Date: 30 April 2015 14:00 - 15:30 BST

Registration is FREE!

 

Attendees must register on the PSI website (www.psiweb.org) in order to obtain the dial-in details and the webinar link.

 

Chair: Alun Bedding (Roche)

Discussant: Ethymios Manolis (EMA)

 

From dose-response to dose-exposure-response - Bjoern Bornkamp (Novartis)

In the past decade a lot of attention in pharmaceutical statistics focused on the advantages and disadvantages of going from an ANCOVA analysis, where dose is treated as a categorical variable, to fitting dose-response regression models for the analysis of Phase II dose-response studies.

 

Exposure-response modelling, in its simplest incarnation, just replaces "dose" by an exposure metric for the dose-response regression models. In this presentation I will discuss the advantages of taken into account exposure, pitfalls to avoid and points to take into account when going from a dose-response regression analysis to a cross-sectional dose-exposure-response analysis.

 

“Getting the dose right” - Mike Smith (Pfizer)

Phase 2b dose-ranging trials are a critical part of drug development, since characterization of dose-response for efficacy and/or safety is necessary to enable identification of a narrow range of optimal dose(s) for confirmatory Phase 3 pivotal trials. According to ICH-E4, the goal of dose-response clinical trials is to identify the smallest dose with a discernible useful effect, termed the minimum effective dose. More broadly, the goal of dose-response trials is to identify the smallest dose that meets the target product profile, in terms of both efficacy and safety. Traditionally, dose-ranging trials are designed for pair-wise comparison of each dose group to placebo, and dose-response modeling of the data planned as posthoc exploratory analyses. This approach does not optimize the trial design to meet its goal. Therefore, it is more appropriate to design dose-ranging clinical trials for analysis using model-based methods that integrate dose-response information across all treatment groups. This approach allows optimization of the trial design (number of dose groups, unbalanced sample size) for achieving its goal, and also assesses its sensitivity to the underlying (typically unknown) dose-response relationship.

 

This presentation will provide a roadmap for implementation of model-based design and analysis methods in Phase 2b dose-ranging trials, and its advantages over traditional analysis methods at this stage of drug development. Strategies for integrating model-based analyses within a formal statistical analysis plan, and addressing frequently asked questions from drug development team members will be provided as tools for informing and influencing study teams.