Francis Hsuan

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Clozapine plasma levels were monitored in 16 patients during a series of three consecutive treatments (single dose–multiple dose–single dose). Each patient received a single 75-mg dose (3 × 25 mg) with clozapine tablets, and serial plasma samples were collected over 48 hr after the dose. At 48 hr, a multiple-dose regimen was started, consisting of an(More)
The concept of interchangeable pharmaceutical products has been examined in great detail in the literature. Anderson and Hauck proposed a statistical random coefficient model to study 'switchability', and coined the phrase 'individual bioequivalence' which they defined with a probability-based inequality. Since that paper there has been considerable work(More)
The extent of drug availability is often measured by the area under the concentration-time curve. In animal studies, experimental constraints can limit the number of observations available on each animal. Estimation of area under the curve and its standard error are straightforward when each animal is measured at each time point. Bailer and Nedelman et al.,(More)
We propose an adaptive procedure for dose-finding in clinical trials when the primary efficacy endpoint is continuous. We model the mean of the efficacy endpoint, given the dose, as a four-parameter logistic function. The efficacy endpoint at each dose is distributed according to either a normal or a gamma distribution. We consider the cases of fixed(More)
In December of 1997, the FDA proposed a draft guidance for future in vivo bioequivalence studies. The guidance suggested specific criteria for new drug sponsors to show individual bioequivalence (IBE). The criteria use a mixed-scaling aggregate strategy. It has been generally accepted that, under some particular situations, the proposed criteria would(More)
The U.S. FDA's newly issued guidance on bioequivalence recommends the use of individual bioequivalence (IBE) for highly variable drugs and possibly for modified release dosage forms. The recommended approach to the analysis is to follow the methodology of Hyslop, Hsuan and Holder (HHH), based on a linear mixed model. A limitation of the HHH method is that(More)
In order to establish bioequivalence between two formulations in a crossover trial, it is common to assume a mixed-effect analysis of variance (ANOVA) model and perform two one-sided tests. When the analysis is done on the untransformed data, the numerators of the test statistics are not, in general, treatment contrasts. Consequently, the standard errors of(More)
In medical practice, it has been realized that noncompliance may have an impact on the therapeutic effect of a drug therapy, regardless of race, gender, and education of patients. Therefore, it is of interest to study the impact of noncompliance on drug absorption through in vivo testing. Efron and Feldman examined dose-response relationship when(More)
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