Bioequivalence and Bioavailability Forum

Hi Mittyri,

❝ ❝ Many companies use PHX/WNL for NCA only (and run the stats in SAS).

❝

❝ I heard that some CRO's do that, could you explain it?

1. I see it in many publications and the majority (!) of reports moving around my desk.
   When I search the forum with the keyword “SAS” I get 1,000+ hits. SAS+bioequivalence gives 49,000 -hits.
   
2. I will try at the end (educated guesses / crystal ball gazing / tassology).

❝ Don't they trust the BEQ module in Phoenix/WinNonlin?

Duno. Given the posts in the forum asking for solutions in SAS maybe those members could answer this question?

❝ As you wrote here, there are some discrepancies between WNL partial tests and SAS Type III, but is it so important thing for final results? I don't think so...

Correct; doesn’t matter at all. The residual variance / means – and therefore, the PE and CI – are independent from this stuff.

❝ Why are they paying the double price (SAS+WNL)?

I guess it is a combination of tradition, using what they have already, etc. SAS is part of the bio­sta­tis­tical curriculum (though R is catching up). I know some (young) statisticians which are familiar with SAS and had no idea about NCA when they start their career in the industry. Instead of pro­gramming macros themselves and/or trusting what’s on the net^1,2 they tell their boss “It will take weeks to code/validate that. Let’s pay some bucks for a Kodak³”… Sooner or later one will not only need NCA, but more sophisticated features like Nonparametric Superposition, basic modeling in order to optimize sampling schedules, etc. I would not start that from scratch in SAS.
On the other hand agencies published SAS-code for some BE-methods (FDA: RSABE for HVDs and NTIDs; EMA: ABEL). It is certainly easier to copy-paste code compared to setting up / validating it in PHX/WNL (took me some weeks). Up to now nobody succeeded to code this stuff in R.

---

1. Matos-Pita AS, de Miguel Lillo B. Noncompartmental Pharmacokinetics and Bioequivalence Analysis. PharmaSUG (Pharmaceutical Industry SAS^® Users Group), May 22–25, 2005, Phoenix, AZ, USA.
      “The performance and validity of the program was tested against WinNonlin^®, one of the most commonly used programs for pharmacokinetic analysis in the Pharmaceutical Industry. The results of twenty bioequivalence clinical trials were evaluated using both WinNonlin and SAS. PROC COMPARE of SAS was used to test for differences. There was a 100% agreement in all 20 studies.”
   
2. He J. SAS Programming to Calculate AUC in Pharmacokinetic Studies—Comparison of Four Methods in Concentration Data. PharmaSUG, June 1-4, 2008, Atlanta, GA, USA.
   
3. “You Press the Button, We Do the Rest”