Study design within subjects

The subjective and behavioral effects of triazolam were investigated in 20 healthy women, who took oral triazolam 0.25 mg or placebo at the follicular, periovulatory, and luteal phases of their menstrual cycle in a within-subject design (12). After triazolam most of them reported the expected increases in fatigue and decreases in arousal and psychomotor performance. Neither plasma concentrations of triazolam nor mood and performance differed across the three phases. This study shows that the effects of triazolam are highly stable across the menstrual cycle. 

The design of the study should minimize the variability that is not caused by formulation effects and eliminate bias as far as possible. Test conditions should reduce variability within and between subjects. In general, for a pharmacokinetic bioequivalence study involving a multisource and a comparator product, a two-period, single-dose, cross-over study in healthy volunteers will suffice. However, in certain circumstances, an alternative, well-established and statistically appropriate study design may be adopted. 

In practice, the true population means (jUt and jUr) are estimated by the calculated sample averages of the logarithmic parameters of the two formulations (wt and ir). In this context, ABE is declared if the calculated 90% confidence interval (Cl) for the difference of the log means lies within the preset BE limits (23). Assuming the classic two-treatment, two-period, crossover BE study design, with equal numbers of subjects in... 

For drugs with an expected within-subject variabiHty of >30%, a BE study with three-period, R-replicated, crossover design has been proposed (34,35,64). The minimum number of subjects that would be acceptable is 24. The BE assessment comprises two parts an ABEsc evaluation and a point estimate constraint. The BE criterion for both AUC and Cma is defined as... 

The purpose of this section is to present some concepts and terms that will be used in the rest of the book. They include various measures that relate to highway safety, validity and reliability of the measures, experimental versus observational studies, between-subject versus within-subject experimental designs, and statistical versus practical significance. 

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