Join us for a full-day workshop in Cambridge, focused on ethical and methodological issues surrounding adaptive clinical trial designs. This event will bring together leading statisticians, ethicists, industry representatives, policymakers (including the WHO), regulators (including the FDA), and patient advocacy groups to discuss the evolving landscape of adaptive clinical trial designs and their ethical implications.
Speakers and Supports:
• Frank Bretz (Novartis)
• Laura Flight (NICE)
• Rieke van der Graaf (University of Utrecht)
• Thomas Jaki (MRC Biostatistics Unit)
• Jonathan Kimmelman (McGill University)
• Alex John London (Carnegie Mellon University)
• Richard Milne (University of Cambridge)
• Philip Pallmann (University of Cardiff)
• Mark Sheehan (Oxford Population Health)
• Jerome Singh (University of KwaZulu-Natal)
• Sue-Jane Wang (Food and Drug Administration)
• Sofia S. Villar (MRC Biostatistics Unit)
• Haiyan Zheng (University of Bath)
There will also be speakers from the US, UK and EU regulatory authorities.
Why is this workshop important at this time?
Clinical trials play a crucial role in advancing medical knowledge and managing uncertainty by systematically comparing the effects of various interventions. In a confirmatory setting, they provide a structured approach that enables reliable conclusions about the relative safety and efficacy of treatments. However, these trials are complex, require significant time and resources and raise ethical concerns, particularly due to practices such as randomizing participants to different interventions and implementing additional procedures like blood draws or biopsies. If the evidence produced is flawed, it can have serious consequences, potentially leading to the discontinuation of effective therapies or the adoption of interventions that are ineffective or even harmful. Therefore, while the urgency to gain insights and accelerate learning is important, it must be carefully balanced with the need for reliability, generalizability, and the ethical treatment of participants.
Recently, innovative statistical methods have been proposed to allow clinical trials to adapt in various ways. Some forms of adaptation are already widely accepted and commonly used, such as stopping a trial early when treatments are statistically effective or ineffective. However, other forms of adaptation are more controversial. This includes complex computational methods for dynamically adjusting the probability that individuals are randomized to different interventions, aiming to maximize the proportion of participants receiving the most effective treatment, if one exists.
The controversy surrounding these methods raises both ethical and methodological questions. There is ongoing debate about whether, when and which of such methods are more efficient, meaning they can answer research questions with fewer participants without compromising reliability or generalizability. This debate is fueled by competing simulation studies that present conflicting assessments of these designs, as well as concerns that certain approaches, particularly Bayesian designs, may introduce unacceptable bias. Adaptive trials played a crucial role in addressing the COVID-19 pandemic, leading to increased public interest in this methodology and highlighting the need to resolve outstanding uncertainties about their statistical and ethical implications.
Programme
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09:00 – 09:10 |
Welcome and thanks to co-sponsors |
Sofía S. Villar, MRC Biostatistics Unit |
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09:10 – 10:40 |
Statistical methods for adaptive designs (Chair: Sofía S. Villar, MRC Biostatistics Unit) "From routinely used to more complex adaptive designs"
"Adaptive designs in action: basic concepts, efficiencies, and challenges"
“Using Bayesian designs to combine available evidence for better decision making” |
Thomas Jaki, MRC Biostatistics Unit
Philip Pallmann, University of Cardiff
Haiyan Zheng, University of Bath
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10:40 – 11:10 |
Refreshments |
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11:10 – 12:40 |
Ethics aspects for adaptive designs (Chair: Mark Sheehan, Oxford Population Health, University of Oxford) “Ethical Adaptation: From Initiation, Adding or Dropping Arms, and More”
“Adaptive Clinical Trial designs: ethics and governance considerations”
“Ethical assumptions underlying the use of adaptive designs” |
Alex John London, Carnegie Mellon University
Jerome Singh, University of KwaZulu-Natal
Rieke van der Graaf, University of Utrecht
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12:40 – 13:40 |
Lunch |
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13:40 – 15:10 |
Industry and Civil Society Perspectives (Chair: David Robertson, MRC Biostatistics Unit) “Adaptive Designs – The Swiss Army Knife of Modern Clinical Trials?”
“The impact of adaptive designs on health economics and health technology assessments”
“The WHO Report on Adaptive Platform Trials”
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Frank Bretz, Novartis
Laura Flight, National Institute for Health and Clinical Excellence (NICE)
Jonathan Kimmelman, McGill University and Katherine Littler, World Health Organization (WHO) |
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15:10 – 15:30 |
Refreshments |
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15:30 – 17:00 |
Regulatory perspectives (Chair: Alex John London, Carnegie Mellon University) “Update on UK Regulatory Reform and Future Development”
“Regulatory decision making under uncertainty – the role of simple and complex models”
“Adaptive Designs: Key Principles and Some Recommendations from a Regulatory Perspective”
Patient-focus: “Possibilities for patient and public and engagement and involvement in adaptive trials” |
Andrea Manfrin, Medicines & Healthcare Products Regulatory Agency
Andrew Thomson, European Medicines Agency
Gregory Levin, US Food and Drug Administration
Richard Milne, University of Cambridge |
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17:00 – 17:10 |
Closing Remarks |
Alex John London, Carnegie Mellon University |
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17:10 – 18:30 |
Drinks Reception |
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Special thanks to the International Centre for Mathematical Sciences for kindly supporting this event.