PostMarketing Safety Information on Medical Products: Potentials for Improvements

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• Post-Marketing Safety Information on Medical
  Products Potentials for Improvements
• Overview for perspective
• Marc K. Walton, M.D., Ph.D.
• OPPL / FDA
• The views expressed are those of the author, and
  do not represent an official FDA position

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Postmarketing safety information

• Requirements stated in regulations (21CFR 600
  314)
• Review promptly review all AE information (any
  source)
• Reporting PM 15d Alert Reports
• Serious Unexpected AE
• Follow-up information
• Reporting Periodic Reports All additional AEs
  yearly (quarterly first 3 yrs) primarily
  spontaneous reporting
• Added to FDA AERS database
• Includes MEDWATCH direct repots to FDA
• PM Studies - Typically as agreed between FDA and
  manufacturer primarily for topics with known
  basis for reasonable concern

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Postmarketing safety informationCurrent chief
sources

• Agreed-upon PM studies limited to issues where
  there is a basis for reasonable concern
• Spontaneous reports
• Relationship of AE to drug may not be recognized,
  and thus not reported
• Substantial underreporting
• Weak ability to estimate relevant denominator

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Existing Methodology

• Can be useful to refine understanding of known or
  clearly suspected AE related to drug
• Can be useful to detect clinically notable AE
  that occur in a manner revealing relationship
  (e.g., events with temporal characteristic,
  rechallenge, otherwise rare)
• Weaknesses in other situations widely discussed
• One FDA approach to improving medical product
  safety is termed the Sentinel Network

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The Problem

• The effectiveness of Federal government
  postmarket surveillance and risk communication
  efforts have been constrained due to limitations
  in the
• Quality of data
• Quantity of data
• Timeliness of data receipt and analysis
• Capacity to rapidly conduct postmarket safety
  studies, when needed
• Risk communication tools used
• Available resources

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A Proposed Solution

• The private sector has taken steps that can
  facilitate surveillance activities
• Developing new information technology tools
• Exploring informatics methods and applications
• Creating the capacity to conduct postmarket
  safety assessments
• Therefore, link private and public sector efforts
  to address these limitations through better
  integration of the nations postmarket medical
  product safety activities to create a Sentinel
  Network a virtual, integrated, electronic
  medical product safety network

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Sentinel Network

• The network would foster the seamless, timely,
  electronic flow of medical product safety
  information from electronic databases and
  surveillance reporting systems, through risk
  identification and analysis processes, to
  healthcare practitioners and patients at
  point-of-care, while protecting patient privacy
• The network would be assembled through
  public-private partnerships and build on existing
  efforts rather create entirely new systems
• The network would use national and international
  standards

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Components of the Sentinel Network

• Data Collection
• Integrate clinical practice and adverse event
  surveillance
• EHRs
• Integrated databases
• Risk Identification and Analysis
• Integrated research networks
• Data mining tools
• Reach agreement on methodologies
• Conduct subgroup analyses and identify
  biological/genomic markers
• Risk Communication
• Leverage medical communitys expertise
• Integrate new risk information into the workflow
  of clinical practice (e.g., decision support
  systems)

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Legislative Initiatives

• FDARA
• PDUFA, MDUFA reauthorization
• Multiple other potential FDA procedural,
  organizational, responsibility aspects
• Senate version has been passed
• House version in committee
• Final enacted version yet to be determined

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S. 1082 Drug Safety

• FDA shall work to establish within 2 years a
  system(s) for drug safety surveillance
• Described with similar data collection, analysis
  characteristics as were used for Sentinel Network
• Goal of 100 Million patients by July 2012

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S. 1082 Drug Safety Qualified Entities

• (aa) has the research capability and expertise
  to conduct and complete the activities under this
  paragraph
• (bb) has in place an information technology
  infrastructure to support adverse event
  surveillance data and operational standards to
  provide security for such data
• (cc) has experience with, and expertise on, the
  development of drug safety and effectiveness
  research using electronic population data
• (dd) has an understanding of drug development
  and risk/benefit balancing in a clinical setting
  and

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Data Sources and Adequacy

• Claims data
• EMRs
• Compatability of data needs with data sources
• Richness of detail
• Common granularity, format, meaning to permit
  combining information from multiple systems
• Informatics systems in development can be planned
  to satisfy needs
• Data needs driven by clinical question and
  analytic methodology