Minimisation problem...

Dear NMusers I am trying to analyse data from a study in which samples were taken from each subject at 4 different time points (t=0,5,10,14). The problem with the data is that there are many missing data points and there is considerable variation between the subjects. The subjects are in either a control or a test group, and I want to determine whether there is any difference in the data values between these groups. Overall, it looks like the data values increase with time, but there is a suggestion that in the test group the increase is not sustained but returns to baseline levels by t=14, whereas the control group is either levelled off or possibly still rising. I have used a polynomial model to fit the data up to the 3rd power (which I think is probably too much) and included additive parameters to modify each of the coefficients from the polynomial model. The problem I have is as follows: When I use the FOCE method the ETA terms collapse towards zero. The quality of the fit looks poor when judged by a plot of DV against individual predicted values. When I use the BAYES method, I get credible ETA values and a much better fit (i.e., DV vs ipred clusters sensibly around a line of unity). However, I cannot use the OBJV value from the BAYES method to carry out hypothesis testing. The final reported parameter estimates following the BAYES method are sensitive to initial starting values and the number of iterations performed. If I use the parameter values obtained with the BAYES method I can determine an accurate OBJV for those parameter values using FOCE with just 1 evaluation. However, if I perform a minimisation with FOCE starting with those values, the ETA values collapse and the DV vs ipred plot looks awful again. I hope this makes some sense to someone out there - I'm a bit of a novice at NONMEM. I realise the data is far from ideal, but it would be great to get some statistical information about the difference between the two groups. If anyone had any suggestions I would be grateful. The biological interpretation of the experiment will change significantly depending on which way this goes! Thanks Gavin __________________________________________________ Dr Gavin E Jarvis MA PhD VetMB MRCVS University Lecturer Department of Physiology, Development & Neuroscience Physiological Laboratory Downing Street Cambridge CB2 3EG Tel: +44 (0) 1223 333745 Email: <mailto:[email protected]> [email protected]