Validation and power of the Mixture Model
Dear all,
I am a fresh research student. Previously, I had the experience in developing a
pharmacogenetics-based population PK model using NONMEM, but this is the first
time I work with the Mixture Model in NONMEM and I have some questions about it.
I have two datasets on hand, where patients' clearance are believed to be
affected by their genotypes. While I have their genotypic information, I also
wish to know if the Mixture Model in NONMEM can help me accurately categorize
the population even if the genotypic information are "hidden" from NONMEM. The
results turned out to be unsatisfactory somehow. For the subpopulations with a
distinctively different typical values of clearance, the sensitivity and
specificity can approach 100%, but for those with less differences, the average
accuracy drops to 60-70%. Although it is not difficult to understand that the
computer will not be able to categorize these subjects when they have similar
parameters (either mean values too close or variances too large...), I am
wondering if there is any general approach to utilize the best out of the
Mixture Model function.
Regarding the power of the Mixture Model, I wonder if there has been any
validation done before for datasets with different characteristics. For
examples, is there any previous study that looked into the accuracy of the
Mixture Model function and can somehow express the typical accuracy in terms of
the difference in, say, the mean plasma levels, between 2 subpopulations.
Last but not least, it would be great if anyone can kindly advise me any good
teaching materials about the Mixture Model in NONMEM.
Sincerely,
Matthew Hui