BIOEQUIVALENCE REVISITED

被引:103
作者
SHEINER, LB
机构
[1] UNIV CALIF SAN FRANCISCO,SCH MED,SCH PHARM,DEPT PHARM,SAN FRANCISCO,CA 94143
[2] UNIV CALIF SAN FRANCISCO,SCH MED,SCH MED,DEPT PHARM,SAN FRANCISCO,CA 94143
[3] UNIV CALIF SAN FRANCISCO,SCH MED,SCH PHARM,DEPT MED,SAN FRANCISCO,CA 94143
[4] UNIV CALIF SAN FRANCISCO,SCH MED,SCH MED,DEPT MED,SAN FRANCISCO,CA 94143
[5] UNIV CALIF SAN FRANCISCO,SCH MED,SCH PHARM,DEPT LAB MED,SAN FRANCISCO,CA 94143
关键词
D O I
10.1002/sim.4780111311
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The FDA permits marketing of a generic formulation of a drug G for the same indications as a standard preparation S if one can show that G is bioequivalent to S. Present implementation requires convincing evidence that the population mean difference in bioavailability (drug exposure) between the two preparations lies within specified bounds. The basis for this standard does not appear to involve a comprehensive model for the dose-response relationship, or consideration of clinical issues, notably (i) whether a patient is to commence on the drug or to switch from an established regimen to a new one; or (ii) that the risk of inequivalence relates to uncertainty of outcome. In this paper, I propose a comprehensive model for dose response and a tentative model for risk that addresses these issues. Specifically, I propose two new measures of bioequivalence which are based on these models, which differ in the two clinical circumstances above, and which respond to both bias and variance of outcome. I present two examples, and some simulations of the application of the new measures.
引用
收藏
页码:1777 / 1788
页数:12
相关论文
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