Adaptive Trial Design -- MBC Biostatistics and Data Management Committee

You are invited to join the MBC Biostatistics and Data Management Committee for presentations on Adaptive Trial Design

When : Friday, April 13, 2007

From : 12:00-2:00 PM Lunch will be served

Where : MBC Office, One Cambridge Center, 9th Floor, Cambridge, MA

Adaptive Trial Design

Drug development is starting to move from classic trial designs to adaptive trial designs as a way of reducing cost and improving the probability of success. This is an opportunity to hear three experts talk about adaptive trial design. Mark Chang, from Millennium Pharmaceutical Inc., will introduce the general principles of adaptive design and provide an overview of historical development, current state, and the challenges in implementing adaptive designs. Cyrus Mehta, President of Cytel Inc., will share his experiences of implementing adaptive designs with four case studies. Simon Gao, President of Biopier Inc., will discuss requirements and different techniques for monitoring, analysis, and reporting using the clinical reporting system, Clinical Workbench.

Adaptive Design
Yesterday, Today and Tomorrow

Speaker;

Mark Chang, Millennium Pharmaceuticals, Inc.

Overview :
Compared to a classic trial design with static features, an adaptive design allows for changing or modifying the characteristics of a trial based on cumulative information. These modifications are often called adaptations. The word "adaptation" is so familiar to us because we make adaptations constantly in our daily lives according what we learn over time. Some of the adaptations are necessary for survival, while others are made to improve our quality of life. We should be equally smart in conducting clinical trials by making adaptations based on what we learn as a trial progresses. These adaptations are made because they can improve the efficiency of the trial design, provide earlier remedies, and reduce the time and cost of drug development. An adaptive design is also ethically important. It allows for stopping a trial earlier if the risk to subjects outweighs the benefit, or when there is early evidence of efficacy for a safe drug. An adaptive design may allow for randomizing more patients to the superior treatment arms and reducing exposure to inefficacious, but potentially toxic, doses. An adaptive design can also be used to identify better target populations through early biomarker responses.

This talk will introduce the general principles of adaptive designs and provide an overview of historical development, current state, and future opportunities.

---

Flexible Adaptive Trial Design: Four Case Studies

Speaker;
Cyrus R. Mehta, Ph.D. ,President, Cytel Inc.
Overview;
An adaptive trial is one in which interim data from the trial itself is used to modify and improve the study design, without undermining its validity or integrity. Trial sponsors and regulators have expressed a great deal of interest in designing such trials because of their potential benefit for Phase II and Phase III programs. In the Phase II setting an adaptive trial can assign a larger proportion of the enrolled subjects to the treatment arms that are performing well, drop arms that are performing poorly, and investigate a wider range of doses so as to better identify the nature of the dose-response relationship and select doses that are most likely to succeed at Phase III. When the trial proceeds to Phase III an adaptive design can facilitate early identification of efficacious treatments, determine if the trial could be terminated for futility, and make sample size adjustments at interim looks so as to ensure that the trial is adequately powered. In some cases it might even be possible to enrich the patient population by altering the eligibility criteria at an interim look. Thus, adaptive trials have the potential to translate into more ethical treatment of patients within trials, more efficient drug development, and better focusing of available resources. On the other hand, such trials require tremendous up-front planning and simulation to verify their operating characteristics, precisely because they are so flexible. In this seminar we give an overview of adaptive clinical trials, pointing out their advantages as well as their limitations. Many different types of adaptive trials will be discussed including seamless phase II/III trials, Phase III group sequential trials and Phase III trials with sample size re-estimation. The presentation will be conceptual rather than technical and will be illustrated by several examples of actual trials, some of them drawn from our own consulting experience. Logistical and regulatory issues will be discussed.

---

Clinical Workbench™ as IT Infrastructure for Adaptive Designs

Speaker;
Simon Gao, President, BioPIER

Overview;
Issues in trial monitoring and analysis are critical and have to be considered at the planning stage of an adaptive design. In this talk, we will discuss requirements and different techniques for monitoring, analysis, and reporting using a clinical reporting system Clinical Workbench™. We will show you through examples how the system offers the clinical trials team an easy collaborative way to monitor, analyze and report both classic and adaptive trials data. The system supports universal data formats, enables all-aspects of dynamical drill-down and what-if scenarios. Numbers on every summary are traceable to its detailed data listings and corresponding patient profiles. A live demo will be given during the session.