Re: Correlations for power analysis

From: "Jogarao Gobburu 301-594-5354 FAX 301-480-3212" <GOBBURUJ@cder.fda.gov> Subject: Re: Correlations for power analysis Date: Fri, 08 Dec 2000 11:11:00 -0500 (EST) Dear Paul, I am sure you have a reason for being interested ONLY in AUC. The AUC as such will not give you any information unless you have a PK - PD relationship. It is a good idea (after Dr. Sheiner's suggestion at the FDA's CardioRenal Advisory committee meeting held on 20 Oct 2000) to ask the following questions to the domain-experts (clinicians,regulators..): 1. What do you want to know? Domian-experts (DEs) probably want to know THE 2 sampling points that are 'qualified' to predict the AUC (gold standard). 2. What are you willing to assume? DEs probably are willing to assume that the drug's PK/PD can be described by a particular model, that you might have. And that the clinically relevant change is 'so much' (say 20% from baseline) (based on prior experience, time honored ranges, gut feelings, etc). You then translate that to your AUCs. 3. How certain do you want to be? DEs, further, want to know the limited sampling points that render the prediction with a power of 90% (equivalence of limited sampling and gold standard AUCs). So, you take these 'answers' and determine the power of the limited sampling approach to predict AUCs to be within 20% (could be asymmetric) of the gold standard 90% of the times. I would perform Monte Carlo simulations to design the trial. A statistician could derive an analytical solution to this problem, probably. Regards, Joga Gobburu Pharmacometrics, CDER, FDA.