PHARMACOVIGILANCE

1
PHARMACOVIGILANCE
2
Definitions

• Pharmacovigilance
• The Science activities relating to the
  detection, assessment, understanding and
  prevention of adverse affects and other drug
  related problems
• EU Directive 2001/20/EC
• Monitoring
• Reporting
• Responsibilities

3
Legislation

• Made statutory by the EU Clinical Trials
  Directive 1st May 2004
• Legal responsibilities on people involved in
  CTIMPs regarding Collection, Verification, and
  Presentation of Adverse Events reports arising
  from such Trials.

4
Pharmacovigilance and the MHRA

• A common reason a CTA is not granted by the MHRA
  is lack of clearly defined Safety Reporting
  Systems
• Practical knowledge and application of
  Pharmacovigilance is a key MHRA Inspection
  consideration.

5
Definitions (MHRA)
6
Serious Adverse Events (SAE) Serious Adverse
Reaction (SAR) Suspected Unexpected Serious
Adverse Reaction (SUSAR)

• This is an AE/AR/UAR that at any dose
• Results in Death
• Is life threatening
• Requires Hospitalisation or prolongation of
  existing
• hospitalisation
• Results in Persistent or Significant Disability
  or
• Incapacity
• Consists of a Congenital Anomaly or Birth Defect

7
A Useful Hint

• Minimise SUSARs by listing everything you know
  about the Drug.
• If it is not listed in the protocol as an
  expected adverse reaction and it occurs it is
  defined as a SUSAR, and this is a more serious
  occurrence than an SAE or SAR.

8
Assessment of CausalityA medical judgement made
by a qualified medical Practitioner, usually (but
not always) the PI.
9
LEGISLATIVE REPORTING REQUIREMENTS

• To the Sponsor, MHRA, Ethics Committee,
• all other investigators, (must include a
• causality assessment)
• Fatal life/threatening SUSARs within 7 days.
• All other SUSARs No later than 15 calendar
  days.

10
Safety Reports

• Annual Safety Reports A summary -overall safety
  of product, implications for population,
  practical measure of minimisation.
• A log of all Serious Adverse Reactions in that
  year REC, RD and MHRA.

11
Eudravigilanace

• Single safety reporting database for EU, linked
  to EUDRACT
• Processes Pharmacovigilance information between
  European Medicines Agency, MHRA and
  Pharmaceutical Companies
• Openly available.

12
Reporting in UHSM

• Trial Participant Card on enrolment, instructing
  Particpant to contact PI or other members of
  Research Team.
• PI informed, assess event, decision on severity
  and causality
• Report to Sponsor as soon as possible Eleanor
  Thomas Research Governance Manager,
  elllie.thomas_at_manchester.ac.uk
• 0161 291 5773

13
Flow Diagram of Reporting Requirements.
14
UHSM SUSAR form

• University Hospital of South Manchester NHS
  Foundation Trust
• On-Site Suspected Unexpected Serious Adverse
  Reaction (SUSAR) Form
• Trial ID _____________________________
  EudraCT no________________________________
• Subject ID ____________________________ Date
  of Birth __________________
  
• Hospital Number_________________________
  Principal Investigator ________________________
• Drug information
• Drug suspected to have caused reaction
  __________________________________________
• Dose ____________________________ Route of
  Administration ______________________
• Duration of Treatment_____________________________
  ____________________________
• Indication(s) for use_____________________________
  ______________________________
• Batch Number Manufacturers Address
• PLEASE COMPLETE THE DETAILS OF REACTION OVERLEAF
• PI assessment of causality (circle appropriate
  response)
• Not related Unlikely Possibly
  related Probably related
  Definitely related
• Was expedited reporting (to MHRA) necessary?
  Y
  N
• If Y, how many days after event were the
  appropriate authorities notified?
• Date of notification
• Concomitant Drugs and Medical History
• Any other relevant information

15

• University Hospital of South Manchester NHS
  Foundation Trust
• On-Site Clinical Trial Adverse Event Form
• Trial ID _____________________________
  EudraCT no____________________________
• Subject ID ____________________________ Date
  of Birth __________________
  
• Hospital Number_________________________
  Principal Investigator ________________________
• Drug information
• Drug suspected to have caused reaction
  __________________________________________
• Dose ____________________________ Route of
  Administration ______________________
• Duration of Treatment_____________________________
  ____________________________
• Indication(s) for use_____________________________
  ______________________________
• Batch Number Manufacturers Address
• IF THE REACTION IS SERIOUS AND UNEXPECTED,
  COMPLETE A TRUST SUSAR FORM
• PI assessment of causality (circle appropriate
  response)
• Not related Unlikely Possibly
  related Probably related
  Definitely related
• Was expedited reporting (to MHRA) necessary?
  Y
  N
• If Y, how many days after event were the
  appropriate authorities notified?
• Date of notification
• Concomitant Drugs and Medical History
• Any other relevant information

16
Any Questions/Further Advice

• www.corec.org.uk.,
• The MHRA
• The RD Directorate