A Quantitative Process for Enhancing End of Phase 2 Decisions.

The objectives of the phase 2 stage in a drug development program are to evaluate the safety and tolerability of different doses, select a promising dose range, and look for early signs of activity. At the end of phase 2, a decision to initiate phase 3 studies is made that involves the commitment of considerable resources. This multifactorial decision, generally made by balancing the current condition of a development organization's portfolio, the future cost of development, the competitive landscape, and the expected safety and efficacy benefits of a new therapy, needs to be a good one. In this article, we present a practical quantitative process that has been implemented for drugs entering phase 2 at Amgen Ltd. to ensure a consistent and explicit evidence-based approach is used to contribute to decisions for new drug candidates. Broadly following this process will also help statisticians increase their strategic influence in drug development programs. The process is illustrated using an example from the pancreatic cancer indication. Embedded within the process is a predominantly Bayesian approach to predicting the probability of efficacy success in a future (frequentist) phase 3 program.