RE : Weight based dosing

Hi Stefanie, in your article did you take into account that covariates may have clinical correlation? Best regards Nicolas Pr Nicolas SIMON MD PhD Clinical Department Medical School of Marseille France ________________________________________ De : [email protected] [[email protected]] de la part de Stefanie Hennig [[email protected]] Date d'envoi : mercredi 9 décembre 2015 02:59 À : Sultan,Abdullah S; [email protected] Objet : [NMusers] RE: Weight based dosing Dear Abdullah, I assume that you have only looked at the decrease in the variance around CL comparing the base model and the covariate model, when you state : “only explained 9% of the variability”. We have shown that total parameter variability is changing throughout model building and a decrease in unexplained parameter variability is not equal to an increase in explained parameter variability when adding covariates in your model. So the explained parameter variability might have increased by more than 9%. Please see the reference below. This methodology is now also implemented in PsN and you can perform it alongside your covariate model building. You might want to try this. The manuscript below also discusses the difference between improved model fit and clinical significance of a covariate. (Hennig S, Karlsson MO. Concordance between criteria for covariate model building. J. Pharmacokinet. Pharmacodyn. 2014;41:109-125.) Further, I would like to highlight to you that others have previously discussed on NMusers and in the literature that for an easier comparison of study results it is preferred to use a standard weight of 70kg. Also, if you did use an allometric scaling model on CL/F, you would have used an power exponent of ¾ or estimated this exponent, but not a slope. So I am unsure about the slope effect that you are talking about and cannot comment further on this. Best wishes and a Happy holiday season Stefanie _____________________________________________________________ Dr Stefanie Hennig Lecturer | Pharmacometrics School of Pharmacy| Pharmacy Australia Centre of Excellence (PACE) |The University of Queensland, QLD 4072, Australia Phone: +61 7 334 61970, Fax: +61 7 334 61999, Email: [email protected]<mailto:[email protected]> Please note my working days are Monday to Thursday. "You can't fix by analysis what you bungled by design." Light, Singer and Willett The World Conference of Pharmacometrics in Brisbane 2016 http://www.wcop2016.com/ [cid:[email protected]]