Kesselheim Aaron S, Misono Alexander S, Lee Joy L, Stedman Margaret R, Brookhart M Alan, Choudhry Niteesh K, Shrank William H
Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02120, USA.
JAMA. 2008 Dec 3;300(21):2514-26. doi: 10.1001/jama.2008.758.
Use of generic drugs, which are bioequivalent to brand-name drugs, can help contain prescription drug spending. However, there is concern among patients and physicians that brand-name drugs may be clinically superior to generic drugs.
To summarize clinical evidence comparing generic and brand-name drugs used in cardiovascular disease and to assess the perspectives of editorialists on this issue.
Systematic searches of peer-reviewed publications in MEDLINE, EMBASE, and International Pharmaceutical Abstracts from January 1984 to August 2008.
Studies compared generic and brand-name cardiovascular drugs using clinical efficacy and safety end points. We separately identified editorials addressing generic substitution.
We extracted variables related to the study design, setting, participants, clinical end points, and funding. Methodological quality of the trials was assessed by Jadad and Newcastle-Ottawa scores, and a meta-analysis was performed to determine an aggregate effect size. For editorials, we categorized authors' positions on generic substitution as negative, positive, or neutral.
We identified 47 articles covering 9 subclasses of cardiovascular medications, of which 38 (81%) were randomized controlled trials (RCTs). Clinical equivalence was noted in 7 of 7 RCTs (100%) of beta-blockers, 10 of 11 RCTs (91%) of diuretics, 5 of 7 RCTs (71%) of calcium channel blockers, 3 of 3 RCTs (100%) of antiplatelet agents, 2 of 2 RCTs (100%) of statins, 1 of 1 RCT (100%) of angiotensin-converting enzyme inhibitors, and 1 of 1 RCT (100%) of alpha-blockers. Among narrow therapeutic index drugs, clinical equivalence was reported in 1 of 1 RCT (100%) of class 1 antiarrhythmic agents and 5 of 5 RCTs (100%) of warfarin. Aggregate effect size (n = 837) was -0.03 (95% confidence interval, -0.15 to 0.08), indicating no evidence of superiority of brand-name to generic drugs. Among 43 editorials, 23 (53%) expressed a negative view of generic drug substitution.
Whereas evidence does not support the notion that brand-name drugs used in cardiovascular disease are superior to generic drugs, a substantial number of editorials counsel against the interchangeability of generic drugs.
使用与品牌药生物等效的仿制药有助于控制处方药支出。然而，患者和医生担心品牌药在临床上可能优于仿制药。
总结比较用于心血管疾病的仿制药和品牌药的临床证据，并评估社论作者对该问题的看法。
对1984年1月至2008年8月期间MEDLINE、EMBASE和《国际药学文摘》中同行评审出版物进行系统检索。
研究使用临床疗效和安全性终点比较仿制药和品牌心血管药物。我们分别确定了涉及仿制药替代的社论。
我们提取了与研究设计、背景、参与者、临床终点和资金相关的变量。通过Jadad评分和纽卡斯尔-渥太华评分评估试验的方法学质量，并进行荟萃分析以确定总体效应大小。对于社论，我们将作者对仿制药替代的立场分为负面、正面或中性。
我们确定了47篇涵盖9种心血管药物亚类的文章，其中38篇（81%）为随机对照试验（RCT）。在7项β受体阻滞剂RCT中的7项（100%）、11项利尿剂RCT中的10项（91%）、7项钙通道阻滞剂RCT中的5项（71%）、3项抗血小板药物RCT中的3项（100%）、2项他汀类药物RCT中的2项（100%）、1项血管紧张素转换酶抑制剂RCT中的1项（100%）以及1项α受体阻滞剂RCT中的1项（100%）中观察到临床等效性。在窄治疗指数药物中，1项I类抗心律失常药物RCT中的1项（100%）和5项华法林RCT中的5项（100%）报告了临床等效性。总体效应大小（n = 837）为-0.03（95%置信区间，-0.15至0.08），表明没有证据表明品牌药优于仿制药。在43篇社论中，23篇（53%）对仿制药替代持负面看法。
虽然证据不支持心血管疾病中使用的品牌药优于仿制药的观点，但相当数量的社论反对仿制药的互换性。
