Lecture on adverse events, multicenter trial, and closeout for postgrad MDCU students

1. Assessing and Reporting
Adverse Events
Thira Woratanarat MD MMedSc DHFM
Faculty of Medicine, Chulalongkorn University

3. Three categories of adverse event (AE)
• Serious adverse events (SAEs)
• General adverse events (AEs)
• AEs of special interest
• (Unexpected adverse events: UAEs)

4. SAEs
• Death/Life threatening
• Result in (prolonged) hospitalization
• Irreversible, persistent, or significant disability/incapacity
• Congenital anomaly/birth defect
PS: SAEs must be reported to regulatory agencies within a fixed
time period (e.g. 7 days) of their occurrence

5. General AEs
• Complaints by trial participants
• Investigator’s observation
PS: can be very mild to severe, variation in reporting

6. AEs of special interest
• Due to high variation in general AEs reporting, some trials can
designate this kind of AEs since they may seriously affect the
interpretation and applicability of any new interventions.
• For instances, liver function test abnormalities or changes in QT
interval on an electrocardiogram

8. Advantages to AEs assessment
• Prospective safety determination
• Hypothesis testing
• Credibility

9. Classification of adverse events
• International conference on harmonization (ICH): Medical
terminology in 1994
• Medical directory for regulatory activities (MedDRA): Version 2 in
1997
• National Cancer Institute (NCI) Common Terminology Criteria for
Adverse Events v3.0

10. What to consider in reporting AEs
• Ascertainment
• Dimensions: Information richness
• Length of follow-up
• Scientific explanation/biological plausibility
• Timing regarding regulatory requirements
• Solutions and outcomes

12. Multi-center trial
Thira Woratanarat MD MMedSc DHFM
Faculty of Medicine, Chulalongkorn University

13. Multi-center clinical trial
• More difficult
• More expensive
• Less professional rewards: need to share credit
• Logistically challenges
• Challenges in personnel training and data quality control

14. Reasons to conduct multi-center trial
• To recruit adequate number of participants within reasonable time
• More generalizable sample
• Enable investigators with similar interests and skills to work
together on a common problem

15. Management for Multicenter Trial
• Manpower
• Money
• Materials/Instruments/Facilities
• Methods

16. Manpower Management
• Team selection
• Log book
• Protocol training
• Coaching and counseling training
• Ethics requirement training
• Contribution agreement

17. Money Management
• Estimated budget for each site
• Inflation rate and exchange rate variation
• Competitive negotiation comparing to the market

18. Materials/Instruments/Facilities Management
• Standardization process
• Monitoring and evaluation
• Mock-up and training
• Procurement process
• Database keeping: safety and responsibility

19. Methodology Management
• Standard protocol conduct
• Standard informed consent process
• Violation and deviation reporting process
• Standard operating procedures
• Monitoring progression and evaluation process

20. Steps
• Planning committee
• Feasibility assessment of the study
• Not only clinical centers but also coordination center(s): Regional
sites, academic centers, or contract research organizations
• Provision of detailed outline of the study to prospective
investigators as early as possible: Engagement issues
• Monitoring committee: Scientific, DMC/DSMB
• Training and standardization mechanisms
• Performance management and monitoring mechanisms
• Publication, presentation, and authorship policies

21. Closeout
Thira Woratanarat MD MMedSc DHFM
Faculty of Medicine, Chulalongkorn University

22. Termination procedures
• Planning
• Scheduling of closeout visits
• Final response ascertainment
• Transfer of post-trial care

23. Data and other study materials
• Cleanup and verification
• Storage

24. Dissemination of results
• Single vs Multi-center trial
• Target groups
• Scientific meeting presentation: Congress organizer, Investigators,
and Journal editors

25. Post-study follow-up
• Return to normal states
• Tapering period of some drugs/interventions
• Delayed differential effects or events among groups