RE: [NMusers] Baseline as a covariate

2010-08-11 Thread mats karlsson
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

RE: [NMusers] Baseline as a covariate

2010-08-11 Thread Samtani, Mahesh [PRDUS]
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

2010-08-11 Thread Leonid Gibiansky
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] Translate ALAG1 and D1 in ADVAN2 to differential equations

2010-08-11 Thread Luann Phillips
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

2010-08-11 Thread Ken Kowalski
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

[NMusers] Baseline as a covariate

2010-08-11 Thread Peter Bonate
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

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

2010-08-11 Thread bengt . hamren
Expert Modeler position at Novartis Pharmaceuticals (Basel, Switzerland) The company: a global healthcare leader, Novartis has one of the most exciting product pipelines in the industry today. A pipeline of innovative products brought to life by diverse, talented, performance-driven people. A

[NMusers] RE: Rounding errors with TRANSIT model

2010-08-11 Thread Standing Joseph (Great Ormond Street Hospital For Children NHS Trust)
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

Re: [NMusers] Rounding errors with TRANSIT model

2010-08-11 Thread Leonid Gibiansky
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] Rounding errors with TRANSIT model

2010-08-11 Thread Ann Rigby-Jones
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).