Now and again I encounter the situation where when applying a population model where all the etas (for a given parameter) are all determined to be positive (or all determined to be negative)? Is there something that can cause this to happen (such that the estimated population mean is outside the range of individual values?)
Today, when fitting a standard 2 compartment PK model (with inter-individual variability on Cl only) to well defined bi-phasic PK data, using well defined started values (and no upper or lower bounds) I get the following etas (nCl) for the 10 individuals when applying FOCE ELS.