Use of Utility Functions That Combine Safety and Efficacy Endpoints for Early-Phase Trials for Oral Mucositis

• Activity Number: 615
• Type: Contributed
• Date/Time: Wednesday, August 12, 2015 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Kevin Lawson* and Tingting Song
• Companies: PPD and PPD
• Keywords: adaptive designs ; clinical trials ; oral mucositis ; utility functions ; posterior probabilities ; dose level selection

Abstract

In some clinical indications, especially oncology, adaptive designs have been used as the primary mechanism to choose the dose level to take to efficacy trials such as phase 2 or phase 3 trials. Adaptive designs have also been used to consider safety and efficacy together, considering the probability that a given safety threshold or event is reached along with the probability of achieving a desired efficacy outcome. Developing utility functions is one approach that shows great promise. For example, a utility function can be designed such that dose levels having a low probability of exceeding some minimal threshold can be distinguished from dose levels with higher probabilities of achieving that threshold. These adaptive designs allocate more patients to arms having these higher probabilities than lower probabilities and can include in the design the ability to drop arms with very low probabilities. This paper will discuss how to develop endpoints and utility functions for this type of design and show how it can be applied to new therapeutic areas. We will use the treatment of Oral Mucositis, a common side effect of chemotherapy, as an example.