Dear Dennis - Some approaches for you to consider:
1. Brute Force Model: I hope there is some prior information about the CL for poor and extensive metabolizers. I am also assuming the difference between PM and EM is meaningful. In that case, simply assume that this subject is a PM and estimate a fixed effect for the same. The objective function and uncertainty around parameter estimates should support this model over no CYP2D6 model. 2. Kind-of-Bayesian Model: Assuming you have the prior information on CL, provide a prior for the prevalence and magnitude of difference in PMs with perhaps a low uncertainty. This approach formally recognizes prior information, but materially wouldn't be different from the BFM. Either case, in my opinion, you would want to do justice to the 11 subjects who you think are non-PMers with respect to point estimate and variance. The single "PM" subject is unlikely to add conclusive information especially when a key covariate (genotype) is missing. [cid:image001.png@01CD6061.1420F1D0] Joga Gobburu, PhD, FCP, MBA | Professor | School of Pharmacy | School of Medicine Executive Director |Center for Translational Medicine N407, 20 N Pine, Baltimore, MD-21201 Office: (410) 706-5907 | E-mail: jgobb...@rx.umaryland.edu<mailto:shai...@rx.umaryland.edu> To receive latest Pharmacometrics news subscribe at http://www.pharmacy.umaryland.edu/ctm/ To unsubscribe, send email to ctm-unsubscr...@lists.umaryland.edu<mailto:ctm-unsubscr...@lists.umaryland.edu> From: owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com] On Behalf Of Fisher Dennis Sent: Thursday, July 12, 2012 4:25 PM To: nmusers@globomaxnm.com Subject: [NMusers] Mixture model Colleagues I am analyzing data in which there are two distinct populations as a result of CYP2D6 deficiency. In one dataset, there are 18 subjects with rich data; one of these subjects is markedly different. In that the incidence of 2D6 deficiency is reported to be < 10%, one would expect only 1-2 deficient subjects in this sample (consistent with the data here). I was planning to use a mixture model as part of the analysis. However, with only one subject in the deficient population, I am not sure if that is appropriate. Does anyone have any relevant experience or insight into this issue? Dennis Dennis Fisher MD P < (The "P Less Than" Company) Phone: 1-866-PLessThan (1-866-753-7784) Fax: 1-866-PLessThan (1-866-753-7784) www.PLessThan.com<http://www.PLessThan.com>
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