Clinical equivalence of generic and brand-name drugs used in cardiovascular disease: A systematic review and meta-analysis

Aaron S. Kesselheim, Alexander S. Misono, Joy Lee, Margaret R. Stedman, M. Alan Brookhart, Niteesh K. Choudhry, William H. Shrank

Research output: Contribution to journalReview article

297 Citations (Scopus)

Abstract

Context: 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. Objectives: To summarize clinical evidence comparing generic and brand-name drugs used in cardiovascular disease and to assess the perspectives of editorialists on this issue. Data Sources: Systematic searches of peer-reviewed publications in MEDLINE, EMBASE, and International Pharmaceutical Abstracts from January 1984 to August 2008. Study Selection: Studies compared generic and brand-name cardiovascular drugs using clinical efficacy and safety end points. We separately identified editorials addressing generic substitution. Data Extraction: 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. Results: 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 β-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 α-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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)2514-2526
Number of pages13
JournalJAMA - Journal of the American Medical Association
Volume300
Issue number21
DOIs
StatePublished - Dec 3 2008
Externally publishedYes

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Names
Meta-Analysis
Generic Drugs
Cardiovascular Diseases
Randomized Controlled Trials
Drug Substitution
Pharmaceutical Preparations
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Cardiovascular Agents
Prescription Drugs
Information Storage and Retrieval
Platelet Aggregation Inhibitors
Calcium Channel Blockers
Warfarin
Angiotensin-Converting Enzyme Inhibitors
Diuretics
MEDLINE
Publications
Confidence Intervals
Physicians

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Clinical equivalence of generic and brand-name drugs used in cardiovascular disease : A systematic review and meta-analysis. / Kesselheim, Aaron S.; Misono, Alexander S.; Lee, Joy; Stedman, Margaret R.; Brookhart, M. Alan; Choudhry, Niteesh K.; Shrank, William H.

In: JAMA - Journal of the American Medical Association, Vol. 300, No. 21, 03.12.2008, p. 2514-2526.

Research output: Contribution to journalReview article

Kesselheim, Aaron S. ; Misono, Alexander S. ; Lee, Joy ; Stedman, Margaret R. ; Brookhart, M. Alan ; Choudhry, Niteesh K. ; Shrank, William H. / Clinical equivalence of generic and brand-name drugs used in cardiovascular disease : A systematic review and meta-analysis. In: JAMA - Journal of the American Medical Association. 2008 ; Vol. 300, No. 21. pp. 2514-2526.
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abstract = "Context: 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. Objectives: To summarize clinical evidence comparing generic and brand-name drugs used in cardiovascular disease and to assess the perspectives of editorialists on this issue. Data Sources: Systematic searches of peer-reviewed publications in MEDLINE, EMBASE, and International Pharmaceutical Abstracts from January 1984 to August 2008. Study Selection: Studies compared generic and brand-name cardiovascular drugs using clinical efficacy and safety end points. We separately identified editorials addressing generic substitution. Data Extraction: 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. Results: 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 β-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 α-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. Conclusions: 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.",
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AU - Shrank, William H.

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N2 - Context: 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. Objectives: To summarize clinical evidence comparing generic and brand-name drugs used in cardiovascular disease and to assess the perspectives of editorialists on this issue. Data Sources: Systematic searches of peer-reviewed publications in MEDLINE, EMBASE, and International Pharmaceutical Abstracts from January 1984 to August 2008. Study Selection: Studies compared generic and brand-name cardiovascular drugs using clinical efficacy and safety end points. We separately identified editorials addressing generic substitution. Data Extraction: 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. Results: 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 β-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 α-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. Conclusions: 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.

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