SMi Group's Adaptive Designs in Clinical Trials takes place in London in April 2019

1. PLUS TWO INTERACTIVE HALF-DAY POST-CONFERENCE WORKSHOPS
WEDNESDAY 3RD APRIL 2019, HOLIDAY INN KENSINGTON FORUM, LONDON, UK
HIGHLIGHTS FOR 2019:
• See how the regulatory environment for adaptive drug
design is shifting across the continent with insights from the
MHRA, Amgen, AstraZeneca and Berry Consulting
• Explore the therapeutic potential of adaptive designs with
real-world examples from H.Lundbeck, GSK Vaccines, Pfi zer
and Novartis
• Listen to how the latest platform trial case studies, such as
that of the EPAD project and the MS Society initiative, are
impacting pharmaceutical development
• Delve into the long-standing discussion of Bayesian vs.
frequentist designs
• Discover the latest research in response-adaptive designs:
trials for rare diseases and looking forward
CHAIRS FOR 2019:
• Alex Sverdlov, Director, Statistical Scientist, Novartis
• Tom Parke, Director of Software Solutions, Berry Consulting
FEATURED 2019 SPEAKERS INCLUDE:
• Sandeep Menon, Vice President and Head of
Early Clinical Development, Pfi zer
• Simon Wandel, Associate Director, Statistical
Methodology and Consulting, Novartis
• Solange Corriol-Rohou, Senior Director Regulatory
Affairs and Policy, EU, AstraZeneca
• Christine Fletcher, Executive Director Biostatistics, Amgen
• Philip Hougaard, Vice President Biometrics, H. Lundbeck
• Beatrice Panico, Medical Assessor, MHRA
• Kaspar Rufi bach, Principal Statistical Scientist, Roche
• Andrea Callegaro, Senior Manager, Biostatistician,
GSK Vaccines
• Sofi a Villar, Senior Statistician, MRC Biostatistics Unit
Holiday Inn Kensington Forum, London, UK
www.adaptivedesigns.co.uk
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SMi Group Proudly Presents the 11th Annual Conference...
CONFERENCE:
1ST - 2ND
WORKSHOPS: 3RD
APRIL
2019
Adaptive Designs
in Clinical Trials
The latest advances to enhance the precision,
effi ciency and ethical aspects of your clinical trials
B: Design and analysis of clinical trials
evaluating novel digital technologies
Workshop Leader:
Alex Sverdlov, Director, Statistical Scientist, Novartis
Yevgen Ryeznik, PhD, Uppsala University
13.30 - 17.30
A: The FDA – a new guidance
on adaptive designs
Workshop Leader:
Tom Parke, Director of Software Solutions, Berry Consulting
08.30 - 12.30

2. 08.30 Registration & Coffee
08.50 Chairman’s Opening Remarks
Alex Sverdlov, Director, Statistical Scientist, Novartis
THERAPEUTIC POTENTIAL OF ADAPTIVE DESIGNS
OPENING ADDRESS
09.00 Statistical and design considerations in personalised medicine
• Identifying genetic, genomic and clinical characteristics to
predict patient susceptibility
• Biomarkers and the challenges in their use for diagnostics
• Selecting appropriate designs to determine biomarker
performance, reliability and regulatory acceptance
• Case studies for biomarker driven trials
Sandeep Menon, Vice President and Head of Early Clinical
Development, Pfi zer
SPOTLIGHT SESSION
09.40 Adaptive designs in multiple sclerosis clinical trials
• MS Society initiative to establish platform trial
• The practicalities of setting up platform trials
• Methodological challenges in MS trial design
• Ethical and patient perspective on adaptive designs
Emma Gray, Head of Clinical Trials, MS Society
10.20 Morning Coffee
10.50 Adaptive signature designs for cancer vaccines
• Mage-A3: a double-blind, randomised, placebo-controlled,
phase 3 trial
• The practical and operational considerations of
immunotherapeutic adaptive designs
• Futility for subgroup analyses in adaptive signature design
• The future of adaptive designs for cancer vaccines
Andrea Callegaro, Senior Manager, Biostatistician, GSK
Vaccines
DEEP DIVE
11.30 The European Prevention of Alzheimer’s
Disease platform trial
• EPAD is a public-private partnership running
two connected trials:
- A longitudinal cohort study identifying subjects with
biomarker evidence of early Alzheimer’s
- An adaptive platform trial for Proof-of-concept testing of
new preventive treatments, recruiting from the fi rst trial
• Advantages and disadvantages of testing drugs in this
setup compared to classical one-drug trials
Philip Hougaard, Vice President Biometrics, H.Lundbeck
12.10 Networking Lunch
REGULATORY OUTLOOK OF ADAPTIVE DESIGNS
KEYNOTE ADDRESS
13.10 An industry outlook on adaptive designs in clinical trials
• Innovations of adaptive designs in clinical trials
• How has the use of adaptive designs in clinical trials
developed?
• Views on the draft FDA guidance on adaptive designs
• Heads of Medicines Agencies: Clinical Trials Facilitation
Group practical implications
Christine Fletcher, Executive Director Biostatistics, Amgen
13.50 The evolution of adaptiveness
• Recent updates in European guidance
• The MAPPs engagement process
• Critical questions to be asked
• Adaptive approaches to bringing drugs to the market
Solange Corriol-Rohou, Senior Director Regulatory Affairs
and Policy, EU, AstraZeneca
14.30 Afternoon Tea
15.00 A regulatory perspective of adaptive design trials
• Initial Clinical Trial Authorisation (CTA): points to consider
• Regulatory points to consider for submissions with
substantial amendments
• Safety considerations
Beatrice Panico, Medical Assessor, MHRA
15.40 Using Estimand Framework in Adaptive Designs:
The implication of ICH E9 R(1)
• ICH E9(R1) and adaptive clinical trials
• Using estimand framework in adaptive clinical trials
• Design challenges that ICH E9(R1) might bring to adaptive
designs
• Impact of ICH E9(R1) on the analysis of adaptive clinical trials
Macaulay Okwuokenye, Associate Director Biostatistics,
Syros Pharmaceuticals Inc
16.20 Chairman’s Closing Remarks and Close of Day One
Adaptive Designs in Clinical Trials
Day One | Monday 1st April 2019 www.adaptivedesigns.co.uk
Register online at www.adaptivedesigns.co.uk
SPONSORSHIP AND EXHIBITION OPPORTUNITIES
SMi offer sponsorship, exhibition, advertising and branding packages, uniquely tailored to complement your company’s marketing strategy. Prime networking
opportunities exist to entertain, enhance and expand your client base within the context of an independent discussion specifi c to your industry. should you wish to join
the increasing number of companies benefi ting from sponsoring our conferences please call: Alia Malick on +44 (0) 20 7827 6168 or email: amalick@smi-online.co.uk
Supported by
LETTER FROM THE CHAIRS:
Dear participants,
It is eleven years since the start of SMi’s series of conferences
on Adaptive Designs in Clinical Trials and twenty years since I
started working on adaptive trials. There are now multiple threads
that continue to drive the development of adaptive designs,
their acceptance and their use. These threads include the
radical “Platform Trial” design, the impact of advances in digital
technology, the increased potential of personalized medicine and
the attitude of regulators.
With so many evolving themes it is hard, even for an avid practitioner
of adaptive designs, to stay current across all of them which is why
conferences such as this are so useful. With a diverse program and
experienced speakers the conference presents a vibrant and up
to date cross-section of current practice in adaptive clinical trial
design.
As the chairs of this event, we look forward to personally welcoming
you to this must-attend conference in London this April.
Tom Parke, Alex Sverdlov,
Director, Director,
of Software Solutions Statistical Scientist,
Berry Consulting Novartis

3. 08.30 Registration & Coffee
08.50 Chairman’s Opening Remarks
Tom Parke, Director of Software Solutions, Berry Consulting
CLINICAL APPROACHES OF ADAPTIVE DESIGNS
OPENING ADDRESS
09.00 Digital therapeutics: an integral component of digital
innovation in drug development
• The potential for reducing current costs of medical care
• The unmet medical needs addressed by digital therapeutics
• Emerging pathways to regulatory approval
• How innovative business models are enabling further
growth in digital therapeutics
Alex Sverdlov, Director Statistical Scientist, Novartis
09.40 Applying adaptive designs in industry
• Overview of adaptive designs at BI
• Joint escalation models in oncology dose finding
• Early phase basket designs and GoNoGo decision making
• Blinded sample size reassessment – is there a future?
Frank Fleischer, Expert Statistician Methodology,
Boehringer-Ingelheim
10.20 Morning Coffee
10.50 Extrapolation in clinical trials and beyond
• Basics of extrapolation: when is it applicable - and when not
• Extrapolation from adults to children: “adaptive” borrowing
• Bridging studies
• Beyond individual studies: extrapolation via mixture models
for meta-analysis
Simon Wandel, Associate Director, Statistical Methodology and
Consulting, Novartis
11.30 Continuous Decision Making within a Clinical Trial
• Overview of Decision Making in Early clinical development at
AstraZeneca
• Incorporating continuous decision making into the framework
• Standardizing tools/ figures to convey the information
• Statistical risks and considerations in adopting this approach
Paul Frewer, Early Clinical Development, AstraZeneca
12.10 Networking Lunch
STATISTICAL APPROACHES OF ADAPTIVE DESIGNS
SPOTLIGHT SESSION
13.10 Forward looking response-adaptive designs
• The benefits of forward looking response-adaptive
randomisation in adaptive designs
• Trials for rare diseases and finding treatments that
work subgroups
• Type 1 error inflation due to an unknown time trend
over the course of the trial
Sofia Villar, Senior Statistician, MRC Biostatistics Unit
Panel Discussion
13.50 Bayesian vs. frequentist designs incorporating
multiple treatment arms
• Response-adaptive randomisation
• Triangular tests
• Dropping poorly-performing arms in multi-arm
multi-stage designs
• Flexibility in Bayesian vs. frequentist designs
Moderated by:
Michael Proschan, Mathematical Statistician,
National Institute of Allergy and Infectious Diseases, USA
Panellists:
Kaspar Rufibach, Principal Statistical Scientist, Roche
Alex Sverdlov, Director, Statistical Scientist, Novartis
Sofia Villar, Senior Statistician, MRC Biostatistics Unit
14.30 Planning a phase 3 trial with time-to-event endpoint
• The MIRROS phase 3 trial
• Futility interim analysis using a mechanistic simulation model
• Sample size planning
• Exploration of operating characteristics of the futility interim
analysis
Kaspar Rufibach, Principal Statistical Scientist, Roche
15.10 Afternoon Tea
15.40 Defining decision rules based on simulated development
programs
• Go/no go decision after phase 2 and futility analysis in phase
3 trials based on estimated probability of success
• Probability of success is estimated using simulations taking
into account observed association between short-term and
long-term endpoint from phase 2
• Simulation of complete phase 2 and 3 development program
allows to define appropriate decision boundaries
Heiko Goette, Biostatistician, Merck KGaA
16.20 Chairman’s Closing Remarks and Close of Day Two
Adaptive Designs in Clinical Trials
Day Two | Tuesday 2nd April 2019 www.adaptivedesigns.co.uk
Alternatively fax your registration to +44 (0)870 9090 712 or call +44 (0)870 9090 711
MARKETING OPPORTUNITIES
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Supported by

4. The FDA – a new guidance
on adaptive designs
Workshop Leader:
Tom Parke, Director of Software Solutions, Berry Consulting
HALF-DAY POST-CONFERENCE WORKSHOP A
Wednesday 3rd April 2019
08.30 – 12.30
Holiday Inn Kensington Forum, London, UK
Overview of the workshop:
The new FDA draft guidance on Adaptive Trials is a signifi cant
change from the 2010 version of the draft guidance. This
workshop will look at the changes and what it means for
submitting proposals for adaptive trials to the FDA.
The workshop will cover:
• How to submit adaptive designs to regulators
• What the contents of the documents should be
• What simulation details need to be submitted
• What problems to expect
• How to submit simulation results
• How to submit simulation software
Why you should attend?
• Attend this workshop if you would like to understand:
• How the new guidance refl ects changes at the FDA
• How to justify the use of an adaptive design to the FDA
• How to document an adaptive design
• How to organise, perform, and report the clinical trial
simulations necessary to support an adaptive design
• How to report the results of an adaptive design
Programme
08.30 Registration and Coffee
09.00 Opening remarks and introductions
09.10 A look at the draft guidance in detail
• Changes to the detailed principles
• Classes of adaptive designs
• Operational details and considerations
• Regulatory interaction and submission guidance
09.50 Describing and justifying a proposal to perform
an adaptive trial
• Statistical effi ciency
• Ethical considerations
• Operational considerations
• Broader questions the trial might address
• Stakeholder fl exibility
10.30 Morning Coffee
11.00 Trial simulation necessary to support
a complex trial design
• How to simulate trials
• The art of simulating clinical trials – choosing
scenarios choosing operating characteristics
• Avoiding doing too much
• Showing type-1 error control
11.40 Submitting the results of an adaptive trial
• Analysis of results and analysis code
• Interim analyses and results
• Interim communications
12.20 Closing remarks
12.30 End of workshop
About the workshop leader
Tom Parke is Director of Software Solutions for Berry
Consultants. Tom joined Berry Consultants in 2016 having
previously worked at Tessella, a UK scientifi c software
company where he fi rst met and worked with Don Berry.
In 1998 Tom managed the development and running of a
software system to support Pfi zer’s ASTIN Stroke trial – a ground
breaking response adaptive randomization dose ranging trial
designed by Don Berry and Peter Mueller.
Following that he managed multiple projects to support
different aspects of many adaptive clinical trials, mostly
designed by Berry Consultants, and projects to develop
clinical trial simulators, fi rst with Pfi zer, then Wyeth, and
fi nally with Eli Lilly to develop FACTS. Latterly, as well as
managing the continuing development of FACTS, Tom has
researched the estimation of expected Net Present Value of
development programs leading to the development of the
QUOTES software package.
Tom originally graduated with joint First Class Honors in Maths
and Computer Science from Bristol University, and enjoyed
two decades in the software industry (inmos, Imperial
Software Technology and then Praxis - which became part
of Deloittes) before stumbling upon the wonderful world of
adaptive clinical trials.
Berry Consultants
Berry Consultants is a statistical
consulting company specializing in
the Bayesian approach to medical
statistics, an approach that is radically
changing the way research is done
throughout the medical industry in
both device and drug development.
Berry Consultants employs world renowned experts in
Bayesian statistics and strives to set the standard for innovative
clinical trial design and analysis in the statistical and medical
communities.

5. Design and analysis of clinical trials
evaluating novel digital technologies
Workshop Leader:
Alex Sverldlov, Director, Statistical Scientist, Novartis
Yevgen Ryeznik, PhD, Uppsala University
HALF-DAY POST-CONFERENCE WORKSHOP B
Wednesday 3rd April 2019
13.30 – 17.30
Holiday Inn Kensington Forum, London, UK
Overview of the workshop
Digital technologies (such as wearable devices, smartphone
apps) are increasingly used in clinical research and
development. Despite numerous pilot clinical studies
evaluating merits of digital technologies, there is still little
knowledge on how to properly design and run such studies,
and how to analyse the collected experimental data. The
current course will cover several important statistical aspects
of clinical trials evaluating digital technologies.
Why you should attend?
Attend this workshop if you would like to understand:
• Potential challenges and benefi ts of utilizing digital
technologies in clinical research
• What trial designs are available for evaluating digital
technologies
• How to analyze data generated by digital technologies
• Current regulatory pathways to the approval of digital
therapeutics
Programme
13.30 Registration and Coffee
14.00 Opening remarks and introductions
14.10 Innovative designs for developing mobile
health interventions
• Micro-randomized trials
• MOST and SMART designs
• Choice of sample size
• Data analysis aspects
14.50 Digital biomarkers as screening/diagnostic tools
• Challenges and opportunities
• Classifi cation problems
• Building predictors of clinical outcomes
15.30 Afternoon Tea
16.00 Digital therapeutics
• Addressing unmet medical need
• Emerging business models
• Clinical trials to develop digital health
interventions
16.40 Current regulatory landscape for digital health
technologies
• Pathways to regulatory approval of a device
• Existing regulatory guidelines
• Examples of successful approvals
17.20 Closing Remarks
17.30 End of Workshop
About the workshop leaders
Alex Sverdlov has worked as a statistical scientist in
biopharmaceutical industry since 2007. He has been involved
in active research on adaptive designs for clinical trials to
improve effi ciency of drug development. He edited a book
“Modern Adaptive Randomized Clinical Trials: Statistical and
Practical Aspects” which was published by CRC Press in 2015.
Alex’s most recent work involves design of proof-of-endpoint
clinical trials evaluating digital technologies in neuroscience.
Since 2014, Yevgen Ryeznik is a Ph.D. student in Uppsala
University, Uppsala. Before that, he had a 2-year experience
of working as a SAS programmer and clinical data analyst in
the Ukrainian department of Quartesian LLC, a CRO located
in Princeton, NJ. For the last ten years, he has been actively
involved in research on optimal designs and adaptive
randomization for clinical trials, mainly, trials with time-to-
event outcomes. Yevgen’s most recent research interests are
digital therapeutics and mobile health, and applications of
deep learning for biopharmaceutics.

6. ADAPTIVE DESIGNS IN CLINICAL TRIALS 2019
Conference: Monday 1st Tuesday 2nd April 2019, Holiday Inn Kensington Forum, London, UK
Workshops: Wednesday 3rd April 2019, London, UK
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