1. 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

2. 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

3. Research & Drug Discovery Preclinical Studies Phase IPhase IIPhase III INTRO TO THE PHARMACETICAL R&D: DRUG DISCOVERY AND DEVELOPMENT PROCESS 3 6-7 years 3-6 years 0.5-2 years 5.000-10.000 compounds 2505 1 (Efpia, 2011) Market Approval Clinical Trials

4. CLINICAL TRIAL NETWORK Sponsor Site 4

5. CLINICAL TRIAL NETWORK CRO Sponsor Site 5

6. CLINICAL TRIAL NETWORK CRO Sponsor Site 6

7. 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. 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

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

10. 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

11. 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

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

13. Erika Buonansegna PhD Student Technical University of Denmark DTU Management Engineering Produktionstorvet, Bygning 426 2800 Kgs. Lyngby Denmark erbou@dtu.dk 13