Re: Sample size

From ETTEE@cder.fda.gov Wed Jun 18 14:29:43 1997 Subject: Re: Sample size It would be useful to use your mean PK parameters from Phase I study(ies) with the appropriate model to obtain informative times (using the SAMPLE module in ADAPT II)and create sampling blocks (windows) around the informative times. Patients should then be randomly allocated to these times. The idea here is to be able to describe the population profile. This informative profile (block) randomized design protects against model misspecification. The issue of obtaining 2 samples/subject depends on the number of parameters you want to estimate. If, for instance, you are dealing with a one compartment model with intravenous input(s) you will be able to obtain reliable (accurate and precise) estimates for both fixed and random effects parameters with the above sampling design. It would be best to carry out a simulation study to determine the appropriate sample size for your study. There are a few references which I think would be helpful: (1) Jones CD, Sun H, Ette EI. Designing cross-sectional pharmacokinetic studies: implications for pediatric and animal studies. Clin Res Regul Affairs 1996; 13 (3&4): 133-165. (2) Ette EI, Sun H, Ludden TM. Design of population pharmacokinetic studies. Proc Am Stat Assoc (Biopharmaceutics Section) 1994; pp 487 - 492. (3) Ette EI, Sun H. Sample size and population pharmacokinetic parameter estimation. Clin Pharmacol Ther 1995; 57 (2): 188. Ene.