of TIRF prescriptions for patients without cancer, overall and by brand; and percentage of TIRF prescriptions for patients without known opioid tolerance, defined as patients prescribed at least 60 morphine milligram equivalents per day, overall and by brand.
There were 99 601 TIRF prescriptions written by 8619 clinicians to 10 472 patients. Most of the patients (79%) were younger than 65 years (mean [SD] age, 56 [13] years), and most (67%) did not have cancer. Implementation of TIRF-REMS was associated with a 26.7% relative level decrease in TIRF prescribing (95% CI, -33.3% to -19.4%; P < .001) but was followed by 2.0% monthly increases in prescribing (95% CI, 1.3% to 2.7%; P < .001). Sensitivity analyses that accounted for overall opioid prescribing trends were consistent with these findings. Furthermore, there were no significant changes associated with REMS implementation in the level (0.47%; 95% CI, -5.36% to 4.69%; P = .85) or trend (0.16%; 95% CI, -0.06% to 0.37%; P = .15) of the percentage of prescriptions for patients without cancer. However, a sensitivity analysis that used a broader cancer definition found implementation was associated with a 7.2% (95% CI, -13.5% to -0.48%; P = .04) level decrease in the percentage of TIRF prescriptions for patients without cancer. Lastly, the TIRF-REMS was associated with a 22.5% level decline in the percentage of TIRF prescriptions for patients without known opioid tolerance (95% CI, -36.1% to -5.95%; P = .01) followed by 1.98% monthly decreases (95% CI, -3.19% to -0.80%; P = .001).
Implementation of the TIRF-REMS Access Program, a restrictive drug distribution program, was associated with a temporary reduction in the rate of TIRF prescribing to Medicare Part D beneficiaries, and with a sustained decrease in the percentage of TIRF prescriptions for patients without known opioid tolerance. Implementation may have also been associated with a temporary decrease in the percentage of TIRF prescriptions for patients without cancer.
经粘膜快速释放芬太尼（TIRF）药物是一种强效、快速作用的阿片类药物，用于治疗对其他全天阿片类镇痛药耐受的癌症患者的突破性疼痛。2012 年 3 月，美国食品和药物管理局批准了一项风险评估和缓解策略（REMS），要求开处方者、分销商、药店和患者参加 REMS，以开具、分发或接收 TIRF 药物。
评估 TIRF-REMS 准入计划与 TIRF 处方之间的关联。
设计、地点和参与者：使用全国医疗保险 D 部分受益人的 TIRF 处方的中断时间序列分析，从 2010 年到 2014 年。数据于 2017 年 8 月至 2018 年 7 月进行分析。
每 100000 名医疗保险 D 部分受益人的 TIRF 处方率，总体和按癌症状况分层；无癌症患者 TIRF 处方的百分比，总体和按品牌分层；以及无已知阿片类药物耐受性患者 TIRF 处方的百分比，定义为每天至少开 60 毫克吗啡当量的患者，总体和按品牌分层。
有 8619 名临床医生为 10472 名患者开出了 99601 份 TIRF 处方。大多数患者（79%）年龄小于 65 岁（平均[标准差]年龄，56[13]岁），大多数（67%）没有癌症。TIRF-REMS 的实施与 TIRF 处方的相对水平下降 26.7%（95%CI，-33.3%至-19.4%；P<.001）相关，但随后每月处方增加 2.0%（95%CI，1.3%至 2.7%；P<.001）。考虑到整体阿片类药物处方趋势的敏感性分析与这些发现一致。此外，REMS 实施与无癌症患者处方比例的水平（0.47%；95%CI，-5.36%至 4.69%；P=.85）或趋势（0.16%；95%CI，-0.06%至 0.37%；P=.15）均无显著变化。然而，一项使用更广泛癌症定义的敏感性分析发现，实施与无癌症患者 TIRF 处方比例的 7.2%（95%CI，-13.5%至-0.48%；P=.04）水平下降相关。最后，TIRF-REMS 与无已知阿片类药物耐受性患者 TIRF 处方比例的 22.5%水平下降相关（95%CI，-36.1%至-5.95%；P=.01），随后每月下降 1.98%（95%CI，-3.19%至-0.80%；P=.001）。
TIRF-REMS 准入计划的实施，即一项限制性药物分发计划，与医疗保险 D 部分受益人的 TIRF 处方率的暂时下降以及无已知阿片类药物耐受性患者的 TIRF 处方比例的持续下降相关。实施可能还与无癌症患者 TIRF 处方比例的暂时下降有关。
