Bioequivalence and Bioavailability Forum

Dear MGR,

❝ We are going for a 2stage approach for EMA using Potvin B method.

Welcome to the club .

❝ Is this type of analysis can be done by WinNonlin 5.2 or 6.3?

Do not have this software, but I think Helmut has posted here about this.
You may find some material in his lectures also, some decided to the 2-stage evaluation.

❝ Moreover is there any articles/guidelines for the SAS code?

AFAIK there is no decided article/guideline containing SAS code in this respect. But it should not that hard to code it:

For stage 1 use the code for classical ABE for a 2x2 cross-over, but instead of calculating 90% CIs derive the CIs to the confidence level (1-2*0.0294) = 94.12%.
The power inspection step and the sample size estimation are a little bit hairy in SAS. Don't really know if Proc Power can be used for that. I suggest to use some tool external to SAS. You may guess what I recommend (if you ever have seen or heard about): R-package PowerTOST.

For stage 2 evaluation (if a second stage becomes necessary) use a model with the effects:

• treatment
  
• stage
  
• period within stage
  
• sequence
  
• stage*sequence interaction (according to EMA Q&A)
  
• subject nested within sequence and stage

and derive again 94.12% CIs.

Here my SAS code for that:
Proc GLM data=yourdata;
  class treatment period stage sequence subject;
  model &lnval = treatment stage period(stage) sequence
                 stage*sequence /*acc. to EMA Q&A*/
                 subject(sequence*stage) / CLparm alpha=0.0588 ss3;
  ODS output estimates=_est2;
  estimate 'T-R' treatment -1 1;
  where stage in(1 2);
run; quit;
That is it. Not so difficult, isn't it?
Hope this helps.

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BTW: There is a new revision of the EMA Q&A quite recently (09-May-2014) out there:
EMA/618604/2008 Rev. 9