Document Detail

Role of modelling and simulation in Phase I drug development.
MedLine Citation:
PMID:  11297895     Owner:  NLM     Status:  MEDLINE    
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, although of longer history, does not presently have the same impact on drug development. However, trends such as 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 the role of M&S, its main advantages and the obstacles to its rational use, an expert meeting was organised by COST B15 in Brussels, January 10-11, 2000. This article presents the views expressed at that meeting. Although it is clear that M&S occurs in only a minority of Phase I clinical trials, it is used for a large number of different purposes. In particular, M&S is considered valuable in the following situations: 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 profile from single dose, bridging studies and formulation development. One or more of the following characteristics of 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 fulfill an important role in reshaping the early trials by more effective extraction of information from studies, better integration of knowledge across studies and more precise predictions of trial outcome, thereby allowing more informed decision making.
L Aarons; M O Karlsson; F Mentré; F Rombout; J L Steimer; A van Peer;
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences     Volume:  13     ISSN:  0928-0987     ISO Abbreviation:  Eur J Pharm Sci     Publication Date:  2001 May 
Date Detail:
Created Date:  2001-04-12     Completed Date:  2001-07-05     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9317982     Medline TA:  Eur J Pharm Sci     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  115-22     Citation Subset:  IM    
School of Pharmacy, University of Manchester, Manchester, UK.
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MeSH Terms
Clinical Trials, Phase I as Topic* / methods
Computer Simulation*
Drug Design
Models, Biological*
Outcome and Process Assessment (Health Care)
Research Design

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