SPI Infoamtion

Table of Contents

Executive summary

Introduction and background to clinical trials
Financial considerations & planning of clinical trials
Cost analysis of clinical trial authorization by responsible authorities
Cost analysis of clinical trial review by ethics committees
Review and cost analysis of investigator fees by selected country
Review and cost analysis of laboratory fees, pharmacy costs and clinical trial liability insurance by selected country
Review and cost analysis of CRO salaries by selected country

Chapter 1 Introduction and background to clinical trials

Summary
Introduction and background to pharmaceutical industry issues

High risks and costs associated with drug development

Escalating costs associated with clinical trials
Global increase in the number of clinical trials conducted
Longer R&D timelines
Increased attrition rates during pharmaceutical research and development

Improvement to R&D productivity and reducing time to market for next generation drugs
New business models for the pharmaceutical industry
Introduction to clinical trials and clinical trial studies

What is a clinical trial
Clinical trials of pharmaceutical agents

Types of clinical trial

Drug development process

Drug discovery
Preclinical development
Clinical trial phases

The role of the chief investigator
Clinical trial protocol and procedure
Determination of the clinical trial size
The role of the co-coordinating centre and trials unit
The role of the trial co-coordinator
The trial principal investigator
Forms and data management
Trial data analysis and evaluation
Ethical issues and conduct of clinical trail research
Interpretation and publication of clinical trial results

Clinical trial study design and planning

Clinical trial study design
Clinical trial study protocol

Clinical trial sponsors
Identifying and recruiting patients for clinical trials
Contract research organizations (CRO)

What are CROs
The role of CROs

Principle pharmaceutical and pharmaceutical regulatory agencies

The European Agency for the Evaluation of Medicinal Products (EMEA)
The United States Food and Drug Administration (US FDA)
Japanese Ministry of Health, Labor and Welfare (MHLW)

Chapter 2 Financial considerations and planning of clinical trials

Summary
Introduction
Key variables to consider for resource budgeting and allocation
Elements of successful budgeting
Development of the clinical trial protocol
Design and planning the clinical trial

Clinical trial design
Clinical trial planning
Multi-purpose studies

Clinical trial budget development process and cost analysis

Direct costs

Commonly overlooked clinical trial budget items

Chapter 3 Cost analysis of clinical trial authorization by responsible authorities

Summary
Introduction
Authorization process for clinical trials
European authorization process for clinical trials
Comparison of fees incurred: in the principal Western European countries

France
Germany
Italy
Spain
United Kingdom
Selected other Western European countries

Denmark
Sweden
Finland
Norway
The Netherlands

Comparison of fees incurred in the principal Central and Eastern European countries

Russia
Czech Republic
Poland
Hungary

Comparison of fees incurred in the principal Latin American countries

Argentina
Brazil
Mexico

Comparison of fees incurred in the principal Asian countries

India

Application and authorization process fees: India

China

Authorization process for clinical trials: United States

Chapter 4 Cost analysis of clinical trial review by ethics committees

Summary
Introduction
Fees for assessment of clinical trial applications by Research Ethics Committees (ECS) in the principal Western European countries

France
Germany
Italy
Spain
United Kingdom
Selected other Western European countries

Denmark
Sweden
Finland
Norway
The Netherlands

Fees for assessment of clinical trial applications by research ethics committees in the principal Central and Eastern European countries

Russia
Czech Republic
Poland
Hungary

Fees for assessment of clinical trial applications by research ethics committees in the principal Latin American countries

Argentina
Brazil
Mexico

Fees for assessment of clinical trial applications by research ethics committees in the principal Asian countries

India
China

Fees for assessment of clinical trial applications by research ethics committees (RECs) in the United States

Chapter 5 Review and cost analysis of investigator fees by selected country

Summary
Introduction
Analysis of investigator fees: Phase I

Review and cost analysis of investigator fees in the principal Western European countries (Phase I)
Review and cost analysis of investigator fees in selected Central and Eastern European countries (Phase I)
Review and cost analysis of investigator fees in the selected Latin American countries (Phase I)
Review and cost analysis of investigator fees in the selected Asian countries (Phase I)
Review and cost analysis of investigator fees in the United States for Phase I and comparison with other selected countries

Analysis of investigator fees: Phase II

Review and cost analysis of investigator fees in the principal Western European countries (Phase II)
Review and cost analysis of investigator fees in the selected Central and Eastern European countries (Phase II)
Review and cost analysis of investigator fees in the selected Latin American countries (Phase II)
Review and cost analysis of investigator fees in selected Asian countries (Phase II)
Review and cost analysis of investigator fees in the United States for Phase II and comparison with other selected countries

Analysis of investigator fees: Phase III

Review and cost analysis of investigator fees in the selected Central and Eastern European countries (Phase III)
Review and cost analysis of investigator fees in the selected Latin American countries (Phase III)
Review and cost analysis of investigator fees in selected Asian countries (Phase III)
Review and cost analysis of investigator fees in the United States for Phase III and comparison with other selected countries

Analysis of investigator fees: Phase IV

Review and cost analysis of investigator fees in the selected Central and Eastern European countries (Phase IV)
Review and cost analysis of investigator fees in the selected Latin American countries (Phase IV)
Review and cost analysis of investigator fees in selected Asian countries (Phase IV)
Review and cost analysis of investigator fees in the United States for Phase IV and comparison with other selected countries

Summary of investigator fees analysis: Phase I-IV, by therapeutic area and by selected geographic regions

Chapter 6 Review and cost analysis of laboratory fees, pharmacy costs and clinical trial liability insurance by selected country

Summary
Review and cost analysis of laboratory fees by selected country
Introduction

Laboratory fees: key variables

Review and cost analysis of laboratory fees in the principal Western European countries versus the United States
Review and cost analysis of laboratory fees in the principal Central and Eastern European countries versus the United States
Review and cost analysis of laboratory fees in the principal Latin American countries versus the United States
Review and cost analysis of laboratory fees in the principal Asian countries versus the United States
Other laboratory test costs and budget preparation fees
Review and cost analysis of pharmacy costs by selected country
Introduction
Comparison of pharmacy costs in the selected countries
Comparison of the average pharmacy fees in the selected geographic regions
Review and cost analysis of patient clinical trial liability insurance by selected country
Introduction
Comparison of clinical trial liability insurance requirements in the principal Western European countries
Comparison of clinical trial liability insurance requirements in the principal Central and Eastern European countries
Comparison of clinical trial liability insurance requirements in the principal Latin American countries
Comparison of clinical trial liability insurance requirements in the principal Asian countries
Clinical trial liability insurance requirements in the United States
Comparison of clinical trial liability insurance

Chapter 7 Review and cost analysis of CRO salaries by selected country

Summary
Evolution of the industry
Structure of CRO operating expenses reporting systems

Direct expenses
Research and development
Selling, general and administrative

Comparison of CRO salaries in the principal Western European countries
Comparison of CRO salaries in the principal Central and Eastern European countries
Comparison of CRO salaries in the principal Latin American countries
Comparison of CRO salaries in the principal Asian countries

Chapter 8 Appendix

Methodology statement

Primary data and information gathering
Secondary data and information gathering
Market share analysis and market forecast predictions
Definitions of product lifecycle stages

Glossary of abbreviations and acronyms

List of Figures
Figure 1.1: Key issues facing pharma and biotech companies
Figure 1.2: New Drug Approvals and R&D spending
Figure 1.3: Change in investment level by development phase between 2001 and 2007
Figure 1.4: Pharmaceutical research and development expenditure (2004-2009e)
Figure 1.5: Biotech R&D spending ($bn), 2004-2009e
Figure 1.6: Change in investment level by development phase, 2001-07
Figure 2.7: Overall clinical trial costs in various countries compared to the United States
Figure 2.8: Protocol target population checklist
Figure 2.9: Protocol feasibility checklist
Figure 2.10: Protocol budgetary considerations
Figure 2.11: Review and approval process for new clinical trials (Europe)
Figure 2.12: General review and approval process for new clinical trials (USA)
Figure 2.13: Budget process
Figure 3.14: Procedure for starting a clinical trial in the EU
Figure 3.15: Regulatory flowchart - Argentina
Figure 3.16: Regulatory flowchart - Brazil
Figure 3.17: Regulatory flowchart - Mexico
Figure 3.18: Application and approval procedure for clinical trials in China
Figure 4.19: Registered research ethics committees (REC) by Region . Brazil 2008
Figure 5.20: Key factors influencing the investigator fees
Figure 5.21: Relative cost per patient (CPP) by therapeutic area for investigators
Figure 5.22: Average per patient investigator fee ($) for Phase I by selected Western European countries, 2009
Figure 5.23: Average per patient investigator fee ($) for Phase I by therapeutic area, Western Europe, 2009
Figure 5.24: Average per patient investigator fee ($) for Phase I by selected Central and Eastern European countries, 2009
Figure 5.25: Average per patient investigator fee ($) for Phase I by therapeutic area in select CEE countries 2009
Figure 5.26: Average per patient investigator fee ($) for Phase I by selected Latin American countries, 2009
Figure 5.27: Average per patient investigator fee ($) for Phase I by therapeutic area in select Latin American countries, 2009
Figure 5.28: Average per patient investigator fee ($) for Phase I by selected Asian countries, 2009
Figure 5.29: Average per patient investigator fee ($) for Phase I by therapeutic area in select Asian countries, 2009
Figure 5.30: Average per patient investigator fee ($) for Phase I by selected countries, 2009
Figure 5.31: Average per patient investigator fee ($) for Phase I by therapeutic area, selected countries, 2009
Figure 5.32: Average per patient investigator fee ($) for Phase II by selected Western European countries, 2009
Figure 5.33: Average per patient investigator fee ($) for Phase II by therapeutic are in selected Western European countries, 2009
Figure 5.34: Average per patient investigator fee ($) for Phase II by selected CEE countries, 2009
Figure 5.35: Average per patient investigator fee ($) for Phase II by therapeutic area in selected CEE countries, 2009
Figure 5.36: Average per patient investigator fee ($) for Phase II by selected Latin American countries, 2009
Figure 5.37: Average per patient investigator fee ($) for Phase II by therapeutic area in select Latin American countries, 2009
Figure 5.38: Average per patient investigator fee ($) for Phase II in selected Asian, 2009
Figure 5.39: Average per patient investigator fee ($) for Phase II by therapeutic area in select Asian countries, 2009
Figure 5.40: Average per patient investigator fee ($) for Phase II in selected countries, 2009
Figure 5.41: Average per patient investigator fee ($) for Phase II in selected therapeutic areas, 2009
Figure 5.42: Average per patient investigator fee ($) for Phase III in selected Western European countries, 2009
Figure 5.43: Average per patient investigator fee ($) for Phase III in selected Western European countries, by therapeutic area, 2009
Figure 5.44: Average per patient investigator fee ($) for Phase III in selected CEE countries, 2009
Figure 5.45: Average per patient investigator fee ($) for Phase III in selected CEE countries, by therapeutic area, 2009
Figure 5.46: Average per patient investigator fee ($) for Phase III in selected Latin American countries, 2009
Figure 5.47: Average per patient investigator fee ($) for Phase III in selected Latin American countries, by therapeutic area, 2009
Figure 5.48: Average per patient investigator fee ($) for Phase III in selected Asian countries, 2009
Figure 5.49: Average per patient investigator fee ($) for Phase III in selected Asian countries, by therapeutic area, 2009
Figure 5.50: Average per patient investigator fee ($) for Phase III by selected countries, 2009
Figure 5.51: Average per patient investigator fee ($) for Phase III by therapeutic area, in selected countries, 2009
Figure 5.52: Average per patient investigator fee ($) for Phase IV in selected Western European countries, 2009
Figure 5.53: Average per patient investigator fee ($) for Phase IV in selected Western European countries, by therapeutic area, 2009
Figure 5.54: Average per patient investigator fee ($) for Phase IV in selected CEE countries, 2009
Figure 5.55: Average per patient investigator fee ($) for Phase IV in selected CEE countries, by therapeutic area, 2009
Figure 5.56: Average per patient investigator fee ($) for Phase IV in selected Latin American countries, 2009
Figure 5.57: Average per patient investigator fee ($) for Phase IV in selected Latin American countries, by therapeutic area, 2009
Figure 5.58: Average per patient investigator fee ($) for Phase IV in selected Asian countries, 2009
Figure 5.59: Average per patient investigator fee ($) for Phase IV in selected Asian countries, by therapeutic area, 2009
Figure 5.60: Average per patient investigator fee ($) for Phase IV by selected countries, 2009
Figure 5.61: Average per patient investigator fee ($) for Phase IV by therapeutic area, in selected countries, 2009
Figure 5.62: Average per patient investigator fee ($) for Phase I-IV by selected geographic regions, 2009
Figure 5.63: Average per patient investigator fee ($) for Phase IV by therapeutic area in selected countries, 2009
Figure 6.64: Comparison of average pharmacy fees in selected geographic regions ($), 2009
Figure 7.65: Multinational CRO average salaries per international employee in the principal Western European countries
Figure 7.66: CRO average salaries by employee type in the principal Central and Eastern European countries $000s/per Annum, 2009
Figure 7.67: CRO average salaries by employee type in the principal Latin American countries $000s/per Annum, 2009
Figure 7.68: CRO average salaries by employee type in the principal Asian countries $000s/per Annum, 2009

List of Tables
Table 3.1: Fees for authorization for Phase I clinical trial (ISS) Italy
Table 3.2: Fees for authorization of a clinical trial (UK)
Table 3.3: Fees for substantial amendments of a clinical trial (UK)
Table 3.4: Fees for authorization for clinical trials: Russia
Table 3.5: Guidelines and forms for authorization of clinical trails Czech Republic
Table 3.6: Documents required for initial application Czech Republic
Table 3.7: Documents required initial application Czech Republic
Table 3.8: Fees for authorization for clinical trials: Poland
Table 3.9: Application fees according to the drug and cosmetics act India
Table 4.10: Ethical committee fees for clinical trials: Russia
Table 5.11: Principal clinical trial cost centers
Table 6.12: Laboratory test fees United States versus Europe ($) (central laboratories)
Table 6.13: Laboratory test fees United States versus the Central and Eastern European countries ($), 2009
Table 6.14: Laboratory test fees United States compared to principal Latin American countries ($), 2009
Table 6.15: Laboratory test fees United States Compared to Principle Asian countries ($), 2009
Table 6.16: Laboratory test shipping temperate considerations in the mature and emerging clinical trial markets
Table 6.17: Pharmacy fees in the principal Western European countries ($), 2009
Table 6.18: Pharmacy fees in the principal Central and Eastern European countries ($)
Table 6.19: Pharmacy fees in the principal Latin American countries ($)
Table 6.20: Pharmacy fees in the principal Asian countries ($)
Table 6.21: Regulatory requirements: clinical trial liability insurance Western, Central and Eastern Europe
Table 6.22: Regulatory Requirements: Clinical Trial Liability Insurance Asia, Latin America and the United States
Table 7.23: Multinational CRO average salaries Per International Employee in the Principle Western European countries $000s/per annum
Table 7.24: CRO average salaries by employee type in the principal Central and Eastern European countries $000s/per Annum
Table 7.25: CRO average salaries by employee type in the principal Latin American countries $000s/per Annum, 2009
Table 7.26: CRO average salaries by employee type in the principal Asian countries $000s/per Annum, 2009