Number of subject and population PK/PD modeling

From: "Gordi, Toufigh" Toufigh.Gordi@cvt.com Subject: [NMusers] Number of subject and population PK/PD modeling Date: Thu, January 13, 2005 8:29 pm Dear all, I am involved in planning a concentration-response study in dogs, with a maximum of 6 dogs included. Each dog will receive a minimum of 2 different (single) doses. I am pushing for a proper PK/PD evaluation of the compound, including a population approach. I believe everybody would agree that 6 is a small number. However, this is quite normal to have few larger animals in pre-clinical studies. One of the problems I face is the word "population" approach, which to many people means that one must have a large number of subjects in order to be able to apply the methodology. I don't think that's the case but have problems putting it in simple words why such approach can be taken even with a small "population" of 6 animals. Are there any publications that discuss this issue? In general, are there any situations where a "normal" PK modeling approach (e.g. using ADAPT or WinNonlin) is superior to a mixed-effect modeling approach? I am not concerned with population models being more complicated or take longer time. I am more interested to know whether the former produces better and more reliable estimates than the latter. Best regards, Toufigh Gordi