Clinical Equivalence of Generic and Brand-Name Drugs Used in Cardiovascular Disease A Systematic Review and Meta-analysis

Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02120, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 01/2009; 300(21):2514-26. DOI: 10.1001/jama.2008.758
Source: PubMed


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.

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Available from: Alexander S Misono, Mar 05, 2015
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    • "Similar uncertainty concerns clinical equivalence of generics and brand-name products used for cardiovascular (CV) diseases . A recent literature systematic review reported that most studies included small populations and were only powered to assess differences in pharmacokinetic parameters, rather than clinical outcomes [15]. Furthermore , most investigations included young and healthy subjects, which make available evidence of questionable relevance for diseased patients [16]. "
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    ABSTRACT: Background Use of generic drugs can help contain drug spending. However, there is concern among patients and physicians that generic drugs may be clinically inferior to brand-name ones. This study aimed to compare patients treated with generic and brand-name statins in terms of therapeutic interruption and cardiovascular (CV) outcomes. Methods 13,799 beneficiaries of the health care system of Lombardy, Italy, aged 40 years or older who were newly treated with generic or brand-name simvastatin during 2008, were followed until 2011 for the occurrence of two outcomes: 1) therapeutic discontinuation and 2) hospitalization for CV events. Hazard ratios (HR) associated with use of generic or brand-name at starting therapy (intention-to-treat analysis) and during follow-up (as-treated analysis) were estimated by fitting proportional hazard Cox models. A Monte-Carlo sensitivity analysis was performed to account for unmeasured confounders. Results Patients who started on generic did not experience a different risk of discontinuation (HR: 0.98; 95% CI 0.94 to 1.02) nor of CV outcomes (HR: 0.98; 95% CI 0.79 to 1.22) from those starting on brand-name. Patients who spent > 75% of time of follow-up with statin available on generics did not experience a different risk of discontinuation (HR: 0.94; 95% CI 0.87 to 1.01), nor of CV outcomes (HR: 1.06; 95% CI 0.83 to 1.34), compared with those who mainly or only used brand-name statin. Conclusions Our findings do not support the notion that in the real world clinical practice brand-name statins are superior to generics for keeping therapy and preventing CV outcomes.
    Full-text · Article · Oct 2014 · European Journal of Internal Medicine
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    • "However, about 60% of drug products marketed in Brazil are generic and similar drug products. Even though, there are some concerns about the efficacy, safety and quality of generic and similar drug products (Agudelo and Vesga, 2012; Endrenyi and Tothfalusi, 2010; Gauzit and Lakdhari, 2012; Tschabischer et al., 2008, Bialer, 2007; Kesselheim et al., 2008; Borgherini, 2003; Davit et al., 2009; Meredith, 2003; Durden and Hughes, 2010; van Wijk et al., 2006). According to ANVISA requirements, both generic and similar drug products have to confirm inter-changeability by pharmaceutical equivalence, and when appropriate, bioequivalence (Brasil, 2007a;b). "
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    ABSTRACT: Pharmaceutical equivalence is an important issue in the regulatory approval of generic and similar drug products, particularly for those that will not be tested for bioequivalence. However, there is no scientific approach that provides us an objective measure of quality and similarity of the results obtained for testing (generic or similar) and branding drug products simultaneously. This paper describes a new multivariate similarity factor for the assessment of in vitro therapeutic equivalence between two medicines by using pharmaceutical equivalence study . We performed pharmaceutical equivalence studies for acyclovir cream, metronidazole injection, meropenem for injection and atropine sulfate injection. All tests and assays results were standardized using an appropriate desirability function. Multivariate similarity factors for pharmaceutical studies were calculated based on individual acceptance factors and similarity deviations for brand, generic, and similar drugs . We found a perfect correlation among multivariate similarity fact or and regulatory requirements. The multivariate similarity factor is a useful tool for in vitro therapeutic equivalence assessment, and may be used for regulatory approval of generic and similar drugs.
    Full-text · Article · Feb 2014 · African journal of pharmacy and pharmacology
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    • "Yim [12] in their stimulation study of Area Under the Curve (AUC) of brand-name and generic preparations has highlighted the potential dangers of switching from one generic preparation to another. Kesselheim et al. [13], on the other hand in their systematic review of majority of randomized controlled trials of cardiac drugs show that despite the proof of similar bioequivalence of brand name and generic drugs there is reluctance and negativity amongst clinicians toward use of generic drugs. Richton-Hewett et al. [14] in their study highlight the medical and economic consequences on the health care system when switching from brand-name to generic preparations of oral warfarin. "
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    ABSTRACT: The appropriateness of use of generic instead of brand-name medication remains unresolved and controversial in several areas of medicine. Some evidence suggestive of variations in bioavailability and clinical effectiveness between different formulations make policy decisions occasionally difficult. The use of generic olanzapine is a widely acceptable practice on the basis of quality, safety and efficacy data and has been adopted in several countries. The case of a 14 year old boy with bipolar affective disorder, autism and intellectual disability who had brand-name to generic olanzapine switch associated with rapid deterioration of his mental state is described. This clinical change was not related to any physical illness or other medication adjustment and resolved as rapidly when generic olanzapine was switched back to the brand-name formulation. Caution should be exercised when policy for switching from brand-name to generic psychotropic medications are made, especially when using medications off label, in extremes of age and in those patients with co-morbid complicating factors such as intellectual disability.
    Full-text · Article · Oct 2013 · BMC Psychiatry
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