Transcript here

Creation of a mechanism for the
exchange of knowledge on Clinical
Added Value for Orphan Drugs (CAVOD)
Meeting EUCERD
October 24th, 2011
Pascale Augé (former Ernst & Young), Head of Tech
Transfer & Entrepreneurship, Institut Pasteur
The nine objectives of the study on the creation of a
mechanism of exchange of knowledge on CAVOD (1/2)
►
1. To describe the regulatory process followed by an orphan medicine, from Orphan Designation at
the European level to reimbursement in the Member State and examine to what extent the
information produced by the authorities responsible for Orphan Designation and Marketing
Authorization is directly useful for the medicine reimbursement decision process.
►
2. To describe the Health Technology Assessment expertise (focusing on relative efficacy and
relative effectiveness) used at national level for this purpose and the level of involvement of existing
international Health Technology Assessment networks.
►
3. To describe what expertise is used when the medicine is prescribed to all the targeted population
of patients affected by a certain rare disease and how the heterogeneity of a disease expression is
appraised (e.g. differences of weight, age, clinical manifestations, history of treatments taken by each
patient, differences of social situation, patient ability to comply with the constraints imposed by the
treatment, etc.), with the aim to identify the data collection which could be considered as
acceptable to establish the relative effectiveness and, based on this data, to generate an assessment
of real clinical added value.
►
4. To propose a format for the Common Assessment Report for clinical added value for orphan
medicines structured in a usable way for national decision makers, keeping in mind that this
Common Assessment Report should be flexible enough to be used for the revision of this report.
2011
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The nine objectives of the study on the creation of a
mechanism of exchange of knowledge on CAVOD (2/2)
►
5. To define, in consultation with the EC competent Units, the European Union Committee of Experts on
Rare Diseases (EUCERD), EMA, COMP and other EMA Committees (CHMP, CAT and PDCO), which is the most
appropriate structure for performing this Task at a coordinated EU level:
(a) Which could be the most appropriate mechanism of coordination with the HTA organizations in Europe,
the COMP and other EMA committees, in terms of governance and in order to obtain the highest scientific
added value?
(b) Which could be the most appropriate composition of this mechanism of coordination?
(c) What are the financial implications for setting up a new structure or using an existing structure?
►
6. To formulate recommendations for principal Tasks of this mechanism of coordination taking into account
that expressed opinions should be in the form of non-binding Common Assessment Reports on the
scientific assessment of the relative effectiveness of orphan Medicines approved at the EU level and for
the set up of the modus operandi of the dialogue with Member States to facilitate coordination of possible
additional national requirements (e.g. registries, real life studies).
►
7. To propose possible articulation between these Common Assessment Reports on the Clinical Added
Value of Orphan Medicines and CHMP (Committee for Human Medicinal Products) post-marketing
obligations to avoid duplication and make the most of available resources.
►
8. To stick to what can be implemented within the current legislative framework on pharmaceutical
products, including the role of EMA.
►
9. To envisage potential enlargement of these assessment and related mechanisms of cooperation to the
broader context of HTAs and to all types of medicines, not just orphan medicines.
2011
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Basic principles of the CAVOD process
►
CAVOD main objective: to facilitate MS informed decision on the scientific
assessment of the clinical effectiveness of an orphan drug
►
Geographical scope: EU level & institutions and the 27 member state (MS)
►
CAVOD project takes into account and build on the basis of and in partnership with
existing previous and simultaneous initiatives or structures on orphan drugs
development, HTA and market access:
EMA: COMP, CHMP
protocol assistance, risk
management plan
Centers of Expertise (CE)
for Rare Diseases &
European Reference
Networks (ERN)
Tapestry Networks - Pilots of multistakeholder consultations in earlystage drug development
2011
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EUnetHTA
Joint Action I & II
Facilitating
decision-making process
for market access of
orphan drugs
Corporate Social
Responsibility project with
DG Enterprise, EC
CAVOD Study
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Europlan & national plans for
Rare Diseases
EUCERD
EuroScan
Positionning of the CAVOD process
The CAVOD process will contribute to make a bridge and develop a continuum between premarket authorization practices (clinical development) at EU level and post-marketing
authorizations practices at member state level:
►
Marketing Authorization (MA)
Pre-Marketing Authorization phases
Pre-clinical
phases
Marketing
Authorization
process
Clinical
Trials
COMP orphan designation
Post-Marketing Authorization phases
Scientific
evaluation
of HTA
Economic
evaluation
of HTA
Pricing /
Reimbursement
Product
launch
….
HTA
reassess
ment
CHMP positive opinion COMP re-assessment designation (significant benefit)
Pre-Marketing & post-Marketing Authorizations’ phases
CAVOD process
Pre-clinical
phases
Clinical
Trials
COMP orphan designation
►
2011
CAVOD process
Marketing
Authorization
process
Economic
evaluation
of HTA
Pricing /
Reimbursement
OD Product
launch
….
HTA
reassess
ment
CHMP positive opinion
COMP
Marketing Authorizations(MA) at EC level and MS level
re-assessment designation
(significant benefit)
The CAVOD mechanism should also help to bridge the gap between regulators and HTA
bodies
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General methodology
►
Extensive data collection, via literature, interviews and questionnaires, on the regulatory
processes (and particularly those applicable to orphan drugs) in the relevant institutions and
national authorities involved in relative effectiveness assessment of drugs at MS level.
►
Creating a trusted, solid and long-term relationship between the stakeholders (and in
particular between EU and MS level stakeholders) through productive working sessions and
workshops to reach a consensus solution that can be implemented in the future.
Stakeholders worked together in a real committed way to develop the
new proposal for the CAVOD process
►
Defining the process associated with the CAVOD mechanism
►
Evaluating the budget impact of this new process for the exchange of knowledge in terms of
governance, operational function and decision-making process, in order to evaluate the cost of
such mechanism.
►
Drafting and finalizing the Final Recommendation report, including a format for the Common
Assessment Report, CAR, for the scientific assessment of the relative effectiveness of orphan
medicines.
2011
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Update on the methodology
► Interviews/meetings
with the 9 different types
of stakeholders including:
►
►
►
►
►
►
►
►
►
Questionnaires for the HTA national
authorities including, among which:
EC/EAHC
►
HTA bodies
EMA (COMP, CHMP, Secretariat)
►
Government healthcare department officers
HTA national authorities in MS
Payers (ESIP)
European networks (EUNetHTA, HTAi, EUCERD)
► Working sessions and workshop:
Patient organizations (EURORDIS…)
►
1st working session: March 1st
Industry organizations (EBE, EFPIA…)
Other initiatives (Orphanet, Swedish Presidency Initiative,
►
CAVOD mechanism, model, structure and
national plan for RD…)
organization
► Meeting with stakeholders:
►
EUnetHTA (May 2011)
►
EBE (Feb, May 2011)
►
EFPIA (May 2011)
►
EUCERD (Ocotber 2011)
►
2nd working session: March 31st,
►
►
3rd workshop: May 27th,
►
2011
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the relevant process and criteria for the
scientific assessment of CAVOD
CAVOD Study
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final workshop coupled with EURORDIS Round
Table of Companies (ERTC) on the
“Mechanisms for the Implementation of the
Clinical Added Value (Relative Efficacy or
Relative Effectiveness) of Orphan Drugs, so
called CAVOD”
19 attendees at the 1st working session on CAVOD
mechanism, model, structure and organization
NAME
Organization
Hans-Peter Dauben
DIMDI
François Meyer
HAS
Francis Pang
SHIRE
Meindert Boysen
NICE
Ana Palma
GENZYME
Wim Goettsch
CVZ
Jérôme BOEHM
DG Sanco
Domenica Taruscio
ISS
Anders Lamark Tysse
DG Sanco
Flaminia Macchia
EURORDIS
Antoni MONTSERRAT
MOLINER
DG Sanco
Marc Bogaert
Plan Belge pour Les
Maladies Rares
Matus Ferech
DG Sanco
Georgios Margetidis
EAHC
Iñaki Gutiérrez
Ibarluzea
EUROSCAN
Kerstin Westermark
EMA, COMP; MPA
Carla Hollak
AMC UVA
NAME
Eric Abadie
Hans-Georg Eichler
2011
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Organization
EMA, CHMP
AFSSAPS
EMA
18 attendees at the 2nd working session on relevant process and
criteria for the scientific assessment of CAVOD
Name
Organization
Name
Organization
Georgios Margetidis
EAHC
Wim Goettsch
HTA body (CVZ) / EUnetHTA
WP5
Birthe Byskov-Holm
EMA (COMP)
François Meyer
HTA body (HAS)
Eric Abadie
EMA (CHMP)
Meindert Boysen
HTA body (NICE)
Hans-Georg Eichler
EMA (Secretariat)
Ulrich Siering
HTA body (IQWIG)
Yann Le Cam
Patient association
EURORDIS
Claudio Frank
HTA body (ISS)
Christine Leopold
Reimbursement body (GOEG)
Flaminia Macchia
2011
Carla Hollak
EUCERD /
AMC UVA
Francis Arickx
Reimbursement body (RIZIV /
INAMI)
Francis Pang
EBE / Shire
Pierrick Rollet
EBE / GSK
Wills Hughes-Wilson
EBE / Genzyme
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Alexandre Delacoux
CAVOD Study
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EBE
81 attendees at the final workshop of the Eurordis –
Ernst & Young Round Table of Companies (ERTC)
“Mechanisms for the Implementation of the Clinical
Added-Value (Relative Effectiveness) of Orphan Drugs,
CAVOD”
Name
List of participant
Organisation
Ruben Giorgino
Helsinn Health Care Switzerland
Josie Godfrey
Alicia Granados
National Specialised Commissioning Team,
NHS United Kingdom
Genzyme Spain
Lesley Greene
COMP, EMA United Kingdom
Laura Gutierrez
Celgene International Switzerland
Iñaki Gutiérrez Ibarluzea
Jakub Adamski
Ministry of Health Poland
François Anger
ADDMEDICA France
Francis Arickx
Pascale Augé
National Institute for Health and Disability
Insurance Belgium
Ernst & Young France
Fabrizia Bignami
EURORDIS France
Karin Blumer
Novartis International AG Switzerland
Pertti Happonen
Basque Office for Health Technology
Assessment Basque Country
Finnish Medicines Agency Finland
Anne-Mary Bodin
EURORDIS France
Adam Heathfield
Pfizer United Kingdom
Jill Bonjean
EURORDIS France
Thierry Heinrich
Talecris Germany
Enobia Pharma Belgium
Birthe Holm
COMP, EMA Denmark
Giorgio Buseghin
Centre for Health Technology Evaluation,
NICE United Kingdom
Chiesi Farmaceutici S.p.A. Italy
Stéphanie Hoffmann
David Caponera
Aegerion Pharmaceuticals, Inc. USA
Ulrike Jägle
Novartis International AG Switzerland
Germano Carganico
Rare Partners Srl Italy
Mohit Jain
Talecris Germany
François Cornu
Aegerion Pharmaceuticals, Inc. France
Ana Jerónimo
INFARMED Portugual
Alvarez, Cuervo
Virginia Pharma Mar, S.A. Spain
Anna Korecka-Polak
Stéphanie Daireaux
Ernst & Young France
Dorica Dan
Romanian National Alliance for Rare
Diseases Romania
DIMDI Germany
Agency for Health Technology Assessment
in Poland Poland
University Hospital Motol Czech Republic
Meindert Boysen
Hans-Peter Dauben
Ri De Ridder
Emma Eatwell
National Institute for Health and Disability
Insurance Belgium
Genzyme Belgium
Katia Finck
European Medicines Agency (EMA) United
Kingdom
Ministry of Health Care & the Elderly
Pharmaceutical Policy & Monitoring,
Directorate of Malta
Shire Pharmaceuticals, HGT France
Juan-Manuel Fontanet
Universitat Autònoma de Barcelona Spain
Sylvain Forget
Swedish Orphan - Biovitrum France
Marie-Christine Fortun
Orphan Europe (Recordati group) France
Gatermann Ruediger
CSL Behring Germany
Pamela Gavin
National Organization for Rare Disorders
(NORD) USA
Hans-Georg Eichler
Jennifer Farrugia
2011
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Wills Hughes-Wilson
Kateřina Kubáčková
Lucie Kutikova
Yann Le Cam
Patrick Le Courtois
Lugdivine Le Dez
Christine Leopold
Kevin Loth
Flaminia Macchia
Georgios Margetidis
Maria Mavris
Joan Mendivil
Isabelle Mercier
François Meyer
Fredrik Moen
Elena Molina Vázquez
Genzyme Belgium
Amgen Europe Switzerland
EURORDIS France
European Medicines Agency (EMA) UK
Alexion Pharma Belgium Sprl Belgium
Austrian Health Institute Austria
Celgene International Switzerland
EURORDIS Belgium
The Public Health Executive Agency
Luxembourg
EURORDIS France
Bayer Hispania, S.L. Spain
Millenium: The Takeda Oncology company
USA
Haute Autorité de Santé (HAS) France
AstraZeneca Belgium
Swedish Orphan Biovitrum S.L. Spain
CAVOD Study
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Antoni Montserrat
Jean Mossman
Hicham Naim
Alan Newlands
Gérard Nguyen
Célia Oculi
Francis Pang
Samantha Parker
Elisabeth Paternostre
Fabien Peuvrelle
Robert Pleticha
Massimo Radaelli
Pierrick Rollet
Alric Ruether
Peter Saltonstall
Laura Sampietro Colom
Ad Schuurman
Sylvie St-Laurent
Jan-Maarten Ten Brundle
Geraint Thomas
Josep Torrent-Farnell
Anders-Lamark Tysse
Jutta Ulbrich
Kerstin Westermark
Martine Zimmermann
European Commission/ DG Health and
Consumers Luxembourg
Mark Krueger & Associates, Inc. USA
Ernst & Young Switzerland
Clovis Oncology United Kingdom
Rett Syndrome Europe France
Ernst & Young France
Shire Pharmaceuticals, HGT United
Kingdom
Orphan Europe (Recordati group) France
Sanofi-Aventis R&D France
Celgene International Switzerland
EURORDIS France
ARIAD Pharmaceuticals, Inc. USA
GSK rare diseases United Kingdom
Institute for Quality and Efficiency in
Health Care Germany
National Organization for Rare Disorders
(NORD) USA
HTAi Spain
Department of the Dutch Health Care
Insurance Board Netherlands
Pfizer France
Baxter World Trade Belgium
GlaxoSmithKline United Kingdom
COMP, EMA Spain
European Commission- DG SANCO
Belgium
Bayer Schering Pharma AG Germany
COMP, EMA Sweden
Alexion Europe France
Definitions of clinical added value: relative efficacy /
relative effectiveness (1)
Time of
positive opinion
of CHMP (T0)
Efficacy…
T0 +DT
(3/5 years)
Relative efficacy
Relative effectiveness
►
►
Relative efficacy is the extent to
which an intervention does more
good than harm under ideal
circumstances, compared to one or
more alternative interventions
►In certain
Relative effectiveness can be defined as
the extent to which an intervention
does more good than harm compared
to one or more intervention
alternatives for achieving the desired
results when provided under the usual
circumstances of health care practice.
HTA practices, the terms « Clinical effectiveness » are also used
►Within rare
diseases and in particular ultra-rare diseases, comparators may particularly be
complex to handle
(1) Definitions aligned with :
2011
EUnetHTA JA WP5: REA of Pharmaceuticals, Draft Background review, April 2011
High Level Pharmaceutical Forum, Core principles on relative effectiveness, Dec 2010
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Basic fundamentals
Scope & mandate of CAVOD mechanism (1/2)
►Avoid
duplications at EU level
►Build on an existing
system/initiative
► Preferred
option: EUnetHTA
►2
additional options (hCMDEMA or EUCERD-EAHC)
►Open, rigorous and
transparent
► Contribution of stakeholders
system
open and committed way
►Flexible system
►A process
►Quick operational implementation
►Run pilots as
2011
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in a real
and not a new structure
early as 2012
Basic fundamentals
Scope & mandate of CAVOD process (2/2)
►CAVOD
process associated with
EUnetHTA current & future initiatives as
the rare diseases arm, so called EUnetHTACAVOD.
►Secondary role shall
be to:
►Act
as a “knowledge center” and collect all
possible information on rare diseases and
healthcare solutions
Contribute to developing a continuum
between pre-market and post-marketing
authorizations
►
►Central role shall
be to:
► Exchange valuable and trustable
►Be
information on rare diseases and drugs
Develop and make available methodology
and tools for scientific HTA assessment
adapted for OD
►
Proceed to the EUnetHTA-CAVOD
assessment according to necessary timepoints
►
Organize continuous evidence collection
for OD as post-marketing activities
►
the first operational implementation
phase of a process delivering at EU level
relative effectiveness assessment dedicated to
rare diseases
►A
sub-group of EUnetHTA in charge of OD
with a general function of linking with
existing initiatives, projects, bodies &
institutions for all matters relating to OD
and dedicated HTA (EMA, national HTA bodies,
EUCERD, MEDEV, PPRI, PHIS, HTAi, INATHTA,
EURORDIS… )
2011
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The approach of the EUnetHTA-CAVOD process: « à la
carte » system adapted for the various HTA bodies’ needs
►
A four-layer approach was proposed following interviews with key stakeholders in order to
better fit with the needs of the different national authorities involved in health technology
assessment (HTA) processes:
► the
Information exchange
Methodology /
Toolkit dedicated to
orphan drugs
“information exchange” primary layer would support member
states in giving them the opportunity to access the most complete
information on the orphan drug, the targeted pathology, the
epidemiology (associated with EUnetHTA JA WP6 and EMA (SAWP,
CHMP, COMP))
► the “methodology/toolkit
dedicated to orphan drug” secondary layer
would support member states in giving a methodological support
specific to orphan drug in order to run their own assessment
(associated with EUnetHTA JA WP4 )
EUnetHTA-CAVOD
analysis
► the
Additional evidence
generation
► the
2011
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“EUnetHTA-CAVOD analysis” layer would propose reports
focused on relative effectiveness to MS which do not have the time
and/or resource to run their own assessment and report (associated
with EUnetHTA JA WP5)
“additional evidence generation” layer, would aim at proposing
recommendations for post-marketing evidence generation addressing
uncertainties based on National and European shared views
(associated with EUnetHTA JA WP7 and EMA (CHMP))
CAVOD Study
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Strong collaborations will be needed between the
EUnetHTA-CAVOD process and other initiatives
Information exchange
Methodology /
Toolkit dedicated to
orphan drugs
• National HTA bodies and national authorities in MS
• EUCERD : WG on Public Health Indicators
EUnetHTA-CAVOD
analysis
• National HTA bodies and national authorities in MS
• European Reference Networks : Centers of Expertise for Rare
Diseases
• Industry : evidence manufacturer dossier
Additional
evidence
generation
2011
• EMA : all data and reports
• EUCERD : Mapping of initiatives in the field of RD
• European Reference Networks : Centers of Expertise for RD
• EuroScan, PHIS, PPRI, MEDEV, ISPOR, ISPE :
information-sharing initiatives
• Orphanet : Encyclopedia, database and directory
Page 15
• EMA : CHMP, SAWP, protocol assistance, Risk management plan
• EUCERD : Coding and classification of RD, registry methodology and
common criteria and framework
• European Reference Networks
• Tapestry Networks : platform for early advice
• Industry
CAVOD Study
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Ambition of the EUnetHTA-CAVOD process : early and
long-term follow up
►A
four periods’ approach was proposed following workshop with key stakeholders in order to:
►
facilitate information exchange before the CHMP opinion (even at protocol assistance) and
EC marketing authorisation between EUnetHTA and EMA
► deliver
compilation report and evidence generation plan
► monitor
and adapt the evidence generation plan
► perform
the relative effectiveness assessment
Significant Benefit, COMP
CHMP opinion, T0
Period 2:
for simple
Period 1:
Compilation
for EMA / EUnetHTA
report &
coordination
evidence
generation plan
Protocol
assistance
EC marketing
authorisation
T0 + 90 days
Period 3:
for follow up of the
evidence generation plan
Time
2011
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T0+ΔT
(after 3 to 5 years, flexible
depending of the disease)
CAVOD Study
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Period 4:
relative
effectiveness
assessment
Principle of EUnetHTA-CAVOD process, early and longterm process along the life cycle of an orphan drug
Time
New evidence generation
EUnetHTA-CAVOD reports
brindging the gap between EMA and
HTA bodies
Interaction between EMA & EUnetHTA
CHMP positive
opinion
• Get requirements from HTA bodies on the OD
• Alignment with the benefit / risk management
plan of this OD
• EUnetHTA-CAVOD brings to EMA its experience /
expertise on relative effectiveness and evidence
generation
T0
European Evidence Generation Plan (EEGP)
EC marketing
authorization
T0 + 90days
Based on the benefit risk management plan from
EMA, identification of knowledge gaps and
prioritization of uncertainties
Recommendations on new evidence generation
for relative effectiveness (2)
Follow-up monitoring of the EEGP
• Yearly follow-up of the EEGP
(1) Approach aligned with High Level Pharmaceutical Forum. Core
principles on relative effectiveness, Good practice prinicples 1, 2,
3, 4, 5. Dec 2010.
Compilation Report (1)
• Bring together all available information on
relative efficacy in a meaningful way
• Factual, no opinion, possible analysis of data
quality
(2) Approach aligned with High Level Pharmaceutical Forum. Core
principles on relative effectiveness, Good practice prinicples 4, 5,
6, 7. Dec 2010.
Relative Effectiveness Analysis
• Analysis mainly based on evidence generated
in post-MA studies according to the EEGP
T0 + ΔT
2011
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Information
exchange
CAVOD Study
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and
Methodology /
toolkit for
orphan drugs
Interaction process to bridge the gap between pre- &
post-marketing practices
►
One or more representative(s) of EUnetHTA-CAVOD as permanent participant to COMP and
associated COMP working groups
►
One or more representative(s) of EUnetHTA-CAVOD as non-permanent participant to SAWP,
PDCO, CAT, CHMP (on an adhoc basis)
►
One/two representative(s) of COMP as permanent participant to EUnetHTA-CAVOD work
(EUnetHTA assembly when rare diseases are concerned)
►
One representative of SAWP, PDCO, CAT, CHMP as non-permanent participant to EUnetHTACAVOD work (on an adhoc basis)
►
One representative of rare diseases’ patient organisation (EURORDIS) as permanent participant to
EUnetHTA-CAVOD work
►
One representative of rare disease specific patient organisation as non-permanent participant to
EUnetHTA-CAVOD work (on an adhoc basis)
►
One representative of manufacturer as non-permanent participant to EUnetHTA-CAVOD work (on
an adhoc basis)
2011
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Interaction process EUnetHTA-CAVOD/EMA from the
protocol assistance to the MA & Risk management plan
The objective of the interaction between EUnetHTA-CAVOD and EMA is to build a bridge and develop a
continuum between pre-market authorization practices (clinical development) at EU level and post-marketing
authorizations practices at member state level.
►
Through this process, the National HTA bodies through EUnetHTA are engaged collectively and bring their
experience together to give inputs and valuable requirement to the EMA prior to the Risk management plan.
►
Member states will be able to contribute to the Risk management plan.
EUnetHTA-CAVOD
EMA
►
2011
Marketing Autorisation review process, prior to CHMP opinion
Exchange of information with
EUnetHTA-CAVOD PM *
Identification
of the project
manager PM
Evidence
requirement
gathering from
HTA bodies
Exchange of
information with
the rapporteur of
OD at the CHMP
Recommendation
paper for EMA
Writing of
recommendation
paper
•Focused on HTA expectations for evidence generation
• Based on national HTA bodies experience of the disease
&/or drug
One EUnetHTA-CAVOD PM for 4 days (FTE)
Page 19
* Discussion to consider
at the CHMP committee
including EUnetHTACAVOD PM ?
CAVOD Study
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Compilation report at T0: Factual presentation of all available
information in a meaningful way
►
The objective of the compilation report is to have a common format, which offers a factual
presentation of all available information in a meaningful way and to make the most of stakeholders’
knowledge.
►
This will be useful :
►
To avoid duplication of work between HTA agencies
►
To support in their assessment MS which have not enough time/resources
►
To increase transparency by providing a EU central report
At T0 , CAVOD may focus on domains 1&2 and 6 to 9 when possible as there is often a limited amount
of information for domains 3&4
►
Evidence requirement
• Manufacturer report (optional)
• EMA data and documents developed under
the scope of OD analyses by the COMP,
CHMP, CAT, PDCO
• Clinical trials’ dossier
• Non EU information on the drug itself or on
available alternative therapies
• Natural history of the disease
• Clinical nature and impact of the diseases
• Current management of the disease and
therapy limitations
• Patient & clinical experts perspective
• Compassionate use information, …
2011
Page 20
Organisation
Compilation Report
• Template elaborated
by the EUnetHTA-CAVOD
scientific secretariat
• Implementation of a
pilot with an orphan
drug to be selected
• Keep flexibility
• Quality control role
• Dissemination
CAVOD Study
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EUnetHTA-CAVOD scientific secretariat
• Gathering the data within CAVOD partners
• Additional bibliography search
• Report drafting and writing
• 1 analyst (FTE) for 2 months
EUnetHTA-CAVOD assembly:
• focused on quality control
Timing
• 60-90 days, prior to MA from EC
Involvement of the MA holder
European Evidence Generation Plan, EEGP
►
The objective of the European evidence research plan is to allow more consistency in terms of
evidence generation between expectations of MS in alignment with EMA/PRA.
►
CAVOD should identify information gaps, agree on the uncertainties, prioritize them and decide
which new evidences are needed to perform a relative effectiveness assessment in the future
►
The EEGP will propose studies on top of the studies proposed in the Benefit/risk management plan
and will not be mandatory for companies
Evidence requirement
EMA information input
• EPAR
• Risk management plan
MS inputs
• Data generated by the evidence generated
for the compilation report
• Rapid single assessments (HTA) preliminary
elements of the OD established by MS
(including value judgment & post-MA studies
requirement) when possible
2011
Page 21
Organisation
EEGP
• Recommendation for
evidence generation to
support relative
effectiveness
• Additional requests
on top of the B/R
management plan
• Non-mandatory plan
CAVOD Study
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This presentation, reserved for your internal use, is indissociable from the contextual elements used as a basis for its elaboration and from the spoken comments accompanying it.
EUnetHTA-CAVOD scientific secretariat
• Drafting of a briefing document / knowledge
gap analysis
• Writing of the EEGP draft
• 1 analyst (FTE) for 1 month
EUnetHTA-CAVOD assembly
• Identification and prioritization of uncertainties
• Recommendation for new evidence generation
Timing
• At the time of MA from EC
Involvement of the MA holder
Follow-up monitoring of the EEGP
►
The objective of the follow-up monitoring project is to ensure a regular update on the generation of
evidence to :
►
monitor the feasibility of the EEGP
►
facilitate the information-sharing on a specific orphan drug and rare disease/therapeutic
indication that could be useful information for other orphan drugs or other rare disease
conditions,
►
prepare the relative effectiveness assessment performed at T+DT
Evidence requirement
EMA information input
• Safety update reports from the EMA
MS information input
• MS healthcare information systems
MA holder input
• EEGP evidence generation results
Other input (ERN …)
• Disease registries or equivalent
2011
Page 22
Organisation
Follow up monitoring
•Regular gathering &
update of evidence
generation according to
EEGP (yearly basis)
•Template for the follow-up
reports (flexible)
•Follow-up reports of
evidences
CAVOD Study
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This presentation, reserved for your internal use, is indissociable from the contextual elements used as a basis for its elaboration and from the spoken comments accompanying it.
EUnetHTA-CAVOD scientific secretariat
• Gathering the data
• Follow-up report drafting
EUnetHTA-CAVOD assembly
• Validation of follow-up reports
• Analysis of any discrepancies in the EEGP
Timing
• once a year
Involvement of the MA holder
Relative effectiveness analysis at T0+ΔT
►
The objective of the relative effectiveness (RE) assessment report is to perform an analysis of
the relative effectiveness of a drug on the basis of the evidence generated through the risk
management plan and the European Evidence Generation Plan
Evidence requirement
• Evidences generated according to:
• Risk management plan
• European Evidence Generation
Plan
• Safety update reports from the EMA
• Follow up monitoring reports
• Target population
• Data extrapolation of T0 to T0+ΔT
• Clinical end-points (efficacy and
effectiveness)
• Choice of the control
• Survey/clinical outcomes
Organisation
Relative effectiveness
assessment
• Methodology based on
the HTA core model and
EUnetHTA WP5 REA
• Template elaborated
by the EUnetHTA-CAVOD
scientific secretariat
• Pilot with an OD
EUnetHTA-CAVOD scientific secretariat
• Coordination with the manufacturer
• Synthesis of the RE analysis report
EUnetHTA-CAVOD assembly
• Reviewer team of 6-8 people
• Drafting of the RE analysis report
• Review of the RE analysis report draft by
the Co-Reviewer team
• Validation & opinion on relative
effectiveness
Timing : 6 - 12 months
Involvement of the MA holder
2011
Page 23
CAVOD Study
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“information exchange” primary layer as a link
between partners to centralize information
Information exchange
Methodology /
Toolkit
CAVOD
analysis
Additional
evidence
generation
Objective: collect data and information, provide repository
Sources
►
EUnetHTA-CAVOD potential partners
Manufacturer report (manufacturer submission, Current
►
EMA : all data, reports and documents
developed under the scope of drug analyses
by the COMP, CHMP, CAT, PDCO, PRAC
Information-sharing initiatives (EuroScan,
PHIS, PPRI, MEDEV, ISPOR, ISPE)
Orphanet : Encyclopedia, database and
directory
EUCERD : Mapping of initiatives in the field
of RD
European Reference Networks
Eurordis
►
Manufacturer
►
management of the disease and therapy limitations)
►
►
►
Expert knowledge (Clinical nature and impact of the
diseases, Current management of the disease and therapy
limitations, Patient/ disease registries…)
►
Clinical guidelines
Publications by other HTA-organizations
►
(Clinical nature and impact of the diseases, Current management of
the disease and therapy limitations)
►
Literature (Clinical nature and impact of the diseases, Current
►
management of the disease and therapy limitations
►
►
EPAR/NPAR
Unpublished (raw) clinical data (Available
►
compassionate use data/ ATU,
►
Confidential data (Accessible data from MS healthcare
information systems (e.g. Belgium))
►
2011
Benefit/risk management plan & B/R safety
update report(s) (starting 2012)
Page 24
CAVOD Study
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Information exchange
the “methodology/toolkit dedicated to
orphan drug” secondary layer
►
CAVOD
analysis
Additional
evidence
generation
The type of evidences (1) covered by the clinical added value are based on
the EUnetHTA JA WP4 & WP5 & HTA core model and adapted to the
specificity of orphan drug
(1) Approach aligned with the EUnetHTA JA WP5:
►
1. Health problem and current use of the technology
►
2. Description and technical characteristics of technology
►
3. Safety
►
4. Effectiveness
►
5. Costs, economic evaluation
►
6. Ethical aspects
►
7. Organizational aspects
►
8. Social aspects
►
9. Legal aspects
Sources:
2011
Methodology /
Toolkit
REA of Pharmaceuticals, Draft Background review,
April 2011:. WP5 model
already considered
as part of EMA scope
to be particularly considered as being part
of rare diseases’ specificity
Draft Backgroung review, EUnetHTA JA WP5: Relative Effectiveness Assessment (REA) of Pharmaceuticals; April 2011
EUnetHTA WP4 – HTA Core Model for Medical and Surgical Interventions, Dec ember 2008
Page 25
CAVOD Study
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This presentation, reserved for your internal use, is indissociable from the contextual elements used as a basis for its elaboration and from the spoken comments accompanying it.
Assumptions for the cost of the CAVOD process
Candidates for each timing of CAVOD process
Protocol assistance - Interaction with EMA
MA application - Interaction with EMA & compil report
MA granted - EEGP
Follow up
RE assessment
Total number of candidates followed each year
2012
1
1
1
0
1
3
2013
68
10
6
1
0
79
2014
68
10
6
7
0
85
Hypothesis of time/phase/candidate (in days)
Interaction with EMA
Compilation report & EEGP
Follow up
Relative effectiveness assessment
2011
Page 26
2016
68
13
8
21
0
102
CAVOD group
0,06
0,1
0,1
0,15
0,3
0,05
0,3
Scientific advice
CHMP MA application
COMP review of designation
Compilation report
European evidence generation plan
Time/phase in 2022 (in days)
Interaction with EMA
Compilation report & EEGP
Follow up
RE assessment
TOTAL
2015
68
13
8
13
0
94
CAVOD group
8,1
5,4
1
4,8
19,3
2017
78
13
8
28
1
120
2018
78
13
8
30
6
127
CAVOD Project Manager
3
5
2
1
2
0
20
CAVOD Project Managers
355
36
0
160
551
CAVOD Study
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This presentation, reserved for your internal use, is indissociable from the contextual elements used as a basis for its elaboration and from the spoken comments accompanying it.
2019
78
16
10
32
6
132
2020
78
16
10
34
8
136
2021
81
16
10
36
8
141
2022
81
16
10
38
8
143
Scientific secretariat
1
3
1
25
8
0,5
12
Scientific secretariat
145
480
19
96
740
Three scenarios & three different direct costs with the
EUnetHTA option presenting the highest cost synergies
Direct costs borne by CAVOD for each scenario from 2012 to 2022
3 500 000 €
3 000 000 €
2 500 000 €
2 000 000 €
1 500 000 €
1 000 000 €
500 000 €
0€
2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022
Scenario 1 - EUnetHTA
Scenario 2 - CMDh like
Scenario 3 - EAHC
Distribution of direct costs borne by CAVOD for each scenario in 2022
3 500 000 €
Surveillance committee
3 000 000 €
Scenarios
Scenario 1
Scenario 2
Scenario 3
2 500 000 €
Budget 2022
without
synergies
2,9 m€
3,3 m€
3,1 m€
2 000 000 €
Budget 2022
with
synergies
1 m€
2011
352 066 €
459 579 €
1 500 000 €
2,6 m€
3 m€
500 000 €
0€
Page 27
800 000 €
External experts for RE assessment
800 000 €
1 000 000 €
Administrative functions
537 567 €
Scientific secretariat
537 567 €
268 783 €
376 297 €
157 300 €
196 837 €
800 998 €
Scenario 1 EUnetHTA
Scenario 2 - CMDh
like
CAVOD Study
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This presentation, reserved for your internal use, is indissociable from the contextual elements used as a basis for its elaboration and from the spoken comments accompanying it.
921 998 €
Project Manager - interaction with EMA
380 119 €
Principal group meetings
Scenario 3 - EAHC
hosting
Four pilots to set up & run in 2012 requiring the
support of key stakeholders (EUnetHTA, EMA, MAH…)
►
First Pilot to set up the process for the interaction and information exchange between EUnetHTA and EMA
prior to the CHMP opinion,
►
Second Pilot to run the CAVOD compilation report based on an OMP under final review by the CHMP for the
marketing authorisation,
►
Third Pilot on the development of the European evidence generation plan with an OMP under reception of a
positive opinion of the CHMP including the Risk management plan
►
Fourth Pilot to perform a EUnetHTA-CAVOD relative effectiveness assessment with one orphan drug that is
already on the market in certain countries and that is about to be reviewed by one member state
►
As part of these 4 pilots,
2011
►
EUnetHTA-CAVOD shall have to delegate representatives at the SAWP, the CHMP, prepare the
designation of project manager within its current member representative
►
EMA shall have to open its committees and working groups and in particular the CHMP and the SAWP
to EUnetHTA-CAVOD representatives and delegate COMP and CHMP representatives to EUnetHTA,
►
Manufacturing holders shall support the CAVOD process through the selection of four OMPs designated
product ready to enter the adhoc period of the CAVOD process,
►
EUnetHTA shall have to set up the EUnetHTA scientific secretariat dedicated to CAVOD and further
develop the information exchange center as well as adapt the methodological aspects;
►
EMA shall have to open its data and internal reports related to selected molecule to EUnetHTA-CAVOD
representatives
►
EUCERD shall share with EUnetHTA-CAVOD all information on RD and registry set up
Page 28
CAVOD Study
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Contacts: Ernst & Young Advisory, Paris, France
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92031 Paris-La Défense Cedex
FRANCE