There are three categories of adverse events (AEs) that must be reported in clinical trials: serious adverse events (SAEs), general AEs, and AEs of special interest. SAEs are life threatening, result in hospitalization, cause disability or incapacity, or are congenital anomalies and must be reported to regulatory agencies within 7 days. General AEs include mild to severe complaints or observations. AEs of special interest may affect interpretation of new interventions like changes in liver functions. Proper assessment, classification using systems like ICH and MedDRA, reporting, and follow up of AEs are important for trial safety, credibility, and results.

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

2. Three categories of adverse event (AE)
• Serious adverse events (SAEs)
• General adverse events (AEs)
• AEs of special interest

3. SAEs
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Life threatening
Result in 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

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

5. 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

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

7. 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

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

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

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

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

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

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

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

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

16. 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

17. 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