Drug Creation Process

Learn and Confirm, a New Paradigm for Clinical Development at Wyeth

Wyeth recognizes that a new pharmaceutical environment has arrived, one characterized by stronger pricing pressure for prescription drugs, greater involvement of state and federal governments, stronger regulatory and compliance requirements, and greater consumer choice. In response, Wyeth has launched a transforming initiative to develop the best clinical development model for the 21st century. We believe this will position Wyeth for success in this new environment.

This initiative is known as the Wyeth Clinical Development Model of the Future. The Wyeth team was challenged to radically rethink our business in anticipation of the rapidly changing marketplace and identify industry-leading ideas rather than incremental improvements.

An exploration phase focused on idea generation that would fundamentally enrich and maximize the efficiency of clinical development. In this exploratory phase, the team conducted more than 60 internal interviews with Wyeth executives and managers; 12 cross-industry case interviews; meetings with senior FDA personnel; plus a thorough search of current literature. This resulted in Wyeth adopting novel operational excellence initiatives that will facilitate the new clinical development paradigm.

The overarching theme of the team's actions is that Wyeth cannot adequately respond to the needs of the new and evolving environment using a traditional phased approach to clinical development and instead must adopt a "Learn and Confirm" paradigm as our Clinical Development Model of the Future. The concept of Learn and Confirm emerged from our discussions with the Food and Drug Administration (FDA) and from a paper published in 1997 by L.B. Sheiner. In this paper, Sheiner identified two distinct activities in clinical development, Learning and Confirming. The goal of Learning is to focus on how to use a drug in representative patients to make an acceptable benefit/risk profile likely, while the goal of Confirming is to demonstrate, in a large and representative patient population, that an acceptable benefit/risk profile is achieved.

In summary, Wyeth's Learn Phase will replace phase 1 and phase 2 in the traditional approach. In Learn, we will strive to optimize our understanding of a new drug candidate to maximize its medical value and determine if it justifies continued investment. Specifically, we will identify the optimally tolerated dose range and get a clear understanding of the drug's safety and efficacy profile relative to the critical value drivers for the disease state.

The Confirm Phase will replace the traditional phase 3 and is the high-stakes execution phase in which Wyeth will focus on operational and cost-effective confirmation of the drug's safety, efficacy, and value for successful registration and market launch. During Confirm, we will first establish safety and efficacy in a large and representative patient population, with an acceptable benefit/risk profile; and second, focus on conducting the optimal number of trials to obtain safety and efficacy data in the shortest time feasible. Confirm will embrace recent operational excellence initiatives, such as superior global patient recruiting, remote data capture, working 24/7 and process improvement capability. These initiatives will ensure cost efficiencies and expedite the drug development process at Wyeth.

A transition zone between the Learn and Confirm Phases will ensure that each candidate medicine has achieved a comprehensive set of scientific, regulatory, and commercial objectives to ensure readiness for Confirm investment. Discussions were organized with the FDA and European Agency for the Evaluation of Medicinal Products (EMEA) to seek guidance on Wyeth's ideas for improving the effectiveness and efficiency of clinical trials. The FDA and the EMEA are supportive of the initiative and emphasize the importance of the Learning Phase to improve trial design within the Confirm Phase. The FDA suggested that an industry-wide effort to use such systems and share data could help in designing the best possible clinical trials. Both these regulatory bodies are also very receptive of the adaptive approach to clinical trials and the infrastructure Wyeth is putting in place to enable the resultant data capture and analysis, and acknowledged Wyeth's approach and proposals are consistent with ongoing critical path initiative and considerations for efficient clinical trials.

Adopting the Learn and Confirm paradigm is aiding Wyeth in improving the quality and innovativeness of drug development by optimizing transition times, driving us toward continuous assessment of our candidate medicines, and improving the efficiency of our clinical trial designs. We believe launching this innovative clinical development initiative will position Wyeth for continued success going forward.

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