M. Looby
Pfizer Central Research, Sandwich, UK
Drug development is a sequential process with the aims of establishing efficacy and characterising the dose-regimen vs response relationship.
Early Phase I is generally concerned with safety and toleration aspect of this relationship and provides information for selection of dose regimen in phase II. However, despite the great effort to ensure that Phase 1 data is of the highest quality, it is usually subject to only the most rudimentary non-compartmental analysis and little attempt to made to assess the variability in the observed dose response relationship.
Data (PK and PR interval) from the first two studies (single and multiple dose escalation) on an (anonymous) early development candidate will presented. The standard method for dose decision making, which was implemented, is contrasted with a retrospective implementation of an r- integrated PK/PD approach. The latter involved modelling the PK/PD relationship and using simulation to “extract” the quantile dose response relationship from the model. This “extracted” information is a relevant study summary and provides quantitative hurdles that can be challenged in subsequent studies.
Moreover, since data is being pooled and analysed by a specific model, this approach can be applied across development programmes allowing the fate of response surface to be monitored as more data is accumulated and covariate relationships are characterised.
Reference: PAGE 8 (1999) Abstr 650 [www.page-meeting.org/?abstract=650]
Poster: oral presentation