A presentation by Dr. John Clark, President and Chief Medical Officer at PCSglobal, on European pharmacovigilance issues presented at the 2013 Regulatory Affairs Professional Society Annual Meeting. Major issues and challenges posed by EU (European Union) Regulations are covered in this presentation.

1. The New European PV Legislation:
Issues and Challenges
John A. Clark, MD, MSPH
President and Chief Medical Officer
PCSglobal
Regulatory Affairs Professional Society
2013 Annual Meeting
September 30, 2013

2. Medical Product Safety
Safety-Related Information Systems
PRIMARY PHARMACOVIGILANCE SYSTEMS
l
l
l
l
Expedited adverse event case reports
Signaling and surveillance
Benefit-risk evaluations
Risk management

3. Safety-Related Information Systems
Issues and Challenges Posed by EU Regulations
What are the major issues?
What are the biggest challenges?

4. Safety-Related Information Systems
Expedited Adverse Event Case Reports
SYSTEM ATTRIBUTES
l
l
l
l
l
l
Purpose: identify ADRs with emphasis on
unexpected, serious
Product specificity: non-specific
Information unit: single patient adverse
experience(s)
Basic approach: medical interpretation of
cases
Typical analyses: individual case causality
analysis, review of line listings
Focus: risk

5. Safety-Related Information Systems
Expedited Adverse Event Case Reports
ISSUES
l
Enlargement of ADR definitions
– Global safety experiences
– All conditions of use
– All reporting environments
– All reporters
l
Integration of medical services’ and
manufacturer’s data systems
– Messaging structures
– Product and event dictionaries

6. Safety-Related Information Systems
Expedited Adverse Event Case Reports
CHALLENGES
l
Increased operational complexity
– Comprehensive ADR capture
– Increased scope of ADR
– Processing timelines
l
Integration of medical services data
structures into case report systems
– Electronic reports (ICH-E2B versus HL7 ICSR)
– Event dictionaries (e.g., MedDRA, SNOMED
versus ICD-10, LOINC)

7. Safety-Related Information Systems
Signaling and Surveillance
SYSTEM ATTRIBUTES
l
l
l
l
l
l
Purpose: find safety issues that are unknown or
incompletely understood
Product specificity: both specific and non-specific
Information unit: exposed case series
Basic approach: exposed/control group
comparisons
Typical analyses: increased frequency
assessment, surveillance observed to expected,
case-control study, cohort study
Focus: risk, strength of association, risk factors

8. Safety-Related Information Systems
Signaling and Surveillance
ISSUES
l
Signals from non-interventional
studies
– Defining and retrieving NI studies
– Large number of NI studies now published
every year
Rapid signal work-ups
l Signal tracking
l Signal escalation
l

9. Safety-Related Information Systems
Signaling and Surveillance
CHALLENGES
l
Finding, assessing, and triaging NI study
evidence
– Retrieval definitions
– Impact of results, data quality
– Selection of studies as safety signals
– Archiving of NI study results
Signal evaluation software
l Inter-departmental linkage of signals
l Signal escalation in outsourced environments
l

10. Safety-Related Information Systems
Benefit-Risk Evaluations
SYSTEM ATTRIBUTES
l
l
l
l
l
l
Purpose: evaluate known benefits and risks
of a healthcare product versus a standard
Product specificity: mostly product specific
Information unit: endpoint comparisons
(efficacy, effectiveness, and risk)
Basic approach: weighted comparison of
aggregate benefits versus aggregate risks
Typical analyses: Variants of multiple
criteria decision analysis (MCDA)
Focus: benefit:risk balance

11. Safety-Related Information Systems
Benefit-Risk Evaluations
ISSUES
Integration of BRE processes into existing
operations
l Design of BRE “calculator”
l
– Formal MCDA modeling versus rule-based
– Defining axes and units (scalar, categorical)
Determining risk management responses
l Trend toward products with complex
manufacturing requirements
l

12. Safety-Related Information Systems
Benefit-Risk Evaluations
CHALLENGES
Personnel/teams with wide range of
analytical skills
l Process redesign
l New kinds of modeling and technology
l Information acquisition, transfer, and
visualization
l

13. Safety-Related Information Systems
Risk Management
SYSTEM ATTRIBUTES
l
l
l
l
l
l
Purposes: maximize benefits, minimize risks
Product specificity: entirely product specific
Information unit: time dependent
measurements of key processes/outcomes
Basic approach: key variable trend analyses
Typical analyses: rate trending, surveys,
audits
Focus: optimization of benefit:risk in target
and non-target populations

14. Safety-Related Information Systems
Risk Management
ISSUES
Assuring data integrity
l Measuring program effectiveness
l
– Target population specificity (includes off
label use)
– Ongoing, rather than intermittent
Focus on medication errors and
product monitoring
l Increasingly complex tool kit
l Implementation in multiple territories
l

15. Safety-Related Information Systems
Risk Management
CHALLENGES
Teams with broad range of skills
l Assessing non-routine information
l Measuring effectiveness:
l
– Outcome (versus process) variables
– Medical services activities
l
Integration of data arising from:
– Real time timelines
– Point of use in services organizations
– Multiple countries

16. John Clark, MD, MSPH
PCSglobal
740 Bethlehem Pike
Flourtown, PA 19034
(215) 510-4737
jclark503@comcast.net
john.clark@pcsglobal.org