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Pop PK/PD Simulation Failure (initial omega is not positive-definite)

pk/pd modeling and simulation dosing regimen

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#1 csheme

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Posted 26 January 2017 - 07:07 PM

Is anybody familiar with this error "Model execution failed. Initial omega is not positive-definite", any idea what is going on and how to correct?

 

I am pasting my model code below and link to my phoenix project

 

https://www.dropbox....mp.phxproj?dl=0

 

Thanks greatly!

 

test(){
 deriv(E = Baseline *Kout * (1 - Imax * C / (C + IC50)) - Kout * E)
 cfMicro(A1, Cl / V, Cl2 / V, Cl2 / V2, first = (Aa = Ka))
 dosepoint(Aa)
 C = A1 / V
 sequence{E = Baseline}
 error(CEps = 0.302373)
 observe(CObs = C * (1 + CEps))
 error(EEps = 3.92828)
 observe(EObs = E + EEps)
 stparm(Ka = tvKa * exp(nKa))
 stparm(V = tvV * exp(nV))
 stparm(V2 = tvV2 * exp(nV2))
 stparm(Cl = tvCl * exp(nCl))
 stparm(Cl2 = tvCl2 * exp(nCl2))
 stparm(Ke0 = tvKe0 * exp(nCl2))
 stparm(Baseline =tvBaseline *exp(nBaseline))
 stparm(Kout = tvKout * exp(nKout))
 stparm(Imax = tvImax)
 stparm(IC50 = tvIC50 * exp(nIC50))
 fcovariate(Grp)
 fixef(tvKa = c(, 0.279796, ))
 fixef(tvV = c(, 13.3159, ))
 fixef(tvV2 = c(, 217.745, ))
 fixef(tvCl = c(, 2.24389, ))
 fixef(tvCl2 = c(, 0.275072, ))
 fixef(tvKe0 = c(, 1, ))
 fixef(tvBaseline = c(, 100, ))
 fixef(tvKout = c(, 0.00241883, ))
 fixef(tvImax(freeze) = c(, 1, ))
 fixef(tvIC50 = c(, 0.00692223, ))
 ranef(diag(nBaseline, nKe0, nKin, nKout, nIC50, nKa, nV, nV2, nCl, nCl2) = c(0, 0, 0.19246735, 0.18668364, 1.5661644, 0.053794223, 0.121, 0.34, 0.113, 0.014))
}
 


Edited by csheme, 26 January 2017 - 07:08 PM.


#2 serge guzy

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Posted 26 January 2017 - 07:24 PM

Is anybody familiar with this error "Model execution failed. Initial omega is not positive-definite", any idea what is going on and how to correct?

 

I am pasting my model code below and link to my phoenix project

 

https://www.dropbox....mp.phxproj?dl=0

 

Thanks greatly!

 

test(){
 deriv(E = Baseline *Kout * (1 - Imax * C / (C + IC50)) - Kout * E)
 cfMicro(A1, Cl / V, Cl2 / V, Cl2 / V2, first = (Aa = Ka))
 dosepoint(Aa)
 C = A1 / V
 sequence{E = Baseline}
 error(CEps = 0.302373)
 observe(CObs = C * (1 + CEps))
 error(EEps = 3.92828)
 observe(EObs = E + EEps)
 stparm(Ka = tvKa * exp(nKa))
 stparm(V = tvV * exp(nV))
 stparm(V2 = tvV2 * exp(nV2))
 stparm(Cl = tvCl * exp(nCl))
 stparm(Cl2 = tvCl2 * exp(nCl2))
 stparm(Ke0 = tvKe0 * exp(nCl2))
 stparm(Baseline =tvBaseline *exp(nBaseline))
 stparm(Kout = tvKout * exp(nKout))
 stparm(Imax = tvImax)
 stparm(IC50 = tvIC50 * exp(nIC50))
 fcovariate(Grp)
 fixef(tvKa = c(, 0.279796, ))
 fixef(tvV = c(, 13.3159, ))
 fixef(tvV2 = c(, 217.745, ))
 fixef(tvCl = c(, 2.24389, ))
 fixef(tvCl2 = c(, 0.275072, ))
 fixef(tvKe0 = c(, 1, ))
 fixef(tvBaseline = c(, 100, ))
 fixef(tvKout = c(, 0.00241883, ))
 fixef(tvImax(freeze) = c(, 1, ))
 fixef(tvIC50 = c(, 0.00692223, ))
 ranef(diag(nBaseline, nKe0, nKin, nKout, nIC50, nKa, nV, nV2, nCl, nCl2) = c(0, 0, 0.19246735, 0.18668364, 1.5661644, 0.053794223, 0.121, 0.34, 0.113, 0.014))
}
 

Dear colleague

You can put initial variance of 0. This is what cause the problem.

 ranef(diag(nBaseline, nKe0, nKin, nKout, nIC50, nKa, nV, nV2, nCl, nCl2) = c(0, 0, 0.19246735, 0.18668364, 1.5661644, 0.053794223, 0.121, 0.34, 0.113, 0.014))
}

 

If there is no variance, then just change the code into

 stparm(Ke0 = tvKe0 )
 stparm(Baseline =tvBaseline)

 

 ranef(diag(nKin, nKout, nIC50, nKa, nV, nV2, nCl, nCl2) = c(0.19246735, 0.18668364, 1.5661644, 0.053794223, 0.121, 0.34, 0.113, 0.014))
}

 

Also

 stparm(Ke0 = tvKe0 * exp(nCl2))   this should be originally  stparm(Ke0 = tvKe0 * exp(nKe0))
 
 



#3 csheme

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Posted 26 January 2017 - 07:51 PM

Serge, there is nothing to say except that you are the best!

 

Thanks for the quick fix.







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