Re: population size and confidence power

From: "Leonid Gibiansky" leonidg@metrumrg.com Subject: Re: [NMusers] population size and confidence power Date: Mon, April 4, 2005 3:27 pm Lin, SAS will not help you. You will need either a good consultant who knows the drug and can estimate the size based on his/her knowledge and intuition and/or a simulation study. The population size will depend on: Study design (dosing and sample times) Complexity of the PK behavior (one-exponential vs two-exponential vs. three exponential decay, linear or nonlinear, etc.) Precision of the PK measurements (intra-patient PK variability) Variability of the PK parameters (inter-patient PK variability) Precision of the PD measurements (intra-patient PD variability) Variability of the PK/PD parameters (inter-patient PK/PD variability) When you know these parameters (or guess based on either earlier studies or similar drugs), you simulate the study, fit the model and look on the results (parameter bias, precision, confidence interval of the parameter estimates). You may need to do it more than once to investigate how results depend on your assumptions. Simulations may include extra layer or uncertainty (about population parameters: rather than select values for simulations you may assume their distributions). As a rough estimate, 6 is definitely too small, 1000 should be sufficient. I would say 200-300 should be sufficient unless you have a high variability of PK and/or PK/PD parameters or strong non-linearity. Leonid