RE: BOV

From: Michael.J.Fossler@gsk.com Subject: RE: [NMusers] BOV Date: Wed, September 22, 2004 2:53 pm Hi Yaning; My comments: Occasion could be either location or time period. I don't buy it. Time is Time and location is location - with the right design you should be able to estimate the contribution of both to your variance. Also, there are clinically meaningful ways in which site could affect your results, e.g., they could be excessively sloppy/skilled at sampling and recording times, they could mis-treat the samples resulting in some degradation of drug, etc. The point is, the two effects are distinct. The hospital/region example is used to simply the problem and explain a concept. In fact, anything in sequence is confounded with time. Sure, that's why you randomize to sequence. I still contend in your example that you are unable to measure the true effect of occasion because it is perfectly confounded with site (i.e., you can substitute either variable in the analysis and get the same answer). Let's use time period as the occasion (e.g. in a crossover experiment). Suppose the whole experiment is conducted in one hospital and there are 4 periods. Analogous to my previous example, in the simple scenario(same BOV in all occasions), BOV is just the within-subject variance across periods. I agree with this, with the caveat that the design allows you to model occasion distinctly from some other effect. If you stick with your example, where site 1,2,3,4 is perfectly correlated with occasion 1,2,3,4 , then I disagree with your interpretation. With your example, I still maintain that you can't assign that bit of variance as either contribution due to occasion or by site, since they are perfectly correlated . In the complex scenario (different BOV in all occasions), the interpretation will be different. Basically we assume different variance at each period, say, BOV1<BOV2<BOV3<BOV4. What is the between-occasion here? It is not between period 1, period 2, period 3 and period 4. It is between period1(in this current experiment) and period1' (if we can repeat the whole crossover experiment) for BOV1. This second level of between-occasion in this case is nothing but the true measurement error (replicates within a subject for the same period). Here period 1 in the current experiment is analogous to the hospital in New York. Period 1 in the current experiment and period1' in a repeated experiment are two hospitals in New York. In your design I didn't see any replicates within a subject for the same occasion. It also seem to me that you are adding additional occasions and sites here (or am I just a dumb pill-counter? :^)). Anyway, I eagerly await another one of Ken's lucid explainations of this topic... Mike ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Michael J. Fossler, Pharm. D., Ph. D., F.C.P. Principal Clinical Pharmacokineticist Clinical Pharmacokinetics, Modeling & Simulation GlaxoSmithKline (610) 270 - 4797 FAX: (610) 270-5598 Cell: (443) 350-1194 Michael_J_Fossler@gsk.com ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~