Re: GAM analysis and further action

From: Nick Holford n.holford@auckland.ac.nz Subject: Re: [NMusers] GAM analysis and further action Date: Thu, 30 Mar 2006 09:15:46 +1200 Denis, We all understand that clinicians are too busy to pay attention to the details of science and need simple tables and rules of thumb so they can get on with more important things like diagnosing von Heffalumps Syndrome. I think modellers have an obligation to get the science correct first. Then this can be simplified for the clinicians. In the paediatric area the clinicians have learned empirically to use bigger mg/kg doses in small children compared with adults. But there is no physiological basis for this rule of thumb. Clinician 'scientists' have attempted to interpret the larger mg/kg doses in a variety of speculative ways but they provide no evidence for children being really any different from adults. An allometric perspective indicates that there is really no difference between children and adults when body size is appropriately adjusted (assuming all other covariates are equivalent in children and adults). Similar considerations apply to other covariates e.g. with a continuous covariate such as renal function the model should try to predict renal function in a continuous way. Later when a regulatory label is written or other attempts are made to communicate the science to the clinicians it can be simplified into ranges of creatinine clearance and associated dosing rates. Nick -- Nick Holford, Dept Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556 http://www.health.auckland.ac.nz/pharmacology/staff/nholford/