Nick Holford
New Zealand
The population PKPD approach offers a consistent conceptual framework for understanding the actions of drugs in humans in the context of evolving disease. The development of drugs with delayed onset of action due to slowly changing biochemical and structural factors presents a new challenge to the design of clinical trials which may last for several years and involve new biomarkers for drug action with poorly understand properties as clinical surrogates. Population models for the kinetics of disease progress may be more critical than pharmacokinetics in the ability to understand and optimise long term clinical trials. Optimisation of clinical trial design can be based on the power to reject a null hypothesis, on the precision and bias of a critical effectiveness parameter or on the cost-informativeness required to achieve an adequate product label. The ability to distinguish among 3 potential models for drug action on disease progress has been studied using a combination of the Pharsight Computer Assisted Trial Design system, NONMEM and a set of custom designed script driven tools using tcsh and awk. The number and spacing of repeated measures of disease status and the duration of the trial were more influential than the number of subjects in optimising the trade off between statistical power and cost of a trial.
Reference: PAGE 7 () Abstr 280 [www.page-meeting.org/?abstract=280]
Poster: oral presentation