Re: [NMusers] Reporting Modeling Results

Leonid,

I have considered this. The problem is that the structural model
parameters are not the problem. The fits without scaling were given
initial estimates that were close to the expected values that were
scaled from the median weight-normalized model. The CI's from the
bootstrap from this fit are very reasonable. The estimates for the
parameters from the covariate model describing CL maturation is where
the problem arises. These should be no different than the estimates from
the original model.

JM

>>> Leonid Gibiansky <LGibiansky_at_quantpharm.com> 10/25/07 5:30 PM >>>
Hi John,
The code seems to be good, and the results, in my opinion, should not
depend on scaling. One idea: if you started both sets of problems (with
and without scaling) from the same initial conditions (while the
solutions differ by factor 5 or so), nonmem could have difficulties
finding the correct minimum when started far from optimum. If your
initial conditions were coming from 10.4 kg-normalized solution, then it

could explain wider CI for the non-normalized problem: some of those
runs did not converged or converged to a local minima. If this is true,
you may want to repeat the non-normalized set with the initial
conditions closer to the solution (if you choose to use non-normalized
problem as the final model).
Leonid

--------------------------------------
Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
web: www.quantpharm.com
e-mail: LGibiansky at quantpharm.com
tel: (301) 767 5566




John Mondick wrote:
>
>
> $PK
>
> TVCL = THETA(1)*(WT/10.4)**0.75
> BETA = THETA(5)
> TCL = THETA(6)
> FCL = 1-BETA*EXP(-(AGE-1)*0.693/TCL)
> TVCL2 = TVCL*FCL
> CL = TVCL2*EXP(ETA(1))
>
> TVV1 = THETA(2)*(WT/10.4)
> V1 = TVV1*EXP(ETA(2))
>
> TVV2 = THETA(3)*(WT/10.4)
> V2 = TVV2*EXP(ETA(3))
>
> TVQ = THETA(4)*(WT/10.4)**0.75
> Q = TVQ
>

Received on Thu Oct 25 2007 - 18:29:03 EDT