Bioequivalence and Bioavailability Forum

Dear Helmut,

Thanks for your detailed explanation.

❝ When we talk about the CV in a crossover (simple 2×2×2, Higher-Order, or replicate) design, generally the intra-subject CV (CVw) is meant.

Question: Is CVw a pooled CV? So the CV we usually talk about is the pooled CV? The reason why I ask this question is when we do sample size calculation of bioequivalence study in clinical trails, I always see people write the CV of Cmax/AUC is XX%, I'm not sure whether the CV means CVw or CVwr.

❝ To complicate things: CVwT and CVwR could be directly estimated from the FDA’s mixed-effects model (as you did in your OP).

❝ If the study is balanced, correct. Otherwise we would have to weigh the variances by the degrees of freedom. See also this post.

PROC MIXED;
CLASSES SEQ SUBJ PER TRT;
MODEL Y = SEQ PER TRT/ DDFM=SATTERTH;
RANDOM TRT/TYPE=FA0(2) SUB=SUBJ G;
REPEATED/GRP=TRT SUB=SUBJ;
ESTIMATE 'T vs. R' TRT 1 -1/CL ALPHA=0.1;

Question: Based on the code provided by FDA, I can get two residuals which are Swt and Swr. If I need to calculate confidence interval, then I should first determine whether the design is balanced or not, and then find appropriate way to calculate Sw based on Swt and Swr. Then use Sw to calculate CVw, then use CVw to calculate confidence interval. I can follow the link you provided above. Are those steps correct? Thanks.

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Edit: Standard quotes restored; see also this post #8. [Helmut]