Re: PPC

Paul, Its not clear to me if you did a VPC (visual predictive check) using just the final estimates of the parameters) or tried to do a posterior predictive check (PPC) including uncertainty on the parameter estimates in the simulation. I dont have any experience with PPC but I dont think its helpful for model evaluation. Its more of a tool for understanding uncertainties of predictions for future studies. I assume you dont have complications like informative dropout processes to complicate the simulation so if you did a VPC and the median of the predictions doesnt match the median of the observations then your model needs more work. Some negative concs are OK but 'impossibly high values' point to problems with your model. So I think you can safely say the VPC has worked very well -- it has told you that you need to think more about your model. You might find some ideas in these references: 1. Tod M, Jullien V, Pons G. Facilitation of drug evaluation in children by population methods and modelling. Clin Pharmacokinet. 2008;47(4):231-43. 2. Anderson BJ, Holford NH. Mechanism-Based Concepts of Size and Maturity in Pharmacokinetics. Annu Rev Pharmacol Toxicol. 2008;48:303-32. Nick Paul Matthew Westwood wrote: > Hello all, > > I wonder if someone can give me some tips on PPC. > I am working on a midazolam dataset with a pediatric population, and have > decided to use PPC as a model validation technique. The dataset I am modelling > has up to 43 patients, at different ages, different weights, different times of > dosing and sampling, and different doses. I simulated 100 datasets using NONMEM > VI, fixing all parameters to the final estimates from the model. The simulated > datasets produced had a large proportion of negative concentrations, and also a > few impossibly large concentration values. Also the median, 5th and 95th > percentiles were not very promising, and the resulting graphs not very clean. > Firstly, can I use PPC with any degree of confidence with a dataset such as > this, and if so, do I omit the negative concentration values from the analysis? > > Thanks in advance for any help given. > > Paul Westwood, > PhD Student, > QUB, > Belfast. -- Nick Holford, Dept Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand [EMAIL PROTECTED] tel:+64(9)373-7599x86730 fax:+64(9)373-7090 http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford