RE: Simulations: Can subject specific initial values be used?

From: Bachman, William (MYD) bachmanw@iconus.com Subject: RE: [NMusers] Simulations: Can subject specific initial values be used? Date: Tue, March 30, 2004 9:37 am Pavel, On your first question, your problems stem from the use of inappropriate models for interindividual error (which in turn generates negative parameter values). The choice of interindividual error models should be a function of the known or expected distribution of the parameter being modeled. Most PK parameters are log-normally distributed, hence an exponential error model would be appropriate, particularly for CL and V. This has the added benefit of avoiding the negative parameters you get in your simulations. Not all parameters are log-normally distributed. e.g., you may find lags are better modeled with an additive error model. When an exponential error model is not appropriate, reparameterize the model to avoid negative parameters if possible. On your second point, you probably won't need this if you implement the above suggeestions. Also, this is not a good way to approach this problem in my opinion. It seems like a "kludge" solution that could be avoided by reparameterizing your model appropriately. Bill _______________________________________________________