Bioequivalence and Bioavailability Forum

Dear PKPDPKPD!

❝ Thanks for your instructions. However, I have two problems:

❝ 1. The version 5.01 of WinNonLin that I have do not have "Linear" function in the PK/PD/NCA Wizard.

Just looked it up in the release notes, linear models were introducted in v5.1 (23 Oct, 2006). If you have a valid license (which I assume), you may update at no costs.

❝ 2. The approach I would like to use for the assessment of steady state is repeated measures ANOVA of log concentrations instead of linear regression you are describing, since I am comparing the pre-dose concentrations in several subjects on three consecutive days.

❝ If I have one dependent variable (concentration) and subject as a random effect (??), and day as a fixed effect (???), how can I use Lin Mix to do the calculations.

OK, ANOVA is not included in WinNonlin; you will have to fight through a Linear Mixed Effects Model (which is always a little bit tricky). One hint: all effects are fixed!
Since I haven't done this myself yet, maybe another member of the forum can fill in the gap?
...or ask Pharsight's support - and be patient!

I know some colleagues are using repeated measures ANOVA; I never could understand why.
The outcome is always a yes/no result.
What if you get a significant result - would you really throw away the entire study?
If you are testing individual subjects, you have the option - providing you have stated such a procedure in the protocol - to exclude only these subjects from the evaluation since they did not reach steady state.

❝ In the linear regression while assessing the slope, should it be 95% or 90% CI?

95% since p = 1-alpha, where alpha=0.05. This is only a convention.

In BE we are only using a 90% CI, because in patients BA of the test can either be lower (5%) or higher (5%) then BA of the reference.
Therefore the individual patient's risk is kept at 5%.