RE: Plcebo Corrected PK/PD

From: "Nick Holford" n.holford@auckland.ac.nz Subject: RE: [NMusers] Plcebo Corrected PK/PD Date: Fri, March 4, 2005 11:10 am Joga Gobburu wrote: I am not sure why you conclude that the variability in drug effect cannot be estimated from a parallel group design. I would include disease progression as part (perhaps the major part) of the response seen in the placebo treatment group. By making assumptions about the time course of the disease/placebo response and how it interacts with the drug effect then one can estimate the population parameters and between subject variability for all components (disease, placebo, drug). Making assumptions is a necessary part of this kind of modelling. The models can be quite helpful for interpretation of clinical trials and have been used successfully for clinical trial simulation and prospective design of trials. Nick Holford NHG, Peace KE. Results and validation of a population pharmacodynamic model for cognitive effects in Alzheimer patients treated with tacrine. Proceedings of the National Academy of Sciences of the United States of America 1992;89(23):11471-11475 Lockwood P. Application of clinical trial simulation in Alzheimers disease. In: Danhof M, Karlsson MO, Powell RJ, editors. 4th International Symposium on Measurement and Kinetics of In Vivo Drug Effects; 2002 April 26; Noordwijkerhout, The Netherlands; 2002. -- 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/