RE: Non-physiological parameters at lowest OBJ

From: Ken Kowalski <Ken.Kowalski@pfizer.com> Subject: RE: [NMusers] Non-physiological parameters at lowest OBJ Date: 8/5/2003 10:36 AM Justin, What do you mean by physiologically impossible? If they are truly outside the feasibility domain of the parameter space (e.g., negative rate constants) then it is certainly prudent to constrain your search. However, if the estimates you obtained are theoretically feasible but physiologically unreasonable then we should be careful with placing constraints. Assuming the latter, I'd be inclined to investigate what is the root cause for the convergence to two different optimums. For example, you might inspect the histograms of your ETAs for any bi-modality. Perhaps the sensitivity to starting values is related to one particular parameter and if its distribution is bi-modal then depending on where the starting value is relative to its modes it may converge to different estimates. I wouldn't be inclined to accept either the constrained or unconstrained model fit without first pursuing the diagnostic plots and other suggestions that Bill has suggested. You may find a new avenue of model building (e.g., a mixture model) that may lead to a more stable and reasonable model fit with a lower OBJ then what you have with your current constrained and unconstrained model fits. Ken