Emerging Clinical Trial Locations: Market dynamics and the changing healthcare and regulatory environment

Table of Contents

Executive summary

• Introduction
• Conducting clinical trials in emerging markets
• India
• China
• Latin America
• Central and Eastern Europe

Chapter 1 Introduction

• Summary
• Introduction
• Generic competition
• Intellectual property protection
• Managing regulatory compliance
• Cost containment and government funding restrictions
• Obtaining and maintaining competitive advantage
• Recruitment and retention of a skilled workforce
• Improvement to R&D productivity
• High risks and costs associated with drug development
  • Escalating costs of clinical trials
  • Global increase in the number of clinical trials conducted
  • Longer R&D timelines
  • Increased attrition rates during R&D
• Clinical trial study design and planning
• Clinical trial study design
• Clinical trial study protocol
• Clinical trial sponsors
• Identifying and recruiting patients
• Role of CROs
• Information technology and new technology platforms
• Drivers of development
  • Advantages associated with EDC
  • Advantages of electronic Clinical Trial Management Systems
  • (CTMS)
  • Cost saving
• Issues and challenges
  • Electronic records and signatures
  • Integration and linkage of electronic systems
  • Security and confidentiality of patient data

Chapter 2 Conducting clinical trials in emerging markets

• Summary
• Introduction
• Market drivers
• Rapid recruitment of patients and clinical trial investigators
• Significant cost benefits
• Improving transparency and efficiency of regulatory systems
• Harmonization and standardization of regulatory requirements
• Expansion of CROs
• Conducive hospital infrastructure and healthcare systems
• Enhanced clinical site effectiveness
• Future commercial value
• Key barriers
• Concerns over the clinical trial transparency
  • Publication bias
  • Selective reporting
  • Duplicate publication
  • Conflict of interest
• Availability of demographic and epidemiology data
• Critical components concerning capacity building
• Assimilation of individual national regulations and guidelines
  • United States
  • Japan
  • European Union
• Language translation
• Ethical challenges
  • Health needs of the population under study
  • Respect for potential and enrolled subjects
  • Ethical oversight
  • Lack of review by institutional review board (IRB)
  • Absence of informed consent
  • Scientific validity
• Inadequate protection of intellectual property
• Clinical trial logistics
  • Import licenses and applications
  • Customs regulations
  • Storage, handling and distribution
• Selecting an appropriate CRO
• Patient enrolment
  • Site selection
  • Site activation
  • Patient recruitment

Chapter 3 India

• Summary
• Introduction
• Geographic
  • Political
  • Economic
• Market dynamics
• Vital statistics
• Population statistics
• Epidemiology and prevalence of major disease
• Pharmaceutical market
• Biotechnology market
• CRO market
• Clinical trial market
  • Geographic focus of the Indian clinical research industry
• Market drivers
• Population ethnicity and genetic diversity
• Large complement of trained medical specialists in India
• Significant cost savings
• Government incentives
• Creation of the Clinical Trials Registry - India (CTRI)
• Sophisticated logistics and clinical research infrastructure
• Comprehensive IT and IT enabled support (ITES) base
• Key barriers
• Ethical issues
• Lack of experienced investigators
• Inability to detect and monitor ADRs
• Bribery and corruption
• Healthcare
• Healthcare system
  • National level
  • State level
  • Regional level
  • District level
  • Sub-divisional/Taluka level
  • Community level
  • Primary health centre (PHC) level
  • Sub health centre (SHC) level
• Hospital resources
• Regulation and legislation
• Regulatory authorities
  • The Ministry of Health and Family Welfare
  • Central Drug Standard Control Organization (CDSCO)
  • Drug Controller General of India (DCGI)
  • Indian Council of Medical Research (ICMR)
• Clinical trial regulation
  • Harmonization of the clinical trial approval process
• Legislation
  • Patent law and WTO TRIPS
  • Schedule Y Drugs and Cosmetics Act and Rule
  • Summary of the recent regulatory and legislative changes
• Evolution of the regulatory environment
  • Expected improved collaboration: DCGI with international agencies
  • Anticipation of approval for early phase studies in India
  • Registration and regulation of CROs in India
  • Future reform and emphasis on improved pharmacovigilance in
  • India
  • India to implement an electronic management system
• Outlook

Chapter 4 China

• Summary
• Introduction
• Geographic
• Political
• Economic
• Market dynamics
• Vital statistics
  • Population statistics
  • Epidemiology and prevalence of major disease
• Pharmaceutical market
• CRO market
  • Overseas CROs
  • Joint venture companies
  • Local CROs
• Clinical trial market
• Market drivers
• Rapid patient recruitment from large pool of treatment naive patients
• Well-trained and motivated clinical trial investigators
• Major cost savings
• Increasing importance of the pharmaceutical market in China
• US government opens FDA offices in China
• Financial support and incentives from the Chinese government
• Creation of the Chinese Clinical Trial Register (CHiCTR)
• Key barriers
• Cultural and linguistic
• Delays to application and gaining approval
• Due diligence required to ensure intellectual property protection
• Issues over importation and importation licenses
• Monitor compliance of SFDA GCP with ICH GCP
• Healthcare
• Healthcare system
  • Overview
  • Healthcare reforms
  • Healthcare institutions
• Hospital resources
• Regulation
• Regulatory authorities
  • State Food and Drug Administration (SFDA)
  • Department of drug registration
• Clinical trial regulation
  • Application and approval of the new drug clinical trial study
  • Registration approval for the manufacture of the new drug
• market
• Legislation
  • Patent Law and WTO TRIPS
  • Drug Administration Law of the People' s Republic of China
• Outlook

Chapter 5 Latin America

• Summary
• Introduction
• Geographic
  • Brazil
  • Argentina
  • Mexico
• Political
  • Brazil
  • Argentina
  • Mexico
• Economic
  • Brazil
  • Argentina
  • Mexico
• Market dynamics
• Vital statistics - Brazil
  • Population statistics
  • Epidemiology and prevalence of major disease
• Vital statistics - Argentina
  • Population statistics
  • Epidemiology and prevalence of major diseases
• Vital statistics - Mexico
  • Population statistics
  • Epidemiology and prevalence of major disease
• Pharmaceutical market
• CRO market
• Clinical trial market

• Market drivers
• Significant cost savings
• High concentration of population in urban centers
• High ethnic diversity
• High patient enrolment, compliance and retention rates
• A major growing Latin American pharmaceutical market
• Reverse seasons advantages
• Commonality of Spanish language
• Accessibility to medical professionals and clinical trial investigators
  • National clinical trials register - Argentina

• Key barriers
• Concerns over intellectual property protection
• Inconsistent regulatory environment
• Cultural challenges and issues

• Healthcare
• Healthcare system- Brazil
• Hospital resources - Brazil
• Healthcare system - Argentina
• Hospital resources - Argentina
• Healthcare system - Mexico
• Hospital resources - Mexico
• Regulation and guidelines
• Regulatory authorities
  • The Pan American Network for Drug Regulatory Harmonization
  • (PANDRH)
  • ANVISA - Brazil
  • Brazilian Research Ethics Commission (CONEP)
  • ANMAT - Argentina
  • SSA - Mexico
  • COFEPRIS - Mexico
• Clinical trial regulation
  • Brazil
  • Argentina
  • Mexico
• Guidelines
  • Good Clinical Practices: Document of the Americas
  • The Buenos Aires Declaration on Ethics and Clinical Trials
  • Import licenses for drugs in clinical trials - Mexico
• Outlook

Chapter 6 Central and Eastern Europe

• Summary
• Introduction
• Geographic
  • Czech Republic
  • Poland
  • Russian Federation
• Political
  • Czech Republic
  • Poland
  • Russian Federation
• Economic
  • Czech Republic
  • Poland
  • Russian Federation

Market dynamics

• Vital statistics
  • Population statistics
  • Epidemiology and prevalence of major diseases
• Pharmaceutical market
• CRO market
  • Czech Republic
  • Poland
  • Russian Federation
• Clinical trial market
  • Czech Republic
  • Poland
  • Russian Federation

Market drivers

• Large eligible treatment naive population who exhibit high retention rates
• Large pool of dedicated, well trained and motivated investigators
• Cost savings
• Centralized healthcare systems and well-developed referral systems
• Entry of Russian Federation into the World Trade Organization (WTO)
• Positive assessments by the US FDA (Poland)

Key barriers

• Poor hospital infrastructure with inadequate medical equipment
• Cultural differences and issues
• Potential delays importing the study drug (Russia)
• Concerns and issues obtained from regulatory inspections by the FDA
• (Russia)
• Lack of clinical trial experience amongst hospital staff and hospital services

• Healthcare
• Healthcare system - Czech Republic
• Hospital resources - Czech Republic
• Healthcare system - Poland
  • Ministry of Health
  • National health fund
  • Territorial self-government administrations
• Hospital resources - Poland
• Healthcare system - Russian Federation
• Hospital resources - Russian Federation
• Regulation and legislation
• Regulatory authorities
  • SUKL - Czech Republic
  • NIL - Poland
  • RZN - Russian Federation
• Clinical trial regulation
  • Czech Republic
  • Poland
  • Russian Federation
• Legislation
  • Poland removes tax block for clinical trials
  • Decree no. 226/2008 on good clinical practices - Czech Republic
  • Russia
• Outlook

Appendix

• Introduction to clinical trials
• Clinical trial phases
  • Phase I
  • Phase II
    • Phase III
    • Phase IV
  • What is a clinical trial
  • Clinical trials of pharmaceutical agents
  • Types of clinical trial
  • Pilot studies
  • Proof of concept (PoC) trials
  • Randomized clinical studies
  • Controlled clinical trials
  • Parallel studies
  • Parallel group trials
  • Cohort studies
  • Case control studies
• Role of the chief investigator
• Clinical trial protocol and procedure
• Determination of the clinical trial size
• Role of the coordinating centre and trials unit
• Role of the trial coordinator
• The trial principle investigator
• Forms and data management
• Trial data analysis and evaluation
• Ethical issues and conduct of clinical trial research
• Interpretation and publication of clinical trial results
• Principle 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)
• Methodology statement
• Primary Data and Information Gathering
• Secondary data and information gathering
• Definitions of Product-Life Cycle stages
• Glossary of abbreviations and acronyms
• Index

List of Figures

• Figure 1.1: Key issues facing Pharma and Biotech companies
• Figure 1.2: Cost of bringing a drug to market ($m), 1975-2008
• Figure 1.3: Pharmaceutical R&D expenditure ($bn), 2004-2009e
• Figure 1.4: Biotechnology R&D expenditure ($bn), 2004-2009e
• Figure 1.5: Cost of clinical trials in the US ($bn), 2005-2011e
• Figure 2.6: Comparison of locations across selected countries
• Figure 2.7: Korean Food and Drug Administration (KFDA) Approval Process
• Figure 2.8: CRO Segment Leaders
• Figure 2.9: Enhanced clinical site effectiveness (patients per site) in the emerging countries
• Figure 2.10: Fewer ineffective sites in the emerging countries
• Figure 2.11: Critical components for capacity building/conducting clinical trials
• Figure 2.12: Assessing clinical trial location feasibility
• Figure 2.13: CRO selection criteria
• Figure 3.14: GDP in India (%) by sector
• Figure 3.15: Projected growth of healthcare industry in India ($bn), 2008-2022
• Figure 3.16: Population projection (millions) in India, 2000-2020
• Figure 3.17: Pharma industry in India ($bn), 2007-2010
• Figure 3.18: Market share (%) between MNCs and local pharmaceutical companies in India, 2003-2007
• Figure 3.19: Outsourced clinical trial market in India (US$), 2002-2010
• Figure 3.20: Clinical trials in India (by phase), 2009
• Figure 3.21: Types of disease and types of hospitals in India
• Figure 3.22: Cost of clinical trials (%) in India vs US
• Figure 3.23: Structure of healthcare system in India
• Figure 3.24: Current organogram of the Ministry of Health and Family Welfare
• Figure 3.25: Proposed organogram of the Ministry of Health and Family Welfare
• Figure 3.26: Approval categories of global clinical trials in India
• Figure 4.27: Administrative divisions of the People' s Republic of China
• Figure 4.28: Pharma market in China ($), 2007-2008
• Figure 4.29: CRO market in China (US$), 2007-2012
• Figure 4.30: Cost of clinical trials (%) in China vs western countries
• Figure 4.31: The Chinese Healthcare System
• Figure 4.32: NRCMCS medical cover cost and benefits in China
• Figure 4.33: Current drug approval and evaluation process in China
• Figure 4.34: Application and approval procedure for clinical trials China
• Figure 4.35: Location of accredited sites for clinical trials in China
• Figure 5.36: Population projection (' 000s) - Brazil, 2000-2050
• Figure 5.37: Population projection (thousands) - Argentina, 2000-2050
• Figure 5.38: Population projection (thousands) - Mexico, 2000-2050
• Figure 5.39: Forecast growth ($bn) Latin America pharmaceutical market, 2008-2013
• Figure 5.40: Latin America pharmaceutical market 2008
• Figure 5.41: No. of clinical trials in Latin America, 2000-2008
• Figure 5.42: Clinical trials by phase in Latin America (number of trials), 2008
• Figure 5.43: Registered Research Ethics Committees (REC) by Region - Brazil 2008
• Figure 5.44: Regulation of clinical trials in Latin America 2007
• Figure 5.45: Regulatory flowchart - Brazil
• Figure 5.46: Regulatory flowchart - Argentina
• Figure 5.47: Regulatory flowchart - Mexico
• Figure 6.48: Pharmaceutical market by selected Central and Eastern European countries, 2007
• Figure 6.49: Clinical trials Europe
• Figure 6.50: Clinical trials by phase (no trials) in the Czech Republic, 2008
• Figure 6.51: Clinical trials market ($m) in Poland, 2007-2010
• Figure 6.52: Clinical trials by therapy area (%) in Russia, 2008
• Figure 6.53: Clinical trials by phase (%) in Russia, 2008
• Figure 6.54: FDA inspection deficiencies in Russian sites