Bioequivalence and Bioavailability Forum

Hi BEQool,

❝ […] is Gender*Treatment also a between-subject factor (like Sequence and Gender here)?

If you replace gender by sex, yes. Muse about it. BTW, you could even drop sequence from the model…

❝ In the article Evaluation of sex-by-formulation interaction in bioequivalence studies of efavirenz tablets by González-Rojano et al. it doesnt say anything about which factor they used (within- or between-subject) to test Gender*Treatment interaction.

See p. 1731, right column, top. That’s the model proposed by the FDA earlier:* $$\eqalign{Y&|\;\text{sequence},\,\text{sex},\,\text{sequence}\,\times\,\text{sex},\\ &\phantom{|}\;\text{subject}(\text{sequence}\,\times\text{sex}),\;\text{period},\\ &\phantom{|}\;\text{treatment},\,\text{sex}\,\times\,\text{treatment}}$$ I employed it also in my meta-analysis. The ‘purpose’ of this model is only to assess the interaction. Since treatment appears twice in the model, it is not possible to get an unbiased estimate of it (for a similar story see this article).

❝ Additionally, how do you know which factor is a within-subject and which is a between-subject? If anyone has an explanation in simple words

In simple words? I’ll try. For a given subject anything which remains constant throughout a study leads to a between-subject factor (e.g., sex, sequence, stage, group, site). Everything else leads to a within-subject factor (e.g., treatment, period).

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• Chen M-L, Lee S-C, Ng M-J, Schuirmann DJ, Lesko LJ, Williams RL. Pharmacokinetic analysis of bioequivalence trials: Implications for sex-related issues in clinical pharmacology and biopharmaceutics. Clin Pharm Ther. 2000; 68(5): 510–21. doi:10.1067/mcp.2000.111184