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

Dear Leonid, Nick and Bill, Thank you very much for responding to my question! Sorry my original question was not detailed enough, let me try it again: I have a hazard function h(t) which is concentration dependent: h(t)=h0(t)*(1-CP(t)/(EC50+CP(t))), where CP(t) is the drug exposure at time t, h0(t) is the baseline hazard function without drug (may be a constant). Definition of EC50 is as usual. The cumulative hazard H(t) is integral of h(x) from time 0 to t, and the survival function S(t)=exp(-H(t)). Let's make it simple, assume the concentration follows a one-compartment model and it's a bolus IV dose, CL and V are known. Also assume h0(t) is a constant lambda, along with EC50 are known. Every time a dose is introduced, the amount is the same. Here is how I intend to simulate the event (repeated) history for one subject: At time 0, a unit dose is introduced, CP(t) can be determined, therefore S(t) can be determined (maybe through the $DES, not necessarily a closed form). The time of first event will be simulated by first generating a random number u1 from Uniform[0,1], and then solve the equation S(t1)=u1. That's why I need to inverse the survival function. Right at time t1 following the first event, I'll introduce another unit dose. Because most likely the concentration coming from the first dose has not reached zero by time t1, the survival function starting from t1 could be different than the survival function starting from the first dose (time 0). I'll follow the same procedure to simulate a t2, which is the time from first event to second event, and another unit dose will be introduced at time t1+t2. This process will continue until a certain cut-off time point has been met. That's why I said the dosing is dynamic. Hope this time I've stated it clear enough. It's just one thought on how to do the simulation, I'd like to get some advice on how this can be accomplished in NONMEM. Kind Regards, Yaming