## CFDA: Yet another story? [RSABE / ABEL]

Hi libaiyi,

» I want to know how to figure out that whether the results are bioequivalence?
• If the 90% CI of the GMR lies entirely within the (expanded) BE limits
bioequivalence demonstrated with p ≤0.05.
• If at least one of the confidence limits is outside the (expanded) BE limits
indecisive (BE not demonstrated due to lacking power; may be possible in another study with a higher sample size).
• If the 90% CI of the GMR lies entirely outside the (expanded) BE limits (i.e., lower CL > upper limit or upper CL < lower limit)
bioinequivalence proven with p ≤0.05. Don’t perform another study: Reformulate.

» According to CFDA (China Food and Drug Administration) guidelines, when CVwR of Cmax is larger than 0.3, BE limits are fixed at (69.83, 143.19).

Weird – do you have a reference? Feel free to post in Chinese; we have some native speakers here.
This would add another story to the two we already have (see this thread in all of its beauty). I have some doubts whether that is really what the CFDA wants. Would be a step back to what was used in some European countries 25+ years ago.

» Can we use the results from Mixed Model by SAS directly to determine if it falls between the limits or not?

First you have to clarify which method for HVD(P)s the CFDA accepts.
1. Like the EMA (ABEL): SAS-code given in the Q&A-document. Proc GLM, not Proc Mixed.
2. Like the FDA (RSABE): SAS-code given in the progesterone guidance. Decision not based on the “implied” scaled limits but the upper 95% confidence bound of (YT – YR)2 – θs²wR must be ≤0. Proc Mixed for full replicate studies (TRTR|RTRT, TTRR|RRTT, or TRT|RTR) and Proc GLM for partial replicate studies (TRR|RTR|RRT).
If swR <0.294 (conventional ABE) Proc Mixed and BE if 90% CI within 80.00–125.00%.
3. Your story: Proc Mixed if the CFDA follows the FDA or Proc GLM if like the EMA.

Dif-tor heh smusma 🖖
Helmut Schütz

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