Bioequivalence and Bioavailability Forum

Hi everyone,

I have a question about the simulation from a HDV paper written by SH Haidar et al¹:

Study Design
Three sequence, three period, two treatment partially replicated crossover bioequivalence studies, with 36 subjects (12 in each sequence) were simulated using S-Plus (Insightful Corp., Seattle, Washington)... The three-way cross over design was selected because it appeared to provide a more practical and efficient approach for scaling, compared with a full replicate, four-way cross over study design. Sequences used in the study are provided below:
No subject-by-formulation interaction was assumed. For most tests, the true %CV values considered for the simulations were 30%, 40%, 50% and 60% for the test and reference. Additionally, the impact of a more variable test product was evaluated by keeping the true %CV at 30% for the reference product, while varying the %CV of the test product between 30% and 60%. The parameters were assumed to be log normally distributed...

The statement in red... How does one simulate that for a 3-period, partial replicate T vs 2xR design in terms of varying the test's CV while keeping reference CV constant? I can see it being done for a full replicate design. Maybe I am not thinking straight...

Thanks
John

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1. SH Haidar, F Makhlouf, DJ Schuirmann, T Hyslop, B Davit, D Conner, L Yu.
   The AAPS Journal, Vol. 10, No. 3, September 2008 (DOI: 10.1208/s12248-008-9053-4)