FYI: ED Laplace doesn't work in current version of PopED

[mattfidler]

See lines:

https://github.com/andrewhooker/PopED/blob/ee8f50b9666e14e84fad60ed794386452136c3c5/inst/examples/ex.2.d.warfarin.ED.R#L63-L69

This doesn't work.

I was thinking it was my implementation but it doesn't work in the examples either.

[mattfidler]

Also an imported nonmem or monolix model has the prior covariance matrix which could be used for this procedure. With that in mind this could be populated by matching rules, but I need to understand the flags:

• The flags are 1 for normal
• 4 for lognormal
• What are 2-3?

And understand differences in parameterization.

Currently lognormal is:

par <- tPar*exp(eta.par)

But this is also lognormal:

par <- exp(tpar + eta.par)

Though nlmixr2 defines these differently; for:

• par <- tpar*exp(eta.par), tpar is untransformed and eta.par as transformed with exp
• par <- exp(tpar+eta.par), tpar is and eta.par are transformed with exp and are mu-referenced.

par <- tpar + eta.par

This is identified as mu-referenced and untransformed. We also identify expit() and probitInv() for these parameters.

Also it seems that you are not using the standard deviation for specifying variability (it is CV%?, or is it something else? does it change based on transformation?)

Just wondering here. Perhaps I missed it in the documentation.