RE: ADAPT II with SAMPLE option

From: "Stephen Duffull" sduffull@pharmacy.uq.edu.au Subject: RE: [NMusers] ADAPT II with SAMPLE option Date: Wed, 19 Apr 2006 08:02:40 +1000 Hi Nele I have no experience at using ADAPT/ADAPT II. But I can confirm that your model with 8 sampling times does not produce a singular matrix. Indeed I tried this example in POPT (for Population OPTimal design http://www.uq.edu.au/pharmacy/sduffull/POPT.htm) and your original 8 sampling times was sufficient to provide good estimates for all your fixed and random effects parameters (I perturbed the zero time to 0.01; and assumed a lognormal variance for all of your BSV terms of 0.1). And this optimizes fine as well. I used 1200 as the dose. However you mention a [constant] rate of 1200 - which doesn't exist in your first order input model: >> (CL=6.6, Vc=36.6, KA=1.91, CLd=18.5, Vp=33.1, all to be estimated) Since you have an additive error component then if the dose is actually lower than 1200 units (e.g. 12 or 1.2 units) then the information matrix will quickly become poorly conditioned (although not singular for MATLAB). I hope this is of general interest. Regards 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