Mauricio Sampaio
★    

Brazil,
2016-11-03 19:54
(2701 d 20:04 ago)

Posting: # 16769
Views: 6,167
 

 Any post about difference between 4x4 and 4x2 in bioequivalence studies? [Design Issues]

I am looking for a post in this forum that explain what is the best design to replicate a bioequivalence study. The 4x4 or 4x2? Normally, I use 4x4 this is a best choice? Or I can use 4x2 with same eficcacy?
Helmut
★★★
avatar
Homepage
Vienna, Austria,
2016-11-03 20:38
(2701 d 19:19 ago)

@ Mauricio Sampaio
Posting: # 16770
Views: 5,324
 

 Not more than 2 sequences in full replicates

Hi Mauricio,

❝ I am looking for a post in this forum that explain what is the best design to replicate a bioequivalence study.


Maybe there is one but the search function is slow those days. The data base seems to be corrupted and I didn’t have the time to repair it yet. :-(

❝ The 4x4 or 4x2? Normally, I use 4x4 this is a best choice? Or I can use 4x2 with same eficcacy?


To clarify: By 4×2 do you mean RTRT|TRTR and by 4×4 RTRT|TRTR|RRTT|TTRR or yet another one (e.g., TRRT|RTTR|TTRR|RRTT)? The notation used by PowerTOST is treatments × sequences × periods.

library(PowerTOST)
print(as.data.frame(known.designs()[8:9, ]), row.names=FALSE)

 no design    df df2 steps bk bknif   bkni                      name
  6  2x2x4 3*n-4 n-2     2  1   1/4 0.2500 2x2x4 replicate crossover
  7  2x4x4 3*n-4 n-4     4  1  1/16 0.0625 2x4x4 replicate crossover


Since both have the same degrees of freedom they should have the same efficacy.

But: IIRC, in the late 1990 Donald Schuirmann argued against more than two sequences in full replicate designs. See also Appendix B of the FDA’s guidance.

Dif-tor heh smusma 🖖🏼 Довге життя Україна! [image]
Helmut Schütz
[image]

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Astea
★★  

Russia,
2016-11-04 09:22
(2701 d 06:36 ago)

@ Helmut
Posting: # 16772
Views: 5,298
 

 Not more than 2 sequences in full replicates

Dear Helmut!

If we deal with 2x4x4 of the kind TRRT|RTTR|TTRR|RRTT what variance should be used for scaling approach?

"Being in minority, even a minority of one, did not make you mad"
Helmut
★★★
avatar
Homepage
Vienna, Austria,
2016-11-11 21:52
(2693 d 18:05 ago)

@ Astea
Posting: # 16798
Views: 4,936
 

 Only RR is used

Hi Astea,

❝ If we deal with 2x4x4 of the kind TRRT|RTTR|TTRR|RRTT what variance should be used for scaling approach?


For the EMA (also fashionable in Russia) only the reference’s data are used anyway. Use the same fixed effect model with sequence+subject(sequence)+period like in the Q&A-document. Doesn’t matter that we have four sequences instead of two.

For the FDA it should be possible as well but see the end of this post.

Dif-tor heh smusma 🖖🏼 Довге життя Україна! [image]
Helmut Schütz
[image]

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Mauricio Sampaio
★    

Brazil,
2016-11-11 19:39
(2693 d 20:18 ago)

@ Helmut
Posting: # 16797
Views: 4,929
 

 Not more than 2 sequences in full replicates

Hi Helmut...

❝ To clarify: By 4×2 do you mean RTRT|TRTR and by 4×4 RTRT|TRTR|RRTT|TTRR or yet another one (e.g., TRRT|RTTR|TTRR|RRTT)?


YES!!!!

❝ But: IIRC, in the late 1990 Donald Schuirmann argued against more than two sequences in full replicate designs. See also Appendix B of the FDA’s guidance.


Thank you so much. Really, 2 more sequences are a waste of time to prove a bioequivalence result! :cool:
UA Flag
Activity
 Admin contact
22,957 posts in 4,819 threads, 1,638 registered users;
69 visitors (0 registered, 69 guests [including 9 identified bots]).
Forum time: 15:58 CET (Europe/Vienna)

Nothing shows a lack of mathematical education more
than an overly precise calculation.    Carl Friedrich Gauß

The Bioequivalence and Bioavailability Forum is hosted by
BEBAC Ing. Helmut Schütz
HTML5