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Registerif Clast is zero in bear [🇷 for BE/BA]
Dear yjlee168!
Thanks a lot for your answer!
The problem is in understanding definitions, there are so many AUC (see this thread)...
WinNonLin use definitions AUClast for AUC to the last mesuarable concentration and AUCall for all square under the curve. There are also two types of AUC0-inf: predicted and observed. I think, BEAR calculates AUC0-inf=AUClast+Cobs/lambdaz, isn't it?
I've made several calculations and came to the conclusion that when we manually select points in the situation with last zero point we get wrong results on AUCinf. Correct method as you already pointed out was to exclude the last point or to name it NA:
There are some my calculations below:
initial data:
"subj","seq","prd","time","conc"
1,2,2,0,0
1,2,2,0.25,36.1
1,2,2,0.5,125
1,2,2,0.75,567
1,2,2,1,932
1,2,2,1.5,1343
1,2,2,2,1739
1,2,2,3,1604
1,2,2,4,1460
1,2,2,8,797
1,2,2,12,383
1,2,2,24,0
that is demo 2x2x2 data with zero last point.
If we try to calculate this set with manual selection of points (3) we get:
BEAR:
AUC=AUCall=14013.275
AUCinf=AUCinf_obs on AUCall=14013.275
Alternative calculation in another program ("by hand" in excel):
points 3: 9 to 11
Cmax 1739
AUClast 11715,275
AUCall 14013,275
AUCinf_pred on AUClast 14054,16
AUCinf_obs on AUClast 14004,99
AUCinf_obs on AUCall 14013,275
But when we exclude the last point or name it "NA" the calculations are correct:
exclude point:
"subj","seq","prd","time","conc"
1,2,2,0,0
1,2,2,0.25,36.1
1,2,2,0.5,125
1,2,2,0.75,567
1,2,2,1,932
1,2,2,1.5,1343
1,2,2,2,1739
1,2,2,3,1604
1,2,2,4,1460
1,2,2,8,797
1,2,2,12,383
BEAR
AUC 11715.275
AUCinf 14004.992
Alternative:
AUClast 11715,275
AUCall 11715,275
AUCinf_pred on AUClast 14054,1622
AUCinf_obs on AUClast 14004,9918
Naming the last point "NA":
"subj","seq","prd","time","conc"
1,2,2,0,0
1,2,2,0.25,36.1
1,2,2,0.5,125
1,2,2,0.75,567
1,2,2,1,932
1,2,2,1.5,1343
1,2,2,2,1739
1,2,2,3,1604
1,2,2,4,1460
1,2,2,8,797
1,2,2,12,383
1,2,2,24,NA
BEAR:
AUC=AUClast=AUCall=11715,275
AUCinf=AUCinf_obs on AUClast 14004,9918
Alternative calculation:
AUClast 11715,275
AUCall 11715,275
AUCinf_pred on AUClast 14054,1622
AUCinf_obs on AUClast 14004,9918
Thanks a lot for your answer!
The problem is in understanding definitions, there are so many AUC (see this thread)...
WinNonLin use definitions AUClast for AUC to the last mesuarable concentration and AUCall for all square under the curve. There are also two types of AUC0-inf: predicted and observed. I think, BEAR calculates AUC0-inf=AUClast+Cobs/lambdaz, isn't it?
❝ ❝ It allows calculation only for the manual selection of points.
❝
❝ Not quite correct here. You may not require manual selection for data points if you remove the zero conc. after Tmax or just input as 'NA'.
I've made several calculations and came to the conclusion that when we manually select points in the situation with last zero point we get wrong results on AUCinf. Correct method as you already pointed out was to exclude the last point or to name it NA:
There are some my calculations below:
initial data:
"subj","seq","prd","time","conc"
1,2,2,0,0
1,2,2,0.25,36.1
1,2,2,0.5,125
1,2,2,0.75,567
1,2,2,1,932
1,2,2,1.5,1343
1,2,2,2,1739
1,2,2,3,1604
1,2,2,4,1460
1,2,2,8,797
1,2,2,12,383
1,2,2,24,0
that is demo 2x2x2 data with zero last point.
If we try to calculate this set with manual selection of points (3) we get:
BEAR:
AUC=AUCall=14013.275
AUCinf=AUCinf_obs on AUCall=14013.275
Alternative calculation in another program ("by hand" in excel):
points 3: 9 to 11
Cmax 1739
AUClast 11715,275
AUCall 14013,275
AUCinf_pred on AUClast 14054,16
AUCinf_obs on AUClast 14004,99
AUCinf_obs on AUCall 14013,275
But when we exclude the last point or name it "NA" the calculations are correct:
exclude point:
"subj","seq","prd","time","conc"
1,2,2,0,0
1,2,2,0.25,36.1
1,2,2,0.5,125
1,2,2,0.75,567
1,2,2,1,932
1,2,2,1.5,1343
1,2,2,2,1739
1,2,2,3,1604
1,2,2,4,1460
1,2,2,8,797
1,2,2,12,383
BEAR
AUC 11715.275
AUCinf 14004.992
Alternative:
AUClast 11715,275
AUCall 11715,275
AUCinf_pred on AUClast 14054,1622
AUCinf_obs on AUClast 14004,9918
Naming the last point "NA":
"subj","seq","prd","time","conc"
1,2,2,0,0
1,2,2,0.25,36.1
1,2,2,0.5,125
1,2,2,0.75,567
1,2,2,1,932
1,2,2,1.5,1343
1,2,2,2,1739
1,2,2,3,1604
1,2,2,4,1460
1,2,2,8,797
1,2,2,12,383
1,2,2,24,NA
BEAR:
AUC=AUClast=AUCall=11715,275
AUCinf=AUCinf_obs on AUClast 14004,9918
Alternative calculation:
AUClast 11715,275
AUCall 11715,275
AUCinf_pred on AUClast 14054,1622
AUCinf_obs on AUClast 14004,9918
—
"Being in minority, even a minority of one, did not make you mad"
"Being in minority, even a minority of one, did not make you mad"
Complete thread:
- bear v2.7.0 released yjlee168 2015-12-07 09:18
![[Mix]](https://static.bebac.at/img/mix.png "open in Mix view")
- Suggestion ElMaestro 2015-12-07 10:12
- Suggestion yjlee168 2015-12-07 10:55
- Suggestion Helmut 2015-12-07 14:01
- Suggestion yjlee168 2015-12-07 18:51
- Suggestion Helmut 2015-12-07 14:01
- Suggestion yjlee168 2015-12-07 10:55
- bear v2.7.0 released Astea 2015-12-10 16:36
- if Clast is zero in bear yjlee168 2015-12-10 17:23
- if Clast is zero in bearAstea 2015-12-10 20:50
- if Clast is zero in bear yjlee168 2015-12-11 03:28
- if Clast is zero in bear Astea 2015-12-11 09:39
- if Clast is zero in bear yjlee168 2015-12-11 17:16
- if Clast is zero in bear Astea 2015-12-11 09:39
- if Clast is zero in bear yjlee168 2015-12-11 03:28
- bear v2.7.1 yjlee168 2015-12-15 10:21
- bear v2.7.1 Astea 2015-12-15 19:32
- BLLOQ ≠ 0 with measured drug plasma conc. yjlee168 2015-12-15 20:17
- BLLOQ ≠ 0 with measured drug plasma conc. Helmut 2015-12-16 01:45
- BLLOQ ≠ 0 with measured drug plasma conc. yjlee168 2015-12-16 11:38
- BLLOQ ≠ 0 ∀ t > 0 Helmut 2015-12-16 12:40
- BLLOQ ∋ { 0, ≈0, BLLOQ{...} ∀ t > 0} yjlee168 2015-12-16 18:22
- BLLOQ at first two time ponts, AUC calculation Astea 2016-01-30 17:11
- zero-zero with AUC calculation in bear yjlee168 2016-01-30 19:00
- BQL rules in bear mittyri 2016-02-01 22:16
- BQL rules in bear yjlee168 2016-02-02 10:59
- possible solutions? yjlee168 2016-02-02 21:30
- zero (0), missing (NA), or BLLOQ (0 or NA) in bear yjlee168 2016-02-03 09:04
- zero (0), missing (NA), or BLLOQ (0 or NA) in bear mahmoud-teaima 2016-02-08 21:28
- Please avoid Full Quotes (“TOFU”)! Ohlbe 2016-02-09 00:51
- error message in bear mahmoud-teaima 2016-02-09 04:55
- please check your dataset file yjlee168 2016-02-09 06:40
- please check your dataset file mahmoud-teaima 2016-02-09 15:00
- please check your dataset file yjlee168 2016-02-09 15:38
- please check your dataset file mahmoud-teaima 2016-02-09 15:00
- A possible R bug? yjlee168 2016-02-09 19:14
- Please avoid Full Quotes (“TOFU”)! Ohlbe 2016-02-09 00:51
- zero (0), missing (NA), or BLLOQ (0 or NA) in bear mahmoud-teaima 2016-02-08 21:28
- BQL rules in bear mittyri 2016-02-01 22:16
- zero-zero with AUC calculation in bear yjlee168 2016-01-30 19:00
- BLLOQ at first two time ponts, AUC calculation Astea 2016-01-30 17:11
- BLLOQ ∋ { 0, ≈0, BLLOQ{...} ∀ t > 0} yjlee168 2015-12-16 18:22
- BLLOQ ≠ 0 ∀ t > 0 Helmut 2015-12-16 12:40
- BLLOQ ≠ 0 with measured drug plasma conc. yjlee168 2015-12-16 11:38
- BLLOQ ≠ 0 with measured drug plasma conc. Helmut 2015-12-16 01:45
- BLLOQ ≠ 0 with measured drug plasma conc. yjlee168 2015-12-15 20:17
- bear v2.7.1 Astea 2015-12-15 19:32
- if Clast is zero in bearAstea 2015-12-10 20:50
- if Clast is zero in bear yjlee168 2015-12-10 17:23
- Suggestion ElMaestro 2015-12-07 10:12
Ing. Helmut Schütz