TITLE: Adaptive Designs in Clinical Trials
SPEAKER: Vlad Dragalin, J&J
Moderator: Ivan S. F. Chan
Abstract:
Adaptive clinical trials offer powerful opportunities to improve decision-making, efficiency, and ethical conduct in drug development by using accumulating data to modify a study in a pre-specified and scientifically justified manner. When well designed and carefully implemented, adaptive approaches can support earlier stopping for futility or success, sample size re-estimation, treatment or dose selection, population enrichment, multi-arm multi-stage strategies, and seamless Phase 2/3 development, while preserving the validity and interpretability of trial results.
This half-day course will provide a practical overview of adaptive clinical trial design, moving from foundational concepts to implementation considerations that are essential for regulatory-ready studies. The session will review key classes of adaptive designs, including group sequential designs, adaptations based on combination tests or the conditional error principle, sample size reassessment, adaptive treatment selection, enrichment designs, and designs involving multiple treatments, endpoints, or patient subgroups. Particular attention will be given to the role of simulation in evaluating operating characteristics, including type I error control, power, estimation reliability, and the consequences of design choices under realistic clinical development scenarios.
The presentation will also discuss the evolving regulatory framework for adaptive designs, with emphasis on the principles reflected in ICH E20: adequacy of the design within the broader development program, the importance of prospective planning, control of erroneous conclusions, reliability of estimation for benefit-risk decisions, and maintenance of trial integrity through appropriate blinding, information flow, and independent oversight. Both frequentist and Bayesian perspectives will be considered, including how Bayesian decision rules may be calibrated to frequentist error-rate requirements and how hybrid approaches can be used to combine flexibility with regulatory confidence.
By the end of the course, participants will have a structured understanding of when adaptive designs may add value, what statistical and operational risks must be addressed, and how to design adaptive trials that are efficient, reliable, and suitable for regulatory evaluation. The presentation is intended for statisticians, clinical development scientists, regulatory colleagues, and decision-makers interested in translating adaptive design methodology into sound clinical development practice.
Instructors’ Biography:
Vlad Dragalin is a Vice President, Scientific Fellow in Quantitative Sciences at Janssen Pharmaceutical Companies of Johnson & Johnson. Vlad is the Head of QS Consulting and is chairing the QSTEPS (QS Technical Excellence and Program Strategy) Advisory Committee. He joined Janssen in 2014 as the Head of the Adaptive Clinical Trial Center of Excellence. Vlad is a well-known adaptive design expert with 35 years of experience in developing the statistical methodology of adaptive designs and with more than 20 years of experience in pharmaceutical industry, including positions of increasing responsibilities at GlaxoSmithKline, Wyeth, Pfizer, Quintiles, and Aptiv Solutions. Vlad is a PhRMA representative on ICH E9(R1) Expert Working Group and on ICH E20 Expert Working Group. He is a member of PhRMA Clinical Development Workgroup. Vlad is a Fellow of the American Statistical Association and an Associate Editor of the Journal of Biopharmaceutical Statistics and Statistics in Biopharmaceutical Research.