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桓兴医讯 2006年至2016年美国食品和药物管理局批准的癌症药物上
文章来源:北京市朝阳区桓兴肿瘤医院 点击数: 发布时间:2018-04-19 15:18
美国《临床肿瘤学杂志》2018年4月11日在线先发
2006年至2016年美国食品和药物管理局批准的癌症药物上市后不论有无随机对照试验支持的药品说明书修订
目的
癌症药物经食品和药物管理局批准后,对其适应症、剂量和相关毒性的修改常见。目前还不清楚没有随机对照试验(RCT)支持的获批药物是否会影响药品说明书的这类修改。
方法
我们在Drugs@FDA网站上检索了2006年1月至2016年12月期间批准的用于实体瘤的新药适应症。我们从药品说明书上收集了自2017年10月批准的药物研究特点、监管途径和说明书修订信息,若药物说明中有这种界定的修订信息,则考虑为说明书修订有重大调整。我们采用逻辑回归分析,对有随机对照试验支持的适应症和没有随机对照试验支持的适应症进行了比较,用Benjamini-Hochberg错误发现率方法对多种情况加以校正。
结果
我们甄别出59种药物,有109个实体肿瘤适应症。其中17个适应症(15.6%)没有随机对照试验支持,且随时间推移适应症未变。没有随机对照试验支持的适应症可能更需要伴随诊断检测(比值比[OR],3.90;P=0.02)、更需要纳入替代终点作为主要终点(OR,7.88;P<0.001)、更需要接受突破性治疗设计(OR,7.62;P=0.006)或加速批准(OR,17.67;P<0.001)。没有随机对照试验支持的适应症与获批后对常见不良事件进行修订的几率更高显著相关(71%对29%;OR,5.78;P=0.002)。我们还观察到,获批后对警告和注意事项进行重大修改的几率并无显著提高(88%对62%;OR,4.61;P=0.051)。获批后对适应症和用途、剂量和给药途径、黑框警告、禁忌症的重大修订,两组相当。
结论
起初没有随机对照试验支持的癌症药物的适应症,上市后对药物安全性说明的修订更多。卫生专业人员在开具没有随机对照试验支持而获批的药物处方时,应当警惕尚不清楚的不良事件。
北京市朝阳区桓兴肿瘤医院 桓兴医讯编译组 孟祥志
2018年4月19日 星期四
Postmarketing Modifications of Drug Labels for Cancer Drugs Approved by the US Food and Drug Administration Between 2006 and 2016 With and Without Supporting Randomized Controlled Trials
Daniel Shepshelovich, Ariadna Tibau, Hadar Goldvaser, Consolación Molto, Alberto Ocana, Bostjan Seruga...Show More
Purpose
Modifications in cancer drug indications, dosing, and related toxicities after Food and Drug Administration approval are common. It is unclear whether drug approval without a supporting randomized controlled trial (RCT) influences the probability of such modifications.
Methods
We searched the Drugs@FDA Web site for new drug indications for solid tumors approved between January 2006 and December 2016. Study characteristics, regulatory pathways, and label modifications from approval to October 2017 were collected from drug labels. Label modifications were considered to be major if defined as such in the drug label. Indications approved with and without supporting RCTs were compared using logistic regression. The Benjamini-Hochberg false discovery rate method was used to adjust for multiplicity.
Results
We identified 59 individual drugs for 109 solid tumor indications. Of these, 17 indications (15.6%) were not supported by an RCT, with no change over time. Indications not supported by RCTs were more likely to require companion diagnostic tests (odds ratio [OR], 3.90; P = .02), to include surrogate end points as primary outcomes (OR, 7.88; P < .001), and to receive breakthrough therapy designation (OR, 7.62; P = .006) or accelerated approval (OR, 17.67; P < .001). Indications not supported by RCTs were associated with significantly higher odds of postapproval modifications in common adverse events (71% v 29%; OR, 5.78; P = .002). A nonsignificantly higher odds of postapproval major modifications in warnings and precautions was also observed (88% v 62%; OR, 4.61; P = .051). Postapproval major modifications in indication and usage, dosing and administration, boxed warnings, and contraindications were comparable in the two groups.
Conclusion
Cancer drug indications not supported initially by RCTs are associated with more postmarketing safety-related label modifications. Health care professionals should be vigilant for unrecognized adverse effects when prescribing drugs approved without a supporting RCT.

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