OverviewThis 2 ½ day event is the first joint DIA/EMA workshop on statistical methodology inclinical research and development. In 2009 a Biostatistics Drafting Group was formedat the EMA, comprising 10 statisticians from National Competent Authorities. TheEuropean Medicines Agency and its statistical experts will contribute to this workshopand share their expertise. The workshop will examine the ever important role ofstatistics in clinical R&D and will also discuss new applications of statistical methods.

Objectives• To provide a forum for lively and informative discussions of the application of and

research in statistics in clinical R&D

• To bring together professionals from across the drug development arena to share

experiences and knowledge

• To provide up-to-date information on the present regulatory scene in relation to

statistics

• To explore the progress of the use of new methodologies and other/new areas of

interest for statisticians who work in the field or want to move their career into

this area

Key Topics• Dealing with Missing Data

• Safety Analysis Planning

• Time to Event Analyses

• Quantitative Benefit/Risk Analyses

• Adaptive Designs

Who Will AttendProfessionals with an interest in the application of and research in statistics in thedrug development process from the pharmaceutical industry, academia, regulatoryand governmental agencies, as well as contract research organisations.

Continuing Education InformationThe Swiss Association of Pharmaceutical Professionals (SwAPP) and the SwissSociety for Pharmaceutical Medicine (SGPM) have accredited the 1st Joint DIA/EMAWorkshop on Statistical Methodology in Clinical R&D with 15 credits.

Programme Co-Chairs

Jürgen KüblerGlobal Head, Statistical Safety SciencesNovartis Pharma AG, Switzerland

Thomas LangBiostatisticianAGES PharmMed, Science and InformationAustria

Programme CommitteeGeorg HeinzeAssociate Professor, Section for Clinical BiometricsCenter for Medical Statistics, Informatics andIntelligent SystemsMedical University of Vienna, Austria

Franz KönigCoordinator for Scientific Support and Projects inStatistical MethodologyExpert National Detachee at the European MedicinesAgency, EuropeAssistant Professor, Medical University of Vienna,Austria

Jorgen SeldrupSenior Strategic Biostatistics DirectorQuintiles Ltd., FranceDIA Statistics SIAC Co-Chair

Joachim VollmarExecutive ConsultantInternational Clinical Development Consultants, USA

David WrightSenior Statistical AssessorMHRA, UK

Event #1010727-29 September 2010 Hotel Austria Trend Savoyen, Vienna, Austria

1st Joint DIA/EMA Workshop on Statistical Methodology in Clinical R&D

MONDAY | 27 SEPTEMBER 201009:00 Registration and Welcome Coffee

09:45 Opening RemarksJürgen Kübler, Global Head, Statistical Safety Sciences, Novartis Pharma AG, SwitzerlandJorgen Seldrup, Senior Director Centre for Statistics in Drug Development Innovation, Quintiles, France and DIA Statistics SIAC Co-Chair

10:00 Session 1A REVIEW OF RECENT ADVANCES IN TECHNIQUES DEVELOPED TO ANALYSE STUDIES WITH MISSING DATASession Chairperson:David WrightSenior Statistical Assessor, MHRA, UK

The CHMP Missing Data guideline has recently been updated. Thissession will explain the key changes that have been made to theguideline and highlight some of the difficulties regulators face whenassessing submissions where ways in which missing data are handledin the analysis can affect the conclusions drawn. The session will giveexamples of the latest methods that are being developed to providemore informative sensitivity analyses. The limitations of theseapproaches will be explored and recommendations made on whatfuture research should be conducted to improve these methods.

What has changed in the Revised CHMP Guideline on Missing Data inConfirmatory Clinical Trials?David Wright, Senior Statistical Assessor, MHRA, UK

Working with the CHMP Guideline for Missing Data: Practicalapproaches using pattern mixture modelsJames Roger, Director Research Statistic Unit, GlaxoSmithKline, UK

11:30 Coffee Break

12:00 Session 1 continued

Working with the CHMP Guideline for Missing Data: Illustrative examples from clinical trialsMichael O’Kelly, Senior Strategic Biostatistics Director, Centre for Statistics in Drug Development, Innovation, Quintiles Ireland Ltd., Ireland

Panel discussion and Q & A with session speakers

13:30 Lunch

14:30 Session 2COMPREHENSIVE PLANNING OF SAFETY ANALYSES IN CLINICAL DEVELOPMENTSession Chairperson:Joachim VollmarExecutive Consultant, International Clinical Development Consultants, USA

According to the current practice, safety analyses are currentlyconducted by applying descriptive statistics to routinely collectedsafety data. Recently, a thorough definition of potenial and knownrisks, as well as the continuous and comprehensive evaluation of theserisks, has been proposed by various groups. This session will reviewthe current state of the general principles and the latest regulatoryguidance, as well as aspects of the implementation of these newrequirements in clinical development.

Working Cross-functionally on Safety Analyses: Experiences from a phase IIIb projectSheila Dickinson, Senior Expert Statistician, Novartis Pharma AG,

SwitzerlandBest Practice in Meta-Analyses for SafetyRobert T. O'Neill, Director, Office of Biostatistics, CDER, FDA, USA

16:00 Coffee Break

16:30 Session 2 continued

Graphical Approaches for Safety Signal Detection - Efforts of the FDA-PhRMA-Academia Working GroupAndreas Brückner , Statistician, Bayer-Schering Pharma, Germany

Panel discussion and Q & A with session speakers, Robert Hemmings, Statistics Unit Manager, MHRA, UK, Chairperson of the EMA Biostatistics Drafting Group, EU & Jürgen Kübler, Global Head, Statistical Safety Sciences, Novartis Pharma AG, Switzerland

18:00 Reception with the DIA European Statistics SIAC (Special Interest Area Community)

19:00 End of Day 1

TUESDAY | 28 SEPTEMBER 201009:00 Session 3

TIME TO EVENT ANALYSES AND BIOMARKER SELECTIONSession Chairperson:Georg HeinzeAssociate Professor, Section for Clinical Biometrics, Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Austria

Drug development can be considerably speeded up by the use ofbiomarkers and surrogate endpoints. However, it is still the hardclinical endpoint, such as death, that is of primary concern. Thissession will provide an overview of current methods for time to eventanalysis including modeling and evaluation of time dependent effectsand a comprehensive review of biomarker selection from a largenumber of candidates, often exceeding the number of subjects. Thesession will be complemented by the discussion of statistical issues inthe design of studies with a time to event outcome from a practicalpoint of view.

Time to Event Analyses with Time-dependent EffectsDaniela Dunkler, Biostatistician, Medical University of Vienna, Austria

Methods for Biomarker Selection with a Time to Event OutcomeHege Marie Bøvelstad, Department of Mathematics, University ofTromsø, Norway

10:30 Coffee Break

11:00 Session 3 continued

Statistical Considerations in the Design of Time to EventHans-Ulrich Burger, Biostatistics Section Leader, F. Hoffmann-La Roche AG, Switzerland

Panel discussion and Q & A with session speakers

12:30 Lunch

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Unless otherwise disclosed, DIA acknowledges that the statements made by speakers are their own opinion and not necessarily that of the organisation they

represent, or that of the Drug Information Association.

Speakers and agenda are subject to change without notice. Recording of any DIA tutorial/workshop information in any type of media, is prohibited

without prior written consent from DIA.

3

14:00 Session 4QUANTITATIVE BENEFIT/RISK ANALYSESSession Chairperson:Jürgen KüblerGlobal Head, Statistical Safety Sciences, Novartis Pharma AG, Switzerland

Benefit-risk evaluations have traditionally been conducted usingmainly qualitative approaches. Recently, there is a growing interest inutilising quantitative approaches to facilitate informed decision makingin this space. This growing interest has both stimulated research in thearea and brought in new practical implementations. This session willprovide an overview on challenges and opportunities in this field witha strong focus on recent case studies. Speakers and panelists fromregulatory and industry will discuss these case studies and explorefuture directions.

A Perspective on Characterising Benefits and Risks Derived fromClinical Trials: Can we do more?Robert T. O'Neill, Director, Office of Biostatistics, CDER, FDA, USA

Case Study 1: Using desirability indices for dose findingDidier Renard, Modelling & Simulation, Statistics, Novartis Pharma AG,Switzerland

15:30 Coffee Break

16:00 Session 4 continued

Case Study 2: Benefit/risk analysis in late stage developmentAlfons Lieftucht, Manager, Decision Sciences, GlaxoSmithKline, UK

Panel discussion and Q & A with session speakers andRobert Hemmings, Statistics Unit Manager, MHRA, UK, Chairperson of the EMA Biostatistics Drafting Group, EU

17:30 End of Day 2

WEDNESDAY | 29 SEPTEMBER 2010

09:00 Session 5CURRENT TOPICS IN ADAPTIVE DESIGNSSession Chairperson:Franz KönigCoordinator for Scientific Support and Projects in Statistical MethodologyExpert National Detachee at the European Medicines Agency, EuropeAssistant Professor, Medical University of Vienna, Austria

Adaptive clinical trial designs have attracted increasing attentionbeyond the statistical community over recent years. The expectation isthat studies which are thoroughly planned and conducted, and whichare based on adaptive design methodology, may increase theefficiency of the drug development process by making better use ofthe resources, as long as the basis for regulatory decision making is notcompromised. In this session we will discuss topics which have recentlyattracted much interest and are areas of controversy betweenmembers of academia, industry and regulatory agencies. This includestopics from adaptive dose finding studies to confirmatory designs.Adaptive designs which allow treatment or population selection at anadaptive interim analysis will be discussed. Presentations will covertopics such as how to test primary and secondary endpoints inadaptive interim analyses strictly controlling type I error and the role ofclinical trial simulation in adaptive design planning.

Adaptive Enrichment Designs with Population Selection at InterimSue-Jane Wang, Associate Director, Pharmacogenomics and AdaptiveDesign Office of Biostatistics, CDER, FDA, USA

Adaptive Designs with Treatment Selection at Adaptive InterimAnalysesGernot Wassmer, Managing Director, ADDPLAN GmbH, Germany

10:30 Coffee Break

11:00 Session 5 continued

Adaptive Dose-finding StudiesBjörn Bornkamp, Statistical Methodologist, Integrated Information Sciences, Novartis Pharma AG, Switzerland

Adaptive Designs - Three years on Robert Hemmings, Statistics Unit Manager, MHRA, UK, Chairperson of the EMA Biostatistics Drafting Group, EU

Panel discussion and Q & A with session speakers

12:30 End of Workshop

HOTEL INFORMATION

The DIA has blocked a number of rooms at the:

Austria Trend Hotel Savoyen

Rennweg 18

1030 Vienna, Austria

Tel: +43-1-20633-9102

Fax: +43-20633-9110

Email: reservierung.savoyen@austria-trend.at

Website: www.austria-trend.at/sav

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