pmda’s recent developments in enhancement of drug safety ... · “safety” is one of the main...
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PMDA’s Recent Developments in Enhancement of Drug Safety Measures
Mie IkedaOffice of Safety I, PMDA
24th AnnualEuroMeeting
26-28 March 2012Copenhagen, Denmark
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DisclaimerThe views and opinions expressed in the following PowerPoint slides are those of the individual presenter and should not be attributed to Drug Information Association, Inc. (“DIA”), its directors, officers, employees, volunteers, members, chapters, councils, Special Interest Area Communities or affiliates, or any organization with which the presenter is employed or affiliated.
These PowerPoint slides are the intellectual property of the individual presenter and are protected under the copyright laws of the United States of America and other countries. Used by permission. All rights reserved. Drug Information Association, DIA and DIA logo are registered trademarks or trademarks of Drug Information Association Inc. All other trademarks are the property of their respective owners.
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“Safety” is one of the main targets of PMDA Second Mid-term plan(FY2009-FY2013)
“Strengthening and Improvement of Safety Measure Operations” (Excerpt from Second Mid-term plan)
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AnalysisCollection of Information
Planning and Implementation of Safety measures
Hypothesis
PMDA/MHLW Policy to enhance safety measures
Reinforcement of Scientific Safety Evaluation System
More Effective Dissemination of Safety information
Revision if necessary
Enhancement ofInformation Collection
System of sharing information for Proper use of drugs
Evaluation of hypothesis
Promotion of transparency
Transparency
Crisis management
New Risk management
system
• Prevention of serious drug safety-related crisis from Japan• Effective encouragement of proper drug use.• Ensuring credibility to post-market safety management system.
Goal
Assessment of Safety measure effects
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AnalysisCollection of Information
Planning and Implementation of Safety measures
Hypothesis
PMDA/MHLW Policy to enhance safety measures
Reinforcement of Scientific Safety Evaluation System
More Effective Dissemination of Safety information
Revision if necessary
Enhancement ofInformation Collection
System of sharing information for Proper use of drugs
Evaluation of hypothesis
Promotion of transparency
Transparency
Crisis management
New Risk management
system
• Prevention of serious drug safety-related crisis from Japan• Effective encouragement of proper drug use.• Ensuring credibility to post-market safety management system.
Goal
Risk Management Plan Guidance
(Draft)
(1)MIHARI project(2)EMR network
project
Assessment of Safety measure effects
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1. MIHARI PROJECT2. EMR NETWORK PROJECT3. INTRODUCTION OF
RISK MANAGEMENT PLAN
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1. MIHARI PROJECT2. EMR NETWORK PROJECT3. INTRODUCTION OF
RISK MANAGEMENT PLAN
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THE PROJECT TO UTILIZE ELECTRONIC MEDICAL INFORMATION (HEALTH CLAIM DATA, MEDICAL RECORDS, ETC) FOR SAFETY MEASURES.
What is the "MIHARI project" ?
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LAUNCHED IN FY2009.
"MIHARI" MEANS "MONITORING" IN JAPANESE. ALSO CALLED THE "MEDICAL INFORMATION FOR RISK ASSESSMENT INITIATIVE“
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This MIHARI's logo is made from crossed 4 arrows colored blue and green. Two blue arrows show two types of data sources (claim data and medical record data) and two green arrows show two types of analysis methods (pharmacopeidemiological analysis and data-mining analysis), respectively. These 4 arrows indicate that various kinds of data are analyzed from many directions in the MIHARI project.
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Background of MIHARI project
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Establishment of the Framework for Drug Safety Analysis with Secondary Use of Electronic Health Information*
Necessity of Drug Safety Analysis Using Expanded Data beyond Spontaneous Adverse Drug Reaction Reports
Strengthening and Improvement of Drug Safety Measure Operations in PMDA
<ADVANTAGES > Target population analysis Comparative evaluation Quantitative assessment Easier and prompt data collection
(compared with primary data research)
*Data from insurance claims and electronic medical records
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To ensure access to existing electronic healthinformation (EHI) such as medical records andclaim data
To develop methodology and technique to use EHIfor quantitative risk evaluation of drugs employing pharmacoepidemiological analysis
To develop methodology and technique to use EHI for evaluation of impact of regulatory actions on drug safety.
To establish framework for secondary utilization of EHI as a basis for taking safety measures.
MIHARI project - Objectives
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• Several data sources are examined at pilot studies in MIHARI– Health Insurance Claim Data– Diagnosis Procedure Combination (inpatient
claim) Data– Electronic Medical Record Data
etc.
Data Sources to be Examined
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Investigation Stages
Ensuring Access to Electronic Health
DataData collection schemeData cleaning method
Evaluation of Data Characterization
Data validationData limitation
Data UtilizationEpidemiological
studiesInterpretation of study
results
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Goal
Safety Measure
SpontaneousADR Report DB
Electronic Health Information Databases
ClaimDB
DPC (inpatient)
DB
Medical Records
DB
Drug UseResult Survey
DB
After 2013
Safety Evaluation
LiteraturesOverseas
Regulatory Actions
Presentation in Academic Conference
etc.
Current Status
Risk Communication
PMDA
MHLW
MedicalInstitutions
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Pilot Studies Using Claim DataSignal Detection Signal Refinement Signal Evaluation
Data mining Primary detection of exhaustive combination of event and drug
Drug use survey Survey for patient background or prescription trendin a specific population defined by diagnosis or drug Evaluation of effects of regulatory actionsSurvey for prescription trend or compliance of cautions after a regulatory action is taken
Alert detection Secondary detection of specific combination of event and drug by pharmacoepidemiological methods
Risk estimationQuantitative risk estimation for specific combination of event and drug by pharmacoepidemiological methods
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Flow of a Pilot Study
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Claim DB
Extracted Data Data set for analysis
Results
Ex.2 Distribution of age
Num
ber o
f pat
ient
s
Boxed Warning
6 7 8 9 10 11 12 1 2 3Calendar time
Ex.3 Trend of prescription
DefinitionsData set
specifications
Durations Number of dispensing
1 week 2,544
2 weeks 406
3-4 weeks 1,012
5-8 weeks 417
9-12 weeks 503
Over 12 weeks 72
Ex.1 Dispensing Duration
Example:Drug use survey and Evaluation of effects of regulatory actions
Analysis protocol
Num
ber o
f pat
ient
s
Result Image
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Necessity of Data Source Variety
Claim data
Medical Record
data
Drug Use Result Survey
data
DPCdata
ICSR data
Data base size
Detailed medical InformationLab test results
Detailed ADR informationADRsSuspected drugsEvent Dates
Standardized and manydata elementsDiseases with severityDates of prescriptionsSurgeries
• All data sources are not perfect and have limitations• Necessity to select the most appropriate data source,
depending on a purpose
Longitudinal data
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• Japanese– Reports from pilot studies are available
http://www.info.pmda.go.jp/kyoten_iyaku/mihari.html
• Englishhttp://www.pmda.go.jp/english/service/mihari_project.html
Web Pages of MIHARI
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1. MIHARI PROJECT2. EMR NETWORK PROJECT3. INTRODUCTION OF
RISK MANAGEMENT PLAN
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Development of an electronic medical record (EMR) data utilization network with collaborative hospitals and PMDA
Establishment of standardized database and analytic system in each hospital
Establishment of common work space for analysis accessible to collaborative hospitals and PMDA
Aim to expand the network to wider hospitals in the future
Utilization of EMR data for accurate and prompt benefit/risk assessment by applying epidemiological methods
Outline of EMR Network Project
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Securing access to 10 million individual’s EMR data in order to strengthen drug safety
Enable to collect accurate and detailed safety data which have not been spontaneously reported by pharmaceutical companies
Objective
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Network of
the Collaborative
Hospitals
Collaborative Hospital
• Budget approved FY2011 Governmental to initiate “Safety 10Mil. Data project”• The network construction will be completed by FY2013.
Health RecordsClaim Data
Desired Outcomes:• Promote risk & benefit review of medical technologies and provide safer healthcare. • Enable the government to take rapid and appropriate measures for drug safety.
ResearchersJoint Study
Collaborative study
Data request
Collaboration
Quick actions Ordering Data Laboratory Data
Database
Database
Database
Database
EthicalCommittee
Database
Electronic Medical Record Network Projectfor Drug Safety
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1. MIHARI PROJECT2. EMR NETWORK PROJECT3. INTRODUCTION OF
RISK MANAGEMENT PLAN
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Risk Management Plan GuidanceRisk Management Plan (RMP) Guidance (Draft) was made available for public consultationon April 20, 2011 (Period of public consultation: by October 31,2011)
This guidance is intended to propose a standard concept for “Pharmacovigilance Plan” and “Risk Minimization Plan”By MAH (marketing authorization holder)
RMP Guidance is expected to be finalized andNotified early FY2012
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Introduction of RMP -Background• In Japan, various kind of risk management
strategies have already been taken to ensure post-marketed drug safety. (…and have been fairly effective. )(eg. Spontaneous reporting system, Use result survey, EPPV,revision of package insert, Preparation and provision of Medication guide for patients)
• However, these safety measures are not necessarily taken systematically and consistently. (No explicit guidance which measure should be taken for what kind of drug)
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Pre-market review Approval Post-market
JP
US
EU
Phamacovigilance measures JP, US, EU
Pharmcovigilance planFor NME
Post-marketcommitment
Periodic report 6-10 yearsRe-examination
Re-evaluationIf necessary
REMS(high risk NME)
Periodic report
REMS(high risk NME)
RMP(NME)
Post-marketCommitmentIf necessary
PSUR
RMP(NME)
Spontaneous ADR, infection ReportingADR/AE reporting
ADR/AE reporting
ADR/AE reporting
Post-marketCommitmentIf necessary
Spontaneous ADR, infection Reporting
Spontaneous ADR, infection Reporting
EPPV(NME 6mo.)
Streamlined risk management strategies (pending)
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renewal renewal
Pharmacovigilance strategiesincluding Pharmacovigilance Plan
will be integrated into RMP
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MAH should identify safety issues of drug as Safety Specification according to the characteristics of each drug (eg. trearment population, target disease)
MAH should develop “Pharmacovigilance plan” and “Risk Minimization Plan” based on Safety Specification.
Features of RMP guidance draft (1)
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MAH should consider to collect information on drug efficacy/effectiveness by conducting post-market surveillance/study on efficacy/effectiveness.
Timely and appropriate assessment of impact, and revision of RMP if necessary.
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Features of RMP guidance draft (2)
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Risk Minimization PlanPharmacovigilance Plan
Routine
Additional
Safety Specification
Important Specified RisksImportant Potential RisksImportant missing Information
Additional measuresNecessary?
(Assessment)※ No
Yes
※:In deciding the measures to be taken, good consideration is required to avoid excess burdens and confusion in real clinical settings.
Conceptual diagram of RMP
Spontaneous ReportLiterature search
Package InsertPrecautions
• Enhancement of Spontaneous Report Collection by EPPV
• Use result survey• Specified use result survey
• Post-market Clinical Trial
•Information dissemination by EPPV•Medication guide for patients•Educational program•Limiting access•Revision of precautions
Pharmacovigilance Planand / or
Risk Minimization Plan?(Assessment)※
Additional vigilance plan
Additional Risk Minimization plan
Risk A
ssessm
ent
(Perio
dical re
ports)
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Enhancement of post-marketing drug safetyPromotion of Benefit-risk evaluation of
post-marketed drugs.Improvement of Safety measure
operations through evaluation based on benefit-risk analysis.
Introduction of RMP – Expectations
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Thank you for your kind attention!