Adaptive Designs for Clinical Trials 
Event Information
Document Title
Agenda
| Pre-Conference Workshop Monday, April 21, 2008 | PRE-CONFERENCE WORKSHOP | DAY ONE | DAY TWO | | ||||
| Designing Adaptive Clinical Trials | ||||
| 7:30 | Registration Opens & Morning Coffee | |||
| 8:30 | Chairperson's Remarks Mark Chang, Ph.D., Scientific Fellow, Millennium Pharmaceuticals | |||
| 8:45 | Adaptive Design Optimization Adaptive clinical trial designs open a whole new territory for drug development. An adaptive design can improve the efficiency of the trial design, provide earlier remedies, and reduce the time and cost of drug development. However, because there are many adaptive design methods available, how to optimize your adaptive design becomes a critical issue. Included in this discussion will be the issues and methods for adaptive optimization:
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| 9:45 | Designing, Monitoring, and Modifying an Adaptive Trial The process of implementing an adaptive design in a clinical trial will be reviewed with the emphasis on three major steps: planning, simulating, and executing. The first step involves the review of the clinical plan, identification of the protocol design requirements, and the review of potential designs that can best address these requirements. The simulating step consists of comparing the different design options on simulated data for a set of scenarios, reviewing their operating characteristics, and fine-tuning design parameters. As a result, the most appropriate design is selected for implementation. The execution step comprises the finalization of the protocol, SAP, DMC charter, and then conduct of the interim analyses with the pre-planned adaptations. Vladimir Dragalin, Ph.D., Senior Director, Global Biostatistics, Wyeth Research | |||
| 10:15 | Networking Break | |||
| 10:45 | Barriers, Strategies, and Technologies Adaptive designs allow for planned changes to occur during a study on the basis of accumulating data. This now moves the level of decision to within the study rather than occurring solely after study completion. However, this change can represent a real challenge when working within current systems and procedures. The greater acceptance and utilization of adaptive designs is therefore very much about change management. Not only a change in statistical methodology, but also a change in logistical support, and importantly a change in attitude to how we do studies and the strategy to development. This presentation will identify some of the barriers to implementation and offer strategies and technologies for solutions. Judith Quinlan, Ph.D., Director Statistics, GlaxoSmithKline | |||
| 11:15 | Implementing the IT Infrastructure Adaptive designs represent the opportunity to gain dramatic efficiencies during the drug development process. To date, most adaptive trials have been done as a one of a kind trial. The next stage is to move into adaptive trials across the entire drug development portfolio. One major component of this shift is the use of Information Technology to ease the transition and reduce the effort required to run adaptive trials. This presentation will discuss how an IT infrastructure can be built to support adaptive trials. The presentation will also cover key guidelines for the implementation of this new IT infrastructure and outline a strategy for staged implementation. Jerald Schindler, Dr. P.H., Vice President, Biostatistics and Research Decision Sciences, Late Stage Clinical Development Statistics, Merck Research Laboratories | |||
| 12:00 | Lunch on your own | |||
| Main Conference - Day One Monday, April 21, 2008 | PRE-CONFERENCE WORKSHOP | DAY ONE | DAY TWO | | ||||
| 1:00 | Opening Remarks & Keynote Introduction Vladimir Dragalin, Ph.D., Senior Director, Global Biostatistics, Wyeth Research | |||
| Keynote Address | ||||
| 1:15 | Adaptive Trials: Unlocking the Opportunity and the Competitive Advantage Over the past few years we have heard about the benefits of adaptive trials. How do we maximize the opportunity? This session will provide a roadmap to the opportunity and will also provide a strategy for the implementation of adaptive trials. The successful implementation of adaptive trials will clearly give some companies a major competitive advantage over others. However, not all companies implementing adaptive trials will see the same benefit. This session will illustrate how some companies will emerge as clear leaders who have derived maximum benefit while others will lag behind. The presentation will also provide some general rules to follow which will help lead to dramatic successes in the implementation of adaptive trials. Jerald Schindler, Dr. P.H., Vice President, Biostatistics and Research Decision Sciences, Late Stage Clinical Development Statistics, Merck Research Laboratories | |||
| Advancements in Adaptive Designs | ||||
| Featured Presentation | ||||
| 2:00 | FDA Designed Trials to Provide Guidance on the Effective Use of Medicines Under the Critical Path initiative at FDA, there has been a focus on developing better markers and evaluative tools for measuring safety and toxicity of new medicines. However, regulators must also develop the flexibility and scientific approaches to incorporate these tools into the development process, and into the FDA’s product approval benchmarks. Dr. Gottlieb will focus on how the FDA can design trials that generate and incorporate new and improved scientific information that will help us guide the more effective use of medicines. Scott Gottlieb, M.D., Resident Fellow, American Enterprise Institute - Former Deputy Commissioner, Medical & Scientific Affairs, FDA | |||
| Technology Workshop | ||||
| 2:30 |  Design and Implementation of Late-Stage Adaptive TrialsSound statistical principles combined with careful planning of the logistical details are essential for successful implementation of an adaptive clinical trial. In this presentation we will share our experience as consultants involved in several late stage adaptive designs. Topics will include preservation of type-1 error, power, parameter estimation, multiple testing, population enrichment, the crucial role of simulation and the creation of an adaptive interim analysis charter to protect the study from biases. Actual cases will be used to illustrate all these topics Cyrus R. Mehta, Ph.D., President and Co-Founder, Cytel Inc. | |||
| 3:00 | Impact of Dose-Selection Strategies on the Probability of Success in Phase III A number of adaptive dose-ranging designs have recently been described and evaluated by PhRMA's Adaptive Dose-Ranging Studies Working Group. This presentation will further evaluate dose selection strategies by assessing their impact on the probability of success in Phase III. Safety and efficacy will be addressed simultaneously. Phase III designs with one or two doses of the test drug will be considered. Zoran Antonijevic, MS, Senior Director, Strategic Development/Biostatistics, Quintiles | |||
| 3:30 | Networking Break & Opening of Exhibit/Poster Viewing | |||
| 4:00 | Recent Advances in Adaptive Methodologies This talk provides an overview of some recent advances in statistical methodology for adaptive designs. We consider the calculation of overall confidence intervals and p-values for adaptive designs as well as the application of adaptive designs in dose-finding studies. In the latter case, the focus is on application in studies with a survival endpoint. It is shown that there exist straightforward solutions when using the combination testing principle for combining the stages of the trial. Gernot Wassmer, Ph.D., Associate Professor for Biostatistics, University of Cologne, Germany | |||
| Technology Workshop | ||||
| 4:30 | Scaling Up: Moving Adaptive Clinical Trials to the Mainstream Many companies have tried Adaptive Clinical Trials, in one guise or another. As interest and enthusiasm builds new questions arise: How do we get the company to take this seriously? What does the company need to do to take it seriously? Running one was fun, but a lot of work! How are we going to cope with 10 or 20 in one year? This talk will look at scaling up the use of Adaptive Clinical Trials across three areas:
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| 5:00 | Networking, Exhibit/Poster Viewing & Cocktail Reception Sponsored by  | |||
| 6:00 | End of Day One | |||
| Main Conference - Day Two Tuesday, April 22, 2008 | PRE-CONFERENCE WORKSHOP | DAY ONE | DAY TWO | | ||||
| 7:30 | Registration & Morning Coffee | |||
| 8:15 | Chairperson's Remarks Judith Quinlan, Ph.D., Director Statistics, GlaxoSmithKline | |||
| Keynote Address | ||||
| 8:30 | Experience with Adaptive Dose-ranging Studies in "Learn" Choosing the correct dose to take into confirmatory trials is a key challenge in drug development. Objective of this talk is to share our experience so far in implementing adaptive dose-ranging studies and to evaluate whether they did indeed allow earlier and better decision making. Michael Krams, M.D., Assistant Vice President, Clinical Development, Adaptive Trials, Wyeth Research | |||
| Adaptive Designs Case Studies | ||||
| 9:30 |
The PhRMA Adaptive Design Working Group has actively been collecting x-industry experiences with adaptive designs. This presentation will summarize their findings and learning experiences, with particular emphasis on identifying the phases where adaptive designs are being mostly used. Also, which disease areas, types of adaptive design strategies, and the types of adaptations most commonly used. Judith Quinlan, Ph.D., Director Statistics, GlaxoSmithKline | |||
| 10:10 | Networking Break & Exhibit/Poster Viewing | |||
| 10:45 |
An NCI review of a Phase II trial caused the reconsideration of how the agent would be administered, efficacy would be assessed, and dosing would be determined, resulting in personalized therapy and Bayesian regression to continually update dosing. The effect of the developmental context on the design and use of simulations to identify design assumptions will be emphasized. Daniel Normelle, Ph.D, Associate Professor, Department of Radiation Oncology, University of Michigan | |||
| Technology Workshop | ||||
| 11:15 |  Adaptive Trials - Automating the Entire Adaptive Process from Endpoint Data Collection to Randomization and Supply Forecasting
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| 11:45 | Networking Lunch & Exhibit/Poster Viewing | |||
| 1:30 |
Lately there have been many presentations given concerning the application of adaptive design principles to specific drug development situations. However, few have discussed team reactions during the planning of a complete development program. This presentation will focus on actual team reactions arising in the early phases of a clinical program. Many such reactions can be predicted simply from past experience but looking at actual cases may suggest various strategies that could be used to mitigate the difficulties that can arise in adopting adaptive methodology. Patrick Kelly, Ph.D., Technical and Scientific Development Leader, AstraZeneca | |||
| 2:00 |
The presenter will focus on the experience proposing and implementing the first large adaptive trial at GlaxoSmithKline. The discussion will address the clinical questions leading to the choice of an adaptive design and the statistical methods. Focus will be on the actual implementation and the impact of real-world issues resulting from the trial. An assessment of what went well, what did not, and what has been done differently since will be discussed. Nancy Burnham, Manager, Statistics, GlaxoSmithKline | |||
| Implementation and Logistics of Adaptive Trials | ||||
| 2:30 | Chairperson's Remarks Greg Enas, Ph.D., Director, US Regulatory Affairs, Eli Lilly | |||
| 2:45 | Scaling Adaptive Design Programs As an organization matures in its implementation of adaptive designs, focus shifts from executing individual designs to building capabilities to enable ongoing, efficient delivery of multiple designs. This requires a program management approach to coordinate implementation of the enabling infrastructure (e.g., processes, tools, education), change management efforts, and required management processes. Daniel Burns, Ph.D., Director, Adaptive Trials, Clinical Development, Wyeth Research | |||
| 3:15 | Adaptive Designs - a Panacea ? Adaptive designs can be flexible or inflexible. The latter are usually preferred for registration trials on the grounds of credibility. Reviewed are the advantages and disadvantages of adaptive design for sample size re-estimation and for seamless Phase II/III transition as well as discussing the general experiences as a DSMB member of three trials; one completed, one in progress and one proposed. Bruce Turnbull, Ph.D., Professor of Statistics, Cornell University | |||
| 3:45 | Networking Break & Last Chance to View Exhibits and Posters | |||
| 4:15 | Adaptive Designs in Dose-Ranging Studies Insufficient exploration of the dose response relationship often leads to a poor choice of the optimal dose used in the confirmatory trial that, consequently, might lead to the failure of the trial and even to the whole clinical program. Even though the regulatory agencies prefer sponsors to limit the use of adaptive designs in confirmatory trials, they are supportive and encourage the deployment of appropriately planned adaptive designs in dose-ranging studies. Recently, several adaptive designs for dose selection have been proposed that are based on both efficacy and safety. How adaptive model-based designs can be implemented by studying simulations similar to three case studies with different desirable efficacy and toxicity responses from several therapeutic areas will be discussed. Olga V. Marchenko, Director, Biostatistics Consulting, Oncology, i3 Statprobe | |||
| 4:45 | How and When to Involve Regulators Regulators are currently in "wait and see" mode when considering the use of adaptive clinical trials to establish the evidence required for marketing authorization of any new synthetic or biologic drug product. It is imperative that sponsors engage regulatory agencies to ensure that adaptive trials are developed that engenders agency confidence. We highlight regulatory practices that should enable agreements to be obtained. An overview of the EMEA guidance document will be discussed. Greg Enas. Ph.D., Director, US Regulatory Affairs, Eli Lilly | |||
| 5:15 | Close of Conference | |||
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