Bioequivalence and Bioavailability Forum

Dear Ben!

❝ The only thing I wanted to conclude here is that nQuery does not use AS 243 and I wanted so see whether nQuery uses AS 184 or not.

Actually we simply don’t know. Couldn’t find a hint in the code… Are you good in reverse-engineering?

❝ For the latter one would need a C lib or something similar (yeh I like C ).

Rather a decompiler.

❝ […] but let me ask two more things.

❝ First, there still are some discrepancies, e.g. in case of T/R=1, CV=7.5% (see e.g. #4266): for n=4 power.TOST "exact" gives 0.7290143 whereas nQuery gives 0.71559 (for n=6: 0.9869919 vs. 0.97943). I guess it's just not the same exact method that is implemented? (rounding?)

No idea.

❝ Secondly, on your lecture slide 33 (see above) you wrote Diletti et al. (1991) uses method "noncentr. t" and algorithm "Owen's Q". Shouldn't it then be method "exact"?

Well, cough. This presentation is history. I’m not a fan of rewriting the past.
In future presentations I will try to make it more clear…

• Strictly speaking the ‘exact’ method based on Owen’s Q is also numeric approximation of the difference of two integrals of the bivariate noncentral t (which are not solvable in closed form).
  
• Methods based on the noncentral t (approximating the above).
  
• Methods based on the shifted t (approximating the above).

It’s always difficult what we define (or accept) as ‘exact’. F.i. in PK we can only calculate t_max for a one-compartment open model, extravascular administration (solve the root of the first derivate of the function). For more than one compartments the first derivate is not accessible in closed form. Nevertheless we can obtain the maximum (and its time) at any wanted numeric precision by an iterative procedure – even by means of a pocket calculator. Exact or not?