The Emerging Role of Postmarketing Clinical Research - Regulatory issues, strategic drivers and overall trends

http://www.companiesandmarkets.com/Summary-Market-Report/the-emerging-role-of-postmarketing-clinical-research-regulatory-issues,-strategic-drivers-and-overall-trends-44867.asp

Market - Information Technology
Published Date - 01/05/2008
Report Type - Market Report
Country - Global
Number of Pages - 121

Electronic - £2,025.00

Report Summary

Emerging Role of Postmarketing Clinical Research: Regulatory Compliance, Product Differentiation and Key Issues

Report overview

The pharmaceutical industry has recently endured intense speculation and negative publicity as a result of high profile product withdrawals caused by inadequate safety profiles. Regulatory bodies have responded swiftly; the FDA now requires mandatory surveillance data submission for drugs under increased scrutiny, and the EMEA is close to implementing similar strategies as part of drug policy harmonization initiatives for phase IV trials. Postmarketing clinical research has also become a key feature of product lifecycle management. Phase IIIb/IV trials are increasingly being used in company specific initiatives to provide strategic guidance in areas such as payor approval and reimbursement, indication expansion, franchise development and marketing.

‘Emerging Role of Postmarketing Clinical Research’ is a new report published by Business Insights that uses detailed case studies and market scenarios to examine the latest issues surrounding phase IV trial applications. The potential to leverage competitive advantage with postmarketing research is assessed by measuring the implications for formulary access, product marketing, indication expansion and reimbursement coverage. This report also explores the regulatory issues and requirements affecting mandatory postmarketing trial conduct and identifies the key components of effective phase IV trial design and completion.

Identify the latest regulatory developments affecting postmarketing clinical research, use case studies to evaluate recent phase IV trial implementations and understand the competitive potential of successful trial designs...

Key findings...

• US Government initiatives have almost doubled the number of post-approval commitments since 2003-2004, following growing numbers of black box warnings and late-stage drug withdrawals.
• The EMEA and FDA will continue to harmonize regulatory approaches for phase IV monitoring and study commitments in areas of common interest, including pandemic vaccines, medicines for children, rare diseases and cancer medicines.
• Big Pharma companies conducted 145 (75%) of the 243 industry trials publicly registered with the FDA between 1998-2007. Of these trials, 109 were independently undertaken by big pharma as strategic initiatives. Average Big Pharma patient numbers (1743) far exceeded those of mid-tier biopharma companies (952).
• The implementation of a networked model of stakeholder involvement has become crucial to the success of drug developers by enabling access to new development platforms and facilitating effective trial management/sponsorship
• Active controls featured in 71 industry-sponsored trials, the majority of which were conducted under randomized, open label, parallel assignments. Of the 14 registered trials for medical devices, seven were undertaken with active control comparators in an interventional setting.

Key questions answered...
• How will the rising significance of postmarketing research cause pharma and biotech companies to restructure?
• How can phase IIIb/IV trials be used to successfully manage product lifecycles and market positioning?
• To what extent will the increased regulatory demands over postmarketing data collection and submission impact the pharma industry?
• What are the precise requirements for clinical data submission and how are these relevant to company-specific initiatives?
• How can market competition influence trial design and conduct?
• How has the FDA Amendment Act of 2007 affected prescription drug regulations and postmarketing commitment criterion?

Key issues examined...
• Revised R&D resource allocation. As regulators and companies increasingly apply postmarketing surveillance to justify product positioning and long term safety/efficacy profiles, financial investment in phase IIIb/IV trials will grow at a relatively higher rate than other stages of clinical development.
• New regulatory policies. The FDA will soon require mandatory submission of phase IV surveillance data over a large patient population. In addition, products approved on the grounds of accelerated procedures, or those which incorporated surrogate endpoints/biostatistical modelling techniques in early phase data, will require further commitment studies after conditional approval.
• Impact on lifecycle management. Marketing and product labelling companies are under pressure to justify claims through postmarketing study data submission, whilst indication expansion development strategies require postmarketing product data submission to support applications for extended approval.
• Importance of trial design/management. With multiple applications for trial data, trial design and management is crucial in identifying potential issues or adjustments as early as possible. Proactive adaptive designs and electronic data capture techniques are necessary for the ongoing analysis of collated datasets.

Top reasons to purchase this report

• Assess the industry impact of recent regulatory developments in postmarketing commitment trials and surveillance studies

• Use detailed case studies to understand the influence of phase IV trials upon lifecycle management, indication expansion and reimbursement

• Identify how postmarketing strategies can enhance product differentiation, market development and formulary coverage

• Evaluate the operational objectives and trial management/outsourcing trends for phase IV trials across key industry sectors

Table of Contents
The Emerging Role of Postmarketing Clinical Research Executive Summary 8
Background to postmarketing research 8
Mandatory postmarketing trial requirements 8
Phase IV trials for market development 10
Impact of competitive pressures and pipeline strength on phase IV trials 11
Appropriate trial design 12
Chapter 1 Background to postmarketing research 16
Summary 16
Introduction 17
The clinical trial landscape 19
Priorities and end-points in clinical development 20
Safety and full market approval 22
Health-economic arguments 23
Life cycle management 23
Product positioning and differentiation 23
Chapter 2 Mandatory postmarketing trial requirements 28
Summary 28
FDA regulations for postmarketing trials 29
Postmarketing commitment trials (PMC) 29
Direct and indirect drivers for PMC conduct 33
Indirect driver: Public health priorities 33
Direct driver: Orphan drugs 34
PMC Case Study: Iressa 35
PMC Case study: Vioxx 37
Postmarketing surveillance studies (PMS) 38
PMS study drivers 39
PMS design limitations 39
FDA Amendment Act (FDAAA) 42
Industry implications of FDAAA 43
Public submission of datasets 43
EMEA 45
Terms of marketing approval agreement 45
Joint FDA-EMEA drug monitoring initiatives 45
Trials for improved clinical guidance 47
Chapter 3 Phase IV trials for market development 50
Summary 50
Introduction 51
Phase IV trials for formulary access 54
US – the importance of comparative effectiveness 56
EU – the importance of added therapeutic value 58
Postmarketing trials for indication expansion 59
The Rx to OTC switch 62
Off-label physician use and risk management 64
Product development for indication expansion 66
Line extensions 68
Case Study: Line extension launch profiles 68
Case study: Zoloft (sertraline) 69
Reformulations 71
Follow-on compounds 71
Phase IV trials for multiple indication expansion strategies 71
Case study: Zyprexa 72
Case study: Alimta (Pemetrexed) 74
Enhanced market positioning 77
Marketing regulations 77
Head to Head trials 78
Case study: Zyprexa vs Risperdal 79
US Direct to Consumer (DTC) regulations 80
EU marketing regulations 80
Influence of sponsorship on trial endpoint 81
Impact of budget constraints 82
Big pharmaceutical firms 83
Mid tier biopharma and biotechnology firms 83
Big pharma’s scale advantage 85
Case study: Novartis 86
Case study: Glivec (Imatinib mesylate) 88
Case study: Aclasta (zoledronic acid) 89
Misuse of phase IV trials and regulator scrutiny 90
Chapter 4 Impact of competitive pressures and pipeline strength on phase IV trials 94
Summary 94
The impact of competition 95
Market scenario: Cardiovascular 97
Case study: Diovan 99
Market scenario: oncology 100
Antineoplastics - market drivers for phase IV trials 102
Chapter 5 Effective phase IV trial design 106
Summary 106
Introduction 107
Endpoint designation and trial purpose 107
Patient and physician recruitment 108
Recruitment bottlenecks 110
Design limitations 110
Study design 112
Data management and adaptive clinical trial designs 113
Operational management 114
Chapter 6 Appendix 117
Primary research methodology 117
Glossary 118
Index 120
List of Figures
Figure 2.1: Projected R&D spend by phase 2005-2009 ($bn), 19
Figure 2.2: Postmarketing research and product lifecycle 20
Figure 3.3: NDA and ANDA requirements for postmarketing status reports 31
Figure 3.4: Biological product reporting requirements for postmarketing status reports 32
Figure 3.5: Sales of Iressa in the US, 2003-2007 ($m) 36
Figure 3.6: Vioxx sales in the US, 2003-2004 ($m) 38
Figure 3.7: Implication of FDA requirement of REMS 41
Figure 3.8: Implications of tightened FDA policies 43
Figure 4.9: Market drivers for postmarketing research 51
Figure 4.10: Declining return on R&D investment (US, 1990-2004) 52
Figure 4.11: Payor’s influence gain in prescribing decisions; US market, share of voice, 2007 56
Figure 4.12: Marketing and product development strategies using phase IV trials 60
Figure 4.13: Phase IV for product lifecycle management 62
Figure 4.14: Sales summary for Zoloft in the US, 2000-2006 70
Figure 4.15: Use of postmarketing trials for lifecycle management of Zyprexa, US and EU5, 2000-2007 ($m) 73
Figure 4.16: Effect of indication expansion on sales of Alimta in the US, 2004-2007 ($m) 76
Figure 4.17: Big pharma phase IV trials by strategic purpose, USA, 1998-2007 86
Figure 4.18: Number of phase IV trials by different ‘Big pharma’ companies 87
Figure 5.19: Impact of market competition on phase IV trial design and objective 95
Figure 5.20: Global cardiovascular product pipeline, Q1 2008 98
Figure 5.21: Diovan sales in the US, 1998-2007 ($m) 100
Figure 5.22: Global cancer product pipeline, Q1 2008 101
Figure 5.23: Number of phase IV trials vs sales growth, USA, 2003-2007 103
Figure 6.24: Factors influencing successful Phase IV conduct 107
Figure 6.25: Advantages and disadvantages posed by phase IV study designs 112
List of Tables
Table 2.1: Phase IIIb vs Phase IV postmarketing studies 18
Table 4.2: On-label indication expansion drivers 67
Table 4.3: Declining incremental sales revenue return with subsequent line extension launches 69
Table 4.4: Zyprexa- Pivotal phase IV trials for indication expansion and formulary access 74
Table 4.5: Industry vs non-industry trial objectives 82
Table 4.6: Trial characteristics by commissioning organization, 1998-2008* 85
Table 6.1: Influence of study participation on subsequent drug prescribing 109
Table 6.2: Advantages and disadvantages of using adaptive clinical trial designs 114