[e-drug] Clinical equivalence of generic and brand-name CVS drugs-JAMA (4)

e-drug
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E-DRUG: Clinical equivalence of generic and brand-name CVS drugs-JAMA (4)
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Dear Kevin,

We fully agree with the Authors of the JAMA article, when the point are the
fact that journal editorials are often inappropriately biased against
generics, while the generics for cardiovascular conditions considered in this review were found to be clinically equivalent to innovator products.

Our concern is not about the category of "generics" (the availability of
generics of assured quality have proven to be a fundamental tool to address
public health needs, especially in resource-constrained settings), but about any automatic generalizations or extrapolations of such findings between contexts that are deeply different in terms of regulation standards and enforcement. According to WHO, "many low income countries cannot ensure the safety, efficacy and quality of medicines circulating on their markets because they are resource constrained in terms of staffing, standards, systems, and training"; and the Global Fund's recently updated Quality Assurance Policy, aims at assuring compliance with the requirements of the WHO Pre-Qualification Programme and of stringent Regulatory Authorities.

While we are concerned that automatic extrapolation of the findings of the
JAMA articles to different contexts could be dangerous, we find that it would be extremely interesting to look at the proof of clinical equivalence also in different contexts and diseases, to build evidence-based knowledge of the situation in the field and to contribute to protecting and promoting public health.

Your remark on the fact that counterfeited medicines represent a serious
danger to individual and public health, too, is absolutely correct. However, given the criminal intent of counterfeiters, who always act, fraudulently and deliberately, outside the control of Regulatory Authorities, we feel that the two problems should be analysed separately.

Jacque Pinel, pharmacist
Raffaella Ravinetto, pharmacist, Institute of Tropical Medicine Antwerp
Daniel Vandenbergh, pharmacist
Sophie-Marie Scouflaire-Mallet, pharmacist
Jean-Michel Caudron, pharmacist
http://pharmahook.blogspot.com/
rravinetto@itg.be

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E-DRUG: Clinical equivalence of generic and brand-name CVSdrugs-JAMA (5)
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Hi all

While the arguments about the importance of medicines regulatory authorities' performance in relation to assuring the safety, quality and efficacy of all medicines (generic and brand name) and the need to separate considerations of quality and criminal counterfeiting made by Ravinetto and colleagues are valid, I would like to take issue with one of their proposals.

They state that: "While we are concerned that automatic extrapolation of the findings of the JAMA articles to different contexts could be dangerous, we find that it would be extremely interesting to look at the proof of clinical equivalence also in different contexts and diseases, to build evidence-based knowledge of the situation in the field and to contribute to protecting and promoting public health."

Would it be ethical to conduct repeated clinical studies, in which participants are randomised to receive brand or generic versions of pharmaceutical equivalents (or alternatives, in the sense of different salts, for example) and then subjected to additional investigations, to provide evidence that is predictable from the accepted scientific basis for determining therapeutic equivalence (such as bioequivalence studies)?

In the original JAMA paper cited (Kesselheim A et al. Clinical Equivalence of Generic and Brand-Name Drugs Used in Cardiovascular Disease. A Systematic Review and Meta-analysis. JAMA 2008;300(21):2514-2526) the following details are provided on the studies included in the analysis: "Nearly half of included studies (23/47, 49%) were primarily bioequivalency studies, in which pharmacokinetic comparisons occurred along with clinical end points,and more than a third (18/47,38%) involved only healthy, young subjects. Less than half of the articles (21/47,45%) were published since 2000 and only 17 (36%) were conducted in the United States". In other words, much of the evidence included in the meta-analysis was not from clinical studies in typical patient populations with cardiovascular disease and much of the effort dated from the early days of bioequivalence testing (for example; 8/11 included studies involving diuretics were from the 1980s).

Should we not be putting more effort into securing funding for and conducting head-to-head comparisons of therapeutic alternatives rather than trying to bolster a scientific approach that is widely accepted? At the same time, should we not strengthen understanding of the science of bioequivalence amongst prescribers, dispensers and patients?

regards
Andy