Simulation with confidence and prediction intervals

Phoenix Certara Forums Modelling and Simulation
1

Hi,

I ´ve fitted single dose PD data using a population approach. Now I would like to use my model to simulate median curves, confidence interval sas well as prediction intervals for other dose levels than those previously studied. What ´s the best and easiest way to do this in Phoenix?

Many thanks,
Karin

2

Hi Karin,

It is not clear what kind of model are you using let us assume it is a continuous PD with kin kout or emax type of model.

Simulating median curves can be easily done by asking for a table with a sequence of time and then zeroing the random effects you will get the equivalent of PRED at any time you want. To get Prediction intervals you simulate keeping the random effects as the model estimated them say 1000 times and then you compute pointwise prediction intervals.

To get confidence intervals on the median you will need to simulate with uncertainty this is currently not supported out of the box and you will need a creative approach:

  • use simulation mode using the variance covariance matrix of fixed effects to simulate say 1000 times and you will get 1000 simulated medians with uncertainty then you can compute the CI using percentiles
  • use the bootstrap based uncertainty so you simulate 1000 times using the 1000 different group of estimates to get 1000 medians and then you compute a CI around the median
3

Hi,

Thanks for your reply which made things a bit more clear although there are still some question marks, e.g. what do I need to specify in the model in order to use the theta variance covariance matrix in the simulation?

I ´ve attached my project and if you would have the time to use it to demonstrate how to run these simulations it would be very much appreciated.

Many thanks,

Karin

Sim mean with prediction and confidence intervals.phxproj (892 KB)

4

when you run a vpc it will give you prediction intervals

Sim mean with prediction and confidence intervals.phxproj (2.55 MB)