1. New Approaches to SAE Reconciliation for Paper and EDC Studies: A Collaborative Perspective Shannon Labout, CCDM Senior Consultant PSDM Meeting 22-May-2008 Weesp, The Netherlands

2. New Approaches to SAE Reconciliation: An Integrated Approach New Approaches to SAE Reconciliation: Outline Introduction Background Example project Collaboration Opportunities (discussion points)

3. New Approaches to SAE Reconciliation: An Integrated Approach Background Six Sigma methodology - DMAIC Define – process improvement goals / defects Measure – how many? what does each one cost? Analyze – how will making an improvement reduce defects/costs? Improve - implement the improvement Control – control the defects so they don’t occur

4. New Approaches to SAE Reconciliation: An Integrated Approach Project Background Project Assumptions and Scope Use existing technologies Limit project to evaluate SAE collection / reporting process SAE data query process Process for delivering safety data to statisticians

5. New Approaches to SAE Reconciliation: An Integrated Approach What is our Current Approach? Collect SAEs using parallel processes - clinical and safety Separate entry process Separate data collection forms Separate query process Reconciliation process is required Differences between databases Potentially different responses to queries

6. New Approaches to SAE Reconciliation: An Integrated Approach Safety SOPs Serious? Record on CRF No Yes Report to Sponsor Within specified Reporting period Event entered Into Safety database Event entered Into Clinical database Current Approach to SAE Reconciliation Expedited Reporting Clinical data CDM SOPs Site records event Safety Query Process CDM Query Process

7. New Approaches to SAE Reconciliation: An Integrated Approach Current Approach: Problems SAE Reconciliation must be done as a separate process Two databases with the same data Duplicate queries may be sent to the site Two organizations managing the same data Safety – for PV and reporting Clinical – for analysis and submission

8. New Approaches to SAE Reconciliation: An Integrated Approach Current Approach: Problems SOPs not aligned between clinical and safety They work in “silos” May not even know what the other group is doing Site is confused and frustrated Queries from two groups on same data

9. New Approaches to SAE Reconciliation: An Integrated Approach Current Approach: Problems Possible for events to be unreported in one system Potential need for query responses to be reconciled Time is lost managing duplicate processes and then cleaning up the mess Costs are higher than they need to be

10. New Approaches to SAE Reconciliation: An Integrated Approach Safety SOPs Serious? Record on CRF No Yes Report to Sponsor Within specified Reporting period Event entered Into Safety database Event entered Into Clinical database Current Approach to SAE Reconciliation Expedited Reporting Clinical data CDM SOPs Site records event Safety Query Process CDM Query Process complex duplicate work not aligned

11. New Approaches to SAE Reconciliation: An Integrated Approach Project Plan Identified that we have a problem What exactly is causing the problem, though? How do we fix it? Need to gather some data and analyze Methodology chosen: DMAIC

12. New Approaches to SAE Reconciliation: An Integrated Approach Project – Define /Measure/Analyze/Improve/Control Defect An SAE term that must be manually reconciled Clearly defined Measurable operational defect Includes all reconciliation activities (including data entry verification)

13. New Approaches to SAE Reconciliation: An Integrated Approach How many defects (SAEs)? We can count them We can put a cost to each one 1000 SAEs per year 60 minutes to reconcile each one Data entry verification Query management Database reconciliation $5/minute to do this work Project – Define/ Measure /Analyze/Improve/Control

14. New Approaches to SAE Reconciliation: An Integrated Approach Project – Define/Measure/ Analyze /Improve/Control Determine the cost to the organization N*T*C = cost to the organization N = Number of defects T = Time to reconcile each defect C = Cost per time unit 1000 * 60 * 5 = $300,000 / year What can we change that will improve this?

15. New Approaches to SAE Reconciliation: An Integrated Approach Safety SOPs Serious? Record on CRF No Yes Report to Sponsor Within specified Reporting period Event entered Into Safety database Event entered Into Clinical database Current Approach to SAE Reconciliation Expedited Reporting Clinical data CDM SOPs Site records event Safety Query Process CDM Query Process WHY are we entering this data twice?

16. New Approaches to SAE Reconciliation: An Integrated Approach Project – Define/Measure/Analyze/ Improve /Control Decision to simplify the process Single data collection process Eliminates duplicate query process What would the results be Number of defects potentially reduced Time to reconcile reduced (data entry verification, simple verification, query resolution) to 15 minutes per SAE Single query process (data only queried once)

17. New Approaches to SAE Reconciliation: An Integrated Approach Project – Define/Measure/Analyze/ Improve /Control How much improvement? N*T*C = cost to the organization 1000 * 15 * 5 = $75,000 $300,000 - $75,000 = $225,000 saved each year Even if the number of defects remains the same

18. New Approaches to SAE Reconciliation: An Integrated Approach Project – Define/Measure/Analyze/Improve/ Control Align SOPs and WPGs between clinical and safety Monitor the process with audits and documentation TRAINING!

19. New Approaches to SAE Reconciliation: An Integrated Approach New Approach: Solutions Enter data into only one system Databases do not have to be reconciled with each other Safety manages SAE queries, clinical all others No duplicate queries are sent to the site Time is gained by managing a single query process Site has only one query process to deal with Reduces site frustration and confusion

20. New Approaches to SAE Reconciliation: An Integrated Approach New Approach: Solutions SOPs aligned between clinical and safety Collaboration Cooperation Communication Shared responsibility High Quality – Lower ongoing costs – Better Timelines

21. New Approaches to SAE Reconciliation: An Integrated Approach Serious? Yes Report to Sponsor Within specified Reporting period Current Approach to SAE Reconciliation Expedited Reporting Clinical data CDM SOPs Site records event Safety Query Process Event entered Into Safety database Safety SOPs simplified aligned

22. New Approaches to SAE Reconciliation: An Integrated Approach Discussion Points Other Opportunities for Collaboration Process mapping – find what is necessary, what is not: Align processes across other internal groups Different regulatory requirements –must meet all needs Different organizational goals  PV – safety for all drug products  Clinical – analysis and submission data  Clinical – site, science, patient safety, informed consent Shared training / cross training  Build understanding  Build cooperation New technologies / EDC and eSource

23. New Approaches to SAE Reconciliation: An Integrated Approach Thank you! Contact information slabout@csscomp.com www.cssinformatics.com slabout@csscomp.com www.cssinformatics.com