Statistical approaches to indirectly compare bioequivalence between generics: a comparison of methodologies employing artemether/lumefantrine 20/120 mg tablets as prequalified by WHO

Gwaza, Luther; Gordon, John; Welink, Jan; Potthast, Henrike; Hansson, Henrik; Stahl, Matthias; García‐Arieta, Alfredo

doi:10.1007/s00228-012-1396-1

Cited by 19 publications

(39 citation statements)

References 13 publications

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“…The authors concluded that even with the Bworse^scenario of 9.5 % non-bioequivalent products, this low value provides reassurance of the BE of two generic products that have been shown to be bioequivalent to the same reference product. However, this does not seem to be the worst scenario, but a very favorable one, because point estimate differences between generics can be larger [5,16]. Karalis et al (2013) plotted the probability of accepting BE between generics as a function of their point estimates and concluded that although two generics are bioequivalent to the reference product, this does not ensure that they are bioequivalent to one another [8].…”

Section: Discussionmentioning

confidence: 95%

“…The 90 % CI for the indirect treatment comparisons for each computed scenario was calculated as described previously [5], and brief description of the method is provided as online resource 1.…”

Section: Statistical Analysis Of Indirect Estimatesmentioning

confidence: 99%

“…Different methods to perform indirect comparisons have been described and compared previously by Gwaza et al [5] based on artemether and lumefantrine generics prequalified by the World Health Organization (WHO) [6].…”

Section: Introductionmentioning

confidence: 99%

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Influence of point estimates and study power of bioequivalence studies on establishing bioequivalence between generics by adjusted indirect comparisons

Gwaza

Gordon

Potthast

et al. 2015

Eur J Clin Pharmacol

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Section: Discussionmentioning

confidence: 95%

Section: Statistical Analysis Of Indirect Estimatesmentioning

confidence: 99%

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Influence of point estimates and study power of bioequivalence studies on establishing bioequivalence between generics by adjusted indirect comparisons

Gwaza

Gordon

Potthast

et al. 2015

Eur J Clin Pharmacol

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“…As in Gwaza et al , we selected the data from three bioavailability/bioequivalence studies conducted independently, which are available in WHO public assessment reports at https://extranet.who.int/prequal/ (https://extranet.who.int/prequal/sites/default/files/documents/MA052part6v1.pdf, https://extranet.who.int/prequal/sites/default/files/documents/MA062part6v1.pdf, and https://extranet.who.int/prequal/sites/default/files/documents/MA064part6v2.pdf). The studies compared fixed dose combination artemether/ lumefantrine 20/120mg tablets in adult healthy volunteers with the same brand name drug submitted to the WHO Prequalification of Medicines Programme.…”

Section: Real Example Analysismentioning

confidence: 99%

On assessing bioequivalence and interchangeability between generics based on indirect comparisons

Zheng

Chow

Yuan

2017

Statistics in Medicine

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As more and more generics become available in the market place, the safety/efficacy concerns may arise as the result of interchangeably use of approved generics. However, bioequivalence assessment for regulatory approval among generics of the innovative drug product is not required. In practice, approved generics are often used interchangeably without any mechanism of safety monitoring. In this article, based on indirect comparisons, we proposed several methods to assessing bioequivalence and interchangeability between generics. The applicability of the methods and the similarity assumptions were discussed, as well as the inappropriateness of directly adopting adjusted indirect comparison to the field of generics' comparison. Besides, some extensions were given to take into consideration the important topics in clinical trials for bioequivalence assessments, for example, multiple comparisons and simultaneously testing bioequivalence among three generics. Extensive simulation studies were conducted to investigate the performances of the proposed methods. The studies of malaria generics and HIV/AIDS generics prequalified by the WHO were used as real examples to demonstrate the use of the methods. Copyright © 2017 John Wiley & Sons, Ltd.

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“…Furthermore, these differences could be larger for individual patients. There are, however, a number of mathematical models, which claim to address the potential interchangeability between different generic formulations through indirect comparisons 19 20. In one such analysis, Herranz and colleagues (2013) concluded that generic products were not only bioequivalent with the reference product but also with each other; however, the 80%–125% limits used in these analyses are now considered inappropriate for NTI drugs 21…”

Section: Bioequivalence and Interchangeabilitymentioning

confidence: 99%

Equivalence and interchangeability of narrow therapeutic index drugs in organ transplantation

Johnston¹

2013

Eur J Hosp Pharm

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The calcineurin inhibitors (CNIs), ciclosporin and tacrolimus, are the mainstay of immunosuppression in solid organ transplantation. Generic formulations of these drugs are now available. With increasing pressure on healthcare budgets and the consequent need to match health expectations to available resources, substitution with a generic product appears an attractive option to reduce costs. Approval of generic products differs from innovator drugs, and narrow therapeutic index drugs (NTIs; including CNIs) bring their own particular considerations. With NTIs, small variations in drug exposure could result in reduced immunosuppression or drug toxicity with potentially adverse effects on patient outcomes. NTIs are subject to stricter regulatory approval versus many other generic drugs. However, different generic formulations may still not necessarily be therapeutically equivalent in individuals, raising the possibility of significant differences in exposure between products. Although regional recommendations vary, many guidelines emphasise the need for NTI drug substitution to be initiated by the transplant physician, thus ensuring careful therapeutic monitoring and reduced negative patient impact. The need for therapeutic monitoring during generic substitution has important implications for the overall costs of generic treatment as these costs have to be factored in to the potential savings made from using generic formulations. The reduced acquisition costs of generic products may not necessarily translate into lower overall healthcare costs. This article examines the issue of equivalence and interchangeability of NTI drugs used in organ transplantation, the implications of the approval process for generic drugs on treatment efficacy and safety, and the effective management of substitutions between products.

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Statistical approaches to indirectly compare bioequivalence between generics: a comparison of methodologies employing artemether/lumefantrine 20/120 mg tablets as prequalified by WHO

Cited by 19 publications

References 13 publications

Influence of point estimates and study power of bioequivalence studies on establishing bioequivalence between generics by adjusted indirect comparisons

Influence of point estimates and study power of bioequivalence studies on establishing bioequivalence between generics by adjusted indirect comparisons

On assessing bioequivalence and interchangeability between generics based on indirect comparisons

Equivalence and interchangeability of narrow therapeutic index drugs in organ transplantation

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