Bioequivalence and Bioavailability Forum

Dear Detlew,

you made my day!

❝ Lets go with the numbers of subjects given by you and assume that the estimated CV is obtained always as 20% (statistically only with vanishing probability ):

❝ # R function upper confidence limit of CV - as one liner

❝ CVUCL <- function(alpha=0.05, CV, df){

❝   sqrt(exp(log(1.0 + CV^2)*df/qchisq(alpha,df))-1)

❝ }

❝ gives

❝ design         n   df  upper CL

❝ TRTR|RTRT     20   18   27.94%

❝ TRR|RTR|RRT   30   27   26.03%

❝ TRT|RTR       15   13   30.07%

Interesting that the CV from the partial replicate is (although slightly) more precise than the 4-period 2-sequence full replicate. I didn’t expect that. Which design is the ‘best’? Pros & cons:

• TRTR|RTRT
  Pro: CV_WR and CV_WT estimable, model code from EMA and FDA available (not specified for CV_WT, but trivial), ~33% fewer subjects than in the 3-period designs, sample size tables available.
  Con: Four periods (blood samples, drop-outs), CV slightly less precise than from the partial replicate.
  
• TRR|RTR|RRT
  Pro: Only three periods, code available, most precise estimate of CV_WR, sample size tables available.
  Con: No estimate of CV_WT, ~50% more subjects than in the 4-period replicate (might require slightly more than +50%, sequences multiple of three).
  
• TRT|RTR
  Pro: CV_WR and CV_WT estimable, sample size – marginally – smaller than partial replicate.
  Con: Less precise estimate than from the other designs, no official code, no sample size tables (simulations required).

❝ BTW: May it be that there is an error in this post in calculating SS-intra from MS-intra?

Blast! Will correct it.

❝ The final result is again correct . That remains me on my old school days: Bad school grade (5) if final result correct but intermediate steps with errors .

Happened to me regularly. Especially if the final result came from my neighbor – who was much better in maths than I ever was.