The Programme

The European regulator’s perspective on adaptive designs: Ensuring that your trial is accepted

• What are the NMA and EMEA looking for in adaptive trial submissions? Developing a more thorough understanding of the key factors involved
• How can you make sure your submissions are successful? Establishing the critical characteristics of a successful submission
• Examining European case studies to identify which have been successful and the characteristics which set them apart
• Analysing areas of regulatory concern in late phase trials and identifying possible solutions
• Forecasting the future for adaptive trials from a regulatory perspective

Adaptive clinical designs: understanding the evolving interface between developers and the FDA and other regulators

• Going for an adaptive clinical study design: a “strategic game” with a corporate and a regulatory player
• Regulators on a learning curve: is it a deterrent for developers and how can the situation be improved?
• Trading inherent uncertainty for added insight: a challenging approach for both sides but how can the risks be reduced?
• Trial simulations: developing joint roadmaps for handling clinical decision scenarios
• Analysing pre-scheduling collaborative reviews, discussion and reconsideration in adaptive designs
• Establishing U.S. developments: evolution of the FDA position since the May 2006 Medical Device draft
• Understanding European regulatory frameworks: evolution of the EMEA position since the March 2006 “Reflection Paper”
• Developments at the ICH: towards a globalized position on adaptive designs

Case Study:
Enabling an effective drug supply and distribution system: avoiding costly mistakes

• Ensuring that the supply department is sufficiently capable of dealing with the increased complexity of the supply requirements for an adaptive algorithm
• Just in time delivery: coordinating your approach and avoiding overage and the accompanying financial and logistical consequences
• If a dose arm is created or the sample size changed, how can outage be effectively avoided?
• Setting up your IVRS systems to cope with increased complexity: the basis for an effective supply chain
• Forecasting potential changes to dosage levels and the patient profile: factoring in complexity in order to more accurately control costs and reduce error

Dr Solange Rohou
Director European Regulatory Affairs
AstraZeneca

Case Study:
Dissecting successful and unsuccessful submissions to identify business critical factors that enable you to succeed first time

• Analysing some unsuccessful attempts: identifying why the trials were not approved and the lessons that were learned
• Achieving regulatory acceptance: identifying the characteristics of an acceptable design
• The research process: ascertaining whether or not the trial is well suited to an adaptive approach
• The design: how we went about fulfilling regulatory requirements
• Answering key questions from the agency: identifying areas of regulatory concern and redesigning the trial to take these into account
• Ensuring that interim analyses and final evaluation results in viable data that meets the regulator’s approval

Regulatory Panel Discussion:
An exclusive opportunity to discover first hand what the regulators are looking for and what the future might hold with a view to clarifying your own approach

• Analysing key requirements in early phase adaptive trials: a guide to reducing the regulatory risk of embarking on an adaptive design

• Evaluating areas of concern and pinpointing the key considerations in order maximise the likelihood of regulatory acceptance for seamless trials
• Highlighting the differences between regulatory bodies to ensure that global adaptive designs are compliant internationally
• Phase III: identifying safety concerns and data validity in late phase trials
• Case studies to illustrate when an adaptive Phase III design is likely to be acceptable

Dr Alan Eggleston
Global Head of Sales and Marketing
Cmed (Clinical Research Services) Ltd

Dr Martin Kimber
Clinical Trials Consultant
Tessella plc

Real-Time Data Collection in Adaptive Trials Today

• Examining real-time data capture in adaptive trials: overcoming the challenges and creating the most efficient possible strategy
• Real-time simulations, analysis and decision making: establishing new solutions
• The effective, immediate implementation of those solutions

Coordination and trial planning: maximising the benefits of an adaptive design through effective management

• Critical insight into the breakdown of people involved in an adaptive rather than a traditional trial: preparing for a more flexible operation
• Coordinating more people under increased time pressure: maximising your efficiency in order to take best advantage of the potential benefits
• Ensuring that your study managers are equipped to deal with adaptive trials: establishing the training implications
• Adapting communication strategy to ensure that with increased numbers of investigators involved, protocol amendments can be made quickly in order to save time and resources

Case Study:
Effectively managing patients during a complex adaptive trial

• Maximising the potential for increased efficiency in recruitment: minimising the necessary patient numbers and devising an effective system for maintaining the optimum number of patients as the needs of the trial change
• Creating and maintaining a fast and efficient communication strategy capable of ensuring that your investigators and patients are fully aware of what the trial requires of them
• Ensuring that data collected during interim analysis does not compromise the trial’s blindness in order to meet the requirements of the regulator
• Randomisation challenges: as dosage arms change how can randomisation be effectively achieved?
• The implications for patient information: ensuring that your patient is aware of the logistical implications of participation in an adaptive trial in order to reduce patient drop out and maintain the integrity of the data collected

Panel Discussion:
Developing clinical best practice in adaptive trials

• Co-ordinating the trial from a personnel perspective: avoiding the pitfalls in order to create the most efficient strategy
• Data management in an adaptive trial: maintaining the integrity of your trial by handling data effectively
• Focus on supply chain in order to reduce wastage and maximise efficiency
• From a clinical perspective, do the benefits of adaptive trials outweigh the costs?
• What does the future hold for adaptive trials? Creating a clearer picture of their potential

Designing an adaptive clinical trial: analysing the costs and benefits from a statistics point of view

• Uncovering the latest developments in statistics in adaptive trials and the lessons that have been learned as the number of completed trials increase
•  Key considerations when designing an adaptive trial: preparing you for a new approach
• Identifying the types of adaptive trial and how to determine which variant is most suitable
• Determining the most cost and time effective solution for your drug
• Spotlight on resources: planning for the time and people involved in designing an adaptive trial as opposed to a more traditional format
• Use of Bayesian techniques in adaptive trials
• Design of Phase III trials: examining subgroup selection and other adaptations

Establishing the roles of short term endpoints in clinical trials in order to plan more effectively

• Analysing the criteria for the use of a surrogate endpoint
• Short term endpoints in Phase II proof of concept studies
• Incorporating short term endpoints in Phase II adaptive dose finding
• Using a short term endpoint in a Phase III study with delayed response
• Short and long term endpoints in a seamless Phase II/III trial

• Determining the appropriate type of adaptation: correctly identifying which change should be made
• Choosing the statistical analysis method taking the adaptive nature of the trial into account
• Analysing which outcomes can be used to identify a necessary adaptation: early outcomes, primary endpoints and safety results
• What are the implications for the logistics of the trial?
• Clarifying how to implement early stopping possibilities of an adaptive trial in order to save money without compromising the trial’s integrity

Maximizing the usefulness of adaptive trials in early development

• Why early development is a good setting for adaptive clinical trials?
• Which early development trials are most suited for adaptive clinical trials?
• Finding the right balance between statistical rigor and practical feasibility
• What to worry about when considering a adaptive trial
• Simulation as an indispensable tool to assess performance and feasibility at the design stage
  Exploring some case studies and analysing their outcomes
  

Roundtable discussions will enable peer to peer discussion on critical topics. Each discussion is led by an industry expert and will allow delegates to seek answers to their specific questions.

You can choose to join whichever debates are most relevant to current challenges. All delegates will have the opportunity to participate in 3 different groups over the course of the morning.

Case Study:
Implementing a complex Bayesian adaptive design in drug development

• Understanding the importance of the dose–response for successful drug development
• Achieving efficient characterisation of dose-response
• Planning the study effectively: including regulatory interactions
• An overview of study results and learnings
• Avoiding common pitfalls: focusing on the challenges and how they were overcome in order to develop effective strategies for the future
• Analysing the lessons learned and looking at how they can be implemented

Design and Analysis Issues for Multi-Armed Adaptive Designs

• Flexible adaptive designs
• Multiple testing in multi-armed adaptive designs
• Sample size reassessment as an additional task
• Designing options relevant for assessing the statistical performance
• Estimation procedures
• The need for comprehensive and user friendly software

Case Study:
How to design and manage a seamless Phase II/III trial in order to maximise the potential cost saving

• Under what circumstances is a Phase II/III trial viable and beneficial?
• Scrutinising the design process: what was learned and what would we do differently?
• Overcoming challenges during the trial’s execution: what issues came up, why did they arise and how can they be avoided?
• The regulatory response: the key to a successful submission
• Assessing how the write up and the next stages of drug development are affected by choosing an adaptive trial

Robert Cuffe
Principal Statistician, Infectious Diseases Medicine Development Centre
GSK

Taking a broad view: making adaptive designs work for you

• Learning practical lessons from case studies of adaptive trials and relevant traditionally designed trials
• Planning for the right decisions at early and final analyses
• Combining clinical, statistical, regulatory, commercial and operational concerns to design the best trial
• Weighing the savings against the additional complexity of an adaptive design

Hans Ulrich Burger
Biostatistics Section Leader
Roche

Pavel Pisa
Translational Medicine Leader
Roche

Marc Vandemeulebroecke
Expert Statistician
Novartis

Panel Discussion:
Assessing the business viability of adaptive trials in all phases

• Does the time saved during the execution of the trial justify the extra time taken during the design process?
• What is the potential for time savings and what savings are actually being achieved?
• Examining where improvements could be made in order to enable adaptive trials to reach their potential
• Can efficiencies be made in recruitment or does the increased complexity of the operation cancel out potential efficiency gains from running seamless trials or ending trials early?
• The supply chain: has the drug supply and distribution process proved cheaper than it would be with a traditional trial of similar scale?
• Applying this knowledge to future trials: do adaptive trials save money and time and how can the savings be maximised?

Closing remarks from the Chair