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適応型デザインは、コストを削減しながら、治験を加速させる可能性を持っています。適応型デザインとは、証拠の蓄積に応じて治験の進行中に用量、適格基準、サンプルサイズ、または治療法を調整できることをいいます。適応型治験の最終目標は、最も効率的な方法で患者に最新の技術をもたらすことです。5回目の開催となる年次会議Adaptive Clinical Trialsでは、開発プログラムの中での適応型デザイン、適応型デザインにおけるベイズ分析、用量範囲研究、バイオマーカーによる治験、適応型デザインに関連する法規制上の課題など、様々なトピックを扱います。

RECOMMENDED SHORT COURSE*

(SC4) Adaptive Clinical Trials: Strategies and Tools

 

*Separate registration required

WEDNESDAY, SEPTEMBER 7

7:00 am Registration and Morning Coffee

 

THE USE OF ADAPTIVE DESIGN IN PRACTICE

8:30 Chairperson's Remarks

Jose Pinheiro, Ph.D., Senior Director, Biostatistics, Johnson & Johnson Pharmaceutical Research and Development, LLC

Keynote Presentation 8:40 The Use of Adaptive Design in Practice: A Strategy for the Successful Implementation of Adaptive Designs in Drug Development Jerald S. Schindler, Dr.P.H., Vice President, Late Development Statistics, Biostatistics and Research Decision Sciences, Merck Research Laboratories As pharmaceutical companies complete the initial phase of implementing adaptive clinical trials in practice, new strategies are emerging for the implementation of these trials in future drug development. Companies have already gained experience in all phases of drug development from early MTD trials, through dose response escalation and dose selection, and then to confirmatory trials. This presentation will review the opportunities for adaptive designs in each phase of drug research and will also present an optimized strategy for adaptive drug development in the future. This strategy will be illustrated with examples from our experience using adaptive designs at Merck.

9:10 FDA Draft Guidance on Adaptive Designs: Overview, Key Messages, and Impact

Jose Pinheiro, Ph.D., Senior Director, Biostatistics, Johnson & Johnson Pharmaceutical Research and Development, LLC

The draft guidance on Adaptive Designs (AD) clarifies the FDA position on a wide range of topics related to the planning, execution and analysis of AD, being expected to have a major impact on the future utilization of these methods in clinical drug development. Pharmaceutical companies and the industry trade association, PhRMA, were actively engaged in reviewing the guidance to provide timely feedback to FDA. This presentation will provide an overview of the guidance, focusing on key regulatory concerns and recommendations on the use of AD in clinical trials, and discussing its potential impact on clinical development, as well as reactions from the pharma industry to its release.

10:10 Networking Coffee Break in the Exhibit Hall with Poster Viewing

10:50 The Continual Reassessment Method as a Prototype Adaptive Trial Design: Lessons and Implications

Steven Piantadosi, M.D., Ph.D., Phase One Foundation Chair and Director, Samuel Oschin Comprehensive Cancer Institute

This talk will discuss some of the history and underpinnings of the modified continual reassessment method (CRM) for dose-finding in oncology from the viewpoint of adaptive clinical trial design. The CRM is typical in some ways as a Bayesian design and atypical in others, making it a useful example to understand strengths and weaknesses of adaptive designs. The use of this design for dose-finding in oncology will be discussed as a starting point for reflecting on adaptive designs broadly. Most of the discussion will focus on the CRM itself and dose-finding versus dose-ranging, but some implications for later developmental designs will be highlighted. Practical implementation of the CRM will be illustrated using software developed by the author.

11:20 Sponsored Presentation (Opportunity Available)

11:50 Adaptive Clinical Trials in Neurology

Michael Krams, Ph.D., Vice President, Neurology Franchise, Johnson & Johnson

12:20 pm Using Adaptive Designs and Bayesian Statistics to Enhance the Efficiency of Drug Development

Yili L. Pritchett, Ph.D., Research Fellow, Director, Clinical Statistics, Global Statistics and Data Management, Abbott Laboratories

The challenging environment for finding and developing new drugs has called for innovations. Abbott Global Pharmaceutical Research and Development (GPRD) has embraced the notion of using adaptive designs in clinical programs to enhance efficiency, especially at the stages of poof-of-concept and dose-fining. Statistics organization has played a key role in educating the concept and methods, and in promoting the usage of adaptive designs in the past 4 years. In this talk, we will first share the efforts of promoting adaptive designs as well as the usage of Bayesian statistics within Abbott GPRD. We will then present a couple different types of adaptive designs that were successfully implemented and achieved tangible results. Finally, the process that we created to enable the implementation of adaptive designs will also be shared.

12:50 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

 

ADAPTIVE DESIGN FOR VARIOuS PHASES
OF CLINICAL TRIALS

1:50 Chairperson's Remarks

David Manner, Ph.D., Group Leader, Endocrine Exploratory and Program Medical Statistics, Eli Lilly

Keynote Presentation 1:55 Effective Design of Phase II and Phase III Trials: An Over-Arching Approach Christopher Jennison, Professor of Statistics, University of Bath, UK We consider the joint design of Phase II and Phase III trials following a decision theoretic approach with a gain function arising from a positive Phase III outcome and costs for sampling and time to a positive conclusion. With a prior for the dose response model and a risk curve for the probability that doses fail on safety grounds, the challenge is to optimize study designs for comparing doses in Phase II, choosing the dose or doses to progress to Phase III, and the Phase III design itself. We show it is feasible to tackle this problem and discuss generalizations from an initial, simple formulation.

2:25 Design and Trial Operational Considerations for a Phase II Two-Stage Adaptive Trial

Weili He, Ph.D., Associate Director, Clinical Biostatistics, Merck Sharp & Dohme Corp.

We design a two-stage adaptive design for the purposes of proof-of-concept and obtaining preliminary dose response information for a new chemical entity. Patients will be randomized to receive a high dose of test drug, placebo, and an active control during Stage I. During Stage II, a lower dose of test drug will be added in addition to the treatment arms in Stage I. Since the trial serves multiple purposes, we consider several design issues.

2:55 A Bayesian Adaptive Design Case Study in a Phase III Cancer Trial

Jason Connor, Ph.D., Statistical Scientist, Berry Consultants

This example of a Bayesian adaptive design for a phase III oncology trial incorporates longitudinal modeling of patient outcomes and predictive probabilities. The primary outcome is overall survival and the final analysis is a standard log-rank test. Meanwhile a Bayesian machinery is used ‘behind the curtain' to select the optimal sample size based upon accruing information at predefined sample size selection analyses. At each interim analysis, the adaptive design considers differences in progression-free survival and uses this to predict future overall survival differences based upon an internal and constantly updated longitudinal model. The sample size algorithm is based on two predictive probabilities.

3:25 Networking Refreshment Break in the Exhibit Hall with Poster Viewing

4:00 Case Study: Dose-Finding Studies in Diabetes Drug Development

David Manner, Ph.D., Group Leader, Endocrine Exploratory and Program Medical Statistics, Eli Lilly

In drug development, researchers have many decisions to make regarding the clinical plan to adequately assess the efficacy and safety of a new compound for patients and to optimize commercial outcome. Specifically, in Phase 2 and Phase 3 clinical trials, design parameters and decision criteria should be chosen with the overall clinical plan in mind. For example, in Phase 2 studies, a researcher should consider the impact on phase 3 of design parameters such as of the number of doses, number of patients, duration of study, and whether an adaptive or fixed design is used. A simulation study will be presented to examine the impact of these decisions for an experimental compound in diabetes drug development.

4:30 Panel Discussion: What it Takes to Run a Successful Adaptive Trial

5:00 Interactive Breakout Discussion Groups

Topic: How many doses do you need in a dose ranging study?
Moderator: Vlad Dragalin, Senior Vice President, Innovation Center, Aptiv Solutions

Topic: Adaptive trials in oncology
Moderator: Steven Piantadosi, M.D., Ph.D., Phase One Foundation Chair and Director, Samuel Oschin Comprehensive Cancer Institute

Topic: Clinical IVR/IWR systems in Adaptive Clinical Trials
Moderator: Gayle Flynn, Head of Global Ramos & Supply Chain Analytic, GlaxoSmithKline

6:00-7:00 Welcome Reception in the Exhibit Hall with Poster Viewing

 

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