[NMusers] Rational of using IOV

Hi Nicolas My short answer would be another question: "what is the aim of your analysis ?" IOV is fine to split variability into inter-individual, intra-individual-inter-occasion and intra-individual-intra-occasion random components. This is excellent for data description, and can bring interest

[NMusers] At The Cutting Edge

At The Cutting Edge My client is expanding their Modeling & simulation group and is actively recruiting to add scientists in the United States and Europe. The group is focused on disease progression modeling and the implementation of mechanistic-based approaches. As a key member of this gro

RE: [NMusers] Rational of using IOV

Hi Thierry, Actually, devising a TDM program is precisely when you should be evaluating whether you have substantial IOV. If IOV is considerably greater than IIV then there is little benefit in a TDM program as you point out since a concentration from one occasion may not contain much informat

RE: [NMusers] Rational of using IOV

Dear James, I always thought that intra-individual variability (IIV) classically represented the immovable limit on the gains to be expected from TDM - IOV being indeed used only in a minority of population PK analyses. Both intra- and inter-occasion variability actually represent nuisance. We

RE: [NMusers] Rational of using IOV

Dear Thierry, The article below nicely describes the importance of incorporating IOV since it otherwise might lead to a falsely optimistic impression of the potential value of TDM. Karlsson MO, Sheiner LB. The importance of modeling interoccasion variability in population pharmacokinetic a

RE: [NMusers] Hessian of posterior density is non positive definite during search

Dear Matt & All I'm still battling I'm afraid... Can't seem to get past the SUM OF "SQUARED" WEIGHTED INDIVIDUAL RESIDUALS IS INFINITE problem. I've now log-transformed my data, and deleted all but the first occurrence of a BQL data point from each individual. I'm confident that the initial e

[NMusers] AAPS Modeling and Simulation Focus Group: Call for 2011 Progamming Proposals

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Re: [NMusers] Hessian of posterior density is non positive definite during search

Ann, Several ideas: 1. Fix ALAGs to zero, will it help? 2. Try to shield IPRED from being zero IPRED=LOG(0.0001) IF(F.GT.0.0001) IPRED=LOG(F) Y=IPRED + SIG1*ERR(1) (this could be a bad style, but will allow you to test the code) 3. Try ADVAN6, 8, 13 4. Remove BQL part, fit it as a 3-comp linea

RE: [NMusers] Hessian of posterior density is non positive definite during search

Ann, Because you already log-tranformed your data, you may want to change SIG1*IPRED to SIG1 for DUM. I'm guessing the combination of ALAG and SIG1*IPRED is causing problem. DUM = (LOQ-IPRED)/(SIG1) Best regards, Shelley Xiao Hu (Shelley), Ph.D. Scien

Re: [NMusers] Rational of using IOV

Thierry, Between subject variability (BSV aka IIV) and within subject variability (WSV aka IOV) describe the limits of what we can identify as sources of variability. I don't consider this a nuisance -- it is an opportunity for learning. The random assumption used for estimation of WSV is a

RE: [NMusers] Rational of using IOV

Nick While I agree that BOV is not solely a nuisance parameter it is a design specific parameter and hence can be somewhat of a nuisance. By design specific we can formulate settings in which the design of the study changes the estimate of BOV. To estimate the variance between occasions the d

Re: [NMusers] Rational of using IOV

Steve, I understand that BOV can be a nuisance for designers :-) However, arbitrary is not the same as practical. An arbitrary occasion interval e.g. 1 hour or 1 year, would have no practical application for any real drugs I know about. But from a practical perspective for TCI an occasion du

RE: [NMusers] Rational of using IOV

Hi Steve, I think we can apply some mechanistic insight into IOV in most cases. For example for absorption parameters, it is difficult to see that anything but each dosing occasion would constitute a separate occasion. There may however be situations where it is difficult to judge properly and

RE: [NMusers] Rational of using IOV

Thanks to all for your comments, I didn't expect so much. If the occasion correspond to a specific dose (i.e. 1st dose or later) then the question is, shall we expect a variability related to the duration of the treatment? In that case, we will have as many occasions as doses. The number of