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RegisterBias? [Regulatives / Guidelines]
posted by Helmut 
– Vienna, Austria, 2010-02-05 03:03 (5613 d 06:05 ago) – Posting: # 4712
Views: 24,785
Dear Firefighters!
That’s a perfect starter!
Not 125.00%?
Like me. So I fired up a little simulation. I didn’t care about lognormal errors (too late in the evening).
T1 (mean 95, CV 15%), R1 (mean 90, CV 10%), R2 (mean 110, CV 15%). No identical CVs to add a little spice. Six sequence Williams's design; two setups: no period effect (response 1) and an additive period effect of 10 in P3 (response 2). My target ratios therefore are
R came up with:
Raw mean ratios and pooled CV%s are
WinNonlin 5.2.1 gave:
Full 3-period model:
Next I tortured the software and set R1 or R2 to ‘Missing’ (ignoring the warning messages).
Full 3-period model with missing values:
Last the infamous 2×2 extractions:
As expected PEs are unbiased in either method. In the full (correct, as I would dare to call it) model there is a common CV. Like D. Labes already suspected, CVs in the ‘missing data model’ and in the extracted tables are different. The outcome in some cases is anticonservative. Regulators, do you read this?
❝ […] To make matters worse, I have not read any literature.
That’s a perfect starter!
❝ I could easily be 120% wrong,
Not 125.00%?
❝ I am incompetent to tell…
Like me. So I fired up a little simulation. I didn’t care about lognormal errors (too late in the evening).
T1 (mean 95, CV 15%), R1 (mean 90, CV 10%), R2 (mean 110, CV 15%). No identical CVs to add a little spice. Six sequence Williams's design; two setups: no period effect (response 1) and an additive period effect of 10 in P3 (response 2). My target ratios therefore are
T/R1 105.6%
T/R2 86.47%R came up with:
subject sequence period treatment response 1 response 2
1 1 1 T 120.6 120.6
1 1 2 R1 81.56 81.56
1 1 3 R2 136.7 146.7
2 2 1 R1 96.86 96.86
2 2 2 R2 134.0 134.0
2 2 3 T 95.09 105.09
3 3 1 R2 96.79 96.79
3 3 2 T 82.46 82.46
3 3 3 R1 101.3 111.3
4 4 1 T 114.4 114.4
4 4 2 R2 88.93 88.93
4 4 3 R1 89.56 99.56
5 5 1 R1 99.64 99.64
5 5 2 T 97.84 97.84
5 5 3 R2 117.8 127.8
6 6 1 R2 101.5 101.5
6 6 2 R1 72.80 72.80
6 6 3 T 74.43 84.43
7 1 1 T 76.64 76.64
7 1 2 R1 83.70 83.70
7 1 3 R2 116.8 126.8
8 2 1 R1 86.61 86.61
8 2 2 R2 116.2 116.2
8 2 3 T 84.64 94.64
9 3 1 R2 122.4 122.4
9 3 2 T 104.8 104.8
9 3 3 R1 87.69 97.69
10 4 1 T 96.65 96.65
10 4 2 R2 120.4 120.4
10 4 3 R1 96.99 106.99
11 5 1 R1 96.53 96.53
11 5 2 T 89.58 89.58
11 5 3 R2 77.61 87.61
12 6 1 R2 115.7 115.7
12 6 2 R1 94.51 94.51
12 6 3 T 98.80 108.8Raw mean ratios and pooled CV%s are
T/R1 105.6% (11.9%)
T/R2 86.36% (15.3%)WinNonlin 5.2.1 gave:
Full 3-period model:
PE 90% CI CV%
T/R1 103.81 94.38 114.2 13.59% no period effect
T/R2 84.65 76.96 93.11 13.59%
T/R1 104.1 94.93 114.1 13.09% +P3 effect
T/R2 85.20 77.73 93.39 13.09%Next I tortured the software and set R1 or R2 to ‘Missing’ (ignoring the warning messages).
Full 3-period model with missing values:
PE 90% CI CV%
T/R1 103.81 95.46 112.89 11.24% no period effect
T/R2 84.65 75.93 94.36 14.59%
T/R1 104.1 95.83 112.89 11.03% +P3 effect
T/R2 85.20 76.78 94.55 13.98%Last the infamous 2×2 extractions:
PE 90% CI CV%
T/R1 103.81 95.43 112.93 11.41% no period effect
T/R2 84.65 76.75 93.35 13.29%
T/R1 104.1 94.71 114.31 12.76% +P3 effect
T/R2 85.20 77.20 94.04 13.39%As expected PEs are unbiased in either method. In the full (correct, as I would dare to call it) model there is a common CV. Like D. Labes already suspected, CVs in the ‘missing data model’ and in the extracted tables are different. The outcome in some cases is anticonservative. Regulators, do you read this?
—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!![[image]](https://static.bebac.at/pics/Blue_and_yellow_ribbon_UA.png)
Helmut Schütz
![[image]](https://static.bebac.at/img/CC by.png)
The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz
The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Complete thread:
- EMA BE guideline - final version Ohlbe 2010-01-28 18:31 [Regulatives / Guidelines]
![[Mix]](https://static.bebac.at/img/mix.png "open in Mix view")
- Final version published Helmut 2010-01-29 14:29
- Final version published ElMaestro 2010-01-29 17:02
- Statistix Helmut 2010-01-29 17:30
- Statistix ElMaestro 2010-01-29 18:11
- Calories ;-) Helmut 2010-01-29 19:22
- Calories ;-) ElMaestro 2010-01-29 20:43
- Calories ;-) Helmut 2010-01-29 21:08
- Variable calories d_labes 2010-02-01 12:05
- Calories ;-) ElMaestro 2010-01-29 20:43
- ANOVA only - no doubts Helmut 2010-02-10 23:41
- ANOVA only - no doubts ElMaestro 2010-02-12 21:09
- Statistix Helmut 2010-01-29 17:30
- Final EMA oracle d_labes 2010-02-01 11:53
- Final EMA oracle Helmut 2010-02-01 12:28
- Final EMA oracle ElMaestro 2010-02-01 12:50
- More then two EMA oracles d_labes 2010-02-01 13:30
- Less of an issue ElMaestro 2010-02-01 15:29
- Less or More of an issue d_labes 2010-02-01 16:53
- Less or More of an issue ElMaestro 2010-02-01 17:22
- Less or More of an issue d_labes 2010-02-01 16:53
- Effective with 1 Aug 2010 Helmut 2010-02-02 00:55
- Bias? ElMaestro 2010-02-04 11:27
- Less of an issue ElMaestro 2010-02-01 15:29
- Final EMA oracle Helmut 2010-02-01 13:43
- Final EMA oracle ElMaestro 2010-02-01 14:54
- Final EMA oracle d_labes 2010-02-01 15:20
- Teaching Helmut 2010-02-01 16:07
- Final EMA oracle d_labes 2010-02-01 15:20
- Final EMA oracle ElMaestro 2010-02-01 14:54
- More then two EMA oracles d_labes 2010-02-01 13:30
- Cmin really gone? tmax reappeared? d_labes 2010-02-01 14:02
- Cmin really gone. tmax reappeared - but how? Helmut 2010-02-01 23:30
- Interpol or not d_labes 2010-02-01 14:52
- Interpol! Helmut 2010-02-02 00:02
- Interpol! ray_be 2010-02-03 18:31
- WinNonlin/Phoenix extrapolation to t=tau Helmut 2010-02-03 20:26
- Interpol! ray_be 2010-02-03 18:31
- Interpol! Helmut 2010-02-02 00:02
- Meta-analysis Helmut 2010-02-07 17:41
- Final version published Panks.79 2010-03-08 07:22
- Cmin for MR-formulations? Helmut 2010-03-08 18:16
- Cmin for MR-formulations? Marcel 2010-04-23 10:09
- MR-Guideline? Helmut 2010-04-23 12:34
- Cmin for MR-formulations? Marcel 2010-04-23 10:09
- Cmin for MR-formulations? Helmut 2010-03-08 18:16
- Final version published ElMaestro 2010-01-29 17:02
- Overview of comments published Helmut 2010-02-10 18:33
- Comments commented d_labes 2010-02-11 08:19
- Definition of Cmin by EMEA Ravi 2010-03-13 12:05
- The EMA’s Cmin & WinNonlin Helmut 2010-03-13 12:52
- Final version published Helmut 2010-01-29 14:29
Ing. Helmut Schütz