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We represent a community with a shared interest in data analysis using the population approach.


2001
   Basel, Switzerland

The role of modelling and simulation in the clinical development of anti-cancer agents

L. Aarons, M. Karlsson, F. Mentré, A.V. Peer, F. Rombout, H. Schaefer, J.-L. Steimer, I. Trocóniz

COST B15 working group on modelling in clinical drug development

COST B15 held a meeting in Brussels on the 7-8th March 2001 to discuss the role of modelling and simulation in the clinical development of anti-cancer agents. As well as the working group, 14 experts including oncologists, pk-pd modellers and statisticians, attended the meeting. After introductory talks on clinical drug development, assessment of response/toxicity and dose individualisation, a number of case studies of M&S in oncology were presented. In addition clinical trial design and dose finding were extensively discussed. The role of M&S was assessed in relationship to several pertinent questions in clinical drug development. The questions included: determining the starting dose; dose escalation strategy in Phase I; design of confirmatory trials; describing exposure/toxicity relationships; the role of biomarkers; mechanism-based versus empirical pk-pd models; schedule dependency; and individualisation. In addition to current activities several gaps were identified, which included: the lack of relevant experimental and mathematical models of tumour growth; the lack of collaboration between clinical oncologists and pk-pd modellers; the lack of biomarkers for efficacy; the lack of standardised measures of clinical response; and the limitation in certain circumstances of statistical models for prospective use (eg dropouts). For the future M&S was seen to be fundamental for the implementation of novel experimental designs, including adapted continuous reassessment designs, selection of dose and dosing schedule, selection of patients and tumour types, study design and the incorporation of genotypic and phenotypic information into dose individualisation. A particular challenge that was identified was how to demonstrate the added value that M&S brings to the development of anti-cancer agents. It is planned to publish a summary of the meeting in a European oncology journal. The main issues will be presented at the PAGE meeting.



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