Hi Abdullah: This depends on how you set your criteria for including covariates into the model (the p-value, reduction in OFV, se of the estimated covariate parameter etc). Before starting running covariate models, it is always a good practice to plot BSV (i.e. ETAs) against the available covariates your have (in your case: ETAs versus weight) then if you see biologically plausible covariate relationships then you start testing them. I usually use forward addition (p-value 0.05, delta reduction 3.84 or p-value 0.01, delta OFV 6.63 units) and backward elimination (p-value 0.001, delta increase OFV 10.8 units) and se should be < 51.2%. You don't need to stick with these criteria but you can develop your own. If including a covariate passes all the criteria and is estimated precisely, then I think it should stay in the model. Reduction in BSV > 5% may be significant.
There are various methods for including covariates in the literature, you may need to choose yours! Sincerely, Ahmad Abuhelwa University of South Australia Adelaide, South Australia Australia From: [email protected] [mailto:[email protected]] On Behalf Of Sultan,Abdullah S Sent: Wednesday, 9 December 2015 11:10 AM To: [email protected] Subject: [NMusers] Weight based dosing Hi everyone, I am developing a POP PK model for an anti-infective drug, I am trying to determine if dosing should be weight based or not. The range of weight in the study was 40-100 kg. Weight was statistically significant for Cl/F but only explained 9% of the variability observed for Cl. I used allometric scaling to describe weights effect on Cl/F and slope effect of weight was 0.58, and scaled to 60 kg (the median). Based on the slope effect estimated, AUC is predicted to decrease by 15% for an 80 kg individual, and increase by 25% for an individual that weights 40 kg compared to a 60 kg individual. How much should I trust the slope effect determined by my study? and should I rely on it to develop the dosing regimen? if weight only explained 9% of variability observed with Cl/F, could that indicate that it is not clinically significant and weight based dosing is not required? Thanks, Abdullah Sultan, PhD candidate University of Florida
