In this episode of "In the Interim..." we revisit the ground-breaking seamless phase 2/3 clinical trial for the GLP-1 agonist, dulaglutide—better known as Trulicity. We discuss the intricacies of the adaptive trial design, and the unique features that helped expedite development by 12-18 months. Listeners will gain insight into how Bayesian algorithms and innovative statistical methods were pivotal in navigating a complex trial design, benefiting Eli Lilly's pipeline and changing the landscape of diabetes treatment.

Key Highlights:

• Outline of the trial design and the barriers faced during its inception in 2007-2008.
• Explanation of the Clinical Utility Index and its role in adaptive randomization.
• The DSMB's role and interaction with Bayesian decision-making models.
• Simulation-based design to optimize development efficiencies.
• Insights into the predictive power of the trial on weight loss outcomes in subsequent trials.

Quotes:

• "The trial was run entirely by Bayesian algorithms." – Scott Berry
• "They believed this utility function was absolutely the right way to go forward." – Scott Berry

In this episode of "In the Interim...," we sit down with Dr. Meredith Buxton to explore the evolution of platform trials from I-SPY 2 to GBM AGILE and Beyond. With a rich history in innovative trial design, Meredith shares the journey from pioneering adaptive clinical trials in breast cancer with I-SPY 2 to her current role at the Global Coalition for Adaptive Research (GCAR). This conversation offers insights into accelerating clinical trial timelines, innovative operational frameworks, and their applications across multiple medical domains, making it a must-listen for anyone involved in clinical development and platform trials.

Key Highlights:

• Meredith Buxton discusses the origins and groundbreaking operations of the I-SPY platform in breast cancer.
• Exploration of how the I-SPY 2 model inspired subsequent platform trials in diverse areas such as glioblastoma and COVID-19.
• GCAR's role as a non-profit entity to foster adaptive trial designs and Meredith’s influential contributions to its formation and success.
• Discover the operational complexities and regulatory considerations essential for modern platform trials.
• Insights into Meredith’s vision for the future of drug development and the ongoing necessity for innovation in trial design.

Quotes:

• “The ideas of this are groundbreaking in many ways.” – Scott Berry
• "The I-SPY2 model could be replicated in other spaces." – Meredith Buxton

In this episode of "In the Interim...," Scott Berry and Kert Viele navigate the nuanced debate surrounding the integration of external data in clinical trials. Discover the implications and potential benefits and pitfalls of leveraging historical and real-world evidence in the analysis of clinical trials.

Key Highlights:

• Exploration of how external data can influence clinical trial analyses and the inherent risks versus rewards.
• Examination of the frequentist versus Bayesian perspectives on data integration.
• Discussion of real-world cases where external data has been used.
• Debate on the conservative nature of current scientific approaches and how they may hinder progress.
• Insight into the future of clinical trials harnessing external data – a step towards better medical science.

Quotes:

• "If prior data isn't generally leading us in the right direction, we ought to reconsider the basis of scientific inquiry." – Kert Viele
• "The industry's hesitance to use existing data slows innovation and limits our ability to bring effective treatments to market." – Scott Berry