Title: Improving Regulatory Decisions: Janus Clinical Trials Repository The Sentinel Initiative
1Improving 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
2Outline
- 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
3FDAs 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
4Challenges 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
5Challenges 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
6Leveraging Technology to Make Better Regulatory
Decisions
- Janus Clinical Trials Data Repository
- Sentinel Initiative Active Post-marketing
Surveillance Program
7What 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
8Future State
Technology
Analysis tools
9Janus 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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11FDA 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)
12Sentinel 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
13Mini 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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14Organizations
- 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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16Year 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
17Data Characterization Enrollment
As of 7 Jan 2011
17
18Data Characterization Age
As of 7 Jan 2011
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19Year 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
20Mini-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
21Next 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
22Janus, 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.
23Thank you for your attention
armando.oliva_at_fda.hhs.gov