MATRIX45 © Matrix45, LLC, All rights reserved. Phase 4 and 5: Merging Strategy, Science, & Service Ivo Abraham, PhD © Matrix45, LLC, All rights reserved.

MATRIX45 © Matrix45, LLC, All rights reserved. Page 1 key points  Nomenclature for postmarketing studies  Embedding phase 4 and 5 studies into corporate strategy  Scientific integrity  Evidence bases and clinical practice change  Extending phase 4/5 activities into evidence- based practice support – towards a knowledge- based customer relationship

MATRIX45 © Matrix45, LLC, All rights reserved. Page 2 phase 4 and 5 defined Phase 4 better documenting  efficacy  safety  Interventional / controlled  Principles, methods, and statistics of RCTs  Transition to “real-world” Phase 5 better understanding  effectiveness  uses and outcomes  markets  customers  Non-interventional / noncontrolled  Multitude of methodologies and statistical models  In the “real-world” (if not “real-time”)

MATRIX45 © Matrix45, LLC, All rights reserved. Page 3 Conversion studies, registries, surveys, practice pattern analysis, new indications analysis, risk screening, experience studies, outcomes studies, practice x outcome analysis, clinical market dynamics, pharmaco-epidemiology, data mining / pattern recognition, evidence-based knowledge support, thought leadership, surveillance, pharmaco-economics, … 1  2  technology transfer innovation 3b Focus on: Registration Knowledge phase 4 and 5 defined

MATRIX45 © Matrix45, LLC, All rights reserved. Page 4  Macro-evidence  Evidence from studies + meta-analysis  Formal learning  “Seeing the larger picture” – “many- other-patients“ – “what-patients- should-be-like”  Micro-evidence  Evidence from one's own clinical experience and experimentation  Application in one’s own practice  “Seeing with one's own eyes" - the "my- patients" picture drivers from evidence to practice

MATRIX45 © Matrix45, LLC, All rights reserved. Page 5 drivers corporate strategy  Key objective of post-marketing programs  To address market issues using scientific models and methods to achieve business objectives  Optimize scientific lifecycle – and merge with commercial lifecycle  Good phase 4/5 strategy is enterprise-wide  R&D  Medical affairs  Strategic marketing  Regulatory  Corporate development

MATRIX45 © Matrix45, LLC, All rights reserved. Page 6 drivers corporate strategy  International scope  Understanding regional dynamics within their respective clinical and regulatory contexts  Achieving geographic granularity  Anticipating developments in other regions  Global resourcing, platforming, and coordination for phase 4 and 5 programs

MATRIX45 © Matrix45, LLC, All rights reserved. Page 7 challenge strategy, science, and service  Biopharma  “We want to collect data” … “we want to know” … “large samples” …  Realistic objectives and time frames?  Centers  Trial fatigue and registry fatigue  Remuneration and/or value-added services  Merging strategy, science, and service  Context  Platform

MATRIX45 © Matrix45, LLC, All rights reserved. Page 8 Risk Screening Risk Management Clinical Support Clinical Patient Level Clinical Practice Level Evidence-Based Benchmarks clinical tasking

MATRIX45 © Matrix45, LLC, All rights reserved. Page 9 Patents pending platform

MATRIX45 © Matrix45, LLC, All rights reserved. Page 10  West-European product sales  Global expansion of survey ( ) within and across indications ~ worldwide sales growth from $1.5 billion (1998) to $4.2 billion (2002) implementation of 6-month longitudinal study state-of-the-art symposium opportunities especially phase 5 pays for itself

MATRIX45 © Matrix45, LLC, All rights reserved. Page 11 Opportunities On the Expense and Return-on-Expenses Sides Opportunities On the Expense and Return-on-Expenses Sides opportunities intangible returns  “Intangibles”: prescriber loyalty due to value- added services provided  Ability to manage one’s practice  Ability to provide better patient care  Knowledge-based relationship with biopharma, diagnostics, and medical devices

MATRIX45 © Matrix45, LLC, All rights reserved. Page 12 key points revisited  Phase 4 – controlled Phase 5 - noncontrolled  Post-marketing = integral part of corporate strategy – product, franchise, enterprise  Defensible scientific methods  Micro-evidence = key driver of clinical behavior change  Knowledge-based customer relationships

MATRIX45 © Matrix45, LLC, All rights reserved. Page 13 This slide deck may be downloaded from on post-marketing studies

MATRIX45 © Matrix45, LLC, All rights reserved. Page 14 Our Coordinates Frays Ridge RoadP.B. 55 Earlysville, VA Heverlee 1 USABelgium tel: tel: Lombard #3 Philadelphia, PA USA tel: