Benefit-Risk Appraisal of Medicines (eBook)

Dr Sam Salek, Reader in Pharmacoepidemiology, Director - WSP Centre for Socioeconomic Research; Director - Postgraduate Course in Pharmaceutical Medicine, Cardiff University, UK. Mr Filip Mussen, Johnson & Johnson Pharmaceuticals Research and Development, Belgium. Prof Stuart Walker, President and Founder, International Institute for Regulatory Science, UK.

Benefit-Risk Appraisal of Medicines 3
Contents 7
Foreword 9
Preface 11
1 Concept and Scope of Benefit–Risk Evaluation of Medicines 13
1.1 Historical background 13
1.2 The regulatory systems for assessing medicines 15
1.3 Benefit–risk assessment: definitions 16
1.4 Views and perceptions of benefits and risks of medicines 18
1.5 Stages and concepts in benefit–risk assessment 23
1.6 Benefit–risk assessment: the current regulatory environment 31
1.7 Benefit–risk assessment in other disciplines 31
1.8 Specific methods and models for benefit–risk assessment 33
1.9 Discussions with stakeholders on the concepts and models for benefit–risk evaluation 42
2 Criteria for a Benefit–Risk Model: a Conceptual Framework 43
2.1 Introduction 43
2.2 Regulatory guidelines on benefit and risk criteria 44
2.3 Identification, definition and rationale of relevant benefit and risk criteria 47
2.4 Verification of the list of benefit and risk criteria by means of a survey 71
3 Review of the Current Benefit–Risk Assessment Models 75
3.1 Background 75
3.2 Evaluation of the existing benefit–risk assessment models 77
3.3 Review of models in single clinical trials and for specific medicines 98
3.4 Conclusion 105
3.5 Newer models 108
4 Defining a Systematic Approach to Decision Making 111
4.1 Introduction 111
4.2 Objectives and features of the ideal model for benefit–risk assessment 112
4.3 The use of decision-analysis techniques for the development of the new model 113
5 Development and Application of a Benefit–Risk Assessment Model Based on Multi-Criteria Decision Analysis 123
5.1 Introduction 123
5.2 Conceptualization of the new model 123
5.3 Reasons for using decision analysis techniques in the new model 125
5.4 The use of MCDA in the new model 126
5.5 Development of the new model 128
5.6 Applicability of the new model 145
5.7 Summary 160
5.8 Review of the MCDA model 161
6 A Future Framework for Benefit–Risk Appraisal of Medicines 163
6.1 Background 163
6.2 Development of a benefit–risk framework for regulatory review of new medicines 163
6.3 Prerequisites of a benefit–risk framework for the registration of a new medicine 173
6.4 Current status of benefit–risk assessment among companies and agencies 176
6.5 Constructing a benefit–risk framework 184
6.6 Conclusion 196
Appendices 197
Appendix 1 Summary Reports of the CMR International Institute for Regulatory Science March 2004 and June 2005 Workshops on Benefit–Risk 197
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) 219
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) 245
Appendix 4 Commentaries on ‘A Quantitative Approach to Benefit–risk Assessment of Medicines’ Pharmacoepidemiology and Drug Safety, 2007, 16 263
Appendix 5 Forum on Benefit: Risk Decision Analysis – Summary of Discussions and Recommendations – MHRA (September 2008) 273
References 283
Index 297