B1311
Title: Utility-based optimization of phase II/III programs considering success probabilities for phase III
Authors: Marietta Kirchner - Institute of Medical Biometry (Germany) [presenting]
Meinhard Kieser - Institute of Medical Biometry (Germany)
Stella Erdmann - Institute of Medical Biometry (Germany)
Heiko Goette - Merck Healthcare KGaA (Germany)
Abstract: In drug development, the decision to proceed with phase III is important as it requires significant investments. Due to high failure rates in late development stages, there is a need for a structured framework of quantitative decision-making. Program-wise planning of phase II and III trials is reasonable due to their strong connection: go/no-go decisions after phase II and phase III sample size are based on phase II results, e.g. the phase II treatment effect. As the true treatment effect is uncertain, a high intended statistical power for the phase III trial does not necessarily translate into a high success probability. Program-wise planning of phase II and III based on maximizing expected utility has been proposed to optimize two design aspects of phase II trials: sample size and choice of decision boundaries. Given specific development program characteristics (e.g. costs, gain after successful launch), optimal designs concerning decision rules and sample size allocation can be determined. The proposed utility function is presented with application to different scenarios. Recommendations are given concerning the choice of these two design aspects. In summary, the presented utility function can help optimize design aspects to reach high success probabilities.
