Table of Contents
Foreword vii
Preface ix
1 Concept and Scope of Benefit-Risk Evaluation of Medicines 1
1.1 Historical background 1
1.2 The regulatory systems for assessing medicines 3
1.3 Benefit-risk assessment: definitions 4
1.4 Views and perceptions of benefits and risks of medicines 6
1.5 Stages and concepts in benefit-risk assessment 11
1.6 Benefit-risk assessment: the current regulatory environment 19
1.7 Benefit-risk assessment in other disciplines 19
1.8 Specific methods and models for benefit-risk assessment 21
1.9 Discussions with stakeholders on the concepts and models for benefit-risk evaluation 30
2 Criteria for a Benefit-Risk Model: a Conceptual Framework 31
2.1 Introduction 31
2.2 Regulatory guidelines on benefit and risk criteria 32
2.3 Identification, definition and rationale of relevant benefit and risk criteria 35
2.4 Verification of the list of benefit and risk criteria by means of a survey 59
3 Review of the Current Benefit-Risk Assessment Models 63
3.1 Background 63
3.2 Evaluation of the existing benefit-risk assessment models 65
3.3 Review of models in single clinical trials and for specific medicines 86
3.4 Conclusion 93
3.5 Newer models 96
4 Defining a Systematic Approach to Decision Making 99
4.1 Introduction 99
4.2 Objectives and features of the ideal model for benefit-risk assessment 100
4.3 The use of decision-analysis techniques for the development of the new model 101
5 Development and Application of a Benefit-Risk Assessment Model Based on Multi-Criteria Decision Analysis 111
5.1 Introduction 111
5.2 Conceptualization of the new model 111
5.3 Reasons for using decision analysis techniques in the new model 113
5.4 The use of MCDA in the new model 114
5.5 Development of the new model 116
5.6 Applicability of the new model 133
5.7 Summary 148
5.8 Review of the MCDA model 149
6 A Future Framework for Benefit-Risk Appraisal of Medicines 151
6.1 Background 151
6.2 Development of a benefit-risk framework for regulatory review of new medicines 151
6.3 Prerequisites of a benefit-risk framework for the registration of a new medicine 161
6.4 Current status of benefit-risk assessment among companies and agencies 164
6.5 Constructing a benefit-risk framework 172
6.6 Conclusion 184
Appendices
Appendix 1 Summary Reports of the CMR International Institute for Regulatory Science March 2004 and June 2005 Workshops on Benefit-Risk 185
Appendix 2 Office of Health Economics Briefing: Challenges and Opportunities for Improving Benefit-risk Assessment of Pharmaceuticals from an Economic Perspective - James Cross and Louis Garrison (August 2008) 207
Appendix 3 Reflection Paper on Benefit-risk Assessment Methods in the Context of the Evaluation of Marketing Authorisation Applications of Medicinal Products for Human Use - Committee for Medicinal Products for Human Use (March 2008) 233
Appendix 4 Commentaries on 'A Quantitative Approach to Benefit-risk Assessment of Medicines' Pharmacoepidemiology and Drug Safety, 2007, 16 251
Appendix 5 Forum on Benefit: Risk Decision Analysis - Summary of Discussions and Recommendations - MHRA (September 2008) 261
References 271
Index 285