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Pharmaceutical R&D Process –Why do Clinical Trials Fail?

Erika Buonansegna, PhD StudentDTU Management Engineering

Supervisors:Søren Salomo, DTU Management EngineeringAnja Maier, DTU Management EngineeringJason Li-Ying, DTU Management EngineeringCarsten Schultz, Kiel University, Germany

Collaborating partner:Medidata Solutions, Inc., New York

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 I Phase II Phase III

Test of the prototype

(Cooper, 1994)

Market Approval

gate gate gategate

Clinical Trials

P.I.R

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3

Research & Drug

Discovery

Preclinical Studies Phase I Phase II Phase III

INTRO TO THE PHARMACETICAL R&D: DRUG DISCOVERY AND DEVELOPMENT PROCESS

6-7 years3-6 years 0.5-2 years

5.000-10.000 compounds

250 5 1

(Efpia, 2011)

Market Approval

Clinical Trials

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CLINICAL TRIAL NETWORK

Sponsor

Site

5

CLINICAL TRIAL NETWORK

CRO

Sponsor

Site

6

CLINICAL TRIAL NETWORK

CRO

Sponsor

Site

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• Few studies on CT failure• Little knowledge on determinants of failure in late development

stages• Search for tools to manage CTs

(Centre for Medicine Research in Kennedy, 1997) (DiMasi, 2001)

Reasons for drug failure

lack of ef -ficiency

46%

toxicity17%

commercial reasons

7%

miscellaneous7% pharma-

cokinetics7%

adverse events 16% lack of efficiency

37%

lack of safety20%

commercial reasons34%

miscellaneous9%

RESEARCH MOTIVATION

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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

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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

Term

inati

on

of a

pro

ject

Potential product Not potential product

Com

pleti

on

of a

pro

ject

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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

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MANAGERIAL IMPLICATIONS

• Clinical trial research – Interdependencies– Ranking according to phases– In-depth case studies

• Late development stages in other industries

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FUTURE RESEARCH

Erika BuonansegnaPhD Student

Technical University of DenmarkDTU Management EngineeringProduktionstorvet, Bygning 4262800 Kgs. LyngbyDenmarkerbou@dtu.dk

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