FDA's Mini-Sentinel Program to Evaluate the Safety of Marketed - - PowerPoint PPT Presentation

▶
fda s mini sentinel program to evaluate the safety of
SMART_READER_LITE
LIVE PREVIEW

FDA's Mini-Sentinel Program to Evaluate the Safety of Marketed - - PowerPoint PPT Presentation

Jan 14, 2024 142 likes •638 views

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

slide-1
SLIDE 1

FDA's Mini-Sentinel Program to Evaluate the Safety of Marketed Medical Products Progress and Direction

info@mini-sentinel.org 1

Progress and Direction

Richard Platt

Harvard Pilgrim Health Care Institute Harvard Medical School

for the Mini-Sentinel Investigators

January 31, 2013

slide-2
SLIDE 2

Mini-Sentinel

  • Develop scientific operations for active medical product

safety surveillance

  • Create a coordinating center with continuous access to

2 2

  • 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.

slide-3
SLIDE 3

Mini-Sentinel partner organizations

info@mini-sentinel.org 3

Institute for Health

slide-4
SLIDE 4

Initial needs

Policies

  • Privacy
  • Governance

Data model Procedures at FDA, at Coordinating Center, at Partner sites

Everything!

info@mini-sentinel.org 4

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

Everything!

slide-5
SLIDE 5

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

info@mini-sentinel.org 5

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

slide-6
SLIDE 6

Mini-Sentinel Journal Supplement

  • Supplement to

Pharmacoepidemiology and Drug Safety

  • 34 peer reviewed articles
  • Goals, organization, privacy

policy, data systems,

info@mini-sentinel.org 6

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

slide-7
SLIDE 7

Drugs

info@mini-sentinel.org 7

www.fda.gov/Drugs/DrugSafety/ucm326580.htm; Nov 2, 2012

“This assessment [2used2] FDA’s MiniSentinel pilot...”

slide-8
SLIDE 8

info@mini-sentinel.org 8

Toh Arch Intern Med.2012;172:15821589.

slide-9
SLIDE 9

“we commend the Food and Drug Administration for developing the Mini"Sentinel”

info@mini-sentinel.org 9

  • Katz. Arch Intern Med. 2012;172:1590
slide-10
SLIDE 10

info@mini-sentinel.org 10 www.minisentinel.org/work_products/Statistical_Methods/MiniSentinel_Methods_ReuseofMiniSentinelData.pdf

slide-11
SLIDE 11

info@mini-sentinel.org 11 www.minisentinel.org/work_products/Statistical_Methods/MiniSentinel_Methods_Frameworkf

  • rAssessmentofSignalRefinementPositiveResults.pdf
slide-12
SLIDE 12

In theory there is no difference between theory and practice. In practice there is.

info@mini-sentinel.org 12

In practice there is. Yogi Berra

www.brainyquote.com/quotes/quotes/y/yogiberra141506.html#gsD0IBx3dytirLPX.99

slide-13
SLIDE 13

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

info@mini-sentinel.org 13

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

slide-14
SLIDE 14

PopMedNet Architecture – Deployment Overview

HTTPS, TLS

System Administrator (Two Factor AuthN) Firewall

Internet FISMA Compliant Data Center

urity (IDS/IPS, VPN/RSA)

DataMart Management (Metadata, Authorization) User and DataMart Provisioning And Administration Workflow Job Scheduling Request/ Response Mgr

/ Reverse Proxies/Load Balancers

Firewall

HTTPS, Mutual TLS

Firewall

Data Partner Organization

Data Mart Client Data Source (Common Data

REST

Internet

Data Administrators & Reviewers (Two Factor AuthN)

HTTPS, TLS

DMZ Internal

Investigator Enhanced Investigator Observer

Network Security

PMN Portal

User Account Management (Groups/Roles/User Accounts) User Interface

Web Servers / Re Bal

DMZ Non DMZ (Internal Components)

HTTPS, Mutual TLS

Data Model)

DataWarehouse / Repositories

Optional

Audit

ETL

Optional Site to Site VPN

  • PMN Software – Supports multiple deployment models
  • Agnostic to data center infrastructure and complements existing network infrastructure
  • 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
slide-15
SLIDE 15

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

info@mini-sentinel.org 15

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

slide-16
SLIDE 16

A Mini-Sentinel week

Distributed dataset development/maintenance Query tool development /use Protocol development / implementation Methods development / implementation

info@mini-sentinel.org 16

Methods development / implementation Develop new capacity Contribute to establishing a national resource for

evidence development

slide-17
SLIDE 17

A Mini-Sentinel week

Distributed dataset development/maintenance

info@mini-sentinel.org 17

slide-18
SLIDE 18

Data Refreshes: Data Partner

Data Manager Data Manager Technical Analyst Technical Analyst Data Data Data Manager Data Manager Technical Analyst Technical Analyst Data Data

  • 10. Manage Data Update Process
  • 3. Verify
  • 1. Create

Data Update Work Plan

  • 2. Review Data

info@mini-sentinel.org 18

Data Partner Data Partner Technical Analyst Technical Analyst Data Quality Analyst Data Quality Analyst Data Partner Data Partner Technical Analyst Technical Analyst Data Quality Analyst Data Quality Analyst

  • 6. Transform

& Load Data into CDM 4. Verify/Modify ETL Process

  • 3. Verify

Source Data Availability

  • 5. Extract

Data from Source System

  • 7. Validate

Data Load

  • 8. Create

Query Tool Files Data Quality Checking & Profiling

MSOC MSOC Data Partner Data Partner

  • 2. Review Data

Update Work Plan

slide-19
SLIDE 19

Data Refreshes: Operations Center

Technical Analyst Technical Analyst Data Quality Analyst Data Quality Analyst Technical Analyst Technical Analyst Data Quality Analyst Data Quality Analyst

  • 2. Run

Quality Checking Programs

  • 1. Verify

Current SAS Software Versions

  • 13. Manage Data Quality Checking & Profiling Process

Data Updates

  • 4. Deliver
  • 3. Review &

Remediate Outputs

info@mini-sentinel.org 19

Analyst Analyst Data Quality Analyst Data Quality Analyst Data Manager Data Manager Analyst Analyst Data Quality Analyst Data Quality Analyst Data Manager Data Manager

MSOC MSOC Data Partner Data Partner

  • 6. Approve

Data Partner Update Data Updates

  • 4. Deliver

Summary Outputs

  • 5. Review

Summary Outputs

slide-20
SLIDE 20

120 core data refreshes received since MS began

Data Refreshes

info@mini-sentinel.org 20

How long does it take to approve a refresh? Three weeks to three months

slide-21
SLIDE 21

Standard data checks

100+ tables per data partner per refresh

info@mini-sentinel.org 21

slide-22
SLIDE 22

Data Visualization: After 7th refresh, partner A

info@mini-sentinel.org 22

slide-23
SLIDE 23

Data Visualization: After 8th refresh, partner A

New time period

info@mini-sentinel.org 23

New data problem in old time period

slide-24
SLIDE 24

Data Visualization: After 8th refresh fixed

info@mini-sentinel.org 24

slide-25
SLIDE 25
  • “Eternal vigilance is the

price of liberty”

  • - attributed to

Thomas Jefferson

  • “Eternal vigilance is the

price of reliable data"

  • - Mini-Sentinel

info@mini-sentinel.org 25

slide-26
SLIDE 26

A Mini-Sentinel week

Distributed dataset development/maintenance Query fulfillment tools development /use

info@mini-sentinel.org 26

slide-27
SLIDE 27

Typical Input to Modular Programs

  • Look back XX days
  • Outcome(s)

Start of new treatment episode Start Date End Date

info@mini-sentinel.org 27

  • Look back XX days
  • Inclusion/exclusion condition
  • Outcome(s)
  • Optional: blackout days
  • Optional: extension days

Index Date Time

slide-28
SLIDE 28

Mini-Sentinel Query Fulfillment Process

info@mini-sentinel.org 28

slide-29
SLIDE 29

When existing programs aren’t enough

Modify a modular program, or Create a new program

info@mini-sentinel.org 29

slide-30
SLIDE 30

New Program Development

info@mini-sentinel.org 30

slide-31
SLIDE 31

Uses of the distributed database

1500

Modular Programs

100

Ad Hoc Programs

info@mini-sentinel.org 31

500 1000 Feb-11 Jun-11 Oct-11 Feb-12 Jun-12 Oct-12

MP Queries MP Reports MP Scenarios

50 Feb-11 May-11 Aug-11 Nov-11 Feb-12 May-12 Aug-12 Nov-12

slide-32
SLIDE 32

A Mini-Sentinel week

Distributed dataset development / maintenance Query tool development / use Protocol development / implementation

info@mini-sentinel.org 32

slide-33
SLIDE 33

Protocols in the field now

Impact of labeling change on use of long acting beta

agonists

Rotavirus vaccine and intussusception Human papillomavirus vaccine and

info@mini-sentinel.org 33

Human papillomavirus vaccine and

thromboembolism

Anti-diabetic drugs and acute myocardial infarction

slide-34
SLIDE 34

Protocols under development

Influenza vaccine safety

(same season, sequential analysis)

Metabolic effects of atypical antipsychotics in

children and adolescents

info@mini-sentinel.org 34

children and adolescents

Influenza vaccine and febrile seizures Dabigatran and stroke / bleeding Influenza vaccine and birth defects,

spontaneous abortion

IV iron products and anaphylactoid reactions IV immune globulins and thromboembolic events

slide-35
SLIDE 35

A Mini-Sentinel week

Distributed dataset development / maintenance Query tool development / use Protocol development / implementation Methods development / implementation

info@mini-sentinel.org 35

Methods development / implementation

slide-36
SLIDE 36

Methods

Improving confounder adjustment Validation of health outcomes of interest Data mining for vaccine adverse events Implementing routine prospective surveillance of

info@mini-sentinel.org 36

Implementing routine prospective surveillance of

new products using sequential methods

slide-37
SLIDE 37

A Mini-Sentinel week

Distributed dataset development / maintenance Query tool development / use Protocol development / implementation Methods development / implementation

info@mini-sentinel.org 37

Methods development / implementation Develop new capacity

slide-38
SLIDE 38

Coming in 2013

Prospective surveillance of new products New query tools New bandwidth to respond to more queries New data

info@mini-sentinel.org 38

New data

  • Links to state birth and immunization registries
  • Explore use of inpatient data
slide-39
SLIDE 39

A Mini-Sentinel week

Distributed dataset development/maintenance Query tool development /use Protocol development / implementation Methods development / implementation

info@mini-sentinel.org 39

Methods development / implementation Develop new capacity Contribute to establishing a national resource for

evidence development

slide-40
SLIDE 40

February 10, 2011. Volume 364: 498-9

info@mini-sentinel.org 40

slide-41
SLIDE 41

Continue external engagements

NIH Health Care System Collaboratory Observational Medical Outcomes Partnership (OMOP) Clinical Trials Transformation Initiative

info@mini-sentinel.org 41

Clinical Trials Transformation Initiative ONC Standards & Interoperability Framework

(Query Health)

IOM Roundtable on Value and Science-Driven Health

Care

Academy Health EDM Forum Other new partners as opportunities present

slide-42
SLIDE 42

In conclusion

info@mini-sentinel.org 42

In conclusion

slide-43
SLIDE 43

Key contributors to Mini-Sentinel’s progress

Close, frequent, coordinated interactions between FDA, data

partners, content experts, epidemiologists, and statisticians

Distributed data network Public health practice Focus on defined populations with sufficiently complete data

info@mini-sentinel.org 43

Focus on defined populations with sufficiently complete data

  • First: Claims and administrative data, plus access to full text records
  • Then: electronic medical records, registries, …

Rapid cycle development of capabilities Ability to respond quickly to predefined needs

slide-44
SLIDE 44

“2highlights the necessity of proactive planning2”

Salmon Health Affairs 2012; 31:2518

slide-45
SLIDE 45

Costs and benefits

Up to date distributed database +

hundreds of rapid response queries

Protocol based study

info@mini-sentinel.org 45

Protocol based study Being prepared for pandemic

  • r other crisis
slide-46
SLIDE 46

Expectations confirmed

Standard programs can help FDA quickly interpret

signals from other sources:

  • Dabigatran and bleeding
  • Olmesartan and celiac disease

info@mini-sentinel.org 46

  • Varenicline and cardiac events

Many sophisticated analyses do not require exchange

  • f protected health information
slide-47
SLIDE 47

info@mini-sentinel.org 47

slide-48
SLIDE 48

Thank you!

info@mini-sentinel.org 48

Thank you!