Sarpatwari Ameet, He Mengdong, Tessema Frazer A, Gagne Joshua J, Kesselheim Aaron S
Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 1620 Tremont St., Suite 3030, Boston, MA, 02120, USA.
Drug Saf. 2021 Mar;44(3):327-335. doi: 10.1007/s40264-020-01017-z. Epub 2020 Nov 18.
Risk evaluation and mitigation strategy (REMS) programs are intended to improve safe use of US Food and Drug Administration-approved drugs. However, controversy exists over whether they consistently accomplish this goal.
We aimed to assess how initiation of the erythropoiesis stimulating agents (ESAs) darbepoetin alfa and epoetin alfa changed following implementation and enforcement (following a 1-year post-implementation grace period) of a prominent REMS program warning physicians against use in cancer patients with hemoglobin above 10 g/dL.
Using claims data from a large US commercial insurance company, we conducted interrupted time-series analyses of darbepoetin alfa and epoetin alfa initiation among adult cancer patients in the 12 months before REMS program implementation, after REMS program implementation, and after REMS program enforcement. We also evaluated differences in inappropriate initiation (hemoglobin tests all above 10 g/dL in the prior month) between the periods.
In total, we identified 3456 darbepoetin alfa initiators and 2632 epoetin alfa initiators. Over the study period, the monthly number of initiators per 100,000 patients with cancer fell from 119 to 32 for darbepoetin alfa and from 82 to 34 for epoetin alfa. However, non-significant post-REMS program implementation level and slope changes per 100,000 adult patients with cancer were observed for darbepoetin alfa (level 0.03 [95% confidence interval (CI) -14.98 to 15.05]; slope 1.94 [95% CI -0.22 to 4.10]) and epoetin alfa (level -4.10 [95% CI -16.85 to 8.65]; slope -0.52 [95% CI -2.35 to 1.32]). Non-significant post-REMS program enforcement level and slope changes were also seen for both drugs (darbepoetin alfa level 1.58 [95% CI -0.58 to 3.74, slope -0.28 [95% CI -15.29 to 14.73]; epoetin alfa level 1.58 (95% CI -0.26 to 3.42], slope 5.74 [95% CI -7.01 to 18.49]). Finally, non-significant changes in inappropriate darbepoetin alfa (60% vs. 53% vs. 57%, p = 0.68) and epoetin alfa (53% vs. 53% vs. 46%, p = 0.41) initiation were observed between the three study periods.
REMS program implementation and enforcement were not associated with significant changes in ESA initiation, adding to concerns over the degree to which certain REMS programs enhance patient safety.
风险评估与缓解策略（REMS）计划旨在促进美国食品药品监督管理局（FDA）批准药物的安全使用。然而，对于这些计划是否始终能实现这一目标存在争议。
我们旨在评估促红细胞生成素（ESA）药物阿法达贝泊汀和阿法依泊汀的起始使用情况在一项重要的REMS计划实施及执行后（实施后1年宽限期之后）有何变化，该计划警告医生不要在血红蛋白高于10 g/dL的癌症患者中使用这两种药物。
利用一家大型美国商业保险公司的理赔数据，我们对阿法达贝泊汀和阿法依泊汀在REMS计划实施前12个月、实施后以及执行后的成年癌症患者中的起始使用情况进行了中断时间序列分析。我们还评估了各时期之间不适当起始使用（前一个月血红蛋白检测结果均高于10 g/dL）的差异。
我们总共确定了3456名阿法达贝泊汀起始使用者和2632名阿法依泊汀起始使用者。在研究期间，每10万名癌症患者中阿法达贝泊汀的月起始使用者数量从119降至32，阿法依泊汀从82降至34。然而，对于阿法达贝泊汀，每10万名成年癌症患者在REMS计划实施后的水平和斜率变化不显著（水平0.03 [95%置信区间（CI）-14.98至15.05]；斜率1.94 [95% CI -0.22至4.10]），阿法依泊汀也是如此（水平-4.10 [95% CI -16.85至8.65]；斜率-0.52 [95% CI -2.35至1.32]）。两种药物在REMS计划执行后的水平和斜率变化也不显著（阿法达贝泊汀水平1.58 [95% CI -0.58至3.74]，斜率-0.28 [95% CI -15.29至14.73]；阿法依泊汀水平1.58（95% CI -0.26至3.42]，斜率5.74 [95% CI -7.01至18.49]）。最后，在三个研究时期之间，阿法达贝泊汀（60%对53%对57%，p = 0.68）和阿法依泊汀（53%对53%对46%，p = 0.41）不适当起始使用的变化不显著。
REMS计划的实施和执行与ESA起始使用的显著变化无关，这增加了人们对某些REMS计划在多大程度上提高患者安全性的担忧。
