Pingouinche
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France,
2009-08-19 13:39
(5732 d 05:47 ago)

(edited on 2009-08-19 16:21)
Posting: # 4061
Views: 10,709
 

 2-sequence, 2-period, 2-trt crossover design (R, SAS) [Software]

Hello,

I'm new at BA/BE studies and I don't understand very well how to analyze a crossover experiment with R or SAS.

I'm trying to replicate the results I've read in a book (Design and analysis of bioavailability and bioequivalence studies): a complete example is proposed in section 3.6, data is p.73 and the classic ANOVA table I want to obtain is p.78.

I would like to know how I can obtain such an ANOVA table with R or SAS, with inter- and intra- source of variations separated.

I don't manage to write properly the model, in order to make SAS or R understand that each subject has two measures, and that some factors have to be tested between subject, and others within subjects.

Do you a have a document, or a code "ready to use" which could help me to replicate the results of the book ?

Thanks !


Edit: Subject line changed. [Helmut]
Pingouinche
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France,
2009-08-19 18:21
(5732 d 01:06 ago)

@ Pingouinche
Posting: # 4064
Views: 8,363
 

 2-sequence, 2-period, 2-trt crossover design (R, SAS)

❝ Edit: Subject line changed. [Helmut]


Yes, sorry :-P

More precisely : with the (R) command
anova.table=lm(Result ~ Sequence + Subject:Sequence + Period + Drug, data=crossover)
I get this table :
Analysis of Variance Table

Response: Result
                 Df  Sum Sq Mean Sq F value    Pr(>F)   
Sequence          1   555.7   555.7  4.4106    0.0474 * 
Periode           1     0.9     0.9  0.0074    0.9324   
Drug              1     0.9     0.9  0.0074    0.9324   
Sequence:Subject 22 15553.4   707.0  5.6110 7.586e-05 ***
Residuals        22  2771.9   126.0                     
---
Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1

This new ANOVA table has approximately the same structure as the table in the book, but it is not the good syntax/answer...

Does someone have an idea? :confused:
Helmut
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Vienna, Austria,
2009-08-19 19:05
(5732 d 00:21 ago)

@ Pingouinche
Posting: # 4065
Views: 8,535
 

 R, SAS- codes

Dear Pingouinche,

sorry, but I'm short in time (sometimes I have to work). ;-)

You don’t have to reinvent the wheel!
Chow and Liu’s book gives SAS-code for a 2×2×2 design in the annex. Another one is given in Patterson's/Jones' book.
For S-Plus code see this post (Pikounis); needs some (a few) modifications for [image].
There’s the wonderful bioequivalence package bear for [image]; just have a look in the forum’s category R for BE/BA for a download link, a history of the development, and coding examples.

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Pingouinche
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France,
2009-08-20 00:20
(5731 d 19:06 ago)

@ Helmut
Posting: # 4067
Views: 8,351
 

 R, SAS- codes

❝ sorry, but I’m short in time (sometimes I have to work). ;-)


Yes, I can understand you have to work (just a little :-D) !

You don’t have to reinvent the wheel!

❝ Chow and Liu’s book gives SAS-code for a 2×2×2 design in the annex.


Indeed, there is probably the SAS-code on the book, but... Unfortunately, I don't have the book and the code is not included in the extracts available on Google Books...
Precisely, I'd like to know their code, because whatever I do, I don't manage to obtain the same ANOVA table as them !
Helmut
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Vienna, Austria,
2009-08-20 03:12
(5731 d 16:14 ago)

@ Pingouinche
Posting: # 4068
Views: 8,328
 

 R, SAS- codes

[image]Dear Pingouinche!

❝ Indeed, there is probably the SAS-code on the book,

                   ^^^^^^
The probability is close to 1 (unless you buy a misprint or somebody has ripped these pages out).

❝ Unfortunately, I don't have the book and the code is not included in the extracts available on Google Books...


No? Would you mind looking at page 560? OK, the interesting ones are 561-562. :-D

❝ Precisely, I'd like to know their code, because whatever I do, I don't manage to obtain the same ANOVA table as them !


In your first post you said you read the book. Fine. But f…g Google Books is not a source to gain knowlege from - at least nobody can ‘read a book’ there. The third edition was published this year. If you are with a company which can’t afford a book and give you enough time to study it, change the company. Quickly! If you are a poor fellow, maybe you can get the second edition cheaper or even a used copy. If you are a student, go to your library. Or get a copy of pages 559-576 (2nd ed, 691-714 3rd ed.) from a remote reference provider. It’s even possible to get their ANOVA-table up and running in M$-Excel (see the screenshot in this post). Or search this forum (codes for both SAS and [image] are available).
Sorry for the harsh reply, but please do you homework first. :cool:

See also this post for something you may check.

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Pingouinche
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France,
2009-08-20 11:19
(5731 d 08:07 ago)

@ Helmut
Posting: # 4073
Views: 8,282
 

 R, SAS- codes

❝ If you are a student, go to your library.


Indeed, I am. Mathematician. Doing a short work experience in PK/PD for the summer.
But the poor library of my little university: 1) is closed, 2) doesn't have any book an BA/BE anyway. :-P
I know Google Books is not the best way to learn BA/BE tests, but for me, it's simply the only way.

I'll find something... Thanks.
yjlee168
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Kaohsiung, Taiwan,
2009-08-19 20:42
(5731 d 22:44 ago)

@ Pingouinche
Posting: # 4066
Views: 8,383
 

 2-sequence, 2-period, 2-trt crossover design (R, SAS)

Dear Pingouinche,

❝ [..] Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1

❝ This new ANOVA table has approximately the same structure as the table in the book, but it is not the good syntax/answer...

I'd like to help here, but I don't know which part is not the good syntax/answer. :ponder: The above ANOVA table is quite self-explained.

All the best,
-- Yung-jin Lee
bear v2.9.2:- created by Hsin-ya Lee & Yung-jin Lee
Kaohsiung, Taiwan https://www.pkpd168.com/bear
Download link (updated) -> here
Helmut
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Vienna, Austria,
2009-08-20 03:19
(5731 d 16:07 ago)

@ yjlee168
Posting: # 4069
Views: 8,539
 

 2-sequence, 2-period, 2-trt crossover design (R, SAS)

Hi Yung-jin!

❝ […] The above ANOVA table is quite self-explained.


Yes, but have you noticed that results for period and treatment are numerically identical? Maybe there’s a mistake in the coding of the dataset (levels?).

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yjlee168
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2009-08-20 14:02
(5731 d 05:25 ago)

@ Helmut
Posting: # 4075
Views: 8,304
 

 2-sequence, 2-period, 2-trt crossover design (R, SAS)

Dear Helmut,

❝ Yes, but have you noticed that results for period and treatment are numerically identical?


You're right! I really did NOT notice that part. A typical anova output obtained from bear is shown as follows.
  Dependent Variable: lnAUC0t                                               

Type I SS
Analysis of Variance Table

Response: lnAUC0t
          Df  Sum Sq Mean Sq F value Pr(>F)
seq        1 0.01876 0.01876  0.5138 0.4872
prd        1 0.00789 0.00789  0.2162 0.6503
drug       1 0.04216 0.04216  1.1546 0.3037
seq:subj  12 0.29718 0.02477  0.6782 0.7443
Residuals 12 0.43818 0.03652               

Type III SS
Single term deletions

Model:
lnAUC0t ~ seq + subj:seq + prd + drug
         Df Sum of Sq     RSS     AIC F value  Pr(F)
<none>                  0.438 -84.405               
prd       1     0.008   0.446 -85.905  0.2162 0.6503
drug      1     0.042   0.480 -83.833  1.1546 0.3037
seq:subj 12     0.297   0.735 -93.909  0.6782 0.7443

Tests of Hypothesis for SUBJECT(SEQUENCE) as an error term

Error: subj
          Df   Sum Sq  Mean Sq F value Pr(>F)
prd:drug   1 0.018762 0.018762  0.7576 0.4012
Residuals 12 0.297182 0.024765               

Error: Within
          Df  Sum Sq Mean Sq F value Pr(>F)
prd        1 0.00789 0.00789  0.2162 0.6503
drug       1 0.04216 0.04216  1.1546 0.3037
Residuals 12 0.43818 0.03652               

Intra_subj. CV = 100*sqrt(abs(exp(MSResidual)-1)) = 19.2847 %
Inter_subj. CV = 100*sqrt(abs(exp((MSSubject(seq)-MSResidual)/2)-1)) = 7.6536 %
    MSResidual = 0.03651522
MSSubject(seq) = 0.02476518


❝ Maybe there’s a mistake in the coding of the dataset (levels?).


The period and drug (treatment) could be coded incorrectly in the dataset.

All the best,
-- Yung-jin Lee
bear v2.9.2:- created by Hsin-ya Lee & Yung-jin Lee
Kaohsiung, Taiwan https://www.pkpd168.com/bear
Download link (updated) -> here
yjlee168
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2009-08-20 14:17
(5731 d 05:09 ago)

@ Pingouinche
Posting: # 4076
Views: 8,314
 

 2-sequence, 2-period, 2-trt crossover design (R, SAS)

Dear Pingouinche,

Could you show us your dataset? Just part of it will be enough.

❝ Response: Result
❝                  Df  Sum Sq Mean Sq F value    Pr(>F) 
❝ Sequence          1   555.7   555.7  4.4106    0.0474 *
❝ Periode           1     0.9     0.9  0.0074    0.9324
❝ [...]

Periode? Did you edit the output when you're posting it or was it from the original output? Thanks.

All the best,
-- Yung-jin Lee
bear v2.9.2:- created by Hsin-ya Lee & Yung-jin Lee
Kaohsiung, Taiwan https://www.pkpd168.com/bear
Download link (updated) -> here
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