Re: seeking help on NONMEM code for simulation of Repeated Time to Event Data

From: Nick Holford Date: April 04, 2013 technical Source: mail-archive.com
Yaming, You may wish to consult this document for details of coding time to event models using NM-TRAN. http://holford.fmhs.auckland.ac.nz/docs/time-to-event-webinar.pdf It is really very simple to integrate the hazard numerically using $DES. If you are dealing with only one event per subject then there are no random effects to be estimated in the model and it will run quite quickly with the FO estimation method. Best wishes, Nick
Quoted reply history
On 4/04/2013 9:35 a.m., Yaming Hang wrote: > Dear NONMEM Users, > > I have some questions about how to accomplish the following tasks in NONMEM, would you kindly share your experience with me or provide some suggestions? I’m trying to make a simulation that involves dynamic dosing. Here is the algorithm of simulation: at time 0, a dose is given, then the time to the first event will be simulated based on a certain survival function which depends on the drug exposure. Next, conditioning on that simulated first event time, a second dose will be introduced, and again time to the second event will be simulated. This will be repeated until a certain cut off time point. > > My specific questions are: > > 1. since the dosing history will be depending on the simulated event time, I cannot construct the dosing history in NONMEM data set a prior, how can this be done? > > 2. The survival function is a function of the time-varying drug exposure, therefore I need to inverse an integral which does not have a closed form (i.e. only expressed in differential equation), how can I do that? > > Your help will be much appreciated! > > Yaming Hang -- Nick Holford, Professor Clinical Pharmacology Dept Pharmacology & Clinical Pharmacology, Bldg 503 Room 302A University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand tel:+64(9)923-6730 fax:+64(9)373-7090 mobile:+64(21)46 23 53 email: [email protected] http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford