Statistical Approaches For Assessment Of Bioavailability And Bioequivalence

Bioequivalence investigation is very important to ensure the bioequivalencebetween generic drug and innovator drug and make sure they have the same therapeuticefficacy and safety. It plays an important role in the development and evaluation of newdrug. However there exist a lot of problems in present bioequivalence studies, they haveadverse impact on bioequivalence decision making. Two one-sided t test and confidence interval are the main methods which analysisthe bioequivalence of two formulation in two crossover trial for bioavailability. Themethods in common use worldwide were listed, including two one-sided t test approach,(1? 2α)×100%confidence interval approach. As the accumulating of the practice experiences, people find that the approach ofaverage bioequivalence has various shortcomings. A series of draft guidance of the FDAof US are expected to replace average bioequivalence with individual bioequivalence.The statistical methods of population bioequivalence individual bioequivalence arereviewed. The procedures of small-sample confidence interval for populationbioequivalence and individual bioequivalence are given. An example is also given toillustrate that the conclusions of procedure indibio.m are coincided with those inreferences. In chapter 4,we will introduce the generalized test function and thegeneralized p-value into the assessment of population bioequivalence and individualbioequivalence,and proof that generalized p-value is continuous. The generalizedp-value approach may be an effective method for assessing population bioequivalenceand individual bioequivalence...