Lack of IntersubjectCV in PHX [Software]

posted by yicaoting  – NanKing, China, 2017-09-01 09:09 (1342 d 14:42 ago) – Posting: # 17759
Views: 12,635

(edited by yicaoting on 2017-09-01 09:37)

Dear all,

According to this thread, we know that PHX does not output IntersubjectCV when the Var(Sequence*Subject) is negtive.

Using Ln() tranformation of PK data, I have verfified this using the data in the above thread. My results are identical to those obtained by our Helmut.

But when I analysis the above data using orignal Cmax data (none Ln transformed), I find that PHX does not output IntersubjectCV even the Var(Sequence*Subject) is positive. Some of my results using PHX WNL 7.0:

Dependent Hypothesis        DF    SS        MS          F_stat        P_value
Cmax      Sequence          1   1056.5714   1056.5714   0.017626409   0.89657994
Cmax      Sequence*Subject  12  719310.29   59942.524   1.3991004     0.28488402
Cmax      Formulation       1   37889.286   37889.286   0.8843624     0.36555519
Cmax      Period            1   88706.286   88706.286   2.0704667     0.17574474
Cmax      Error             12  514123.43   42843.619

Cmax   Var(Sequence*Subject)   8549.4524
Cmax   Var(Residual)          42843.6190
Cmax   Intrasubject CV         0.12677478

I don't know how to explain this? I notie that PHX WNL produces no Warning Messages in the output resluts.

But my manual calculation resluts are:
Parameter   Item                  Value
Cmax      Var(Sequence*Subject)     8549.4524
Cmax      Var(Residual)            42843.6190
Cmax      Inter-subject CV(%)        5.6632
Cmax      Intra-subject CV(%)       12.6775

For Non-transformed data analysis, I use these formula:
InterCV = 100 * Sqr(SigmaS2) / LSMeanR
IntraCV = 100 * Sqr(SigmaE2) / LSMeanR
It's noted that here LSMeanR = Mean for None-Ln-transformed data.
they are cited from Page 153 of this book: Shein-Chung Chow and Jen-Pei Liu, Design and Analysis of Bioavailability and Bioequivalence Studies, Third Edition. CRC Press. 2009.

So does PHX WNL miss this? or I am wrong? Can anyone help me to test of this by other software?
Can anyone help me to explain why WNL PHX doesn't calculate this for this dataset? or WNL PHX will never ouput this for BE analysis of None-Ln-transformed data and why?
Be sure, analysis of BE using Original Cmax data without Ln()-transformation.

Thank you for your help and clarification.

I try this in WNL 5.1.1
It only outputs Var(Sequecen*Subject) and Var(Residual), but Inter CV and Intra CV are both not calculated when using None-transformed data. From the comparison of WNL 5.1.1 and PHX 7.0, it seems PHX is improved in this isssue, but still lack of IntersubjectCV.:confused::confused:

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