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Back to the forum  Query: 2018-05-20 12:07 CEST (UTC+2h)
 
Irene_I
Junior

Indonesia,
2018-05-16 09:02

Posting: # 18768
Views: 285
 

 Imbalance dataset analysis with Equivtest 2.0 [Software]

Dear all,
My name is Irene and I'm a newcomer in bioequivalence fields. I would like to ask some question about imbalanced datasets. I have a problem in analyzing 2-treatment, 2-sequence, 2-period crossover bioequivalence study design with imbalanced datasets between sequence.

I have looked for this topics and I found a similar problem here but It seems like nothing has concluded. I'm Sorry but I still do not understand about it.

I conducted a data analysis for imbalance datasets from a journal entitled "Reference Dataset for 2-Treatment, 2-sequence, 2-period bioequivalence studies" (Dataset C) with EquivTest 2.0 and I compared the results with the ones stated in journal. I found that Equivtest 2.0 result (Point of estimate and 90% Confidence Interval) was not identical with EquivTest/PK (the result that stated in the journal). My Equivtest 2.0 result for point of estimates and confidence interval were:

point of estimate (90% CI) : 66.78 (44.94,99.24)

The result according to Journal (EquivTest/PK)
point of estimate (90% CI) : 58.56 (39.41,87.03)


So, is there someone could help me with this problem? :confused:

I strongly appreciate if you could help me about this matter. :-)

Best Regards,


Irene
Helmut
Hero
Homepage
Vienna, Austria,
2018-05-16 11:47

@ Irene_I
Posting: # 18769
Views: 253
 

 EquivTest 2.0: defective!

Hi Irene,

» I conducted a data analysis for imbalance datasets from a journal entitled "Reference Dataset for 2-Treatment, 2-sequence, 2-period bioequivalence studies" (Dataset C) with EquivTest 2.0 and I compared the results with the ones stated in journal. I found that Equivtest 2.0 result (Point of estimate and 90% Confidence Interval) was not identical with EquivTest/PK (the result that stated in the journal). My Equivtest 2.0 result for point of estimates and confidence interval were:
»
» point of estimate (90% CI) : 66.78 (44.94,99.24)
»
» The result according to Journal (EquivTest/PK)
» point of estimate (90% CI) : 58.56 (39.41,87.03)

Congratulations! You discovered yet another defective software. :angry:
The result in EquivTest/PK agrees with ones of other software we have tested (SAS, Phoenix/WinNonlin, R). Screenshot:

[image]


The result you got in EquivTest 2.0 agrees with Kinetica 5.01 – which is wrong.1

Amazingly enough the correct formula taking the number of subjects / sequence (n1, n2) into account is given in the “User Reference Manual”, Chapter 8: Equivalence Testing (p. 166, p. 188 of the PDF) of v2.0 (dated 2001-10-12):

[image]


Did the developers update the manual but not the code

Anyhow, even if you upgrade to EquivTest/PK (of 2006)2 sooner or later you will face other problems. The Welch/Satterthwaite correction for parallel designs with unequal group sizes and/or unequal variances is not supported.3 Furthermore, you will not be able to assess replicate studies intended for reference-scaling according to regulatory requirements (FDA, EMA, WHO, ASEAN States, Australia, Brazil, Egypt, the Russian Federation, the Eurasian Economic Union, New Zealand).

I strongly suggest to get ‘better’ software.


  1. The defect for unbalanced 2×2×2 crossover designs was corrected in Kinetica 5.1 SR1 (2014-12-24). However, the flawed calculation of parallel designs with unequal group sizes was not corrected (see there).
  2. How? On the website of Statistical Solutions Ltd it is not listed any more.
  3. Fuglsang A, Schütz H, Labes D. Reference Datasets for Bioequivalence Trials in a Two-Group Parallel Design. AAPS J. 2015;17(2):400–4. doi:10.1208/s12248-014-9704-6. Free view-only version.

[image]Cheers,
Helmut Schütz 
[image]

The quality of responses received is directly proportional to the quality of the question asked. ☼
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ElMaestro
Hero

Denmark,
2018-05-16 14:07

@ Irene_I
Posting: # 18770
Views: 221
 

 Imbalance dataset analysis with Equivtest 2.0

Haha,

I can't believe it :-D
Thanks Irene_I for this post and for lifting my mood. Keep up the good work.

“A ten-year, double-blind study from the Mayo Clinic concluded that even in late stages of dementia, the last to go is the lobe of the brain in charge of cafeteria layout.” (Serge Storms/Tim Dorsey).


Best regards,
ElMaestro

- Bootstrapping is a relatively new hobby of mine. I am only 30 years late to the party.
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