Re: DV Simulation

From: Nick Holford Subject: Re: [NMusers] DV Simulation Date: Wed, 21 May 2003 08:55:58 +1200 Luciane, You can certainly simulate the DV using the model you have developed. A good reason for doing this is to perform a predictive check i.e. when you simulate from your model do the simulated observations resemble the original observations? There are many ways of answering this question. A relatively simple one is to simulate 1000 DV values at typical time points (e.g. the protocol observation times for your original data set) then find the 95% prediction interval from these 1000 DVs and compare it with a scatterplot of your original data. This is a form of internal validation that the model and parameter estimates are adequate for your data. Because of the approximations NONMEM has to make in its estimation you may be disappointed to find that the predictive check fails. Simply looking at the scatterplot may show you that 95% of your observations do not fall within the prediction intervals. Note that even if your model passes this predictive check it does not say that your model is more generally applicable e.g. to describe a new data set. The only way to test this kind of external validity is to collect new data. Simulation is not enough. Put the final estimates from NONMEM as initial estimates in your NM-TRAN control stream then add this record: $SIMULATION (20030521) ONLYSIM SUBPROBLEMS=1000 It is helpful to put this record somewhere e.g. in $ERROR REPI=IREP ; simulation replication index You will also need to add a suitable $TABLE record e.g. $TABLE ID TIME DV REPI NOAPPEND ONEHEADER FILE=mdl1000.sim The $SIMULATION record uses 20030521 as a random number seed. You should replace this with another big number if you want to create a different simulation data set. The simulated DV values will appear in the table file. You will have to work out your own method for extracting the DV values at each time point and working out the 95% prediction interval. The REPI item in the table file can be helpful in distinguishing each of the 1000 replications. Nick -- Nick Holford, Dept Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556 http://www.health.auckland.ac.nz/pharmacology/staff/nholford/