1. 1 Establishing a MedDRA Safety Surveillance Unit Thanh Van T. Doan, RPh PSI International Inc. Working With MedDRA The New Connaught Rooms London, UK 17 September 1999

2. 2 Background 1997 - PSI International Inc. tasked with the challenge of conceiving, establishing, and maintaining FDA’s Drug Safety Surveillance Unit (DSS) Task includes:  Data entry  Utilizing MedDRA to code all adverse event reports (AERs) received by FDA  PSI International Inc. All Rights Reserved 1999

3. 3 At present …. Receive 4,500 - 5,000 AERs weekly Process 1,000 AERs on a daily basis Average turn around time - 3 days To date …. Over 350,000 AERs processed  PSI International Inc. All Rights Reserved 1999

4. 4 Issues Training High volume Timely processing Quality Assurance  PSI International Inc. All Rights Reserved 1999

5. 5 Issues Development of Standard Operating Procedures (SOPs)  Workflow  Prioritization  Coding procedures — software  PSI International Inc. All Rights Reserved 1999

6. 6 Training Development of training manual — book learning  Objective — uniformity and consistency  Introduction to structure & organization of MedDRA  Introduction to “Principles of Coding”  Coding examples  PSI International Inc. All Rights Reserved 1999

7. 7 Training (2) “Buddy system” — real-time, hands-on training  Learn search strategies  Learn not memorize MedDRA  Reinforce Principles of Coding  Instant feedback  PSI International Inc. All Rights Reserved 1999

8. 8 Principles of Coding Development of coding principles in conjunction with FDA ICH Guidelines for Good MedRA Classification “Living” document - constantly evolving  Discussion of issues at monthly meetings  Revision of principle  PSI International Inc. All Rights Reserved 1999

9. 9 Quality Quality assurance process at 2 stages:  Data entry - Ensure integrity of data  Coding - Ensure uniform and consistent coding - Ensure adherence to coding principles  PSI International Inc. All Rights Reserved 1999

10. 10 Quality (2) Feedback provided by :  Quality assurance (QA) team  FDA - Safety Evaluators (SE) - Modifications to Principles of Coding - Business rule changes  PSI International Inc. All Rights Reserved 1999

11. 11 MedDRA in action Narrative: Information has been received from a 33 y.o. female consumer who has taken Drug X for 30 days. Approximately two weeks after initiating therapy, the patient experienced a seizure. Hospital admission revealed elevated liver enzymes. Drug was discontinued and patient recovered. Follow-up: Patient’s medical history includes hypertension and seizures. On 30-Jan-99 she was admitted to the ER. The following lab levels were observed: AST 651 unit/L, ALT 800 unit/L, LDH 554 unit/L, Alk-P 986 unit/L, K + 3.3 mEq/L. All medications were discontinued. Patient recovered without further complications.  PSI International Inc. All Rights Reserved 1999

12. 12 MedDRA in action (2)  PSI International Inc. All Rights Reserved 1999

13. 13 MedDRA in action (3)  PSI International Inc. All Rights Reserved 1999

14. 14 Legacy Data Conversion  PSI International Inc. All Rights Reserved 1999 Points to consider:  Purpose - MedDRA-sizing vs.useful data  Level at which conversion will take place  Methodology - Automation - use of an algorithm - Manual  Result - QA

15. 15 Legacy Data Conversion (2)  PSI International Inc. All Rights Reserved 1999

16. 16 Legacy Data Conversion (3)  PSI International Inc. All Rights Reserved 1999

17. 17 Other Issues  PSI International Inc. All Rights Reserved 1999 Level of reporting - PT v LLT Quarterly updates - Non-current terms Data retrieval - SSCs Software/ Coding tool Third parties - CROs, other pharmaceutical companies Budgeting resources

18. 18 Take home message...  PSI International Inc. All Rights Reserved 1999 MedDRA - comprehensive tool Training is a must Be PREPARED - - SOPs - Business rules - Coding/classification guidelines Planned approach to conversion of legacy data

19. 19 Copy of presentation will be made available: at www.MedDRAhelp.com  PSI International Inc. All Rights Reserved 1999