Drug Development Office

1
Drug Development Office

• Pharmacovigilance The Eudravigilance Database
• Experience from early phase trials
• 18th November 2004
• Christos Pagonis

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Experience of what?

• Safety data processing before and after

MAY 2004
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Initial thoughts

• Low impact on DDO procedures

• Why?

• DDO has infrastructure to deal with SAEs and SARs
  in real time
• Trials are open label
• Easy to attribute causality
• Only affects AEs that are drug related, serious
  and unexpected

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What was our procedure pre May 2004?

• 1. Adverse Events (AE)

• All AEs defined by CTC (including causality)
• All AEs recorded by Investigator on CRF
• All AEs checked on CRF and at source by visiting
  CRA
• All CRFs bought in house and checked again by CDM
• All data entered onto the database

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What was our procedure pre May 2004?

• 2. Serious Adverse Events (SAE)

• Standard SAE definition used
• Immediate completion of SAE form by PI
• PI submited SAE form to DDO within 3 days
• SAE form checked in house
• SAE circulated to all parties
• All data entered onto the database
• SAEs reviewed monthly by CIRB
• Quarterly safety data listings sent to MHRA

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What was our procedure pre May 2004?

• 3. Serious Adverse Reaction (SAR)

• Investigator notified LREC (? time limit)
• If also unexpected, the DDO notified MHRA by
  post within 7-15 days

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Other Investigators
Investigator
24 hrs
3rd party
Immediately
DDO
7-15 days
1 month
8
What was the workload like?

• Average year at DDO

• 19 Phase I Trials and 1 Phase II
• 150 patients recruited
• 48 SAE reports

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Impact of the EU CT Directive on DDO

• Electronic Reporting to MHRA

• Duplication of data entry
• Cost - 1000 to train one member of staff
• Need to register organisation with Eudravigilance
• Possible additional cost for use of MedDRA

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Impact of the EU CT Directive on DDO

• Reporting SUSAR to (Main) REC

• Sponsor must ensure it is done
• DDO will notify REC of SUSAR
• DDO SOP will be re-written to include REC
  notification

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Impact of the EU CT Directive on DDO

• Monitoring other significant events

• Critical AE - may need reporting to MHRA
• Parallel reporting system developed
• another form

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Other Investigators
Investigator
24 hrs
7-15 days
3rd party
Immediately
DDO
7-15 days
1 month
13
Impact of the EU CT Directive on DDO

• Annual Safety Reports (ASR) - May 2005

• 20 ASRs per year
• ASR Includes
• Concise safety analysis
• Line Listing of SARs (including SUSARs)
• Summary tabulations
• 3rd party SUSARs Significant events?
• Template ASR being developed

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Impact of the EU CT Directive on DDO

• Expected Adverse Reactions

• Include in reference document
• Investigator Brochure
• Protocol
• Summary of Product Characteristics (Data Sheet)

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Impact of the EU CT Directive on DDO

• Summary

• Greater material to process
• SUSARs
• Significant events (Critical AE)
• From 3rd parties
• ASR for each trial
• Global analysis
• Action
• Employ dedicated individual Safety desk