Enhancing Post-Marketing

Surveillance: Lessons from

the Veterans Health
Administration

Fran Cunningham, PharmD

Director Center for Medication Safety PSCI and
Pharmacoepidemiologic/ Outcomes Assessment

VHA National Pharmacy Benefits Management

Strategic Healthcare Group

Robert Campbell, JD, MPH, PhD

Assistant Director for Evaluation, VISN 8 Patient Safety Center of Inquiry
Tampa, FL

Dustin French, PhD

Health Economist, VISN 8 Patient Safety Center
Tampa, FL
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
 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
 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
 Pharmacovigilance in VA
FY 2004–2006
– 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
 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
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
 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
 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
 Adverse Drug Events in VA
Reporting, 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
INTEGRATED DATABASES
 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
 VA Integrated Databases
Linkages with Pharmacy Data
VA National
Health Surveys VA National
Mortality data Patient Care
Databases

Pharmacy Databases

DEpiC
CMS Diabetes Epidemiology
Medicare data Other Potential Data Cohort
- VA Rehab
- VA Dz Registries
 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
 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

NME’s – tracking initiated from inception in system

and formally evaluated every 6 months

Control agent chosen

Rates of exposure and adverse outcomes assessed

 Select Example of VA
Pharmacovigilance/Drug Surveillance
Projects - FY 2005-2007
Fluoroquinolones Galantamine
High Dose Statins Pegylated Interferons
Rosuvastatin Bisphosphanates
Statin-Fibrates PDE V Inhibitors
ARB’s
Cox II Inhibitors
Antipsychotics
Etodolac
Ezetimibe
Accutane Varenacline
Cilostazol Deferasirox
Leflunamide DMARDS
Bevacizumab Vitamin E
LABAs
 VA Sites Conducting
Pharmacoepidemilogic Projects
St. Louis HSR&D (Washington University)
Bedford HSR&D (Boston University)
Pittsburgh HSR&D (Univ of Pittsburgh and Univ of Pennsylvania)
Ann Arbor VAMC HSR&D (Univ of Michigan)
Hines HSR&D (Northwestern University and UIC)
VISN 1 Co-op Studies Program (Harvard)
New Haven VAMC and Center of Excellence (Yale)
Durham VAMC and HSR&D (Duke University)
Minneapolis HSR&D
Dallas VAMC
Birmingham VAMC and HSR&D (Univ of Alabama)
Nashville VAMC and CSP
Houston VAMC and HSR&D
Seattle HSR&D (University of Washington)
San Antonio HSR&D (University of Texas)
VISN 8 PSCI and HSR&D
Post-marketing
Medication Safety:
Paradigm Shifts

Robert Campbell, JD, MPH, PhD

Assistant Director for Evaluation,
VISN 8 Patient Safety Center of Inquiry
Tampa, FL
 Post Marketing Surveillance
Paradigm Shifts

ƒ Adverse Drug Reactions (ADRs)

ƒ Adverse Drug Events (ADEs)

ƒ Other Outcomes and Problems (OOPs)

 Non-FDA Drug Safety Initiatives
Impacting Post Marketing
Surveillance Activities

Risk Management Reporting Systems

Accreditation Programs

Performance Measurement Systems

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
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.
 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 don’t know,” the man answers. The
cop, a bit perplexed, asks, “Then, why are you looking
here if you don’t 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
 Where to look?

ƒ Healthcare system that is fragmented (e.g.

Medicare, Medicaid, HMOs, PPOs).
ƒ EU – Nationally financed healthcare
systems
ƒ US – VHA – Integrated healthcare system
with (inpatient, outpatient, pharmacy, lab,
etc.)
Joining Data Silos for Drug Safety
 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
 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
 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)
 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. <1 week).
Real Time Transaction Data Bases
Data Cubes and Dash Boards (SQL)
Banking Industry, Airline, etc.
Real ID ACT- The Future of Patient
Identification?