Bioequivalence and Bioavailability Forum • SAS code for ABE

Mahmoud
☆

Jordan,
2020-07-03 16:09
(937 d 15:24 ago)

Posting: # 21642
Views: 3,925

SAS code for ABE [Software]

Dear All

in the following SAS code

proc mixed data=d1;

class treat sequence subject period;

model AUCT=sequence period treat/DDFM=kr;

random treat/type=CSH subject=subject G;

repeated/group=treat subject=subject;

estimate 'T-R' treat 1 -1 /cl alpha=0.10;

run;

In the Random statement TYPE=CSH could possibly be replaced by TYPE=FA(1)

FA(1) is not the same as FA0(2)

Thank You

M.Youseed

Edit: Category and subject line changed; see also this post #1. [Helmut]

Helmut
★★★

Vienna, Austria,
2020-07-03 16:46
(937 d 14:46 ago)

@ Mahmoud
Posting: # 21644
Views: 3,294

Origin of SAS code?

Post reply

Hi Mahmoud,

❝ in the following SAS code

where does this code come from? It’s not the standard one recommended by the FDA here and there.

❝ model AUCT=sequence period treat/DDFM=kr;

I would suggest to use DDFM=SATTER (as the FDA recommends). The default of DDFM=KR uses the observed information matrix (SCORING=0) as does jmp. You may run into troubles if your study is re-evaluated in other software which uses the expected information matrix (e.g., Stata, R-package replicateBE). In SAS you can get the expected information matrix by setting SCORING=1.

❝ random treat/type=CSH subject=subject G;

❝

❝ In the Random statement TYPE=CSH could possibly be replaced by TYPE=FA(1)

Acc. to the FDA’s guidance, Appendix E:

In the Random statement, TYPE=FA0(2) could possibly be replaced by TYPE=CSH.

So why compound symmetry in the first place?

❝ FA(1) is not the same as FA0(2)

Of course. FA(q) = factor analytic and FA0(q) = no diagonal factor analytic.
If this is a full replicate design, I would follow the FDA’s recommendation and use FA0(2).
However, in the stupid partial replicate designs (TRR|RTR|RRT or TRR|RTR) the optimizer may fail to converge since the model is over-specified (T not repeated). Then you’ve performed a study and don’t get a result cause SAS shows you the finger.* I suggest to specify FA0(1) instead. State that already in the SAP.

If you are lucky SAS throws only a warning.
Convergence criteria met but final hessian is not positive definite.
But if Murphy’s law hits:
WARNING: Did not converge. WARNING: Output 'Estimates' was not created.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

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Mahmoud
☆

Jordan,
2020-07-03 18:49
(937 d 12:44 ago)

@ Helmut
Posting: # 21646
Views: 3,280

SAS code for ABE

Post reply

Thank you very much

The BE study is (TRRT,RTTR) two sequence four period

                                                         GMR        Lower      Upper



when i used FDA code the result for  Cmax                85.734    79.363     92.617



when i used code FDA but type=FA(1) the result is Cmax   85.925    80.087     92.190

Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post #5! [Helmut]

Helmut
★★★

Vienna, Austria,
2020-07-03 19:00
(937 d 12:32 ago)

@ Mahmoud
Posting: # 21647
Views: 3,250

SAP?

Post reply

Hi Mahmoud,

❝ GMR Lower Upper

❝ when i used FDA code the result for Cmax 85.734 79.363 92.617

❝ when i used code FDA but type=FA(1) the result is Cmax 85.925 80.087 92.190

Are you trying to “rescue” a failed study? What is stated in the SAP?

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

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Mahmoud
☆

Jordan,
2020-07-03 19:17
(937 d 12:15 ago)

@ Helmut
Posting: # 21648
Views: 3,231

SAP?

Post reply

Dear Dr

Thank you very much for your information

in This study I found that and for Cmax Pk that

CVintra =27.3217 and CVinter=20.7271 this is not true in BE studies

From most studies CVinter is more more than CVintra

I think that the two types=CSH or FA0(1) in the FDA code are not suitable to obtain these results

❝ Are you trying to “rescue” a failed study?

Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post #5! [Helmut]

Helmut
★★★

Vienna, Austria,
2020-07-03 19:31
(937 d 12:01 ago)

@ Mahmoud
Posting: # 21649
Views: 3,215

SAP?

Post reply

Hi Mahmoud,

❝ Dear Dr

Still not a doctor. Told you before.

❝ in This study I found that and for Cmax Pk that

❝ CVintra =27.3217 and CVinter=20.7271 this is not true in BE studies

Truth does not belong to the realm of science. :-D

❝ From most studies CVinter is more more than CVintra

Correct; sometimes CV_intra > CV_inter.

❝ I think that the two types=CSH or FA0(1) in the FDA code are not suitable to obtain these results

Why, can you elaborate?

❝ ❝ Are you trying to “safe” a failed study?

❝ No

I see. Please answer my other question (also in the subject line) as well:

❝ ❝ What is stated in the SAP?

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
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jishnu ☆ India, 2022-08-06 20:54 (173 d 10:38 ago) @ Mahmoud Posting: # 23204 Views: 773	SAS code for ABE Post reply
	Hi jordan, Thanks for the following details, but still have some doubts. can you please connect me on +91 9074206778?? regards, Jishnu Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post #5! [Helmut]

Helmut
★★★

Vienna, Austria,
2022-08-06 22:48
(173 d 08:45 ago)

@ jishnu
Posting: # 23206
Views: 829

SAS code for ABE

Post reply

Hi Jishnu – or do you prefer to be addressed by »india« like you did in replying Mahmoud with »jordan«?

❝ can you please connect me on +91 9074206778??

Do you really expect to get called – at their cost – by members of the forum? If you would have clicked on their names, you would have noticed that e.g., Yuvraj is no more active in the forum for twelve years and Emrah for seven. If you want to get contacted, activate the e-mail function in your profile.

I strongly suggest relevant textbooks (all contain SAS code):

Hauschke D, Steinijans V, Pigeot I. Bioequivalence Studies in Drug Development.
Chichester: Wiley; 2007. ISBN 978-0-4700-9475-4.
Chow S-C, Liu J-p. Design and Analysis of Bioavailability and Bioequivalence Studies.
Boca Raton: CRC Press; 3^rd edition 2009. ISBN 978-1-5848-8668-6.
Jones B, Kenward MG. Design and Analysis of Cross-Over Trials.
Boca Raton: CRC Press; 3^rd edition 2015. ISBN 978-1-4398-6142-4.
Patterson SD, Jones B. Bioequivalence and statistics in clinical pharmacology.
Boca Raton: CRC Press; 2^nd edition 2017. ISBN 978-1-4665-8520-1.

If you then still have questions, post again but please, be more specific than:

❝ […] still have some doubts.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
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