No rule fits all [NCA / SHAM]
Hi Astea,
Well.. I don't think there's a simple enough solution which fits all situations.
Say we have
Something is wrong at the point 18h. Could be a good idea to exclude that point from λz estimation, right?
Now imagine we want to get AUC0-18. Since that point exists, we cannot ignore it.
Lin-up,Log-down method claims AUC0-18 = 1320.139
So far so good.
Other next goal is AUC0-17.9, but taking into account not a robust interpolation of the neighbours but intelligent loglinear regression fit given as λz:
AUC0_17.9 = 1224.5557
Are you feeling some PK inconsistency here? Why is AUC18 so differ from the value 0.1h before?
I think this is (only one of many I think!) the reason why the methods differ.
Regarding Cmin as a first point: there could be other situations where to use Cmin from overall dataset (not the dosing period) is not good idea. Ctaupred? OK, but what if λz is not estimable for any reason?
I don't think the default WNL NCA rules will change since it can break a lot of templates and projects. Name it as unhealthy and lazy conservatism
PS: you can ask Certara to add some new optional NCA rule.
❝ Why do algorithms for inter- and extrapolation differ?
Well.. I don't think there's a simple enough solution which fits all situations.
Say we have
Data set
Time Conc
0 1
1 60
2 80
3 100
4 130
5 160
6 130
7 100
8 90
10 70
12 40
14 30
18 60
24 2
Something is wrong at the point 18h. Could be a good idea to exclude that point from λz estimation, right?
Now imagine we want to get AUC0-18. Since that point exists, we cannot ignore it.
Lin-up,Log-down method claims AUC0-18 = 1320.139
So far so good.
Other next goal is AUC0-17.9, but taking into account not a robust interpolation of the neighbours but intelligent loglinear regression fit given as λz:
exp(-lambda*17.9+interc)
[1] 15.0076
AUC0_17.9 = 1224.5557

Are you feeling some PK inconsistency here? Why is AUC18 so differ from the value 0.1h before?
I think this is (only one of many I think!) the reason why the methods differ.
Regarding Cmin as a first point: there could be other situations where to use Cmin from overall dataset (not the dosing period) is not good idea. Ctaupred? OK, but what if λz is not estimable for any reason?
I don't think the default WNL NCA rules will change since it can break a lot of templates and projects. Name it as unhealthy and lazy conservatism

PS: you can ask Certara to add some new optional NCA rule.
—
Kind regards,
Mittyri
Kind regards,
Mittyri
Complete thread:
- AUC0-tau at steady state BNR 2016-03-31 22:46 [NCA / SHAM]
- AUC0-tau at steady state jag009 2016-03-31 23:05
- AUC0-tau at steady state BNR 2016-03-31 23:43
- RTFM Helmut 2016-04-01 00:59
- RTFM BNR 2016-04-01 02:05
- AUC0-τ estimation with time deviations Astea 2019-02-10 16:38
- AUC0-τ estimation with time deviations Helmut 2019-02-10 19:32
- Cτ for lin and lin-up/log-down Astea 2019-02-10 20:50
- Cτ by lin-/lin, lin-up/log-down, and λz Helmut 2019-02-11 01:45
- inter- vs extra- Astea 2019-02-11 19:46
- inter- vs extra- Helmut 2019-02-12 02:20
- No rule fits allmittyri 2019-02-14 12:55
- one size fits all vs goal posts Astea 2019-02-16 08:33
- one size fits all vs goal posts ElMaestro 2019-02-16 13:33
- Bias etc. Helmut 2019-02-16 14:26
- software: NCA not validated Helmut 2019-02-16 13:59
- no way out for NCA validation? mittyri 2019-02-20 21:22
- Default rules mittyri 2019-02-20 21:40
- one size fits all vs goal posts ElMaestro 2019-02-16 13:33
- one size fits all vs goal posts Astea 2019-02-16 08:33
- inter- vs extra- Astea 2019-02-11 19:46
- Cτ by lin-/lin, lin-up/log-down, and λz Helmut 2019-02-11 01:45
- Cτ for lin and lin-up/log-down Astea 2019-02-10 20:50
- AUC0-τ estimation with time deviations Helmut 2019-02-10 19:32
- RTFM Helmut 2016-04-01 00:59
- AUC0-tau at steady state BNR 2016-03-31 23:43
- AUC0-tau at steady state jag009 2016-03-31 23:05