AE, Closeout, and multicenter trial Feb2014
1 like563 views
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.
AE, Closeout, and multicenter trial Feb2014
- 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 • • • • 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 • • • • • • 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 • • • • 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 • • • • • 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