Ομιλία-Παρουσίαση: Edith Frénoy, Director of Market Access/HTA, European Federation of Pharmaceutical Industries Associations (EFPIA) Τίτλος Ομιλίας: «HTA cooperation in Europe: can it support the Greek debate?»

1. HTA cooperation in Europe: can it support the Greek debate?
www.efpia.eu
Presentation

2. 2www.efpia.eu
The European Federation of Pharmaceutical Industries and Associations (EFPIA)
represents the pharmaceutical industry operating in Europe. Through its direct
membership of 33 national associations and 40 leading pharmaceutical
companies, EFPIA is the voice on the EU scene of 1,900 companies committed to
researching, developing and bringing to patients new medicines that will improve
health and the quality of life around the world.
About EFPIA

3. 3www.efpia.eu
Current practice across Europe
European reflections
Impact on Greece?
Outline

4. 4www.efpia.eu
Current practice across Europe
European reflections
Impact on Greece?
Outline

5. 5www.efpia.eu
Health technology assessment is a multidisciplinary
process that summarises information about the medical,
social, economic and ethical issues related to the use
of a health technology in a systematic, transparent,
unbiased, robust manner. Its aim is to inform the
formulation of safe, effective, health policies that are patient
focused and seek to achieve best value.
EUnetHTA definition, available at
http://www.eunethta.net/Public/About_EUnetHTA/HTA/
Health Technology Assessment

6. 6www.efpia.eu
6
Regulatory
Agency
Regulatory
Assesment
Early Regulatory
Scientific Advice
(Benefit-) Risk
Management Plans
Indication Lifecycle Post-authorization StudiesPre-Launch Development Program
National/
regional
HTA
Agencies
HTAEarly Payer/
HTA Advice
“Real-world“
Effectiveness
Pricing, reimbursement,
and funding status
Medicine development lifecycle
Adapted from Ansgar Hebborn, Roche

7. 7www.efpia.eu
Overview of HTA activity
EUnetHTA WP7 research and analysis activity 1: Final report
Key: N=31 countries with England, Scotland and Wales counted separately;
red = no current HTA procedure;
blue = pharmaceuticals only;
yellow = both pharmaceuticals and non-pharmaceuticals

8. 8
CHMP opinion EPAR publication
Timeline (days) Publication of EU REA
EC decision
Sub prep RE & EA F
Submission preparation
Relative Effectiveness &
Economic Appraisal
Sub prep RE & EA F
Sub prep
Sub prep
Relative Effectiveness
appraisal
Final HTA evaluation and/or
decision
Sub prep RE F
Sub prep RE F
Sub prep RE & EA F
Represents ideal timeline but some products
have a different, compatible timeline
In some cases, HTA could be
completed before the EPAR
publication, the but most products have
a different, compatible timeline
P
Sub prep RE & EA F
Sub prep RE & EA F
Sub prep RE & EA F
Submission for orphan medicines and
medicines of exceptional therapeutic
relevance can happen at CHMP opinion
Sub prep RE & EA F
RE & EA F
RE & EA
Submission
S
S
S
S
S
S
S
S
S
S
S
Dossier
submission
S
F
0 100-180 -90 52
Some selected countries

9. Some selected countries
9
CHMP opinion EPAR publication
Timeline (days)
0 100-180 -90 52
EC decision
Sub prep RE & EA
Sub prep RE & EA
Sub prep
Sub prep
Sub prep
RE
In-patient products
P
RE & EA
RE & EA
S
S
S
S
S
Dossier
submission
S
Out-patient products
HTA starts before approval by
SwissMedic (which is on average 90+
days after EC decision)
Sub prep RE & EAS
F
F
F
F
F
F
HTA is requested only for
some medicines
Sub prep RE & EAS F
Value & commercial assessment
Publication of EU REA
Submission preparation
Relative Effectiveness &
Economic Appraisal
Relative Effectiveness
appraisal
Final HTA evaluation and/or
decision
Submission

10. 10www.efpia.eu
French model
Source: F. Meyer

11. 11www.efpia.eu
Current practice across Europe
European reflections
Impact on Greece?
Outline

12. 12www.efpia.eu
A long history of cooperation on HTA
2006 2010 2012 2016 2020
EUnetHTA
Project
EUnetHTA
JA1
Inception
Putting into
practice
Strengthening
practical
application
Turning pilots
into standard
practice
EUnetHTA
JA 2 EUnetHTA
Joint Action 3

13. 13www.efpia.eu
2018 Commission legislative proposal
1
3
MEMBER STATE-
DRIVEN
JOINT WORK
Member States roleMember States role
• In charge of the scientific work and the decisions
• Organised in a member state-led “Member State Coordination Group on HTA” (the coordination group)
JOINT WORK
BASED ON
4 PILLARS
Joint
clinical assessments
Joint
scientificconsultations
Identification of
emerging health
technologies
(horizon scanning)
Voluntary coordination
(other areas of HTA)
SCOPE:
MEDICINAL
PRODUCTS
SUBJECT TO
CENTRALISED
PROCEDURE
New active substances
Align timing to regulatory process to ensure timely availability of the joint assessment :Align timing to regulatory process to ensure timely availability of the joint assessment :
• at time of Commission decision for MA
• but both remaining within appropriate remits
Commission roleCommission role
• Adoption of tertiary (implementing) legislation
• Obligation to verify joint reports before their publication
• Monitor implementationof common rules and use of joint work
New therapeutic indications for existing active substances
Certain medical devices
TIMING
Source: Sanofi

14. 14www.efpia.eu
One single joint clinical assessment mandatory for all centralised
products with mandatory uptake
One common procedural framework and common rules for
clinical assessment
Alignment of timing of joint assessment across all member states
“Absorption” of EUnetHTA work into the permanent system with creation of a
permanent body for all EU member states
Explicit link between joint advice and joint assessment
Key implications

15. 15www.efpia.eu
Progressive phasing-in of future system
Co-decision
procedure
Entry into
Force
Application
(all implementing legislation
in place)
Phase-in period
(the system is fully operational,
gradual increase of joint work)
Fully
operational
Application of prioritisation criteria during the transition period:
 unmet medical need;
 potential impact on patients, public health, or healthcaresystems (e.g. burden of disease, budget impact,
transformative technology);
 significant cross-border dimension/ Union-wide added value
3 Year PERIOD
 Phase-in approach to allow Member States to fully adapt
to the new system
Member States have option to delay their participation in the joint
work on joint clinical assessments and joint scientific consultations
(no obligation to use the output of this joint work at Member State-
level but obligation to use the common rules for their own clinical
assessments)
3 YEAR PERIOD
 Tertiary implementing Legislation
(the implementing and delegated acts)
 Preparatory steps necessary for the joint work.
Joint work continues throughout
Commission
Proposal
(Jan 2018)
Source: Sanofi

16. European network for Health TechnologyAssessment | JA3 2016-2020 | www.eunethta.eu 16

17. European network for Health TechnologyAssessment | JA3 2016-2020 | www.eunethta.eu
Tools & templates
Procedure
manual
describes
processes – to
be replaced by
SOPs
Assessment
template and
Project Plan
template provide
guidance for
reporting
Guidelines
provide
methodological
guidance
Provides
working
framework
through a set
of research
questions*
* + checklist for ethical, organisational, social and legal issues
Submission
File template
is submitted
by
manufacturer–
to be updated
in JA3
+ consideration of
other Core Model
applications

18.  2017 CRA International18
Key attributes of the first three assessments
Midostaurin – Acute Myeloid Leukaemia (AML), Novartis
Indication Population Comparators Outcomes: Efficacy Outcomes: Safety
Midostaurin with standard
chemotherapy in FLT3
positive AML
Adult patients with newly
diagnosed AML who are
FLT3 mutation-positive
• Standard induction and
consolidation
chemotherapy
• Induction and
consolidation
chemotherapy with
daunorubicin 90
mg/m2/day during the
induction phase
Overall survival, event-free
survival, disease free
survival, complete
response, cumulative
incidence of relapse
Any Adverse Events (AEs);
Serious AEs; Grade ≥3
AEs; Discontinuation due
to AE; Death as Serious
AEs; AEs of special
interest
Regorafenib – Hepatocellular Carcinoma (HCC), Bayer
Indication Population Comparators Outcomes: Efficacy Outcomes: Safety
Monotherapy for the
treatment of adult patients
with HCC who have been
previously treated with
sorafenib
Patients with
hepatocellular carcinoma
(HCC) who have been
previously been treated
with sorafenib
Placebo in combination
with best supportive care
(or palliative care)
• Critical: Overall survival
(OS) and quality of life
(HRQoL)
• Important: Progression
free survival
Any Adverse Events (AEs);
Serious AEs; Grade ≥3
AEs; Discontinuation due
to AE; Death as Serious
AEs; AEs of special
interest
Alectinib – Non-small cell lung cancer (NSCLC), Roche
Indication Population Comparators Outcomes: Efficacy Outcomes: Safety
Monotherapy for the first
line treatment of adult
patients with ALK-positive
advanced NSCLC
Subgroup analysis:
Patients with brain
metastases at baseline
Adult patients with
anaplastic lymphoma
kinase (ALK)-positive
advanced non-small cell
lung cancer (NSCLC).
• Crizotinib (direct
comparison)
• Ceritinib (indirect
comparison, Network
Meta Analysis (NMA))
Overall survival,
Progression free survival
Any Adverse Events (AEs);
Serious AEs; Most
Frequent AEs and Serious
AEs, Grade ≥3 AEs;
Discontinuation due to AE;
Death as Serious AEs; AEs
of special interest; AEs
leading to dose reduction

19. 19www.efpia.eu
Current practice across Europe
European reflections
Impact on Greece?
Outline

20. 20www.efpia.eu
Good practices in HTA
15 Guiding Principles for HTA
1 HTAs should have explicit and relevant goals and scope
2 HTAs should be unbiased and transparent
3 HTAs should include all relevant technologies
4 HTAs should have a clear system for setting priorities
5 HTAs should incorporate appropriate methods for assessing costs and benefits
6 HTAs should consider a wide range of evidence and outcomes
7 HTAs should consider a full societal perspective
8 HTAs should explicitly characterize uncertainty surrounding estimates
9 HTAs should consider and address issues of generalizability and transferability
10 HTAs should actively engage all key stakeholder groups
11 Those undertaking HTAs should actively seek all available data
12 The implementation of HTA findings needs to be monitored
13 HTA should be timely but separate from regulatory review
14 HTA findings need to be communicated appropriately to different decision makers
15 The link between HTA findings and decision making needs to be transparent and clearly defined
Drummond et al (2008)

21. 21www.efpia.eu
Good practices in HTA
15 Guiding Principles for HTA
1 HTAs should have explicit and relevant goals and scope
2 HTAs should be unbiased and transparent
3 HTAs should include all relevant technologies
4 HTAs should have a clear system for setting priorities
5 HTAs should incorporate appropriate methods for assessing costs and benefits
6 HTAs should consider a wide range of evidence and outcomes
7 HTAs should consider a full societal perspective
8 HTAs should explicitly characterize uncertainty surrounding estimates
9 HTAs should consider and address issues of generalizability and transferability
10 HTAs should actively engage all key stakeholder groups
11 Those undertaking HTAs should actively seek all available data
12 The implementation of HTA findings needs to be monitored
13 HTA should be timely but separate from regulatory review
14 HTA findings need to be communicated appropriately to different decision makers
15 The link between HTA findings and decision making needs to be transparent and clearly defined
Drummond et al (2008)
Method

22. 22www.efpia.eu
Methods
Law 4512/2018: evaluation procedure Commission Proposal: joint clinical
assessment
Clinical benefit Analysis of the relative effects of the
health technology being assessed on the
patient-relevant health outcomes
chosen for the assessment
Comparison against any reimbursable
treatments already available
Relative effects
Level of credibility of the findings of
clinical studies
Degree of certainty on the relative
effects based on the available evidence
Cost-effectiveness ratio x
Budget impact x
Joint work to pick-up at the earliest in 2023 for interested Member States
In the meantime EUnetHTA continues to work

23. 23www.efpia.eu
Good practices in HTA
15 Guiding Principles for HTA
1 HTAs should have explicit and relevant goals and scope
2 HTAs should be unbiased and transparent
3 HTAs should include all relevant technologies
4 HTAs should have a clear system for setting priorities
5 HTAs should incorporate appropriate methods for assessing costs and benefits
6 HTAs should consider a wide range of evidence and outcomes
7 HTAs should consider a full societal perspective
8 HTAs should explicitly characterize uncertainty surrounding estimates
9 HTAs should consider and address issues of generalizability and transferability
10 HTAs should actively engage all key stakeholder groups
11 Those undertaking HTAs should actively seek all available data
12 The implementation of HTA findings needs to be monitored
13 HTA should be timely but separate from regulatory review
14 HTA findings need to be communicated appropriately to different decision makers
15 The link between HTA findings and decision making needs to be transparent and clearly defined
Drummond et al (2008)
Governance

24. 24www.efpia.eu
Good practices in HTA
15 Guiding Principles for HTA
1 HTAs should have explicit and relevant goals and scope
2 HTAs should be unbiased and transparent
3 HTAs should include all relevant technologies
4 HTAs should have a clear system for setting priorities
5 HTAs should incorporate appropriate methods for assessing costs and benefits
6 HTAs should consider a wide range of evidence and outcomes
7 HTAs should consider a full societal perspective
8 HTAs should explicitly characterize uncertainty surrounding estimates
9 HTAs should consider and address issues of generalizability and transferability
10 HTAs should actively engage all key stakeholder groups
11 Those undertaking HTAs should actively seek all available data
12 The implementation of HTA findings needs to be monitored
13 HTA should be timely but separate from regulatory review
14 HTA findings need to be communicated appropriately to different decision makers
15 The link between HTA findings and decision making needs to be transparent and clearly defined
Drummond et al (2008)
Link to decision-making

25. EFPIA Brussels Office
Leopold Plaza Building * Rue du Trône 108
B-1050 Brussels * Belgium
Tel: + 32 (0)2 626 25 55
www.efpia.eu * info@efpia.eu

26. First step: assessment of the medicine
Haute Autorité de Santé
Clinical evaluation: Commission de la Transparence
SMR: severity, need, B/R
ASMR : therapeutic added value
Economic evaluation : CEESP
Efficiency: cost/efficacy
P&R process (1)
26

27.  2nd step: reimbursement
P&R process (2)
Haute Autorité de Santé
Ministres,
UNCAM
Reimbursement level
important 65%
moderate 30%
small 15%
insuffisant 0%
Clinical evaluation: Commission de la Transparence
SMR: severity, need, B/R
Economic evaluation : CEESP
Efficiency: cost/efficacy
27

28.  2nd step (in parallel): pricing
P&R process (2)
Haute Autorité de Santé CEPS
PRICE
4 determinants : ASMR, price of
comparator, volumes, economic
evaluation
Clinical evaluation: Commission de la Transparence
ASMR : therapeutic added value
Economic evaluation : CEESP
Efficiency: cost/efficacy
28

29. 2016: Stylised comparison between EUnetHTA and national HTA timeline
29
CHMP opinion EPAR publication
Timeline (days) Publication of EU REA
EC decision
Activities prior to
scoping phase
Scoping phase
Assessment
phase
Sub prep RE & EA F
Submission preparation
Relative Effectiveness &
Economic Appraisal
Sub prep RE & EA F
Sub prep
Sub prep
Relative Effectiveness
appraisal
Final HTA evaluation and/or
decision
Sub prep RE F
Sub prep RE F
Sub prep RE & EA F
Represents ideal timeline but some products
have a different, compatible timeline
In some cases, HTA could be
completed before the EPAR
publication, the but most products have
a different, compatible timeline
P
Sub prep RE & EA F
Sub prep RE & EA F
Sub prep RE & EA F
Submission for orphan medicines and
medicines of exceptional therapeutic
relevance can happen at CHMP opinion
Sub prep RE & EA F
RE & EA F
RE & EA
Submission
S
S
S
S
S
S
S
S
S
S
S
Dossier
submission
S
Consistency of timelines
F
0 100-180 -90 52

30. 2017: Stylised comparison between EUnetHTA and national HTA timeline
30
CHMP opinion EPAR publication
Timeline (days)
0 100-180 -90 52
EC decision
Activities prior to
scoping phase
Scoping phase
Assessment
phase
Sub prep RE & EA
Sub prep RE & EA
Sub prep
Sub prep
Sub prep
RE
In-patient products
P
RE & EA
RE & EA
S
S
S
S
S
Dossier
submission
S
Out-patient products
HTA starts before approval by
SwissMedic (which is on average 90+
days after EC decision)
Sub prep RE & EAS
F
F
F
F
F
F
HTA is requested only for
some medicines
Sub prep RE & EAS F
Consistency of timelines
Value & commercial assessment
Publication of EU REA
Submission preparation
Relative Effectiveness &
Economic Appraisal
Relative Effectiveness
appraisal
Final HTA evaluation and/or
decision
Submission

31. 31www.efpia.eu
3
Current EU cooperation
on HTA
• Cooperation beyond 20 20
• Inception Impact Assessment
• Description of the status quo
• Options for the future
• Policy and strategic cooperation
• Art 15 Directive 2011/24
• Set up October 2013
• Multiannual work programme
• Perm anent
HTA
Netw ork
• Scientific and technical cooperation
• Started in the 1990's – EunetHTA 1 & 2
• Joint Action 3 – 20 16 – 20 20
EUnetHTA
Joint
Action
New HTA
I nitiative
Synergy and
complementarity
Source: European Commission
Today: multiple levels

32. 32www.efpia.eu
Initial assessment of pharmaceuticals
EUnetHTA WP7 research and analysis activity 1: Final report