[NMusers] Rounding errors with TRANSIT model

Dear All I'm trying to evaluate a transit model approach in an attempt to better describe early drug concentrations following intravenous injection (1 minute and 10 minute infusions) of a sedative-hypnotic drug. However, every minimisation attempt is terminated due to rounding errors (E=134).

Re: [NMusers] Rounding errors with TRANSIT model

Ann Try ADVAN6 or ADVAN8 or ADVAN13 . Also, TOL=3 is too small. Increase it to 6-7 or even 9, and also change to NSIG=3 SIGL=9 ($EST step, as recommended in the guide). Also, at least initially, I would remove ETAs from the third compartment and from one of the parameters (Q2 or V2) of the seco

[NMusers] RE: Rounding errors with TRANSIT model

Ann I think your model is starting to be over-parameterised: 4 compartments plus lag plus transit (have you plotted the individual alag estimates as they have fairly big omegas?) I think if you cannot describe the data well with a 4 comp linear model, and are seeing differences in PK with diffe

[NMusers] Expert Modeler position available at Novartis (Basel, Switzerland)

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[NMusers] Baseline as a covariate

I'd like to get the group's opinion on something. I have a pharmacodynamic model and the baseline was shown to be a covariate on one of the model parameters. I was hoping to get general thoughts on the use of the baseline as a covariate. Is there a preference for using the observed baseline v

RE: [NMusers] Baseline as a covariate

Hi Pete, In this setting I generally try to first model the baseline response and perhaps pursue alternative structural model forms. For example, I may consider a multiplicative relationship rather than an additive relationship between baseline and placebo/drug effects. However, if the distribut

Re: [NMusers] Translate ALAG1 and D1 in ADVAN2 to differential equations

Xiao, Try running a SIMONLY simulation first. If you are using an additive or additive + constant CV error model, simulation will sometimes generate negative or very tiny DV values. If this is the case, it will cause problems with fitting the model to the simulated data. Luann Xiao Hu wrote

Re: [NMusers] Baseline as a covariate

Hi Peter, I assume from the question that the baseline is the baseline of your modeled PD measure, not of some other value (like the baseline weight), and that you model the actual PD measure, not change from the baseline. Then - it would be more logical to use the model-predicted baseline; -

RE: [NMusers] Baseline as a covariate

Dear Dr. Bonate, Could you kindly elaborate on the structural model that is being used to characterize your PD system? In my limited experience, I have seen the behavior that you describe under 2 circumstances: a) Simple inhibitory Emax PD model with a baseline: Here patients with a higher baselin

RE: [NMusers] Baseline as a covariate

Hi Pete, I think the standard model most of us would use is baseline as a parameter in the model, and like other parameters it would have a variability between subjects. What you describe sounds like a covariance between the baseline parameter and some other parameter. We are used to include such