Differences in access to treatment and care exist within the European Union due to several factors: 1) While the EU has harmonized scientific drug approval, reimbursement decisions are made by individual member states according to subsidiarity principles, leading to availability differences. 2) Drugs approved by EMA may not be marketed or available in all member states. 3) Health systems financing (SHI vs NHS), pricing and reimbursement criteria, and pharmaceutical expenditures vary significantly between countries. 4) These differences present challenges for advocacy and developing policies to improve equitable access across the EU.

1. Access to treatment & care
differences within EU
How to address it in advocacy and policy
David H.-U. Haerry, EUPATI
david@haerry.org

2. Environment
12/07/2019 2
Social networks?
Society?
Regional,
European authorities,
Global authorities

3. Differences within EU – why?
12/07/2019 3
 EU harmonised scientific medicines approval to prepare for the common
market
 Reimbursement remains a national competence - subsidiarity principle -
therefore a Member States responsibility – MS want budget control
 Medicines evaluated by EMA: authorisation valid in the whole of the EU
 Decisions on where a medicine is marketed made by marketing
authorisation holder. EMA has no control over these decisions.
 Result: medicines with central marketing authorisation via EMA may not
be available in all Member States

4. Reimbursement – few rules to follow
12/07/2019 4
 EU Member States required to comply with EU Transparency Directive
 Provisions stipulate decisions on pricing or reimbursement of
medicines have to be taken within 90 days after dossier submission
(within 180 days for joint pricing and reimbursement)
 In reality, these timelines are very often not respected
 Competent authorities required to follow transparent processes in pricing
and reimbursement decisions. National decision has to contain a
statement of reasons based on objective & verifiable criteria that will be
published
 Transparency Directive grants manufacturers possibility of appeal to an
independent body against a pricing and/or reimbursement decision

5. Differences – pharmaceutical expenditure & utilisation
12/07/2019 5
Per capita expenditure – Germany / Denmark?

6. Differences – health systems financing model
12/07/2019 6
 Some western European countries: SHI system “Bismarck system” –
Austria, Belgium, France, Germany. 1990s SHI also introduced in several
CEE & CIS countries.
 SHI: system of financing health care often funded through insurance
contributions made by employers, employees and state subsidies. Many
countries using the SHI approach have mandatory schemes for employed
people whose income does not exceed a certain threshold (insurance
obligation).
 NHS systems financed through general taxation, usually covering all
residents – UK, Italy, Spain, Portugal, Denmark, Sweden
 Scope of services rendered identical for every person covered, services
often offered by public institutions.
 Voluntary health insurance may play a role in any health system

7. Differences – health systems financing model
12/07/2019 7

8. Differences – pricing and reimbursement
12/07/2019 8
 Finland, Sweden: Pricing & reimbursement taken concurrently
 Italy, Portugal: Same institution in charge of decision
 Most countries have price controls for reimbursable medicines only
 Albania, Belgium, Lithuania: price controls for all medicines
 Bulgaria, Iceland, Romania: price controls for prescription only medicines
 Austria, Belgium, Estonia, Romania: apply external reference pricing
 Inpatient sector: Usually procured by tendering through a centralised
procedure, but increasingly joint procedures
 Switzerland: reimbursement decision process in parallel with Swissmedic
regulatory assessment
 Anything goes…

9. Scope of price
regulation
outpatient
sector
12/07/2019 9

10. Practice of
external
reference
pricing
12/07/2019 10

11. Key criteria for reimbursement
12/07/2019 11
Key criteria for reimbursement Countries
Therapeutic benefit of a
medicine
Armenia, Austria, Belgium, Czechia, Croatia, Denmark,
Estonia, Finland, Kazakhstan, Latvia, Lithuania, Malta,
Netherlands, Poland, Portugal, Moldova, Serbia, Slovenia,
Spain, Ukraine
Medical necessity, priority Armenia, Estonia, Finland, Kazakhstan, Netherlands, Norway,
Poland, Moldova, Turkey, Ukraine
Safety Armenia, Bulgaria, Denmark, Estonia, Iceland, Malta,
Netherlands, Poland, Moldova, Russia
Cost-effectiveness Belarus, Czechia, Estonia, Finland, Kazakhstan, Latvia,
Lithuania, Malta, Netherlands, Poland, Turkey, United Kingdom
Budget impact Belgium, Bulgaria, Czechia, Estonia, Finland, Iceland, Latvia,
Lithuania, Norway, Poland, Moldova, Slovenia, Turkey

12. HIV – a lot went well
12/07/2019 12
 Expanded access / compassionate use – FDA, 1987
 Accelerated approval life threatening conditions – FDA, 1992
 Use of surrogate markers instead of clinical end points in pivotal trials – EMA,
NVP approval 1997
 New criteria for conditional approval – Gilead first to apply, access 12 months
accelerated
 Lazarus effect on dying patients & HIV cohort studies in place to proof cost-
effectiveness of expensive treatment
 Cross-Atlantic lobbying for pivotal trial including 2 NCE, ending exposure to
monotherapies & multidrug resistance 2007
 Single tablet regimens for convenience and adherence, while having single
compounds to control toxicities, resistance and adapt drug levels, FDA: 27 NCE
& 14 combos 1987-2017
 Tiered pricing & voluntary licences supporting global access

13. Africa, 1999: mass treatment
for HIV/AIDS is not feasible
13

14. A key moment in the history of HIV
12/07/2019 14
“My generics company
can manufacture
HIV antiretrovirals
for a dollar per day”
Dr Yussef Hamied
Cipla, G8 summit, 2000
Ref: http://fireintheblood.com/

15. Hepatitis C – the silent epidemic
12/07/2019 15
 DAA and combination treatment: Biggest scientific breakthrough for patients
since HAART introduction
 Much shorter treatment cycles, much less toxicity, a lot more effective &
cheaper than previous gold standard
 Interaction with regulators and industry since 2007
 Despite tremendous benefit DAA: bumpy reimbursement, access limitations
even in UK & CH while patients continue to die
 Interesting: HTA bodies assessment in conflict (German IQWiG versus HAS &
Scottish Medicines Consortium; Scotland faster than NICE) – apparent
methodological discrepancies and challenges
 Difficult: convince health authorities about systemic impact condition & to
commit to infectious diseases treatment strategies
 System focus too much on cost containment & for perfection; fails on
robustness. Result: insecurity about treatment uptake on all sides. Level of
insecurity has impact on cost agreements with industry.

16. Hepatitis C – what made it so different from HIV?
12/07/2019 16
 Disease progression very slow
 Patient population diverse – IDU, healthcare system infections, tattoo
studios, haemophilia, perinatal & sexual transmission, mono- & co-
infection
 Weak epidemiological data – WHO expected 180’000’000, now down to
71’000’000. CH estimate 80’000 down to 40’000-50’000
 Diverse treating physicians: gastroenterologists, hepatologists, ID
specialists, addiction specialists. Most patients in GP care
 Patient groups diverse, weaker or not existing
 Collaboration professionals/patients low level
 Research progress very fast: SoC until 2012 35% effective after 9
months & big side effect burden; today 95% in 8-12 weeks, no side
effects
 Old SoC treatment of last resort. DAA treatment ideally earlier.

17. Hepatitis C – what made it so different from HIV? - 2
12/07/2019 17
 Cost effective does not mean cheap
 Health systems only look at total cost. Disease burden high in many
countries
 QALY & QoL gain in treated patients not considered
 Almost no cohorts/registries in place to provide data
 Up to 90% of persons infected unaware of status

18. Hepatitis C – how did health systems react?
12/07/2019 18
USA
 Gilead caused global turmoil announcing 1’000$ pill. Senate hearing on
pricing, poisoning climate beyond Hep C. Slow treatment uptake in most
affected populations (veterans, prisoners, former IDU). Screening strategy in
place.
Portugal, Scotland
 High system awareness, treatment strategies implemented quickly. Portugal:
early deal with Gilead & low price agreement.
Australia
 Hep-C buyers club importing generics from India. Government concludes deal
with all manufacturers, commitment to treat 50’000 patients per year at
3’435AU$

19. Hepatitis C – how did health systems react?
12/07/2019 19
Switzerland
 Patients treated old SoC, 2001-2014: 14’488, SVR 64%, cost per
treatment (48wk) 30’000 CHF
 FOPH unable to negotiate volume deal
 Price setting using “prevalence model” – does not pay out
 Rationing DAA access via limitations, first to F3 & F4
 Patients treated 2015: 2’000-2’300, SVR 95%
 Widening access to F2 leads to less patients treated (!)
 Patients treated 2016: 1’900, SVR 95%
 Harvoni price 12wk: 50’000
 CH clinics report no access for 20%-50% HCV-patients (2017)
 Patients import generics from India, pay themselves (ca 1’500 CHF)
 FOPH refuses supporting hepatitis strategy development
 Efforts to delay access continued until Oct 2017

20. Cost/kg of sofosbuvir API exports Jan 2015 to Jul 2016,
weighted by size of shipment
Gotham D, Barber M, Fortunak J, Pozniak A, Hill A.
Abstract number A-792-0516-01639, presented at AIDS2016, Durban.

21. 50,426€
41,680€
40,556€
37,936€
13,000€
6,008€
3,435€
288€
55€
0 €
15,000 €
30,000 €
45,000 €
60,000 €
Germany
France
UK
Canada
Spain
Brazil
Australia
India
Target
priceinEurosfor12-weekcourse
Sofosbuvir (Sovaldi)
German price: €50,426
Cost price: €55
Sofosbuvir prices:
1. Canada (Quebec): http://www.ramq.gouv.qc.ca/SiteCollectionDocuments/liste_med/liste_med_2016_10_03_fr.pdf
2. France: http://www.medecinsdumonde.org/actualites/presse/2016/09/29/mdm-soppose-au-brevet-sur-le-sovaldir-decision-le-5-octobre-2016
3. Germany: medizinfuchs.de
4. Spain: http://politica.elpais.com/politica/2016/04/05/actualidad/1459873421_480033.html?id_externo_rsoc=TW_CC
6. UK: British National Formulary 2016
7. Brazil: http://www.portaltransparencia.gov.br/despesasdiarias/empenho?documento=250005000012015NE801493
8. Australia: Based on total annual government expenditure (AU$200 million) and 40,000 treated in 2016
9. India: http://hepcasia.com/wp-content/uploads/2016/03/31-Jan-2016-Indian-generic-sofosbuvir.pdf Slide courtesy Andrew Hill
Price of sofosbuvir by country (12 weeks)

22. 50,426€
41,680€
40,556€
37,936€
13,000€
6,008€
3,435€
288€
55€
0 €
15,000 €
30,000 €
45,000 €
60,000 €
Germany
France
UK
Canada
Spain
Brazil
Australia
India
Target
priceinEurosfor12-weekcourse
Sofosbuvir prices:
1. Canada (Quebec): http://www.ramq.gouv.qc.ca/SiteCollectionDocuments/liste_med/liste_med_2016_10_03_fr.pdf
2. France: http://www.medecinsdumonde.org/actualites/presse/2016/09/29/mdm-soppose-au-brevet-sur-le-sovaldir-decision-le-5-octobre-2016
3. Germany: medizinfuchs.de
4. Spain: http://politica.elpais.com/politica/2016/04/05/actualidad/1459873421_480033.html?id_externo_rsoc=TW_CC
6. UK: British National Formulary 2016
7. Brazil: http://www.portaltransparencia.gov.br/despesasdiarias/empenho?documento=250005000012015NE801493
8. Australia: Based on total annual government expenditure (AU$200 million) and 40,000 treated in 2016
9. India: http://hepcasia.com/wp-content/uploads/2016/03/31-Jan-2016-Indian-generic-sofosbuvir.pdf Slide courtesy Andrew Hill
Price of sofosbuvir by country (12 weeks)

23. Swiss Hepatitis Strategy Network
12/07/2019 23
 All 5 University hospitals, additional important hepatitis treatment centres
 Addiction medicine centres
 Conference Cantonal Health Directors
 Swiss Cancer League
 Swiss Prison Doctors Conference
 Professional Societies infectious diseases, gastro-enterology, hepatology
 Departments from different universities
• Nursing Science, Law, Ethics, Health Policy
 3 national PAGs with HIV/HCV focus
 European & global advocacy groups
 Health insurance associations
 Testing laboratories, pharmaceutical industry

24. Swiss Hepatitis Strategy Materials
12/07/2019 24
 Website
 Publications
 Strategy papers

25. Hepatitis C – what do I know today?
12/07/2019 25
 Swiss Health Ministry tried using a new model to set the price
• “Prevalence model” – a trial, it failed
• Ministry tried other mechanisms to force an agreement while denying treatment to
patients – Ministry went as far as stating in public that F2 patients don’t require
treatment because they were not sick
• Ministry did not follow its own legislative framework
• Industry was stubborn until one of them cut a deal for their “Volkswagen treatment”
• Many patients were treated by Volkswagen, which made Mercedes & BMW drop
their prices to same level
 Swiss Health Ministry is clueless about Hepatitis C
• Endless bureaucratic instruments and delaying tactics where used “to gather
evidence” nobody was questioning
• Still refuses to support strategy development, while still keeping one foot in it
 Swiss Health Ministry wants the same price for second line treatment as
for first line. This is not covered by its legislative framework.

26. Example: Myeloma Patients Europe (MPE)
 Myeloma Patients Europe is an umbrella organisation
representing myeloma and AL amyloidosis patient
groups
• 43 member organisations
• 28 European countries and beyond (Russia, Turkey, Israel)
• MPE providing a range of programmes & resources aimed at
building a strong European advocacy community
 MPE recognises
• Challenges & barriers differ from country to country
• GDP differences
• Resource differences
• Health system differences
12/07/2019 26
Slide courtesy MPE

27. Example: Myeloma Patients Europe (MPE) – CEE region
12/07/2019 27
Limited GDP and
expenditure on
healthcare
Affordability of
new and upcoming
medicines
Systemic
government and
infrastructure
challenges
Unequal access to
procedures and
diagnostics
Off-patent medicines
not reaching
patients (e.g. Balkan
countries)
Clinical trials not
launching in some
countries
Complex, expensive
myeloma pathway
Slide courtesy MPE

28. MPE Access survey 2017 – 2018
Does country have at least one of the ESMO recommended treatments
per specific phase?
12/07/2019 28
Country Columna2
Average time
between
onset and
diagnosis
Overall rating
of diagnosis
standards
C
o
l
u
m
n
a
3
Initial
treatment for
patients elegible
for stem cell
transplantation
Maintenance
therapy
following ACT
Initial
treatment for
patient inelegible
for stem cell
transplantation
First relapse
after a
lenalidomide or
thalidomide
based initial
treatment
First relapse
after bortezomib-
based initial
treatment
Second stem
cell
transplantation
Second or
subsequent
relapse
Overall rating
of treatment
standards
Columna1
Multiple
myeloma
crude rate
(2018)
Multiple
myeloma age-
specific rate
(ASR,
European
new) (2018)
Health
expenditure
in US$ PPP
per
inhabitant
(2014)
Luxembourg 1 9 Yes Yes Yes Yes Yes Yes Yes 10 6,4 8,1 6812
Switzerland 2 10 Yes Yes Yes Yes Yes Yes Yes 10 7,9 8 6468
Norway 2 8 Yes Yes Yes Yes Yes
Only for specific
situations
Yes 8 8,9 10,1 6347
Sweden 1 No data Yes Yes Yes No Yes Yes Yes No data 8,2 8,2 5219
Netherlands 2 7 Yes Yes Yes Yes Yes Yes Yes 8 6,9 7 5202
Germany 2 9 Yes Yes Yes Yes Yes Yes Yes 9 8,7 7,6 5182
Austria 1 8 Yes Yes Yes Yes Yes Yes Yes 8 6,4 6,2 5039
Denmark 2 7 Yes Yes Yes Yes Yes Yes Yes 9 6,5 6,5 4782
Finland Don't know 9 Yes Yes Yes Yes Yes Yes Yes 9 8,5 8 3701
United Kingdom (England) 2 7 Yes No Yes Yes No Yes Yes 8 10,1 10,6 3377
United Kingdom (Scotland) 2 7 Yes No Yes Yes Yes Yes Yes 8 10,1 10,6 3377
Italy 1 8 Yes Yes Yes Yes Yes Yes Yes 9 10,2 8,6 3239
Malta 1 9 Yes Yes Yes Yes Yes Yes Yes 7 6,9 7,1 3072
Spain 1 8 Yes Yes Yes Yes Yes Yes Yes 9 7 6,7 2966
Slovenia 2 10 Yes Yes Yes Yes Yes Yes Yes 10 7 6,7 2698
Israel 3 7 Yes Yes Yes Yes Yes Yes Yes 9 2599
Slovak Rep. 3 7 Yes Yes Yes Yes Yes Yes No 5 6,8 8 2179
Czech Republic 2 7 Yes No Yes Yes Yes Yes Yes 7 5,3 5,4 2146
Cyprus 1 7 Yes No Yes Yes Yes Yes No 6 4,8 6,5 2062
Russia 3 7 Yes Yes Yes Yes Yes Yes Yes 9 1836
Hungary 2 8 Yes No Yes Yes Yes
Only for specific
situations
Yes 6 4,6 4,6 1827
Lithuania 2 8 Yes No Yes Yes Yes Yes Yes 8 6,2 6,1 1718
Bulgaria 3 8 Yes No Yes Yes No Yes Yes 7 2,3 2,1 1399
Serbia 2 9 Yes No Yes Yes Yes Yes Yes 8 1312
Romania 2 3 Yes No Yes Yes No Yes Yes 3 3,3 3,4 1079
Latvia 2 7 Yes No Yes No No Yes No 5 5,2 5 940
Macedonia 2 5 No No Yes No No Yes Yes 4 851
Slide courtesy MPE

29. Role of European umbrellas in access
 Identify access barriers via ongoing survey
• Monitor
• Gather evidence
• Escalate if several countries affected by same barrier
 Collaborate with industry
• Trial design, trial roll-out
• Create awareness about access barriers
 Keep close contact with national organisations
• Maintain structured exchange between national and
umbrellas
• Umbrellas need to understand national access barriers to
act as advocates at European level
• Identify access topics, trends & promote information
sharing
• Organise access advocacy capacity buildings
12/07/2019 29
Slide courtesy MPE

30. Identify access challenges & develop solutions
 MPE Access Atlas Programme providing information
& support to members
 Monitor & escalate cross cutting access themes at
European level
 Access Coaching Programme providing personal
support to members working on access at national
level
• Responding to requests for general help or strategy
development
• Provide support on access issues
• Intervene when appropriate
12/07/2019 30
Slide courtesy MPE

31. Resources
12/07/2019 31
Know the system
 EUPATI toolbox: https://www.eupati.eu/what-is-the-toolbox/
 WHO: www.euro.who.int/en/publications/abstracts/medicines-
reimbursement-policies-in-europe
Get the facts together
 MPE Access Atlas
Formulate positions:
 https://www.eurordis.org/news/rare-disease-community-calls-radical-
change-improve-patients-access-medicines
 https://www.eurordis.org/publication/early-access-medicines-europe-
compassionate-use-become-reality