Bioequivalence and Bioavailability Forum

Bag full of bugs [Study Performance]

posted by Helmut – Vienna, Austria, 2014-06-10 02:37 (3601 d 05:00 ago) – Posting: # 13045
Views: 16,633

Hi Khaoula,

I’m too lazy to check with my old installation of Kinetica. But there are some points to note:

❝ SOURCE D.F SS MS F p

❝ Period 1 0.0264787 0.0264787 0.56186 0.4669 NS

❝ Subject(Seq) 13 4.8517 0.373208 7.91934 0.0003379 ***

❝ Formulation 1 0.211625 0.211625 4.4906 0.05391 NS

❝ Sequence 1 0.686301 0.686301 14.5631 0.002141 *** [image]

❝ Error 13 0.61264 0.0471261

❝ Total 29 6.38875

Old story. Kinetica calculates the sequence effect wrong – since ages. See this thread.
Instead of F=0.686301/0.0471261=14.5631 (which is highly significant with p=0.002141) the correct test is against Subject(Seq): F=0.686301/0.373208=1.8389 (which is not significant with p=0.1982).

❝ Root Mean Square Error = 0.217086

The RMSE is a crude estimate of the CV and should be avoided.

❝ ; CV = 0.0347883 [image]

That’s nonsense! ~~Is this part of Kinetica’s original output?~~* Why didn’t you bother to manually calculate the CV according to the formula I gave you above?
\(CV\% = 100\sqrt{e^{0.0471261}-1} = 21.97\%\)

❝ Power of the test = 0.500777 [image]

❝ 1 - ( Power of the test ) = 0.499223

Wrong. If you insist in post hoc power: 0.09885. With a T/R-ratio close to the upper limit of the acceptance range would you really expect a ~50% chance to pass BE in 15 subjects?

❝ around the ratio:[test form]/[ref form])=[1.028, 1.3612] [image]

Yes, but around which ratio? I would guess: \(\sqrt{1.028 \times 1.3612} = {\color{Red} {1.829\ldots}}\) The geometric mean of Test is 559.01 and the one of Reference 461.21. As a first guess of the T/R-ratio we get 461.21/559.01=1.2121. Since this is an imbalanced dataset, we have to use the least squares (or adjusted) means instead, which are 552.58 and 456.58. Therefore, T/R=1.2103. What does Kinetica “calculate” here?

[image]

Due to the bug in Kinetica this is likely wrong. In Phoenix/WinNonlin I got:

Hypothesis       DF    SS        MS       F_stat  P_value

Period            1  0.027982  0.027982  0.07021  0.79519

Sequence*Patient 13  5.181510  0.398578  7.49434  0.00045

Sequence          1  0.105223  0.105223  1.97847  0.18300

Formulation       1  0.271883  0.271883  5.11214  0.04155

Error            13  0.691389  0.053184



T/R 121.02% [90% CI: 104.22%, 140.53%]

BTW:

Parameter              Estimate

Var(Sequence*Patient)  0.172697

Var(Residual)          0.053184

Intersubject CV        0.434173

Intrasubject CV        0.233717

Check: \(CV\% = 100\sqrt{e^{0.053184}-1} = 23.37\%\). [image]

Low for omeprazole, but possible.

If you want an independent evaluation by noncommercial software: In

(you find the script in my lectures) I got:
121.02% [104.22–140.53%] CV 23.37% [image]

❝ I havnt randomisation of subject 15, and then they put the result in kinetica they excluded him,

The randomization of an excluded subject is not required anyhow.

Confirmed. I don’t have the slightest idea how Kinetica gets this number.
Discovered this interesting post at David’s PKPD-list.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

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Complete thread:

randomization khaoula 2014-06-06 14:04 [Study Performance]
- Imbalanced cross-overs Helmut 2014-06-06 14:47
  - Imbalanced cross-overs khaoula 2014-06-06 16:03
    - CV 0.03%? Helmut 2014-06-07 13:52
    - Imbalanced cross-overs jag009 2014-06-09 15:36
      - Imbalanced cross-overs khaoula 2014-06-09 22:07
        
        Bag full of bugsHelmut 2014-06-10 00:37
        
        Randomisation? ElMaestro 2014-06-10 01:00
        
        Randomisation? Helmut 2014-06-10 14:53
        
        Randomisation? khaoula 2014-06-11 00:17
        
        Problems resolved? Helmut 2014-06-11 02:01
        
        Problems resolved? khaoula 2014-07-24 13:36
        
        corrected data in PHX/WNL Helmut 2014-07-27 01:37
        
        Which version of Kinetica? Helmut 2014-06-11 19:51
        
        Which version of Kinetica? khaoula 2014-06-12 00:41
        Which version of Kinetica? khaoula 2014-07-25 00:49
        
        adjusted means (aka LSMs) Helmut 2014-07-27 02:23
        
        adjusted means (aka LSMs) khaoula 2014-08-25 21:41

Bag full of bugs [Study Per­for­mance]

Complete thread:

Bag full of bugs [Study Performance]