Improving Regulatory Decisions: Janus Clinical Trials Repository The Sentinel Initiative

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Improving Regulatory Decisions Janus Clinical
Trials Repository The Sentinel Initiative

• Armando Oliva, M.D.
• Senior Biomedical Informatics Advisor
• Computational Science Center
• Center for Drug Evaluation and Research
• Food and Drug Administration
• March 16, 2011

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Outline

• FDAs mandate
• The challenges in conducting that mandate
• Using informatics to help meet the challenges
• Pre-market assessments Janus
• Post-market surveillance The Sentinel Initiative

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FDAs Mandate

• FDA is responsible for protecting the public
  health by assuring the safety, efficacy and
  security of human and veterinary drugs,
  biological products, medical devices, our
  nations food supply, cosmetics, and products
  that emit radiation.
• FDA regulates 25 cents of every consumer dollar
• Numerous mandates
• Approve safe and effective drugs for marketing in
  the U.S.
• Withdraw unsafe drugs from the market

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Challenges Pre-market

• Largest single recipient of subject-level
  clinical trial data in the world
• Data largely unstructured/poorly structured
• Received in disparate formats
• Analysis, interpretation slow, difficult
• Cross-study analyses are very painful
• e.g. risk of cardiac death across all controlled
  trials of cox2 inhibitors
• Clinical Trials data land-fill

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Challenges Post-Market

• Adverse event reporting is voluntary and
  incomplete
• Estimated only 5 of AEs get reported to FDA
• Discovering post-marketing safety signals is
  slow, inefficient
• Observational data make it difficult to assess
  events with high background rates

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Leveraging Technology to Make Better Regulatory
Decisions

• Janus Clinical Trials Data Repository
• Sentinel Initiative Active Post-marketing
  Surveillance Program

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What is Janus?

• FDAs Enterprise (i.e. Agency-wide) Data
  Warehouse for Subject-Level Clinical Trial Data
• Associated Review Environment (e.g. data
  visualization and analysis software)
• Named after the Roman God of doorways,
  beginnings/endings and transitions. Janus is
  depicted as a head with two faces.
• Joint Project with the National Cancer Institute

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Future State
Technology
Analysis tools
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Janus Milestones

• Phase 1 Proof of Concept
• Create Data Warehouse
• Load and retrieve dummy data
• Completed
• Phase 2 Operational Pilot
• Enhance data validation/load services
• Load and retrieve actual data
• Completed
• Phase 3 Production Environment
• Begin Summer 2011
• Complete 2013

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FDA Amendments Act of 2007 (FDAAA)Section 905
Active Postmarket Risk Identification and Analysis

• Establish a postmarket risk identification and
  analysis system to link and analyze safety data
  from multiple sources, with the goals of
  including
• at least 25,000,000 patients by July 1, 2010
• at least 100,000,000 patients by July 1, 2012
• Access a variety of sources, including
• Federal health-related electronic data (such as
  data from the Medicare program and the health
  systems of the Department of Veterans Affairs)
• Private sector health-related electronic data
  (such as pharmaceutical purchase data and health
  insurance claims data)

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Sentinel Initiative

• Improving FDAs capability to identify and
  evaluate safety issues associated with
  FDA-regulated medical products in near real time
• Enhancing FDAs ability to evaluate safety issues
  not easily evaluated with the passive
  surveillance systems currently in place
• Expanding FDAs access to subgroups and special
  populations (e.g., the elderly)
• Expanding FDAs access to longer term data
• Expanding FDAs access to adverse events
  occurring commonly in the general population
  (e.g., myocardial infarction, fracture) that tend
  not to get reported to FDA through its passive
  reporting systems

Will augment, not replace, existing safety
monitoring systems
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Mini Sentinel www.mini-sentinel.orgHarvard
Pilgrim Healthcare

• Develop the scientific operations needed for the
  Sentinel Initiative.
• Create a coordinating center with continuous
  access to automated healthcare data systems,
  which would have the following capabilities
• Provide a "laboratory" for developing and
  evaluating scientific methodologies that might
  later be used in a fully-operational Sentinel
  Initiative.
• Offer the Agency the opportunity to evaluate
  safety issues in existing automated healthcare
  data system(s) and to learn more about some of
  the barriers and challenges, both internal and
  external.

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Organizations

• America's Health Insurance Plans
• Cincinnati Children's Hospital Medical Center
• Critical Path Institute
• Brigham and Women's Hospital
• Division of Pharmacoepidemiology and
  Pharmacoeconomics
• Division of General Medicine
• Duke U School of Medicine
• HMO Research NetworkGroup Health Research
  InstituteHarvard Pilgrim Health Care Institute
  Henry Ford Research Foundation HealthPartners
  Research Foundation Lovelace Clinic
  FoundationMarshfield Clinic Research Foundation
  Meyers Primary Care Inst(UMass / Fallon)

• HealthCore, Inc
• Humana - Miami Health Services Research Center
• Kaiser Permanente Colorado, Georgia, Hawaii,
  Mid-Atlantic, N. California, Northwest, Ohio, and
  S. California regions
• Outcome Sciences, Inc
• Risk Sciences International
• Rutgers University Inst for Health
• U of Alabama at Birmingham
• U of Illinois at Chicago
• U of Iowa College of Public Health
• U of Pennsylvania School of Medicine
• Vanderbilt U School of Medicine
• Weill Cornell Medical College

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Year 1 activities Data Core

• Data inventory, plus a prioritized list of data
  needs
• Develop and implement Common Data Model
• First version of Mini-Sentinel Distributed
  Database (MSDD), encompassing quality checked
  admin/claims data
• Enrollment
• Demographics
• Utilization (diagnoses, procedures)
• Outpatient pharmacy dispensing claims

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Data Characterization Enrollment
As of 7 Jan 2011
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Data Characterization Age
As of 7 Jan 2011
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Year 1 activities Protocol core

• Identify and characterize Health Outcomes of
  Interest (HOIs) prioritize 20 deserving
  evaluation via literature review and/or record
  review
• Select one HOI for full evaluation
• Develop and test procedures for obtaining full
  text hospitalization records
• Develop and test case identification and
  validation/adjudication process
• Develop protocol for active surveillance of
  drug-associated acute myocardial infarction

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Mini-Sentinel Year 2

• Implementation of active surveillance protocol
  for potential drug-related acute MI
• Evaluation of emerging safety issues for
• New molecular entities (newly approved drugs)
• Drugs that have been marketed for gt2 years
• Evaluation of the impact of regulatory actions
  (e.g., restricted distribution)
• PRISM2
• A continuation of the active surveillance system
  developed last year for H1N1 vaccine safety
  surveillance by HHS, FDA, and CDC
• Institute safety monitoring for a non-influenza
  vaccine
• Add laboratory and vital sign data to MSDD
• Continue methods development

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Next steps

• Long-term, complex initiative
• Implement in stages as scientific methodologies
  and data infrastructure evolves
• Ensure maintenance of privacy and security within
  the distributed system
• Continue to address the concerns of stakeholders
  including patients and the public
• Address how the eventual Sentinel System will
  function as a national resource and complement
  other HHS initiatives using distributed systems
  for comparative effectiveness and quality
  assurance

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Janus, Sentinel, and You

• De-identified EHR data are the desired ultimate
  source for data that eventually used in Sentinel
  and Janus
• How do integrate clinical trial data collection
  processes with EHR systems?
• How should FDA integrate these two programs with
  existing/emerging EHR solutions.

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Thank you for your attention
armando.oliva_at_fda.hhs.gov