The Protocol Deviation Handbook

TABLE OF CONTENT

1. Introduction p.6

2. Definitions p.6

2.1. Escalation 6

2.2. Ethics Committee (EC) 7

2.3. Finding 7 2.4. Institutional Review Board (IRB) 7

2.5. EC/IRB Review Process p. 8

2.6. IRB/EC review of Major Protocol Violations p. 8

2.7. IRB/EC review of Minor Protocol Violations p. 8

2.8. IRB/EC review of Protocol Exceptions p. 8

2.9. Management and Reporting of Protocol or GCP Deviations and Serious Breaches p. 9

2.10. Planned Changes to Research Protocol p. 9

2.11. Principal Investigator p. 9

2.12. Privacy Incident p. 10

2.13. Protocol p. 10
2.14. Protocol Deviation p. 10

2.14.1. Major Protocol Deviation p. 11
2.14.2. Minor Protocol Deviation p. 11
2.14.3. Potential Major Protocol Deviation p. 11
2.14.4. Escalation p. 11

2.15. Protocol Deviation Form p. 11
2.16. Protocol Deviation List p. 12
2.17. Protocol Deviation Review Charter p. 12
2.18. Protocol Deviation Review Committee (PDRC) p. 12
2.19. Protocol Deviation Review Committee Chairperson p. 12
2.20. Protocol Deviation Review p. 12

2.21.Protocol Deviation Review Workflow p. 12

2.22.Protocol Deviation Status p. 13

2.23.Protocol Exception p. 13

2.24.Protocol Violation p. 14

2.24.1.Major Protocol Violation p. 14

2.24.2.Minor Protocol Violation p. 14

2.25.Risk Management Plan  p.15

2.26.Serious Breach p. 15

2.27.Significant Quality Issue p. 15

2.28.Unplanned Changes to Research Protocol p. 15

3. Scope of the Protocol Deviations Procedure 1p.6

3.1. Roles and Responsibilities p. 16

3.1.1. Sponsor / CRO p. 16

3.1.2. Principal Investigator / site personnel p. 17

3.1.3. IRB/EC p. 18
3.1.4. Health Authorities p. 18

3.2. Actions following the reporting of a Protocol Deviation p. 19

3.2.1. Collection/documentation of PDs p. 19

3.2.2. Evaluation of Protocol Deviations p. 19

3.2.3. Corrective And Preventive Actions (CAPA)   p. 21

3.2.4. Warning Letters   p. 21

3.2.5. Potential consequences of PDs   p. 22

3.2.6. Tools for the collection, classification and documentation of PDs    p. 22

3.2.7. Avoiding Common Deviations   p. 22

3.3. Clinical Study Report   p. 23

3.4. New Proposal for Classification of Protocol Deviation   p. 23

4. APPENDIX   p. 26

Table 1. Example of Protocol Deviations   p. 26

Table 2. Impact and Likelihood Risk Scoring   p. 28

Table 3. Example of Protocol Deviation Tracking Log   p. 30