RE: sample size

From: "Steve Duffull" Subject: RE: [NMusers] sample size Date: Mon, November 15, 2004 6:36 am Hi Mats and Pascal Firstly, Mats I agree that analysing the data is always the sensible option (never throwing data away). Secondly, I am not in absolute agreement with Pascal --- it is possible that the population characteristics of some drugs may be able to be determined with as little as 4 patients/animals. For argument, if in the example cited, the system were adequately described by a 1-cpt first order input-output model with exponential BSV on all parameters and mixed residual error function and you had 10 samples per animal for each of the 4 animals and the sampling times extended for at least 3 half-lifes then it is possible to estimate CL, V, Ka and BSV(CL, V, Ka). The standard errors of the BSV parameters are not going to be great but not terrible (approx 70-80%). Estimating the proportional component of the residual variance will be for all intents and purposes not possible. Thirdly, analysing the data using NONMEM and then assessing the design helps to learn about deterministic identifiability issues - i.e. are all parameters (fixed effects and variance effects estimable). I believe that in some cases it is important to be informed from both what is theoretically possible to learn from the design as well as to learn from the actual data gathered from the performing design itself (they may be different things). Steve Stephen Duffull School of Pharmacy University of Queensland Brisbane 4072 Australia Tel +61 7 3365 8808 Fax +61 7 3365 1688 University Provider Number: 00025B Email: sduffull@pharmacy.uq.edu.au www: http://www.uq.edu.au/pharmacy/sduffull/duffull.htm PFIM: http://www.uq.edu.au/pharmacy/sduffull/pfim.htm MCMC PK example: http://www.uq.edu.au/pharmacy/sduffull/MCMC_eg.htm ______________________________________________________