Reportlinker Adds Advances in the Design and Regulation of Adaptive Clinical Trials
NEW YORK, Dec. 8, 2010 /PRNewswire/ -- Reportlinker.com announces that a new market research report is available in its catalogue:
Advances in the Design and Regulation of Adaptive Clinical Trials
As the pharma industry comes under increasing pressure to replenish revenues which are under threat from generic competition, there is an increased focus on technologies and trial designs which aim to maximize success and reduce development time. This report reviews the use of adaptive designs across all phases of development. Dose-ranging and seamless trials are explored through case studies of important adaptive trials. Regulation by the FDA and EMA is covered in detail. The report also reviews logistical and technological aspects of adaptive designs as well as presenting an outlook for their use in drug development.
Scope of this research
• Learn how the largest companies are applying adaptive methods to improve drug development.
• Identify situations in which adaptive trials could benefit drug development in your company.
• Analyze the importance of adaptive trials in the context of a drug's development program and a company's portfolio of compounds.
• Assess how the FDA's draft guidelines on adaptive trials are influencing companies to use adaptive trials in their drug development programs.
• Evaluate the providers of key skills and technologies for adaptive trials.
Research and analysis highlights
The large majority of adaptive trials currently being undertaken in the pharma industry are Phase 2 – 'Learning' – trials that aim to establish the most effective dose and the dose response curve. Exploratory trials may also aim to combine proof of concept with dose finding, stop early for futility or investigate biomarkers and patient subsets.
Ground-breaking research using adaptive designs with biomarkers is currently shaping the future of research in the field of oncology. The highly collaborative I SPY2 study may deliver changes to the field on a number of levels such as demonstrating the feasibility of cooperation at this level and the efficiency of the adaptive design.
Companies are learning how to implement adaptive studies in the confirmatory stages of drug development and regulators are developing their views on what is acceptable. Interaction with regulators to gain acceptance for a particular design and implementation plan, and proper documentation of decisions and actions, are a key success factors.
Key reasons to purchase this research
• What is the current regulatory position on the use of adaptive trials in the exploratory and confirmatory stages of drug development?
• Where and how have adaptive trials been used by the industry already? Which companies are pioneering their use?
• How can adaptive trials improve drug development?
• What are the costs associated with adaptive trials? Can they save money?
• How can adaptive trials be used in clinical trials with biomarkers?
Table of Contents
About the authors 2
Disclaimer 2
Executive summary 9
Introduction 9
Adaptive trials in the 'learn' development phase 10
Adaptive trials in the 'confirm' development phase 10
Simulation in the design of adaptive trials 11
Logistics and technology requirements for adaptive trials 12
Regulation of adaptive trials 13
Outlook for adaptive trials 14
Chapter 1 Introduction 16
Summary 16
Introduction 17
Defining adaptive clinical trials 17
Why adapt? 19
Redesigning drug development 22
Potential advantages of adaptive trials 23
Companies working together 24
Report outline 26
Chapter 2 Adaptive trials in the 'learn' development phase 27
Summary 27
Introduction 28
Finding the right dose 28
The Adaptive Dose-Ranging Studies Working Group 29
Case studies 31
Pfizer's ASTIN study 31
Dose-ranging study in neuropathic pain (Pfizer) 34
Dose-finding study of anti-migraine compound (Merck & Co) 35
Adaptive dose finding study (Wyeth) 36
A Bayesian dose-finding trial in patients with diabetes (Wyeth) 39
A Bayesian adaptive randomization seamless Phase IIa/b study (Abbott Labs) 40
Adaptive Phase I oncology trials: the continual re-assessment method 40
Biomarkers and adaptation in the 'learn' phase 41
Adaptive trials with predictive biomarkers 42
Adaptive signature designs 43
Adaptive randomization designs 44
Case study: Biomarker-Integrated Approaches of Targeted Therapy of Lung Cancer Elimination (BATTLE) Trial 44
Case study: I-SPY2 45
Conclusions 47
Chapter 3 Adaptive trials in the 'confirm' development phase 49
Summary 49
Introduction 50
'Seamless' confirmatory trials 51
Case studies 52
Eli Lilly case study 52
Novartis case study 1 55
Novartis case study 2 58
AstraZeneca case study 59
Napo Pharmaceuticals case study 61
Cempra Pharmaceuticals case study 61
Pros and cons of seamless designs 62
Regulatory view 62
White space 64
When are seamless designs appropriate? 65
Sample size re-estimation in confirmatory trials 66
Conclusions 68
Chapter 4 Simulation in the design of adaptive trials 70
Summary 70
Introduction 71
Clinical trial simulations 71
Including pharmacometric data 73
Providers of clinical trial simulation software 74
Berry Consultants 75
Cytel Inc 76
Documenting simulations 76
Statisticians in drug development 77
Conclusions 77
Chapter 5 Logistics and technology requirements for adaptive trials 79
Summary 79
Introduction 80
Suppliers of clinical technologies 81
Consolidation within the industry 82
Endpoint selection and real-time data collection 83
Technologies for data collection and their integration 83
Case study: Timaeus (Cmed Technology Ltd) 85
Electronic data capture (EDC) 85
Standards in EDC 86
Special considerations for safety parameters 87
Interactive voice recognition and interactive web response 87
Electronic patient reported outcomes (ePRO) 88
Cleaning data 88
Testing data flow 89
Clinical supply management 89
Key challenges in supply chain management 89
IXRS 90
Simulation 90
Case study – clinical trial supply scenario simulation 91
Case study – Wyeth dose finding trial 91
Documenting design decisions 92
Conclusions 93
Chapter 6 Regulation of adaptive trials 94
Summary 94
Introduction 95
The EMA position on adaptive designs 95
FDA draft guidance on adaptive designs 96
Bayesian statistics 97
Regulatory documents 97
Interacting with the FDA 97
Industry response to the draft guidelines 99
Causes for regulatory concern 99
Type 1 error rate control 100
Maintaining confidentiality 100
Conclusions 104
Chapter 7 Outlook for adaptive trials 106
Summary 106
Introduction 107
Impact of adaptive clinical trials on costs and success in drug development 107
Cost savings associated with stopping early 108
Modeling costs and the probability of success 109
Portfolio planning for clinical trials with biomarkers 111
Organizational changes for adaptive trials 113
Outlook for adaptive trials 114
Conclusions 115
Appendix 117
Primary research methodology 117
Acknowledgments 118
Glossary 119
Bibliography 121
Table of figures
Figure 1: Summary of strategic motivations for using adaptive trials 20
Figure 2: Examples of strategic motivations for adapting clinical trials 21
Figure 3: The 'learn and confirm' model of drug development 23
Figure 4: Types of dose finding adaptive trial design tested by the PhRMA Adaptive Dose-Ranging Studies Working Group in 2009 30
Figure 5: Structure of the ASTIN study 32
Figure 6: Data from the ASTIN study 33
Figure 7: Design of an adaptive dose finding study with telcagepant (Merck & Co) 35
Figure 8: The adaptive signature design 43
Figure 9: Design of the BATTLE study to identify molecular signatures targeted by drugs for non-small cell lung cancer 45
Figure 10: Overview of the I-SPY2 trial design 46
Figure 11: Design of operationally and inferentially seamless trials 51
Figure 12: Key elements of Eli Lilly's seamless Phase II/III study in patients with type 2 diabetes 53
Figure 13: Design Eli Lilly's seamless Phase IIb/III study in patients with type 2 diabetes 54
Figure 14: Key elements of Novartis' seamless Phase IIb/III study in COPD 56
Figure 15: Novartis' completed seamless adaptive Phase IIb/III study design 57
Figure 16: Seamless adaptive Phase IIb/III trial designs; Novartis case study 59
Figure 17: HORIZON III Phase II/III clinical study 60
Figure 18: When to use seamless adaptive Phase IIb/III designs 66
Figure 19: The clinical trial design simulation process 72
Figure 20: Information utilized in model-based drug development 73
Figure 21: Choosing an adaptive design: infrastructure and process requirements 81
Figure 22: Providers of clinical technologies to support adaptive trials 82
Figure 23: Automated implementation for adaptive designs 84
Figure 24: Acceptance of different adaptive designs 97
Figure 25: Relationship between the size of Phase IIb and the probability of success in Phase III 110
Figure 26: Relationship between the size of Phase IIb and the product's expected net present value 111
Table of tables
Table 1: Definitions of adaptive clinical trials 18
Table 2: Advantages and disadvantages of using adaptive clinical trial designs 24
Table 3: Bayesian designs can investigate more doses 34
Table 4: Comparison of features of different designs for a dose finding study 37
Table 5: Adaptive dose finding study comparisons: probabilities of success and potential cost savings 38
Table 6: Definitions of four key types of biomarker 41
Table 7: Advantages and disadvantages of seamless adaptive designs 62
Table 8: Consequences of incorrect planning for treatment difference and/or standard deviation 67
Table 9: Leading companies offering statistical expertise for adaptive trials 75
Table 10: Cost savings associated with stopping early for futility 109
To order this report:
Drug Discovery and Development Industry: Advances in the Design and Regulation of Adaptive Clinical Trials
Drug Discovery and Development Business News
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Nicolas Bombourg |
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Reportlinker |
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