Derivation of SAEM C-matrix in Phoenix
Michael R. Dunlavey
Certara/Pharsight
Objectives: In SAEM, the C matrix encodes the relationship between random effects and fixed effects, including covariate effects. The objective is to derive this matrix from a language-based description of the mixed-effect model.
Methods: The method used in Phoenix is to examine the "stparm" statements (statements that define the calculation of structural parameters) and, via symbolic differentiation, determine the relationship between the various fixed effects and the random effects. If the relationship cannot be represented in the restricted form of the C matrix, then use of SAEM is automatically ruled out.
Results: The algorithm for performing this analysis is given.
Conclusions: The method is effective for a wide variety of structural parameter models, including various forms of covariate effects. It is not necessary for a model to be written in a special way in order to be used by SAEM.
References:
[1] Monolix Version 3.1 User Doc, September 2009, pp 9