Re: Centering (was Re: Missing covariates)

Date: Thu, 05 Jul 2001 16:15:34 +1200 From: Nick Holford <n.holford@auckland.ac.nz> Subject: Re: Centering (was Re: Missing covariates) Steve, Steve Duffull wrote: > However if the standardising value is quite different from the mean (or > some other descriptor of the central tendency of the distribution) then > is it possible that the beneficial computational effects of centring > will be lost? eg standardised creatinine clearance is 6 L/h but the > sample average is 4.2 L/h... How far away can the standardised value be > from the centre value to retain centring benefits? > > Any loss of beneficial effects of centring will of course bring all the > usual problems associated with collinearity. I took particular care to write 2 days ago: > No matter what centering value is used for the > estimation [of] the parameter estimates one should consider reporting them using a > standard value. The convenience comes from using a centering value that is the same > as the standard value. i.e. if you think it will improve the numerical aspects of your modelling to use a median weight of say 10 kg for a paediatric group as the centring value rather than a standard value of 70 kg then indeed you should feel free to do so. But when you report the values I suggested that you use the covariate model you have developed to report the values for a standard individual e.g. if you use a simple per kg model for volume of distribution: V=Vpop x WT/10 where 10 kg is the median WT and the estimate for Vpop is 2 L/10kg then you might report Vpop as 14 L/70 kg. Brian Anderson has worked extensively on the weight scaling issue for paediatric pharmacokinetics. He *centred* all his size models using 70 kg even though most if not all subjects in the neonate to adolescent age group had weights less than 70 kg. Parameter estimates were reported per 70 kg and this did not cause any problems for journal reviewers/editors. We did check a few times to see if centring on the median weight made any difference but did not find that it did. This is offered only as anecdotal evidence but does suggest that taking advantage of the convenience of centring on a standard value is not reliably harmful and that it is scientifically acceptable to report standard parameters derived from non-standard subjects. Anderson BJ, McKee D, Holford NHG. Size, myths and the clinical pharmacokinetics of analgesia in paediatric patients. Clinical Pharmacokinetics 1997; 33:313-327 Anderson BJ, Holford NHG, Armishaw JC, Aicken R. Predicting concentrations in children presenting with acetaminophen overdose. J Pediatrics 1999; 135:290-5 Anderson BJ, Woolard G, Holford NHG. A model for size and age changes in the pharmacokinetics of paracetamol in neonates, infants and children. Br J Clin Pharmacol. 2000; 50:125-134 -- Nick Holford, Divn Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x6730 fax:373-7556 http://www.phm.auckland.ac.nz/Staff/NHolford/nholford.htm