DEPARTMENT OF VETERAN AFFAIRS PBM THIAZOLIDINEDIONE REGISTRY

1
Enhancing Post-Marketing Surveillance Lessons
from the Veterans Health Administration

Fran Cunningham, PharmDDirector Center for
Medication Safety PSCI and Pharmacoepidemiologic/
Outcomes Assessment VHA National Pharmacy
Benefits Management Strategic Healthcare
Group Robert Campbell, JD, MPH, PhDAssistant
Director for Evaluation, VISN 8 Patient Safety
Center of InquiryTampa, FLDustin French,
PhDHealth Economist, VISN 8 Patient Safety
CenterTampa, FL
2
Drug Safety and Pharmacovigilance in the
Department of Veterans Affairs National
Overview
Fran Cunningham, Pharm.D. Director Center for
Medication Safety PSCI and Pharmacoepidemiologic/
Outcomes Assessment VHA National Pharmacy
Benefits Management Strategic Healthcare Group
3
Pharmacovigilance in the Department of Veterans
Affairs Overview

• National program initiated - FY 1999
• Optimizing National Rx database for quality and
  research initiatives
• FY 2000/2001
• Pilot drug safety program
• National medication safety and DUE initiated
  focusing on ADEs
• Rx database used for pharmacovigilance efforts
• Sildenafil-NTG interactions
• Protease Inhibitors - CYP 3A 4 inhibitors

4
Pharmacovigilance in VA

• FY 2002/2003
• Integrated databases merged and used as primary
  source for tracking ADEs by national PBM
• First National Pharmacovigilance Projects
• Integrated databases used to assist in formulary
  decisions regarding drug safety
• National pharmacoepidemiolgic studies conducted
• Hines
• Bedford
• New Haven
• Seattle
• Durham
• Houston

5
Pharmacovigilance in VA

• FY 20042006
• Center for Medication Safety PSCI Grant
  co-funded by VACO PBM/SHG and National Center for
  Patient Safety
• Infrastructure for enhanced pharmacovigilance in
  VA developed
• Risk Reduction Program
• Pilot completed program operationalized
• Field investigators conduct pharmacoepidemiologic
  studies
• as a follow-up to pharmacovigilance/drug
  surveillance rapid cycle analysis results
• IOM Presentation

6
Pharmacovigilance in VA

• FY 2006-2007
• Programs continued and enhanced
• Active Surveillance Program pilot
• Sentinel Event Network
• FDA/VA MOU developed and signed
• FDA/VA Charter initiated

7
GOAL of VA PHARMACOVIGILANCE PROGRAM

• Track and evaluate high risk and high volume
  agents in veteran population
• Formalize the national drug safety program with
  emphasis on
• Utilizing integrated databases as the foundation
  of the VA national pharmacovigilance program
• Modernizing and enhancing spontaneous ADE
  reporting

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GOAL of PHARMACOVIGILANCE PROGRAM

• Track inappropriate use of therapy as part of the
  national pharmacovigilance program
• Polypharmacy
• High Doses
• Altered End Organ Function
• NMEs
• Conduct risk reduction efforts
• Develop Active Surveillance Program
• Initiate and encourage drug safety research using
  national databases

9
VA for Pharmacovigilance/Drug Surveillance

• The VA as a resource for surveillance and adverse
  event evaluation
• Older/Sicker patients
• High medication use
• Penetration of new agents is fairly rapid
• Good Information Systems
• Ongoing monitoring of outcomes in place

10
Adverse Drug Events in VAReporting, Tracking,
Monitoring

• Adverse Drug Event Database
• Spontaneous Reporting
• FDA MedWatch Form 3500
• Allergy Reaction Tracking Package (ART Package)
• CPRS Electronic Medical Record
• Every VA Facility
• Adverse Drug Event Tracking and Evaluation Using
  VA Integrated Databases
• Prescription Databases
• Inpatient/Outpatient Files
• Mortality Database

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INTEGRATED DATABASES
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VA National Prescription Database

• Includes data from October 1998 to present
• Provides every individual Rx filled in the VA
• Provides prescription days supply
• Data is specific to outpatient divisions
• Patient identifier is included for every Rx
• Provides cost per unit for every prescription
• Provides dosing instructions for each
  prescription

13
VA Integrated Databases Linkages with Pharmacy
Data
VA National Health Surveys
Mortality data
VA National Patient Care Databases
Pharmacy Databases
DEpiC Diabetes Epidemiology Cohort
CMS Medicare data
Other Potential Data - VA Rehab - VA Dz
Registries
14
VA Databases as a Tool

• VA databases provide the mechanism for
• Medication safety projects and initiatives
• Clinical decisions
• Research
• An effective tool in VA
• Monitoring exposure rate and ADEs
• High risk agents
• New agents
• Agents with newly identified safety information
• An effective tool for evaluation of appropriate
  use
• Safety
• Central Office and Field queries
• Other Government Agencies

15
Safety Evaluations

• Rx databases, electronic medical record
  (inpatient and outpatient files), and mortality
  database are linked at patient level to monitor
  agents
• Patients characterized by demographic, medical
  hx, medication and tx variables
• Patients followed for 12-24 months or greater
• NMEs tracking initiated from inception in
  system and formally evaluated every 6 months
• Control agent chosen
• Rates of exposure and adverse outcomes assessed

16
Select Example of VA Pharmacovigilance/Drug
Surveillance Projects - FY 2005-2007

• Fluoroquinolones
• High Dose Statins
• Rosuvastatin
• Statin-Fibrates
• Cox II Inhibitors
• Etodolac
• Accutane
• Cilostazol
• Leflunamide
• Bevacizumab

• Galantamine
• Pegylated Interferons
• Bisphosphanates
• PDE V Inhibitors
• ARBs
• Antipsychotics
• Ezetimibe
• Varenacline
• Deferasirox
• DMARDS
• Vitamin E
• LABAs

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VA Sites Conducting Pharmacoepidemilogic Projects

• St. Louis HSRD (Washington University)
• Bedford HSRD (Boston University)
• Pittsburgh HSRD (Univ of Pittsburgh and Univ of
  Pennsylvania)
• Ann Arbor VAMC HSRD (Univ of Michigan)
• Hines HSRD (Northwestern University and UIC)
• VISN 1 Co-op Studies Program (Harvard)
• New Haven VAMC and Center of Excellence (Yale)
• Durham VAMC and HSRD (Duke University)
• Minneapolis HSRD
• Dallas VAMC
• Birmingham VAMC and HSRD (Univ of Alabama)
• Nashville VAMC and CSP
• Houston VAMC and HSRD
• Seattle HSRD (University of Washington)
• San Antonio HSRD (University of Texas)
• VISN 8 PSCI and HSRD

18
Post-marketing Medication Safety Paradigm
Shifts
Robert Campbell, JD, MPH, PhDAssistant Director
for Evaluation, VISN 8 Patient Safety Center of
InquiryTampa, FL
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Post Marketing SurveillanceParadigm Shifts

• Adverse Drug Reactions (ADRs)
• Adverse Drug Events (ADEs)
• Other Outcomes and Problems (OOPs)

20
Non-FDA Drug Safety Initiatives Impacting Post
Marketing Surveillance Activities
Risk Management Reporting Systems Accreditation
Programs Performance Measurement Systems
21
Proactive Surveillance Research VISN 8 Patient
Safety Center of Inquiry

• Medication Safety Team
• Falls and medications in the elderly
• Drugs as risk factors for adverse outcomes

22
Drug Safety and Pharmacovigilance in the
Department of Veterans Affairs Methodological
Issues
Dustin D. French, PhD Health Economist Patient
Safety Center of Inquiry. Tampa, FL.
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Drug Safety Lost under the street light?

• A cop walking his beat one night finds a drunk on
  his knees, searching for something on the street.
  The cop asks the drunk, What are you doing?
  Looking for my car keys, says the drunk. The
  cop asks, Where did you lose your keys? I
  dont know, the man answers. The cop, a bit
  perplexed, asks, Then, why are you looking here
  if you dont know where you lost your keys?
  Responds the drunk, Because the light is better
  here, under the streetlight.
• e.g. COX-2 and GI Bleeds

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Where to look?

• Healthcare system that is fragmented (e.g.
  Medicare, Medicaid, HMOs, PPOs).
• EU Nationally financed healthcare systems
• US VHA Integrated healthcare system with
  (inpatient, outpatient, pharmacy, lab, etc.)

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Joining Data Silos for Drug Safety
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What to Look For?

• E.G. COX-2 GI Bleeds or Strokes and MIs
• From Case Reports
• Systems with Biological mechanisms
• Systems without Biological Mechanisms
• Proactive VS Reactive Surveillance for not just
  harms but potential benefits

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How to Look?

• Incidence of adverse outcomes temporally
  associated with medication use (signal detection)
• More sophisticated multivariate modeling (e.g.
  logistic regression, GEE, case cross-over
  designs) of Medications related outcomes
  (drug-drug and drug-disease interactions,
  comorbidities etc.)
• Expert panel review of the national Electronic
  Medical Record (VISTA) of drug related cases from
  signal detection phase

28
VHA Drug Safety Studies

• PDE-5 and NION (AJO 2007)
• Amantadine and CE (Cornea forthcoming)
• Medication profiling (CVS, CNS, MSS) and
  fractures, syncope, MI, etc. (Drugs and Aging
  2005, Br J Clin Pharm 2006, Am J Clin Pharm
  2007).
• Risk Adjusted Models (Pharmacoepidemiology and
  Drug Safety 2005)

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When to Look? Time Frame?

• IBM 3390 - 5.7 million patients, 120 million
  outpatient prescriptions and outpatient care, and
  perform signal detection study, short turn around
  (e.g. lt1 week).
• Real Time Transaction Data Bases
• Data Cubes and Dash Boards (SQL)
• Banking Industry, Airline, etc.
• Real ID ACT- The Future of Patient
  Identification?