Risk Assessment of Observational Data: Good Pharmacovigilance Practices and Pharmacoepidemiologic Assessment

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Risk Assessment of Observational Data Good
Pharmacovigilance Practices and
Pharmacoepidemiologic Assessment

• CDER / CBER Pharmacovigilance Working Group

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Working Group Members

• Jeff Siegel
• Bette Goldman
• Jerry Davis
• Roselie Bright
• Mary Beth Jacobs
• Support
• Aileen Ciampa
• Jane Axelrad
• Virginia Beakes
• Nichelle Cherry
• Jane McCarthy

• Kathy Miracco
• Yi Tsong
• Edward Cox
• Dan Shames
• Susan Lu
• Joyce Weaver
• Marianne Mann
• Judy Staffa
• Carol Holquist
• Min Chen
• Melodi McNeil
• Ralph Schmid

• Group Leads
• Julie Beitz
• Mark Goldberger
• Miles Braun
• Project Manager
• Patrick Guinn

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Workshop Agenda

• Morning
• Overview
• Good Pharmacovigilance Practices
• Presentations, Qs and As
• Afternoon
• Pharmacoepidemiologic Assessment
• Presentations, Qs and As
• Closing Remarks

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Scope of Concept Paper

• Present FDAs preliminary thoughts on
• Important pharmacovigilance concepts
• Safety signal identification
• Pharmacoepidemiologic assessment and
  interpretation of safety signals
• The development of pharmacovigilance plans

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Scope of Concept Paper

• Focus on risk assessment based on observational
  data sources
• Case Reports, Case Series
• Pharmacoepidemiologic Studies
• Registries
• Surveys

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What is Pharmacovigilance?

• All post-approval scientific and data gathering
  activities relating to the detection, assessment,
  understanding, and prevention of adverse effects
  or any other product- related problems
• This includes the use of pharmacoepidemiologic
  studies

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Pharmacovigilance Why?

• At the time of approval, clinical trial data are
  available on limited numbers of patients treated
  for relatively short periods
• Once a product is marketed, large numbers of
  patients may be exposed, including
• Patients with co-morbid illnesses
• Patients using concomitant medications
• Patients with chronic exposure

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Pharmacovigilance Why?

• After marketing, new safety information may
  become available
• Through use of the product domestically or in
  other countries
• Through use of other drugs in the same class
• From preclinical studies
• From pharmacologic studies
• From controlled clinical trials

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What is a Safety Signal?

• An apparent excess of adverse events associated
  with use of a product
• Even a single well-documented case report may be
  viewed as a signal

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What is a Safety Signal?

• Preclinical findings or experience with other
  products in the class may be sufficient to
  generate a signal, even in the absence of case
  reports in patients
• A products risk profile may be characterized by
  several safety signals

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Safety Signals

• Are identified
• From case reports, other sources
• Are evaluated
• In pharmacoepidemiologic studies, registries,
  surveys
• Are interpreted
• In the context of all available safety
  information
• Are monitored
• Through enhanced pharmacovigilance efforts

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What is a Pharmacovigilance Plan?

• A plan proposed by a sponsor
• for the ongoing evaluation of safety signals
  identified with the use of a product
• to monitor at-risk populations which have not
  been adequately studied
• Plan may be developed at the time of product
  launch or after a signal is identified

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What is a Pharmacovigilance Plan?

• A sponsors plan may involve
• Expedited reporting of serious adverse events of
  interest
• Submission of adverse event report summaries at
  more frequent, pre-specified intervals
• Conduct of additional observational studies or
  clinical trials
• Implementation of active surveillance activities
  to identify as yet unreported adverse events

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Active Surveillance May Involve...

• Product-based activities
• Follow cohorts of patients exposed to specific
  products
• Setting-based activities
• Surveillance of healthcare settings (e.g., EDs)
  for events likely to present there
• Event-based activities
• Monitor registries for events that are often
  drug-related (e.g., liver transplant registries)

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• Emerging new safety data may result in ongoing
  revisions to the sponsors pharmacovigilance plan
  for a product

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• While additional safety information is being
  developed, FDA will work with sponsors to
• communicate information about safety signals and
• minimize events occurring in users of a product
  through risk management programs1

1Concept Paper Risk Management Programs
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Workshop Agenda

• Morning
• Overview
• Good Pharmacovigilance Practices
• Presentations, Qs and As
• Afternoon
• Pharmacoepidemiologic Assessment
• Presentations, Qs and As
• Closing Remarks