Adjusted indirect comparisons to assess bioequivalence between generic clopidogrel products in Serbia

Abstract

Aims Generic products can be regarded as therapeutically equivalent and switchable with the reference product. However, switchability between generics is unknown, as direct comparisons between generics are not performed. The aim of this study was to investigate the bioequivalence between generic clopidogrel products by means of adjusted indirect comparisons (AICs). Methods AICs were conducted to assess bioequivalence between 4 generic clopidogrel products that are authorised in Serbia. Generics are considered equivalent to the reference if the 90% confidence intervals (CIs) for the ratios test/reference of the maximum concentration (Cmax) and area under the curve up to the last measurable concentration (AUC0–t) fall within the acceptance range 80.00–125.00%. However, for AICs between generics, the Canadian acceptance criterion for Cmax was employed, where only the point estimate of Cmax needs to be within 80.00–125.00%. Results The 90% CIs of the AICs demonstrated bioequivalence within 80.00–125.00% for all AUC0–t comparisons. The point estimates of Cmax in all AICs were also within this range. Conclusion This study demonstrates that the bioavailability of these 4 generic clopidogrel products authorised in Serbia is very similar. Despite the limited power of AICs, bioequivalence was demonstrated for all 90% CIs of AUC0–t and all 90% CIs of Cmax comparisons were within or very close to the acceptance range, being able to comply with the acceptance criterion employed in Canada for Cmax. Therefore, these 4 generic clopidogrel products authorised in Serbia can be considered switchable with each other in clinical practice based on the adjusted indirect comparisons.

Long non-coding RNAs in brain tumors

“…XIST depletion also exerts tumor suppressive roles in glioma stem cells by upregulating miR-152 ( 90 ). ZEB1-AS1 (antisense to ZEB1) lncRNA represses T cell-specific interleukin expression ( 91 )) regulates the expression of genes encoding cyclin D, CDK2 (cyclin-dependent kinase 2), ZEB1 (zinc finger E-box-binding homeobox 1), MMP2, MMP9, N-cadherin and integrin-β1. Therefore, ZEB1-AS1 regulates EMT and is involved in glioma proliferation, apoptosis and metastasis ( 92 ).…”

Switching among branded and generic medication products during ongoing treatment of psychiatric illness

“…It is possible, therefore, for switches, particularly from one generic product to another, to result in clinically significant increases or decreases in plasma drug levels, with potential effects on efficacy or safety 12. In a single study that assessed bioequivalence among four generic products with the same reference, using adjusted indirect comparisons, each pair demonstrated bioequivalence based on AUC but exceeded the acceptance range in 2 of 6 comparisons for C max 23. A large-scale survey comparing generic products with each other is warranted.…”