Bioequivalence and Bioavailability Forum

Neera
☆

India,
2013-12-13 09:39
(4227 d 01:48 ago)

Posting: # 12053
Views: 4,943

Drug interaction [General Statistics]

Hi,

Greetings to all !!!!

We have conducted a study wherein two different innovator treatments, each comprising single drug are given in the following manner: 1) Reference A alone 2) Reference B alone and 3) Reference A+B. This was a six sequence, 3 period crossover study. The objective was to evaluate occurrence of drug interaction between the study treatments. The data obtained after administration of Reference A+Reference B (combination) is treated as test and each drug (Reference A or Reference B) compared separately with the corresponding reference treatment when given alone. Thus we had Reference A (in combination) Vs Reference A (alone) and Reference B (in combination) Vs Reference B(alone) for the comparison. As each drug (either Reference A or Reference B) is given only in two of 3 study periods, each comparison is to be done as if there are 2 different periods, 2 treatments crossover studies. This will result in degrees of freedom of 1 and 2 different sets of intra-subject variation.

Is this a correct way or is there any alternative way wherein the degrees of freedom could be 2 and only one set of intra-subject variation is present?

Thanks in advance.

jag009
★★★

NJ,
2013-12-13 21:55
(4226 d 13:32 ago)

(edited on 2013-12-13 22:37)
@ Neera
Posting: # 12057
Views: 4,073

Drug interaction

Post reply

Hi,

❝ Is this a correct way or is there any alternative way wherein the degrees of freedom could be 2 and only one set of intra-subject variation is present?

With SAS you just run Proc GLM and do comparisons A+B vs A, A+B vs B. Yes you will end up with 1 set of intrasubject CV due to the pooled variance effect (see previous post).

You can do the same thing in WinNonlin if you don't have SAS. Hope this helps.

John

Helmut
★★★

Vienna, Austria,
2013-12-16 16:13
(4223 d 19:14 ago)

@ jag009
Posting: # 12063
Views: 3,998

Coding for pairwise comparisons

Post reply

Hi John & Neera,

❝ […] Yes you will end up with 1 set of intrasubject CV due to the pooled variance effect.

Alternatively (as suggested in EMA’s GL) you could drop the irrelevant administrations from the pairwise comparisons whilst keeping the sequence/period coding. Recoding the 6×3 Williams’ design…

Seq Per Trt

 1   1   A 

 1   2   B 

 1   3  A+B

 2   1   B 

 2   2  A+B

 2   3   A 

 3   1  A+B

 3   2   A 

 3   3   B 

 4   1   A 

 4   2  A+B

 4   3   B 

 5   1   B 

 5   2   A 

 5   3  A+B

 6   1  A+B

 6   2   B 

 6   3   A

…gives two Incomplete Block Designs allowing separation of CVs:

Seq Per Trt    Seq Per Trt

 1   1   A      1   2   B 

 1   3  A+B     1   3  A+B

 2   2  A+B     2   1   B 

 2   3   A      2   2  A+B

 3   1  A+B     3   1  A+B

 3   2   A      3   3   B 

 4   1   A      4   2  A+B

 4   2  A+B     4   3   B 

 5   2   A      5   1   B 

 5   3  A+B     5   3  A+B

 6   1  A+B     6   1  A+B

 6   3   A      6   2   B

Edit: For details see this article.

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Science Quotes

Neera ☆ India, 2013-12-17 10:00 (4223 d 01:27 ago) @ Helmut Posting: # 12067 Views: 3,929	Coding for pairwise comparisons Post reply
	Thank You ...

Drug interaction [General Sta­tis­tics]

Drug interaction

Coding for pairwise comparisons

Coding for pairwise comparisons

Drug interaction [General Statistics]