FDA's Mini-Sentinel Program to Evaluate the Safety of Marketed Medical Products Progress and Direction Progress and Direction Richard Platt Harvard Pilgrim Health Care Institute Harvard Medical School for the Mini-Sentinel Investigators January 31, 2013 info@mini-sentinel.org 1
Mini-Sentinel • Develop scientific operations for active medical product safety surveillance • Create a coordinating center with continuous access to • Create a coordinating center with continuous access to automated healthcare data systems, and the following capabilities: – Develop and evaluate scientific methods that might later be used in a fully-operational Sentinel System. – Offer FDA the opportunity to evaluate safety issues in existing automated healthcare data system(s) and learn more about barriers and challenges. 2 2
Mini-Sentinel partner organizations Institute for Health info@mini-sentinel.org 3
Initial needs � Policies • Privacy • Governance � Data model Everything! Everything! � Procedures at FDA, at Coordinating Center, at Partner sites � Procedures at FDA, at Coordinating Center, at Partner sites • White papers • Standard operating procedures � Infrastructure at FDA, at Coordinating Center, at Partner sites • Personnel • Hardware • Software info@mini-sentinel.org 4
Mini-Sentinel Distributed Analysis 1 � User creates and submits query (a computer program) 2 � Data partners retrieve query 3 � Data partners review and run query review and run query against their local data 4 � Data partners review results 5 � Data partners return results via secure network 6 Results are aggregated info@mini-sentinel.org 5
Mini-Sentinel Journal Supplement • Supplement to Pharmacoepidemiology and Drug Safety • 34 peer reviewed articles • Goals, organization, privacy policy, data systems, policy, data systems, systematic reviews, stats/epi methods, record retrieval and review, protocols for drug/vaccine studies... • Open access! • http://onlinelibrary.wiley.com/doi/ 10.1002/pds.v21.S1/issuetoc info@mini-sentinel.org 6
Drugs “This assessment [2used2] FDA’s Mini�Sentinel pilot...” www.fda.gov/Drugs/DrugSafety/ucm326580.htm; Nov 2, 2012 info@mini-sentinel.org 7
Toh Arch Intern Med.2012;172:1582�1589. info@mini-sentinel.org 8
“�we commend the Food and Drug Administration for developing the Mini"Sentinel�” Katz. Arch Intern Med. 2012;172:1590 info@mini-sentinel.org 9
www.mini�sentinel.org/work_products/Statistical_Methods/Mini�Sentinel_Methods_Re�use�of�Mini�Sentinel�Data.pdf info@mini-sentinel.org 10
www.mini�sentinel.org/work_products/Statistical_Methods/Mini�Sentinel_Methods_Framework�f or�Assessment�of�Signal�Refinement�Positive�Results.pdf info@mini-sentinel.org 11
In theory there is no difference between theory and practice. In practice there is. In practice there is. Yogi Berra www.brainyquote.com/quotes/quotes/y/yogiberra141506.html#gsD0IBx3dytirLPX.99 info@mini-sentinel.org 12
Mini-Sentinel Distributed Analysis 1 � User creates and submits query (a computer program) 2 � Data partners retrieve query 3 � Data partners review and run query review and run query against their local data 4 � Data partners review results 5 � Data partners return results via secure network 6 Results are aggregated info@mini-sentinel.org 13
PopMedNet Architecture – Deployment Overview Internet Data Administrators & Reviewers HTTPS, System (Two Factor AuthN) Administrator TLS (Two Factor FISMA Compliant Data Center AuthN) Data Partner Organization urity (IDS/IPS, VPN/RSA) / Reverse Proxies/Load User and DataMart Workflow Provisioning And Administration Job Internal DMZ Scheduling Internet Firewall Firewall Firewall DataMart Management Request/ Data Balancers HTTPS, TLS (Metadata, Response Data Mart Source Authorization) Mgr Client (Common HTTPS, Mutual TLS HTTPS, Mutual TLS Network Security REST Web Servers / Re Bal Data Data User Account User Model) Management Interface Optional Site to Site VPN (Groups/Roles/User ETL Accounts) Optional DataWarehouse PMN Portal / Repositories DMZ Non DMZ (Internal Components) Audit Observer Investigator • PMN Software – Supports multiple deployment models Enhanced • Agnostic to data center infrastructure and complements existing network infrastructure Investigator • VM based deployments enabling ease of disaster recovery and planning • Seamless overlay of VPN Connections (Remote Access, Site to Site, Two Factor User Authentication) • Supports consolidation of remote sites into the data center for central management (Data Partner Components can be hosted in a central data center similar to the PMN Portal) • Secure End to End connection (Encrypted Transport using X.509 certificates) • Supports industry standard RBAC configuration for users • Supports Data Source provisioning based on RBAC and additional data source specific metadata • Queries distributed using a PULL model instead of PUSH model
Mini-Sentinel Distributed Analysis 1 � User creates and submits query (a computer program) 2 � Data partners retrieve query 3 � Data partners review and run query review and run query against their local data 4 � Data partners review results 5 � Data partners return results via secure network 6 Results are aggregated info@mini-sentinel.org 15
A Mini-Sentinel week � Distributed dataset development/maintenance � Query tool development /use � Protocol development / implementation � Methods development / implementation � Methods development / implementation � Develop new capacity � Contribute to establishing a national resource for evidence development info@mini-sentinel.org 16
A Mini-Sentinel week � Distributed dataset development/maintenance info@mini-sentinel.org 17
Data Refreshes: Data Partner 10. Manage Data Update Process Data Data Data Data 1. Create Manager Manager Manager Manager Data Update Work Plan Technical Technical Technical Technical Analyst Analyst Analyst Analyst Data Data Data Data Data Data Data Data 2. Review Data 2. Review Data 3. Verify 3. Verify Update Work Source Data Partner Partner Partner Partner Plan Availability 5. Extract Data Quality 4. 6. Transform 8. Create Technical Technical Technical Technical Data from Checking & Verify/Modify & Load Data Query Tool Analyst Analyst Source Profiling Analyst Analyst ETL Process into CDM Files System Data Data Data Data 7. Validate Quality Quality Quality Quality Data Load Analyst Analyst Analyst Analyst MSOC MSOC Data Partner Data Partner info@mini-sentinel.org 18
Data Refreshes: Operations Center 13. Manage Data Quality Checking & Profiling Process Technical Technical Technical Technical 1. Verify 2. Run Data Current SAS Quality Analyst Analyst Analyst Analyst Updates Software Checking Versions Programs 3. Review & Remediate Data Data Data Data Outputs Quality Quality Quality Quality Analyst Analyst Analyst Analyst Analyst Analyst Analyst Analyst 4. Deliver 4. Deliver Summary Outputs Data Data Data Data 5. Review Quality Quality Quality Quality Summary Analyst Analyst Analyst Analyst Outputs 6. Approve Data Data Data Data Data Data Partner Updates Manager Manager Manager Manager Update MSOC MSOC Data Partner Data Partner info@mini-sentinel.org 19
Data Refreshes � 120 core data refreshes received since MS began How long does it Three weeks to take to approve a three months refresh? info@mini-sentinel.org 20
Standard data checks � 100+ tables per data partner per refresh info@mini-sentinel.org 21
Data Visualization: After 7 th refresh, partner A info@mini-sentinel.org 22
Data Visualization: After 8 th refresh, partner A New time period New data problem in old time period info@mini-sentinel.org 23
Data Visualization: After 8 th refresh fixed info@mini-sentinel.org 24
• “Eternal vigilance is the • “Eternal vigilance is the price of liberty” price of reliable data" -- attributed to -- Mini-Sentinel Thomas Jefferson info@mini-sentinel.org 25
A Mini-Sentinel week � Distributed dataset development/maintenance � Query fulfillment tools development /use info@mini-sentinel.org 26
Typical Input to Modular Programs Start Date End Date Start of new treatment episode • Look back XX days • Look back XX days • Outcome(s) • Outcome(s) • Inclusion/exclusion condition • Optional: blackout days • Optional: extension days Time Index Date info@mini-sentinel.org 27
Mini-Sentinel Query Fulfillment Process info@mini-sentinel.org 28
When existing programs aren’t enough � Modify a modular program, or � Create a new program info@mini-sentinel.org 29
New Program Development info@mini-sentinel.org 30
Uses of the distributed database Modular Programs Ad Hoc Programs 1500 100 1000 MP Queries 50 500 MP Reports 0 0 Feb-11 May-11 Aug-11 Nov-11 Feb-12 May-12 Aug-12 Nov-12 MP Scenarios Feb-11 Jun-11 Oct-11 Feb-12 Jun-12 Oct-12 info@mini-sentinel.org 31
Recommend
More recommend
