In this episode of "In the Interim," Dr. Scott Berry discusses the vital topic of ordinal outcomes in clinical trials—a subject as controversial as politics and religion at the dinner table. Using historical examples like James Lind's 1747 scurvy trial and Austin Bradford Hill’s pioneering randomized trial, the episode explores the complexities and ongoing debates about analyzing ordinal endpoints. Berry challenges conventional analysis methods and advocates for more refined, explicit approaches, delivering valuable insights for statisticians, clinicians, and anyone involved in clinical trial designs.

Key Highlights

• Examination of the historical context of ordinal outcomes, starting with James Lind's 1747 scurvy trial.
• Discussion of the first randomized human clinical trial by Austin Bradford Hill and its implications for ordinal endpoint analysis.
• Exploration of the Modified Rankin Score as a current example of ordinal outcomes in stroke trials.
• Critique of conventional methods like dichotomization and proportional odds models for analyzing ordinal data.
• Argument for adopting utility-based approaches in clinical trial analysis for meaningful outcomes.

Quotes

• "Almost every endpoint is ordinal. So you can't escape this." – Dr. Scott Berry
• "My claim is nobody has that weight. But yet, it's very commonly done." – Dr. Scott Berry
• "Hiding behind ad hoc ways to do this, I think just leads us to bad places." – Dr. Scott Berry

In this episode of the podcast, we sit down with Dr. Merit Cudkowicz and Dr. Melanie Quintana to discuss the inception and execution of the Healy ALS Platform Trial, a revolutionary approach designed for efficiency and impactful data collection. With insights from both medical and statistical perspectives, this episode offers a comprehensive understanding of the trial's structure and outcomes, shedding light on its potential to reshape neuro-therapeutics research.

Key Highlights

• Dr. Merit Cudkowicz discusses the motivation behind adopting master platform trials for ALS and the collaboration that brought it to life.
• Dr. Melanie Quintana explains the statistical design of the trial, emphasizing the sharing of control groups and Bayesian methods for efficiency.
• Insights into the FDA's enthusiastic support and the iterative process to align on innovative statistical approaches.
• The dual roles of the trial: significant patient engagement and industry collaboration as facilitating factors for successful trial implementation.
• Discussion on the future adaptation of trial designs based on collected data and emerging biomarkers.

Quotes

• "There was such an energy about your group... everybody had really done their homework." – Dr. Melanie Quintana
• "ALS is a very complex disorder, and we actually did learn a lot." – Dr. Merit Cudkowicz
• "We're adapting with learnings." – Dr. Merit Cudkowicz

In this episode of "In the Interim," Berry's Director of Software, Tom Parke, takes us into the fascinating realm of clinical trial simulation. With Tom joining from the UK, we discuss the intricacies and updates surrounding FACTS, a sophisticated clinical trial simulation software. Learn about its significance in designing adaptive trial designs and its latest enhancements with the release of FACTS 7.1. Discover the balance between expanding features and maintaining user simplicity, ensuring that both Berry Consultants and external users can innovate effectively.

Key Highlights:
• Introduction of FACTS 7.1, emphasizing enhancements in code quality and simulation capabilities.
• Discussion on the history and evolution of clinical trial simulators at Berry Consultants.
• Exploration of FACTS' new features, such as Bayesian predictive probabilities and phase one dose escalation improvements.
• Insight into the challenges of creating user-friendly software with extensive features for trial simulation.
• Plans for future developments, including wizards and enhanced design comparison tools.

Quotes:
• "FACTS turns trial design and statistics into a game—where you can explore and try different options." – Tom Parke
• "You're creating software that allows exploring designs you can't calculate an answer to." – Tom Parke
• "It's all about making sure the designers have the right tools to efficiently explore different trial designs." – Scott Berry

In this episode of "In the Interim," we consider the nuances of adaptive design clinical trials with distinguished guests Dr. Scott Berry and Dr. Kert Viele from Berry Consultants. The conversation centers around the vital question: when should these adaptive designs be implemented? Listeners will gain invaluable insights into the mechanics of adaptive trials, the Bayesian approach, and scenarios where these designs prove most effective. Whether you're involved in clinical research or simply intrigued by the evolution of clinical trials, this episode enriches your understanding with expert perspectives and practical examples.

Key Highlights:

• Dr. Scott Berry and Dr. Kert Viele discuss the core principles and benefits of adaptive design clinical trials.
• A distinction is drawn between adaptive and fixed trials, showcasing the flexibility and efficiency of adaptive methods.
• The speakers explore common adaptations, including sample size modifications and response adaptive randomization.
• Strategies to handle anticipated regret and buyer's remorse in trial design are thoroughly examined.
• The episode provides practical advice on identifying suitable scenarios for adaptive trials, emphasizing the importance of timely information.

Quotes:

• "The promise of an adaptive trial is creating prospective changes based on the accumulating data." – Dr. Scott Berry
• "If I knew enough to perfectly design my trial, I wouldn't need to run my trial because I already know what the answers are." – Dr. Kert Viele
• "Anticipated regret is one of the great answers to when you should adapt." – Dr. Scott Berry
• "You always get a net gain from looking at the data." – Kert Viele

In the inaugural episode of Berry's "In the Interim...," we sit down with the founders of Berry Consultants, Dr. Don Berry and Dr. Scott Berry. Celebrating their 25th anniversary as a company, they explore the pioneering journey of their firm, known for transforming the landscape of clinical trials with their adaptive and Bayesian methodologies. With stories from their early days to innovative projects on the horizon, this episode provides a fascinating look into how Berry Consultants is redefining clinical research and impacting global health.

Key Highlights

• The founding story of Berry Consultants and the inspiration behind their unique approach to clinical trials.
• Challenges faced in pioneering adaptive trials and overcoming regulatory hurdles.
• Key collaborations and the influence of FDA approvals in their adaptive trial designs.
• The revolutionary impact of platform trials developed by Berry Consultants during the COVID pandemic.
• Future innovations and aspirations for the next 25 years in clinical trial design.

Quotes

• "We really were providing the service that they didn’t know they needed." – Dr. Don Berry
• "Our methodology allows the client to be the biggest advocate for the direction they're going." – Dr. Scott Berry
• "We want to change the world, one person at a time." – Dr. Don Berry