Title Page

Contents

Abstract 11

Chapter 1. INTRODUCTION 13

1. Backgrounds 13

2. Study Objective 19

Chapter 2. LITERATURE REVIEW 20

1. COVID-19 Vaccine Benefit-Risk Study 20

2. Structured benefit-risk assessment 25

Chapter 3. MATERIALS AND METHODS 33

1. Study design 33

2. Criteria Selection 37

3. Input data collection 39

4. Preference Score 50

5. Weighting 53

6. Benefit-Risk assessment 58

7. Sensitivity analysis 61

Chapter 4. RESULTS 62

1. Value tree for Benefit-Risk assessment 62

2. Input data for benefit-risk criteria 63

1) Input data for benefit-risk criteria for pre-authorization 63

2) Input data for benefit-risk criteria for post-authorization 67

3) Input data for benefit-risk criteria for pre and post-authorization 75

3. Preference score for benefit-risk criteria 77

4. Weights of the criteria 79

5. Benefit-Risk analysis 81

1) Weighed preferences score for each criterion 81

2) Benefit-score and risk-score 83

3) Benefit-risk (BR) score 85

4) Benefit-risk (BR) profile 87

6. Sensitivity analysis 93

Chapter 5. DISCUSSION 96

1. Discussion 96

2. Limitation 100

3. Conclusion 102

References 103

Appendix 121

논문요약 139

Table 1. The review time for COVID-19 Vaccine approval by the regulatory authority 15

Table 2. Case studies applied MCDA 28

Table 3. The Benefit-risk assessment using MCDA for drug or vaccines 30

Table 4. COVID-19 Vaccine approval by the regulatory authority 34

Table 5. Definitions of the benefit and risk criteria 38

Table 6. Characteristics of eligible studies for Ad26.COV2.S 42

Table 7. Characteristics of eligible studies for mRNA-1273 43

Table 8. Characteristics of eligible studies for ChAdOx1-S 44

Table 9. Characteristics of eligible studies for BNT162b2 45

Table 10. Characteristics of eligible studies for BNT162b2 46

Table 11. List of country-specific adverse event reporting sites for post-authorization 49

Table 12. Demographic characteristics of professionals to weight the criteria 55

Table 13. Input data for benefit criteria for pre-authorization 65

Table 14. Input data for risk criteria for pre-authorization 66

Table 15. Input data for benefit criteria for post-authorization 69

Table 16. County list for adverse events reporting for each vaccine 74

Table 17. Input data for risk criteria for post -authorization 74

Table 18. Summary of input data for benefit and risk criteria for pre-and post-authorization 76

Table 19. Preference score of the benefit and risk criteria for each vaccine 78

Table 20. Weight and standardized weight of the criteria 80

Table 21. Weighted preference score for benefit criteria for pre-and post-authorization 82

Table 22. Benefit score and risk score for each vaccine for pre-and post-authorization 84

Table 23. Benefit-Risk (BR) score for pre-and post-authorization 86

Figure 1. A brief timeline for COVID-19 vaccine rollout 14

Figure 2. Classification of benefit-risk assessment method 27

Figure 3. Overview of MCDA process for the benefit–risk assessment model 36

Figure 4. Input data collection period 39

Figure 5. The preference score conversion for benefit and risk criteria 52

Figure 6. The score for benefit and risk assessment 59

Figure 7. The value tree for benefit-risk assessment of COVID-19 vaccines 62

Figure 8. Forest plots showing the RR of each vaccine for vaccine effect in adults aged 70

Figure 9. Forest plots showing the RR of each vaccine for vaccine effect in seniors aged 71

Figure 10. Forest plot showing the RR of each vaccine for preventing severe COVID-19 72

Figure 11. The rank of COVID-19 vaccines pre-and post-authorization 89

Figure 12. The Benefit-Risk balance for each vaccine 90

Figure 13. The map of benefits versus risks for each vaccine 92

Figure 14. Sensitivity analysis for weight (pre-authorization) 94

Figure 15. Sensitivity analysis for weight (post-authorization) 95