joint research centre - ministero salute · database (db) eu level member states mir form eudamed...
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The European Commission’s scienceand knowledge service
Joint Research Centre
Connecting the dots: globally applicable adverse event terminology,
signal detection and the novel MIR formDr. Claudius Griesinger
Group leader ‘Health technologies’
European Commission, DG Joint Research CentreDirectorate F: Health Consumer, Reference Materials
Unit F.2: Consumer Products Safety
Conferenza Nazionale sui Dispositivi Medici, Rome, 18-19 December, 2017
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OutlineJoint Research Centre
MIR form
IMDRF adverse event terminology
Signal detection & management
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• One of the 33 Directorate Generals of the Commission
• About 3000 staff, ca 75% are researchers
• HQ in Brussels, research facilities in 5 Member States
Examples:
• Migration & demographic change
• Water resources
• ‘Copernicus’ - satellite data analysis
• Chemical safety
• Alternative methods to animal models
• Nanobiosciences
• Vehicle emissions & electromobility
• Renewable energy
• Reference materials & measurements
• Medical technology
JRC online: ‘EU science hub’
https://ec.europa.eu/jrc/en
The Joint Research Centre's mission is to
support EU policies with independent
evidence throughout the whole policy cycle.
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• Directorate "Health, Consumer,
Reference Materials"
• Unit "Consumer Products Safety"
• JRC Medical Medical Devices Task Force
Life sciences buildings, JRC, Ispra campus, Italy
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Conception Implementation Adaptation to technical
progress
JRC JRC
Ca 30% Ca 70%
JRC is involved throughout the policy cycle of EU legislation
JRC
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Joint managementby Commissionservices
Regulation on Medical Devices (MD)
Regulation on in vitrodiagnostics
DG GROW DG SANTE DG JRC
Policy leadNB assessment with MS
Scientific & technical aspects
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• Medical technology: Increasing importance for modern healthcare: improving health and healthy ageingWide range of products – ca 500’000 to 1 million on EU market.
• Creating jobs: > 600'000 people in EU medical technology sector• Competitive: 100 billion in annual sales• Agile industrial fabric: 95% of companies are SMEs
…robotic surgery...diagnostics…imaging …prosthetics…plasters
Medical Technology: key facts
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The silver society: a challenge with considerable global opportunities
UN / WorldBank
China
2028: aged
2035: hyper aged
Emerging markets
will have major
Share of >65
Chart: Standard Chartered (2017) Ageing – Passing the Baton to Asia
Developing socioeconomic models
addressing the challenges:
policies, products & services
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OutlineJoint Research Centre
MIR form
IMDRF adverse event terminology
Signal detection & management
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Why?Manufacturers, regulators and other relevant actors, want to
make sure that cost-effective devices are
safe and efficient/performing as intended.
Patients should receive devices that
• do not cause unnecessary harm ("acute") and
• do not pose unknown or unjustifiable risks ("longer term”)
• improve their health & well-being
Thus, it is important to look out for information that may
indicate specific patterns, trends or that signals risks/concerns
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Post-market & ‘real world data’
Benefit
Risk
Benefit
Risks
Collecting, monitoring data post-market
‘real world data’ is critical:
pre-market clinical data reflect very controlled use and
are often very limited, especially in context of EU model
of fast market access of novel technologies.
BRc = ?
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Evidence Pathway
downstreamupstream
Life cycle assessment
In vitro / in vivo
Toxicity
Bio-compatibility
Modelling/Simulation
Pharmaco-/toxicokinetics
Feasibilitystudies
FIM / phase 0
Patient registries
Incident Reporting, FSCA, PSR etc.
News
Scientificliterature
Extra EU information
Materialcharacterisation
REACH
PROs /UROs
PMCF
Pre-market space Post-market space
Pivotal Studies
preclinical
clinical
Market surveillance/
vigilance
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Regulatoryrecipient
DB
DB
Database (DB)
Member StatesEU level
MIR form
EUDAMED
Manufacturers(serious
incidents)
Sponsors(serious
adverse events)
…
MIR form
SAE form
MS coordination
Improved detection & management of signals;
Detection of trends and patterns
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Background: EU pilot on novel MIR formusing categorised reporting (ISO)
Online:
Search ‘EU bookshop’.
Search for title keywords
MIR form
Pilot MIRform
Voluntary participants from
industry, analysis JRC
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MIR form working group
COMPETENT AUTHORITIES
• Tony Sant, MHRA, UK (co-chair WG)• Paras Shah, MHRA, UK• Audrey Sierra, ANSM, France• Rosaria Boldrini, Ministry of Health, Italy• Bernhard Bichsel, Swissmedic, Switzerland• Kelly Decaluwe, FAGG, Belgium• Christophe Driesman, FAGG, Belgium• Helena Dzojic, MPA, Sweden• Andrea Hanson, HPRA, Ireland• Ulrike Meyer, Swissmedic, Switzerland• Patrick Murphy, HPRA, Ireland• Carmen Ruiz-Villar, AEMPS, Spain• Ekkehard Stösslein, BfArM, Germany
EUROPEAN COMMISSION
• Claudius Griesinger, DG JRC (co-chair WG)• Tim Raemaekers, DG JRC• Marco Nocita, DG JRC• Jean-Francois Roche, DG GROW
(Vigilance WG Chair)
INDUSTRY ASSOCIATIONS
• Philippe Auclair, Abbott• Marta Carnielli, Ortho Clinical Diagnostics• Nicole Denjoy, COCIR• Frederic Melchior, COCIR• Jean-Charles Moreau, Medtronic • Philippe Soly, Philips Healthcare• Dario Pirovano, MedTech Europe• Laure-Anne Thieren, Eucomed• Sophie Vaillot, GE Healthcare• Petra Zoellner, MedTech Europe
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MIR form working group - scope
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Key novelties of the MIR form
Adverse Event Terminology (IMDRF)
Back reporting of similar incident
Clear structure – user friendliness
Fit for novel Regulation
1.Administrative Information2.Medical Device Information3.Information derived from
healthcare professional / user
4.Manufacturer analysis
1.Open comments
1.Adverse Event ‘ footprint’ (AUTO FILL IN)
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OutlineJoint Research Centre
MIR form
IMDRF adverse event terminology
Signal detection & management
Powdery mildew
Rustdisease
Mouldy core
Rustdisease
Mouldy core
Powdery mildew
Rustdisease
Mouldy core
Powdery mildew
Rustdisease
Mouldy core
Powdery mildew
Critical importance of data structureProducts Problems
Medical device problem
Device,IVD
Patient, User,Consumer
Patient problem
Adverse Event Terminology
Cause investigation
Adverse Event terminology: data structure to support
signal detection / pattern recognition & communication
IMDRF “Health Effects”
Terminology set No. 3: Health Effects
Annex E Clinical conditions /symptoms / signs
Annex F Health
impact
E | F ‘Brain haemorrhage’ | ‘extended surgery’
Structured according to organ system / physiological system, e.g. • Cardiovascular• Nervous system • Hormonal system• Reproductive system
Downstream impact, e.g. ‘death’, ‘hospitalisation’, ‘unexpected medical intervention’, ‘wrong intervention due to incorrect diagnosis’
IMDRF Adverse Event Working GroupMeeting at JRC campus, Ispra, Italy, May 2017
2015 Basic issues(methodology,mapping…)
EU proposal:MD problems
2016 EU proposal:Cause investigation
1st Meeting:MD problems
2nd Meeting:Cause investigation
IMDRF consultation:MD problems
2017
IMDRF consultation:cause investigation
PUBLISHED:MD problems EU proposal:
Patient Problems
4th Meeting:Patient problems
PUBLISHEDCause investigation
3rd meeting@ JRC
2018IMDRF consultationPatient Problems
?
PUBLISHED:Patient problems ?
Use of terminology: data interrogation, signal detection, confirmation, exchange of information…
Data structure
Data query (Boolean operators)…Device Device Problem Health effectAND AND
Pacemaker X In back-up mode bradycardiaAND AND
Time
f (I
nci
de
nts
)Visualisation…
Data extraction for further analysis…
associations
Product Health effect Product Product problems
Trends, patterns, signals
associations
Product problems
…over time …over time
Location
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Definition of signal
Signalconveyinginformationon…
…specific occurrence orpresence that is of concern / interests
…and promptsaction
Signal
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f Data structure
‘Qualitative’ ‘Quantitative’
Signal detection is about using information thatcan help identify problems related to the use of medical devices
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Legal anchor: MDR article 90 – vigilance data
• Trends
• Patterns
• Signals
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1 basic aspects
Definitions & basic concepts
2 data sources
Mapping and possible use
3) qualitative
SDExpert
judgment
4 data mining
Quantitativesignal
detection
5) processSignal
management6 data
quality to
enable efficient signal
detection
7 Legal tools linked
to SD
MDR EUDAMED
Open Conceptual Framework
Open = adaptable, amenableto innovationConceptual = based on commonlyunderstood concepts, principles,practicesFramework = providing the theoretical frame for building practical approaches, e.g. …Integrated approach:Integration of1) … data 2) … methods: qualitative &
quantitative (data mining)
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Staged approach
Time
Initial phase• Horizon
scanning• Extra-EU
information • IMDRF AE
terminology• Collection of
MS data
Strategic planning document & Survey of CAs
Kick-off workshop in Ispra
Elaboration of Open Conceptual Framework (7 modules) – further workshops
EUDAMED vigilance gr.
Vigilance expert group
Develop-ment of Integrated Approach
Po
ssib
le
acto
rs International partners (NCAs)
Stakeholders
Info
rmed
&
po
ssib
le li
nks
MDEG / MDCG*
CAMD & MS Joint Action on Market Surveillance
CIE expert group
IVD expert group
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Kick-off workshop: agreements & follow-up
Presentation & discussion of SURVEY
Presentation & discussion of
JRC collection of MS data1) basic aspects
Definitions & basic concepts
2) data sources
Mapping and possible use
3) qualitative
SDExpert
judgment
4) data mining
Quantitativesignal
detection
5) processSignal
management6) data
quality to
enable efficient signal
detection
7) Legal tools linked
to SD
1) basic aspects
Definitions & basic concepts
2) data sources
Mapping and possible use
3) qualitative
SDExpert
judgment
Data management
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Breakout group work: signal definition
JRC proposal:A signal is understood as information arising from one or multiple sources, which prompts concerns and demands attention regarding a medical device or device category and which may justify subsequent verification; {… examples}
Final agreement :
A signal is an indication from any source, which suggests a concern regarding one or multiple medical devices and justifies subsequent action.
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Pharmacovigilance: signal management process
Signal detection ValidationConfirma-
tion
Analysis & prioriti-sation
Assessment Action
EMA
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Integrated approach for SD & management• ‘Integrated’ approaches have been developed in the area of
chemical safety & in particular in the area of alternative (non-animal)
methods for testing chemical hazards (…through data integration).
• They provide strategic outline of how to generate, use, combine data
in view of decision making
Milestones:
REACH Integrated Testing Strategies (ITS) – introduced in 2006/7 with
REACH implementation project 3.3 (led by JRC)
Now accepted and used as
‘Integrated Approaches forTesting & Assessment (IATA)’
by OECD
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Integrated approach for SD & management
Data sources
Methods: qualitative / quantitative
Prioritisation
(Type of) action
compare
weigh
assess
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JRC DATA COLLECTION: increase in incidents
Will very likely increase
further due to
reduction of 30 to 15 days
time window for MIR
under MDR.
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DATA COLLECTION: most reported devices
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“I never made a mistake in my life. I thought I did once, but I was wrong.”
Charles M Schulz,
Creator of ‘ The Peanuts’
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