Bioequivalence and Bioavailability Forum

balakotu ★ India, 2009-08-17 12:06 (5728 d 18:05 ago) (edited on 2009-08-17 13:56) Posting: # 4052 Views: 5,520	2-seq, 4-trt, 4 period cross over (SAS) [Software] Post reply
	Hi all, any body tell me i have 2-sequence, 4-treatment and 4-period cross over study i need SAS Procedure for this study plz help me soon. Ex: `T₁ R₁ T₂ R₂ T₂ R₂ T₁ R₁` Edit: Subject line and category changed. Please see this post. [Helmut]

d_labes
★★★

Berlin, Germany,
2009-08-17 17:33
(5728 d 12:38 ago)

@ balakotu
Posting: # 4055
Views: 4,680

2-seq, 4-trt, 4 period cross over (SAS)

Post reply

Hello Balakotu,

❝ any body tell me i have 2-sequence, 4-treatment and 4-period cross over

❝ study i need SAS Procedure for this study plz help me soon.

❝ Ex:

❝ T₁ R₁ T₂ R₂
❝ T₂ R₂ T₁ R₁

The SASophylistic evaluation uses the same PROC GLM as for the cassical 2x2 cross over.
Here a code snippet:

Proc GLM data=yourdata;

  class tmt period sequence subject;



  model logAUC=tmt period sequence subject(sequence) /SS3;

  random subject(sequence)/test;



  LSMeans tmt/pdiff CL alpha=0.1;

run; quit;

Don't forget the back-transformation of the 90% CI's.

The code assumes that you have a long dataset i.e. rows with
logAUC subject sequence tmt period as variables.

Eventually you have to adjust the alpha depending on the problem.

Edit: Welcome back! How was Salzburg? [Helmut]

—
Regards,

Detlew

balakotu ★ India, 2009-08-18 09:30 (5727 d 20:41 ago) @ d_labes Posting: # 4059 Views: 4,627	2-seq, 4-trt, 4 period cross over (SAS) Post reply
	Dear labes, Thanks for your respond but actually using the above anova procedure we can't calculate Least Squares Means, intrasubject cv and 90% conficence intervals and also anova Least Squares Means shows some missing data here my query is 2-seq, 4-trt and 4-perd cross over study only.

d_labes
★★★

Berlin, Germany,
2009-08-18 16:02
(5727 d 14:10 ago)

@ balakotu
Posting: # 4060
Views: 4,664

Totally unbalanced 4-period cross-over, confounded

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Dear Balakotu,

❝ [...] but actually using the above anova procedure we can't calculate Least Squares Means,intrasubject cv and 90% conficence interevals and also anova Least Squares Means shows some missing data

First I was very surprised about your message. :ponder:

But after looking a little bit closer at your used sequences and after playing with some artificial data using that sequences I understood:
No Least square means estimable and no 90% confidence intervals.
Only the differences T₁-T₂ and R₁-R₂ estimable, that ones you are presumably not interested in, but no CIs. Ups!

Ok, this is a consequence of your design, your used sequences.
This study is totally unbalanced with respect to the occurrence of the 4 treatments in the 4 periods:

T₁ and T₂ only in periods 1/3
R₁ and R₂ only in periods 2/4!

The result is that you cannot estimate the period effects independent from the treatment effects.
As way out you have to assume that there are no such period effects in your model.
Just omit the period term in the Proc GLM above and numerically all is Ok.

But this is a major flaw of your design because period effects are rather common (15-20%) in bioequivalence studies.

BTW: The intra-subject CV is estimable, also in the model with period effects.
BTW2: See Helmut's lectures of better common designs for 4-treatment-4-period studies without restricting assumptions. See also this thread for further discussion of 4-period-4-treatment design issues, I just checked it, your design thoroughly discussed as unsuitable.
And think twice before using such an uncommon design.

----------------------------------------------------------
To Helmut: Salzburg is very fine, but very wet at that time.
Now I understand what it means: Salzburger Schnürlregen!
----------------------------------------------------------

—
Regards,

Detlew

2-seq, 4-trt, 4 period cross over (SAS) [Software]

2-seq, 4-trt, 4 period cross over (SAS)

2-seq, 4-trt, 4 period cross over (SAS)

Totally unbalanced 4-period cross-over, confounded