RE: Sample size requirement for POP PK analysis to identify drug inte ractions

From: "Stephen Duffull" sduffull@pharmacy.uq.edu.au Subject: RE: [NMusers] Sample size requirement for POP PK analysis to identify drug inte ractions Date: Sat, 25 Feb 2006 07:57:18 +1000 Hi Qi Accurate identification of covariates is not a trivial task in any setting. Determining sample size should be considered on a case by case setting. For general consideration you could have a look at Ribbing and Jonsson JPKPD 2004;31:109-134. Essentially the size of the covariate effect, the distribution of the covariate across the study population, the complexity of the structural model (both PK and covariate) etc will influence findings. One option, as you suggest, is to perform simulations to assess the design for estimation of covariate effects. However, this process can be a little slow and requires the user to select designs. You could try assessing the design in an information theoretic approach (e.g. by assessing the population information matrix) and choosing a design that maximises your ability to identify your covariate effect (should one exist). In the latter setting there are various software that can be used to do this, e.g. POPED (which allows you to have a prior on your parameters), PFIM/PFIM_OPT (splus version) or POPT (Matlab version). Good luck. Steve ==================================================================== Stephen Duffull School of Pharmacy, University of Queensland, Brisbane 4072, Australia Tel +61 7 3365 8808, Fax +61 7 3365 1688, Email: sduffull@pharmacy.uq.edu.au www http://www.uq.edu.au/pharmacy/index.html?page=31309 Design: http://www.uq.edu.au/pharmacy/sduffull/POPT.htm MCMC: http://www.uq.edu.au/pharmacy/sduffull/MCMC_eg.htm University Provider Number: 00025B ===================================================================== _______________________________________________________