Pharmaceutical R&D Process – Why do Clinical Trials Fail? Erika Buonansegna, PhD Student DTU Management Engineering Supervisors: Søren Salomo, DTU Management Engineering Anja Maier, DTU Management Engineering Jason Li-Ying, DTU Management Engineering Carsten Schultz, Kiel University, Germany Collaborating partner: Medidata Solutions, Inc., New York 1

Idea generation and evaluation Concept development and product planning Prototype development Test of the prototype Production and Market Introduction Research & Drug Discovery Preclinical Studies Phase IPhase IIPhase III Test of the prototype (Cooper, 1994) Market Approval gate Clinical Trials P.I.R 2

Research & Drug Discovery Preclinical Studies Phase IPhase IIPhase III INTRO TO THE PHARMACETICAL R&D: DRUG DISCOVERY AND DEVELOPMENT PROCESS years 3-6 years years compounds (Efpia, 2011) Market Approval Clinical Trials

CLINICAL TRIAL NETWORK Sponsor Site 4

CLINICAL TRIAL NETWORK CRO Sponsor Site 5

CLINICAL TRIAL NETWORK CRO Sponsor Site 6

Few studies on CT failure Little knowledge on determinants of failure in late development stages Search for tools to manage CTs 7 (Centre for Medicine Research in Kennedy, 1997)(DiMasi, 2001) Reasons for drug failure RESEARCH MOTIVATION

8 Refine the understanding on failures in clinical trials as a late development stage. Research Questions: (1)“What causes failure of clinical trials?” (2)“Can such causes be systematically mapped?” (3)“Does the assessment of clinical trial failures provide insights into a more general concept of NPD failure during later stages of the development process?” RESEARCH AIM AND QUESTIONS

Address clinical trials specificities Expert study 17 interviews Literature review Conceptual framework 9 METHODOLOGY

Success False-positive failures - Difficult subject recruitment for testing -Lack of experience in choosing and monitoring the partners -Lack of feasibility of the testing procedure -High demand for documentation -Many incidents while testing -Unmanageable level of portfolio complexity -Incorrect assessment of the market potential or returns False-negative failures - Difficult subject recruitment for testing -Lack of experience in choosing and monitoring the partners -Lack of feasibility of the testing procedure -High demand for documentation -Many incidents while testing -Unmanageable level of portfolio complexity -Incorrect assessment of the market potential or returns Inevitable failures -Toxicity -Lack of efficacy -Economics Termination of a project Termination of a project Potential product Not potential product Completion of a project Completion of a project 10 CONCEPTUAL FRAMEWORK

Proactive strategies Improving skills of the development team Due diligence in choosing sites and subcontractors E-recruitment tactics Monitoring sites and subcontractors Interim and risk analyses Training for SAEs Feedback from investigators Reactive strategies Fast reallocation of resources Back-up candidates and parallel-track strategy Learning-by-failing mind set 11 MANAGERIAL IMPLICATIONS

Clinical trial research –Interdependencies –Ranking according to phases –In-depth case studies Late development stages in other industries 12 FUTURE RESEARCH

Erika Buonansegna PhD Student Technical University of Denmark DTU Management Engineering Produktionstorvet, Bygning Kgs. Lyngby Denmark 13