Leon Aarons, Mats Karlsson, France Mentré, Ferdinand Rombout, Jean-Louis Steimer and Achiel van Peer.
The COST B15 Working Group on Modelling and Simulation in Clinical Drug Development.
Although the use of pharmacokinetic/pharmacodynamic modelling and simulation (M&S) in drug development has increased during the last decade, this has most notably occurred in patient studies using the population approach. The role of M&S in phase I is of longer history but does not presently have the same impact on drug development. However, trends like the increased use of biomarkers and clinical trial simulation as well as adoption of the learn/confirm concept can be expected to increase the importance of modelling in phase I. To help identify this role of M&S, its main advantages and the obstacles to a rational use of it, an expert meeting on this topic as reflected in the above title was organised by COST B15 in Brussels, January 10-11, 2000. This presentation represents the views expressed at that meeting.
It is clear that M&S occurs in only a minority of phase I clinical trials. Despite this, it is used for a large number of different purposes. In particular, M&S was considered valuable to handle: censoring because of assay limitation, characterisation of non-linearity, estimating exposure-response relationship, combined analyses, sparse sampling studies, special population studies, integrating PK/PD knowledge for decision making, simulation of phase II trials, predicting multiple dose profiles from single dose studies, bridging studies and formulation development.
Although valuable, one or more of the following characteristics of the M&S activities are often present and severely impede its successful integration into clinical drug development: lack of trained personnel, lack of protocol and/or analysis plan, absence of pre-specified objectives, no timelines or budget, low priority, inadequate reporting, no quality assurance of the modelling process and no evaluation of cost-benefit. The early clinical drug development phase is changing and if these implementation aspects can be appropriately addressed, M&S can fulfil an important role in reshaping the early trials by more effective extraction of data from studies, better integration of knowledge across studies and more precise predictions of trial outcome, thereby allowing more informed decision making
Reference: PAGE 9 (2000) Abstr 78 [www.page-meeting.org/?abstract=78]
Poster: oral presentation