Literature DB >> 19050195

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

Aaron S Kesselheim1, Alexander S Misono, Joy L Lee, Margaret R Stedman, M Alan Brookhart, Niteesh K Choudhry, William H Shrank.   

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 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.
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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Year:  2008        PMID: 19050195      PMCID: PMC2713758          DOI: 10.1001/jama.2008.758

Source DB:  PubMed          Journal:  JAMA        ISSN: 0098-7484            Impact factor:   56.272


  85 in total

1.  Relevance of pharmacokinetics in narrow therapeutic index drugs.

Authors:  L Z Benet
Journal:  Transplant Proc       Date:  1999-05       Impact factor: 1.066

Review 2.  Generic substitution of antiarrhythmic drugs.

Authors:  P E Nolan
Journal:  Am J Cardiol       Date:  1989-12-01       Impact factor: 2.778

Review 3.  Formulation substitution and other pharmacokinetic variability: underappreciated variables affecting antiarrhythmic efficacy and safety in clinical practice.

Authors:  J A Reiffel
Journal:  Am J Cardiol       Date:  2000-05-25       Impact factor: 2.778

4.  Generic warfarin: a cost-effective alternative to brand-name drug or a clinical wild card?

Authors:  J M DeCara; S Croze; R H Falk
Journal:  Chest       Date:  1998-02       Impact factor: 9.410

5.  Generic warfarin: implications for patient care.

Authors:  A K Wittkowsky
Journal:  Pharmacotherapy       Date:  1997 Jul-Aug       Impact factor: 4.705

Review 6.  Bioequivalence. An updated reappraisal addressed to applications of interchangeable multi-source pharmaceutical products.

Authors:  A Marzo; L P Balant
Journal:  Arzneimittelforschung       Date:  1995-02

7.  Substitution of generic warfarin for Coumadin in an HMO setting.

Authors:  Paul E Milligan; Gerald A Banet; Amy D Waterman; Susan K Gatchel; Brian F Gage
Journal:  Ann Pharmacother       Date:  2002-05       Impact factor: 3.154

8.  A comparison of antihypertensive effects between two formulations of atenolol: tenolol and tenormin.

Authors:  H T Chiang; Z Y Hou; D K Lee; T L Wu; C Y Chen
Journal:  Zhonghua Yi Xue Za Zhi (Taipei)       Date:  1995-05

9.  Patients' perceptions of generic medications.

Authors:  William H Shrank; Emily R Cox; Michael A Fischer; Jyotsna Mehta; Niteesh K Choudhry
Journal:  Health Aff (Millwood)       Date:  2009 Mar-Apr       Impact factor: 6.301

10.  Implications of intraindividual variability in bioavailability studies of furosemide.

Authors:  A Grahnén; M Hammarlund; T Lundqvist
Journal:  Eur J Clin Pharmacol       Date:  1984       Impact factor: 2.953

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  113 in total

1.  Generic Substitution Issues: Brand-generic Substitution, Generic-generic Substitution, and Generic Substitution of Narrow Therapeutic Index (NTI)/Critical Dose Drugs.

Authors:  Marian Sorin Paveliu; Simona Bengea; Fraga Silvia Paveliu
Journal:  Maedica (Buchar)       Date:  2011-01

2.  From NCE to NICE: the role of pharmacoeconomics.

Authors:  Dyfrig A Hughes
Journal:  Br J Clin Pharmacol       Date:  2010-09       Impact factor: 4.335

Review 3.  The evolution of renin-angiotensin blockade: angiotensin-converting enzyme inhibitors as the starting point.

Authors:  Domenic A Sica
Journal:  Curr Hypertens Rep       Date:  2010-04       Impact factor: 5.369

Review 4.  Switching from brand-name to generic psychotropic medications: a literature review.

Authors:  Julie Eve Desmarais; Linda Beauclair; Howard C Margolese
Journal:  CNS Neurosci Ther       Date:  2010-11-30       Impact factor: 5.243

5.  The diffusion of generics after patent expiry in Germany.

Authors:  Katharina Elisabeth Fischer; Tom Stargardt
Journal:  Eur J Health Econ       Date:  2015-11-16

6.  A comparison of the intrasubject variation in drug exposure between generic and brand-name drugs: a retrospective analysis of replicate design trials.

Authors:  Yang Yu; Steven Teerenstra; Cees Neef; David Burger; Marc Maliepaard
Journal:  Br J Clin Pharmacol       Date:  2016-01-15       Impact factor: 4.335

7.  Factors affecting the opinions of family physicians regarding generic drugs--a questionnaire based study.

Authors:  Pawel Lewek; Janusz Smigielski; Przemyslaw Kardas
Journal:  Bosn J Basic Med Sci       Date:  2014-12-17       Impact factor: 3.363

8.  Sources of regional variation in Medicare Part D drug spending.

Authors:  Julie M Donohue; Nancy E Morden; Walid F Gellad; Julie P Bynum; Weiping Zhou; Joseph T Hanlon; Jonathan Skinner
Journal:  N Engl J Med       Date:  2012-02-09       Impact factor: 91.245

9.  Money left on the table: generic drug prices in Canada.

Authors:  Michael R Law
Journal:  Healthc Policy       Date:  2013-02

10.  Comparison of six generic vancomycin products for treatment of methicillin-resistant Staphylococcus aureus experimental endocarditis in rabbits.

Authors:  P Tattevin; A Saleh-Mghir; B Davido; I Ghout; L Massias; C Garcia de la Maria; J M Miró; C Perronne; F Laurent; A C Crémieux
Journal:  Antimicrob Agents Chemother       Date:  2012-12-17       Impact factor: 5.191

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