BUSINESS BENEFITS FOR 2015:• Understand the objectives of Adaptive

Licensing and MAPPs as the “breakthrough”designations to accelerate the approval of newmedicines.

• Learn how Bayesian Belief Networks cansupport reliability management and decisionmaking.

• Discover novel techniques in CARA andSeamless Adaptive Designs and BayesianBandit models to optimise efficiency in dose-finding strategies.

• Benefit from the talks of industry leaders andCEOs in clinical leadership and learn how realworld evidence can improve adaptive trialdesigns.

SMi Presents the 7th Annual Conference on…20th - 21st

APRIL2015

Marriott Regents Park Hotel, London, UK

Adaptive Designs in Clinical Trials

PLUS TWO INTERACTIVE HALF-DAY POST-CONFERENCE WORKSHOPSWednesday 22nd April 2015, Marriott Regents Park Hotel, London, UK

Bayesian Adaptive Clinical Designs and Strategies Workshop Leader: Dr. Sophie Carr, MD and Principal Analyst,

Bays Consulting Ltd.

8.30am – 12.30pm

Winning with Adaptive Trial Strategies and Clinical ComplianceAcross the Evolving International Regulatory Landscape

Workshop Leader: Robert Clay, Consultant, Highbury RegulatoryScience, Chief Regulatory Officer, Kinapse, Board Director, TOPRA

1.30pm – 5.30pm

CHAIRS FOR 2015: Dr. Graham Clarke, Senior Director and Head ofRespiratory & Inflammation Early ClinicalDevelopment, Quintiles

Robert Clay, Consultant, Highbury Regulatory Science,Chief Regulatory Officer, Kinapse; Board Director,TOPRA

Professor Emeritus Tamás L. Paál, Faculty of Pharmacy,Institute of Drug Regulatory Affairs, University ofSzeged, Hungary and Regulatory Adviser, HungarianMedicines Agency

KEY SPEAKERS INCLUDE: • Dr. Sophie Carr, MD and Principal Analyst, Bays Consulting Ltd. • Loïc Darchy, Head of Statistical Methodology Group,

Sanofi R&D• Dr. Steve Coad, Reader in Statistics, Queen Mary University• Han-Joo Kim, PhD, Associate Director, Biostatistics, Oncology

PCU, Eisai Inc. • Alex Sverdlov, Associate Director of Biostatistics, EMD Serono Inc.

@SMIPHARM

www.adaptivedesigns.co.uk Register online or fax your registration to +44 (0) 870 9090 712 or call +44 (0) 870 9090 711

Book by 19th December and save £400 • Book by 30th January and save £200 • Book by 27th February and save £100

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Register online at: www.adaptivedesigns.co.uk • Alternatively fax

7th Annual Adaptive Designs in Clinical TrialsDay One | Monday 20th April 2015

8.30 Registration & Coffee

9.00 Chairman's Opening RemarksDr. Graham Clarke, Senior Director and Head of Respiratory &Inflammation Early Clinical Development, Quintiles

Statistical Modelling and Adaptive Tools to Leverage Clinical Development

OPENING ADDRESS 9.10 Enhancing study design and biomarker read-outs in early

clinical development•Design strategies in early clinical phase - Phase I/II drug

development process •Implementation of biomarkers and validating end points -

design protocols, optimisation and patient strategies inprecision or personalised medicine.

•Highlight the main challenges to ongoing developments andglobal efforts, including biomarker collection and data lossissues

Dr. Graham Clarke, Senior Director and Head of Respiratory &Inflammation Early Clinical Development, Quintiles

9.50 Succeeding in Bayesian adaptive designs •Understand the key components of Bayesian

statistics to enhance decision - making •Predictive classifiers in the Bayesian belief network •Bayesian survival models and predicting time events in clinical

trials•Operational-risk management: A Bayesian approach to

modelling risk and uncertainties Dr. Sophie Carr, MD and Principal Analyst, Bays Consulting Ltd.

10.30 Morning Coffee

11.00 Group Sequential Enrichment Design incorporating subgroupselection - Application to the optimisation of the cut-off for acontinuous predictive biomarker with time-to-event endpoints•Adapting the Group Sequential Enrichment Design (GSED)

methodology & the Combination Tests (CT) methodology toaddress important problems

•Introducing new performance indicators to assess thesoundness of the subpopulation selection

•Exploring the operating characteristics of GSED and CT designsvia simulations under a wide range of scenarios

Loïc Darchy, Head of Statistical Methodology Group, Sanofi R&D

11.40 Real world patient data in adaptive clinical designs •How real time data monitoring gives higher quality, lower costs

and happier patients •How real world data can improve adaptive trial design•Structure and regulatory challenges and requirements for best

clinical practices set out by the European Commission•Case studies related to current research and the organizationDr. Mohammad Al-Ubaydli, CEO, Patients Know Best

12.20 Networking Lunch

1.30 Afternoon Chairman’s Opening Remarks Professor Emeritus Tamás L. Paál, Faculty of Pharmacy, Instituteof Drug Regulatory Affairs, University of Szeged, Hungary andRegulatory Adviser, Hungarian Medicines Agency

Clinical Innovation through Design, Leadership and Management

1.40 KEYNOTE ADDRESS:•Outlook of clinical trials in the CEE region,

implementation of adaptive protocols•Nature of regulatory framework for these markets•Challenges for harmonization in clinical trial legislation across

the entire European Union member states•Adaptive clinical trial design and adaptive licensingProfessor Emeritus Tamás L. Paál, Faculty of Pharmacy, Instituteof Drug Regulatory Affairs, University of Szeged, Hungary andRegulatory Adviser, Hungarian Medicines Agency

2.20 Clinical trials in neurodegenerative disease•Clinical trials in Neurodegenerative diseases: A zoom on

Alzheimer and Parkinson’s disease•Patient selection and management•Patient care and perspectives•Challenges and ongoing research developments Dr. Filippo Baldacci, Medical Doctor, Researcher, University of Pisa

3.00 Afternoon Tea

3.30 Diffusion of innovation through efficient, yet practical designsand statistical leadership in drug development •Efficient and practical trial design and strategies for leading

cross-functional team•Multiple testing strategies•Statistical modelling and analysis: linking this with clinical outcome•Case studies related to research activitiesHan-Joo Kim, PhD, Associate Director, Biostatistics, OncologyPCU, Eisai Inc.

4.10 FOCUS4: Designing and delivering an Adaptive-Biomarkerdriven Multi Arm Mullti Stage (MAMS) cancer trial•Key barriers in translational research •Designing and Delivering an Adaptive-Biomarker driven trial to

time and target•Advantages and Challenges of implementing novel methodologies•Regulatory compliance and challenges from an academic

perspectiveDr. Kai-Keen Shiu, FOCUS4 Trial Physician MRC Trials Unit, UCL

4.50 Panel Discussion: A rationale on adaptive designs in clinical trials•How are adaptive designs defined and best

identified to improve clinical trials? •How costly are continuous trial modifications and

re-assessment in clinical trials? Does this hamper the adaptivenature of trial design?

•What are the perceptions on real world data integration toincrease flexibility and decision making in trials.

•How significant are adaptive designs in each of the respectiveresearch areas on the panel?

•Compare and discuss biomarker development initiatives in therespective research areas on the panel: Trends and challenges.

Panel leader: Professor Emeritus Tamás L. Paál, Faculty of Pharmacy, Instituteof Drug Regulatory Affairs, University of Szeged, Hungary andRegulatory Adviser, Hungarian Medicines AgencyPanellists: Dr. Graham Clarke, Senior Director and Head of Respiratory &Inflammation Early Clinical Development, Quintiles Dr. Kai-Keen Shiu, FOCUS4 Trial Physician MRC Trials Unit, UCLDr. Mohammad Al-Ubaydli, CEO, Patients Know BestLoïc Darchy, Head of Statistical Methodology Group, Sanofi R&DHan-Joo Kim, PhD, Associate Director, Biostatistics, Oncology PCU, Eisai Inc.

5.30 Chairman's Closing Remarks and Close of Day One

Want to know how you can getinvolved? Interested in

promoting your services to thismarket?

Contact Margaret Mugema,SMi Marketing on +44 (0) 207

827 6072 or email:mmugema@smi-online.co.uk

SPONSORSHIP AND EXHIBITION OPPORTUNITIES

SMi offer sponsorship, exhibition, advertising andbranding packages, uniquely tailored tocomplement your company’s marketing strategy.Prime networking opportunities exist to entertain,enhance and expand your client base within thecontext of an independent discussion specific toyour industry.

Should you wish to join the increasing number ofcompanies benefiting from sponsoring ourconferences please call:

Alia Malick on +44 (0) 20 7827 6168 or email: amalick@smi-online.co.uk

ScientificSpotlight

ScientificSpotlight

Supported by

your registration to +44 (0)870 9090 712 or call +44 (0)870 9090 711

7th Annual Adaptive Designs in Clinical TrialsDay Two | Tuesday 21st April 2015

8.30 Registration & Coffee

9.00 Chairman's Opening RemarksRobert Clay, Consultant, Highbury Regulatory Science, Chief Regulatory Officer, Kinapse, Board Director, TOPRA

Breakthrough Trials and Streaming Through International Regulation and Latest European Laws

KEYNOTE ADDRESS9.10 Regulatory submissions across the international landscape

•Is there a global definition of “adaptive designs?”•Forecasting a global harmonization of regulatory

requirements in adaptive designs •Major Parallels and discrepancies between the FDA, EMA

and Japan’s PDMA that impact key areas of drugdevelopment such as decision making, bias control, pre-clinical studies and error control.

•The processes of universal acceptance of emerging andunconventional adaptive designs.

•The impact of regulatory time lags across internationalterritories on drug development.

Robert Clay, Consultant, Highbury Regulatory Science, Chief Regulatory Officer, Kinapse, Board Director, TOPRA

9.50 Moving from adaptive license to MAPPs (Medicine AdaptivePathways for Patients (MAPPs)•Why we need to think MAPPs (Medicine Adaptive Pathways

for Patients (MAPPs) not AL•What can public-private partnership offer to support

AL/MAPPs •Stakeholder engagement – early involvement is key!Dr. Elin Haf Davis, Director, Enabling Research

10.30 Morning Coffee

11.00 Adaptive designs in neuroscience drug development •Adaptive clinical developments in Parkinson’s disease •Clinical and latest technical collaborations across the PD

community•Overcoming challenges •Applications of adaptive designs in relevant clinical areas

of neuroscienceDr. Richard Wyse, Director of Research & Development,The Cure Parkinson’s Trust

11.40 Pharmacodynamics biomarkers in early phase oncology trials•Use of surrogate markers during dose escalation to

demonstrate proof of mechanism•Biomarker driven early phase oncology trials to demonstrate

proof of biological principle•Case examples and challenges Dr. Sidath Katugampola, Biomarker Development Scientist,Cancer Research UK

12.20 Networking Lunch

Discovering New Opportunities in Adaptive Designs

1.30 Novel Response-Adaptive Designs to enhance

efficiency of clinical trials with time-to-event outcomes

•Response-adaptive randomization designs for multi-armed

survival trials

•Covariate-adjusted response-adaptive randomization

designs for survival trials with predictive biomarkers

•Optimal dose finding designs for time-to-event clinical trials

•Statistical software for implementing novel designs

Alex Sverdlov, Associate Director of Biostatistics, EMD Serono

2.10 Group-sequential response-adaptive designs

•Constructing a group sequential design

•Maintaining the overall type I error rate

•Equal and unequal information levels

•The elements of response-adaptive randomisation

•Incorporating covariate information

Dr. Steve Coad, Reader in Statistics, Queen Mary University

2.50 Afternoon Tea

3.20 Bandit models for the design of adaptive clinical trials in rare

disease

•Multi-armed bandit models for the optimisation of clinical

trials in rare diseases

•Main challenges in multi-armed bandit models

•Bayesian Bandit designs to optimise treatment selection in

multiple-treatment studies

Dr. Sofia S. Villar, Investigator Statistician, MRC Biostatistics Unit

for Trials Methodology Research

4.00 Seamless adaptive designs: Methods for estimating treatment

effects

•Statistical challenges for trials that use adaptive seamless

design

•Methods for point estimation after treatment selection

•Point estimation when the adaptation is selecting the most

promising population

•Estimation when treatment selection may depend on more

than one endpoint.

Dr. Peter Kimani, Assistant Professor in Medical Statistics,

Warwick Medical School

4.40 Chairman’s Closing Remarks and Close of Day Two

Spotlightinnovation

HALF-DAY POST-CONFERENCE AM WORKSHOPWednesday 22nd April 2015

8.30am – 12.30pmMarriott Regents Park Hotel, London, UK

Bayesian Adaptive Clinical Designs and Strategies

Workshop Host: Dr. Sophie Carr, MD and Principal Analyst,

Bays Consulting Ltd.

Overview of the workshop:This workshop will provide attendees with a gentle,broad introduction to the wonders of Bayesiananalysis and its application to the development ofAdaptive Clinical Trials and strategies. Theinteractive workshop will engage attendeesthrough structured exercises, discussion and teamworking. Attendees will leave with a fundamentalunderstanding of how the techniques covered willbenefit their own processes.

Key Benefits of Attending: Not heard of Bayesian analysis? Not sure howBayesian analysis is used strategically withinAdaptive Clinical Trials? Come along to thisworkshop and gain a broad understanding of howthe powerful and elegant Bayesian analysis cansupport your work and enhance yourunderstanding of uncertainty and statistics.

Programme8.30 Registration and Coffee

9.00 Introduction of main principles and identifykey areas of research that benefit fromBayesian modelling

9.30 Learn core skills of how to adapt Bayesianstatistics in research

10.30 Coffee Break

11.00 Structured exercises and team work

11.30 Discussion and evaluation

12.30 Close of Workshop

About the workshop host:Sophie Carr has over fifteen years’ experienceworking with clients to deliver key insights in areasas diverse as policy formulation through to thedevelopment of detailed technical models.Sophie’s knowledge in statistics and facilitatingstructured workshops began during her doctoralresearch which focused on the elicitation ofopinion and values, the results of which were usedas the basis for Bayesian Belief Networks.

Across all sectors of industry, Sophie as undertakenstatistical analysis including: forecasting, timeseries analysis and Bayesian inference; andsupported decision-making relating to capabilityinvestments and strategic planning.

About the organisation: Bays Consulting’s specialty is the application ofBayesian analysis but can also draw upon a broadrange of mathematical and statistical techniques,to build datasets, develop models and createanalysis plans to give the trends, insights, values…the nugget of information needed to impact thebottom line and meet objectives. Our regularcustomers particularly value our commitment todeliver clearly explained results to audiences atevery level of the business.

HALF-DAY POST-CONFERENCE PM WORKSHOPWednesday 22nd April 2015

1.30pm - 5.30pmMarriott Regents Park Hotel, London, UK

Winning with Adaptive Trial Strategies andClinical Compliance Across the Evolving

International Regulatory Landscape.

Workshop Host: Robert Clay, Consultant, Highbury Regulatory Science,

Chief Regulatory Officer, Kinapse, Board Director,TOPRA

Overview of the workshop:The modern adaptive trial design is now well establishedin the design of drug development programmes andaccepted by regulatory agencies. However, theapplication of these designs brings interestingchallenges not only in the design and operation of suchtrials but also the integration of the results from studiesinto a global regulatory and submission strategy. Thisworkshop will examine some of these challenges andreview examples from practice to encourage theoptimal use in development programmes.

Key Benefits of Attending: This workshop is intended for researchers looking utiliseadaptive designs and gain optimal use out of thesemethods. It is anticipated that learning professionals fromvarious backgrounds of medical research and industrywill be able to understand how adaptive designs plays adefinitive role within the framework of clinical researchand healthcare. It will also promote greater dialogueamong industry, regulators and academia.

Programme1.30 Registration and Coffee

2.00 Opening

3.00 Addressing the challenges, perspectives and solutions

3.30 Coffee Break

4.00 Case studies

5.00 Discussion & Q+A

5.30 Close of Workshop

About the workshop host:Bob Clay established his own regulatory consultancypractice through Highbury Regulatory Science, prior tothis he was a VP Global Regulatory Affairs atAstraZeneca with responsibility for oncology, infectionand personalised healthcare. Bob is Chief RegulatoryOfficer at Kinapse and a member of the board ofTOPRA (The Organisation of Professional RegulatoryAffairs). He is a member of the Expert Scientific AdvisoryCommittee for Medicines for Malaria Venture (MMV)and several working groups at CPTR (Critical Path to TBRegimens). Bob is a pharmacist with more than 30years’ experience in drug development, leading theglobal regulatory approval of many products across arange of therapy areas including metabolic diseases,neuroscience, cancer and infection. Bob has heldsignificant leadership roles in regulatory affairs in regionaland global functions at several companies includingAstraZeneca and Pfizer.

About the organisation: Highbury Regulatory Scienceprovides consulting support tosmall and mid-size growingbiotech companies onregulatory and development strategies across arange of therapy areas and regions. We also provideadvice on organisational development andoutsourcing key regulatory activities.

Kinapse provides expertadvisory, capability building andoperational services to the lifesciences industries

ADAPTIVE DESIGNS IN CLINICAL TRIALS Conference: Monday 20th & Tuesday 21st April 2015, Marriott Regents Park Hotel, London, UK Workshops: Wednesday 22nd April 2015, London

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