Mahmoud
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Jordan,
2020-07-03 12:09
(314 d 16:24 ago)

Posting: # 21642
Views: 2,124
 

 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
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Vienna, Austria,
2020-07-03 12:46
(314 d 15:47 ago)

@ Mahmoud
Posting: # 21644
Views: 1,723
 

 Origin of SAS code?

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 🖖
Helmut Schütz
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Mahmoud
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Jordan,
2020-07-03 14:49
(314 d 13:44 ago)

@ Helmut
Posting: # 21646
Views: 1,722
 

 SAS code for ABE

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
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Vienna, Austria,
2020-07-03 15:00
(314 d 13:33 ago)

@ Mahmoud
Posting: # 21647
Views: 1,683
 

 SAP?

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 “safe” a failed study? What is stated in the SAP?

Dif-tor heh smusma 🖖
Helmut Schütz
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The quality of responses received is directly proportional to the quality of the question asked. 🚮
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Mahmoud
☆    

Jordan,
2020-07-03 15:17
(314 d 13:16 ago)

@ Helmut
Posting: # 21648
Views: 1,672
 

 SAP?

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 “safe” a failed study?

No


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
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Vienna, Austria,
2020-07-03 15:31
(314 d 13:02 ago)

@ Mahmoud
Posting: # 21649
Views: 1,665
 

 SAP?

Hi Mahmoud,

» Dear Dr

Not a Dr ;-)

» 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 CVintra > CVinter.

» 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)

» » What is stated in the SAP?

as well.

Dif-tor heh smusma 🖖
Helmut Schütz
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The quality of responses received is directly proportional to the quality of the question asked. 🚮
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