Bioequivalence and Bioavailability Forum

Hi Zhang Yong,

❝ But from the formula in the guidance (page 4, line 5) with Alpha=0.1, I guess the guidance is right, it calulates 90% CI of Swt/Swr, but not 95% CI.

❝ Need your clarification? or FDA is wrong?

The FDA is never wrong. But so am I. The guidance asks to calculate an confidence interval but only the upper confidence limit is assessed. Simply: The 90% CI has an upper and lower 95% CL.

❝ ❝ Personally I would prefer […] to run a mixed effects model with restricted maximum likelihood…

❝ ❝ I got: CV_wR 15.86% and CV_wT 5.73%. Interesting.

❝

❝ I guess your result of 15.86% and 5.73% are obtain from the sheet of "Final Variance Parameters" from ABE results using PHX WNL.

Correct.

❝ Here the CVwr and CVwt are different from those calculated from Swr and Swt.

❝ I prefer the result calculated from Swr and Swt.

❝ What's your opinion?

For my preferences see above. If you have to follow the guidance that’s not an option.

BTW, if you have Phoenix WinNonlin why bother fiddling around in Excel? I have some doubts whether an agency will accept that. At least the EMA wouldn’t. Quoting the Q&A document:

3.3. Alternative computer programs
[…] Results obtained by alternative, validated statistical programs are also acceptable except spreadsheets because outputs of spreadsheets are not suitable for secondary assessment.

BTW, Certara is working on a validated template for PHX WNL and it will be published in the near future.