mattfidler
commented
3 months ago Hi @lirui0321
This is a methodology question, not a simulation issue. Importing from nonme2rx will use the same methodologies mentioned in the above post.
The only method that uses correlations between the omega covariances and fixed effects is a multivariate normal simulation of the full problem. That being said, it would have to simulate an omega matrix that is an invertible non-positive definite matrix. In our (unpublished) tests with other systems, this often quite difficult to acheive.
In the case of nonmem2rx these extra covariances are ignored just like they are in the case of a nlmixr2 model.
Hi Matt,
I have been reading clinical trial instructions you provided here (https://nlmixrdevelopment.github.io/RxODE/articles/RxODE-sim-var.html). In this example, you showed how cov matrix can be incorporated into the simulations. However, the cov matrix here only includes variance and covariance for theta and diagonal elements of omega matrix, but not off-diagonal elements of omega matrix. If I want to incorporate a cov matrix including variance/covariance for off-diagonal omega elements (for example, .cov file from NONMEM), is there a way to do that? The issue is that .cov file comes with off-diagonal names like OMEGA(2,8), but I assume that RxODE model does not know what that means, and I do not know how to pass that info to RxODE. I am assuming you probably had solved this issue when you built the nonmem2rx package, so wonder how you did it.
Thank you!
Rui