NONMEM in drug development

From rs@chdr.leidenuniv.nl Mon Jul 8 22:09:09 1996 Subject: NONMEM in drug development Dear NONMEM users, As you have seen, I received number of replies regarding the challenge about the usefulness of NONMEM in drug development. I passed all information on to my consultant but additionally I would like to summarise the information perhaps for future use. Although much of the work is not published because of time-pressure in the drug development process, several publications have come up: -Holford NHG, Peace K. The effect of tacrine and lecithin in Alzheimer's disease. A population pharmacodynamic analysis of five clinical trials. Europ. J. Clin. Pharmacol. 1994;47:17-24. -Steimer JL, Vozeh S, Racine-Poon A, Holford N, O Neill R (1994) The population approach: rationale, methods, and applications in clinical pharmacology and drug development. In: Welling PE, Balant LP (eds) Handbook of Experimental Pharmacology, Vol. 110 Pharmacokinetics of Drugs. Springer-Verlag Berlin Heidelberg (with a table of 13 references) -Liu and Sambol, Pharmaceutical Research, Vol. 12, No. 3, 438-445, 1995. -Ziad Hussein. two manuscripts that are currently in print, one in British Journal of Clinical Pharmacology and another in Clinical Pharmacology and Therapeutics. To this I would like to add: At the PAGE96 conference (population analysis group europe) Janet Wade indicated that during the 6 months that she has been working for the swedish regulatory agency, she has received 6 protocols indicating that population analysis will be performed (as part of the NDA). some examples of the use of NONMEM in drug development are: -analyses which allow simulations of proposed dosage regimens before the drug is marketed. -meta-analysis. -to allow analysis of experimental design for phase I PK studies, with reduced sampling times because of ethical and/or economical reason. -where very little pharmacokinetics are available from formal Phase I pharmacokinetic studies and data from Phase II/III clinical trials are used for population pharmacokinetic analysis. I may have overcharged the issue by requiring use of NONMEM to be necessary/essential but I thought it might get the ears up! What the replies boil down to is that NONMEM may or may not be essential but it is certainly considered a very useful tool; a view which I second wholeheartedly. Thanks for all your cooperation! Rik Schoemaker