# Dual absorption 2 CMT model fitting error
**URL:** https://discourse.pumas.ai/t/dual-absorption-2-cmt-model-fitting-error/956
**Category:** Uncategorized
**Created:** [November 16, 2023, 4:29pm UTC](https://discourse.pumas.ai/t/dual-absorption-2-cmt-model-fitting-error/956 "2023-11-16T16:29:21Z")
**Posts on this page:** 4
**Page:** 1
### Author:  [@chrisv](https://discourse.pumas.ai/u/chrisv)
#### Post date: [November 16, 2023, 4:29pm UTC](https://discourse.pumas.ai/t/dual-absorption-2-cmt-model-fitting-error/956/1 "2023-11-16T16:29:21Z")
Hello. I have been working on another model, with double absorption (KA1 and KA2) and two compartments. However, I get an error that has caused me problems before. The classic error of gradient = 0 and that a certain parameter is not identified.
OUTPUT: [ Info: Checking the initial parameter values.
[ Info: The initial negative log likelihood and its gradient are finite. Check passed.
Iter Function value Gradient norm
0 1.568802e+03 3.380961e+03
- time: 0.0010001659393310547
ERROR: gradient is exactly zero in tvlag. This indicates that tvlag isn’t identified.
MY MODEL:
mymodel = @model begin
```
@param begin
tvcl ∈ RealDomain(lower=0)
tvv ∈ RealDomain(lower=0)
tvka1 ∈ RealDomain(lower=0.001)
tvka2 ∈ RealDomain(lower=0)
tvq ∈ RealDomain(lower=0)
tvvp ∈ RealDomain(lower=0)
tvlag ∈ RealDomain(lower=0)
tvbio ∈ RealDomain(lower=0)
Ω ∈ PDiagDomain(5)
σ ∈ RealDomain(lower = 0.0001)
end
@random begin
η ~ MvNormal(Ω)
end
@pre begin
CL = tvcl*exp(η[1])
Vc = tvv*exp(η[2])
Ka1 = tvka1*exp(η[3])
Ka2 = tvka2*exp(η[4])
lags = (SR = tvlag,)
bioav = (IR = tvbio*exp(η[5]), SR = 1-tvbio*exp(η[5]))
Q = tvq
Vp = tvvp
end
@dynamics begin
IR' = -Ka1*IR
SR' = -Ka2*SR
Central' = Ka1*IR + Ka2*SR - Central*CL/Vc - (Q/Vc)*Central + (Q/Vp)*Peripheral
Peripheral' = (Q/Vc)*Central - (Q/Vp)*Peripheral
end
@derived begin
conc := @. Central/Vc
dv ~ @. Normal(conc, σ*abs(conc))
end
```
end
param = (
tvcl = 5, tvv = 50, tvka1 = 0.8, tvka2 = 0.6, tvlag = 1000, tvbio = 0.5,tvq=10,tvvp=100,
Ω = Diagonal([0.1,0.1,0.4,0.4,0.1]),
σ = 0.1
)
fit\_results = fit(mymodel, pop, param, Pumas.FOCE())
---
### Author:  [@vijay](https://discourse.pumas.ai/u/vijay)
#### Post date: [November 20, 2023, 4:28am UTC](https://discourse.pumas.ai/t/dual-absorption-2-cmt-model-fitting-error/956/2 "2023-11-20T04:28:43Z")
Dear @chrisv
`lags` and `bioav` should go into the `@dosecontrol` block. So, please re-write your code this way
```julia
@pre begin
CL = tvcl*exp(η[1])
Vc = tvv*exp(η[2])
Ka1 = tvka1*exp(η[3])
Ka2 = tvka2*exp(η[4])
Q = tvq
Vp = tvvp
end
@dosecontrol begin
lags = (SR = tvlag,)
bioav = (IR = tvbio*exp(η[5]), SR = 1-tvbio*exp(η[5]))
end
```
you can read more in the documentation [here](https://docs.pumas.ai/stable/basics/models/#@dosecontrol:-Dose-Control-Parameters)
---
### Author:  [@chrisv](https://discourse.pumas.ai/u/chrisv)
#### Post date: [November 27, 2023, 11:12pm UTC](https://discourse.pumas.ai/t/dual-absorption-2-cmt-model-fitting-error/956/3 "2023-11-27T23:12:15Z")
Thank you for your help! I have changed the code as I show below:
mymodel = @model begin
```
@param begin
tvcl ∈ RealDomain(lower=0)
tvv ∈ RealDomain(lower=0)
tvka1 ∈ RealDomain(lower=0)
tvka2 ∈ RealDomain(lower=0)
tvq ∈ RealDomain(lower=0)
tvvp ∈ RealDomain(lower=0)
tvlag ∈ RealDomain(lower=0)
tvbio ∈ RealDomain(lower=0)
Ω ∈ PDiagDomain(5)
σ ∈ RealDomain(lower = 0.0001)
end
@random begin
η ~ MvNormal(Ω)
end
@pre begin
CL = tvcl*exp(η[1])
Vc = tvv*exp(η[2])
Ka1 = tvka1*exp(η[3])
Ka2 = tvka2*exp(η[4])
Q = tvq
Vp = tvvp
end
@dosecontrol begin
lags = (SR = tvlag,)
bioav = (IR = tvbio*exp(η[5]), SR = 1-tvbio*exp(η[5]))
end
@dynamics begin
IR' = -Ka1*IR
SR' = -Ka2*SR
Central' = Ka1*IR + Ka2*SR - Central*CL/Vc - (Q/Vc)*Central + (Q/Vp)*Peripheral
Peripheral' = (Q/Vc)*Central - (Q/Vp)*Peripheral
end
@derived begin
conc := @. Central/Vc
dv ~ @. Normal(conc, σ*abs(conc))
end
```
end
Then I used my model, population and parameters to fit:
param = (
tvcl = 5, tvv = 50, tvka1 = 0.8, tvka2 = 0.6, tvlag = 1000, tvbio = 0.5,tvq=10,tvvp=100,
Ω = Diagonal([0.1,0.1,0.4,0.4,0.1]),
σ = 0.1
)
fit\_results = fit(mymodel, pop, param, Pumas.FOCE())
Finally, I get the same error but now in KA2:
gradient is exactly zero in tvka2. This indicates that tvka2 isn’t identified.
---
### Author:  [@storopoli](https://discourse.pumas.ai/u/storopoli)
#### Post date: [November 28, 2023, 12:10pm UTC](https://discourse.pumas.ai/t/dual-absorption-2-cmt-model-fitting-error/956/4 "2023-11-28T12:10:32Z")
> [@chrisv](#):
>
> ```julia
> param = (
> tvcl = 5, tvv = 50, tvka1 = 0.8, tvka2 = 0.6, tvlag = 1000, tvbio = 0.5,tvq=10,tvvp=100,
> Ω = Diagonal([0.1,0.1,0.4,0.4,0.1]),
> σ = 0.1
> )
>
> ```
Isn’t this particular initial value of `tvlag` too big?
What happens if you fit with something lower, e.g. `5`?