Access to treatment & care differences within EUHow to address it in advocacy and policy

David H.-U. Haerry, EUPATIdavid@haerry.org

Environment

09/07/2019 2

Social networks?Society?

Regional, European authorities,Global authorities

Differences within EU – why?

09/07/2019 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

Reimbursement – few rules to follow

09/07/2019 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

Differences – pharmaceutical expenditure & utilisation

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Per capita expenditure – Germany / Denmark?

Differences – health systems financing model

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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

Differences – health systems financing model

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Differences – pricing and reimbursement

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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…

Scope of price regulation outpatient sector

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Practice of external reference pricing

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Key criteria for reimbursement

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Key criteria for reimbursement CountriesTherapeutic 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

HIV – a lot went well

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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

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

13

A key moment in the history of HIV

09/07/2019 14

“My generics company can manufacture

HIV antiretrovirals for a dollar per day”

Dr Yussef HamiedCipla, G8 summit, 2000

Ref: http://fireintheblood.com/

Hepatitis C – the silent epidemic

09/07/2019 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.

Hepatitis C – what made it so different from HIV?

09/07/2019 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.

Hepatitis C – what made it so different from HIV? - 2

09/07/2019 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

Hepatitis C – how did health systems react?

09/07/2019 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$

Hepatitis C – how did health systems react?

09/07/2019 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

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.

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Sofosbuvir (Sovaldi)

German price: €50,426Cost price: €55

Sofosbuvir prices:1. Canada (Quebec): http://www.ramq.gouv.qc.ca/SiteCollectionDocuments/liste_med/liste_med_2016_10_03_fr.pdf2. France: http://www.medecinsdumonde.org/actualites/presse/2016/09/29/mdm-soppose-au-brevet-sur-le-sovaldir-decision-le-5-octobre-20163. Germany: medizinfuchs.de4. Spain: http://politica.elpais.com/politica/2016/04/05/actualidad/1459873421_480033.html?id_externo_rsoc=TW_CC6. UK: British National Formulary 20167. Brazil: http://www.portaltransparencia.gov.br/despesasdiarias/empenho?documento=250005000012015NE8014938. Australia: Based on total annual government expenditure (AU$200 million) and 40,000 treated in 20169. 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)

http://www.medecinsdumonde.org/actualites/presse/2016/09/29/mdm-soppose-au-brevet-sur-le-sovaldir-decision-le-5-octobre-2016http://www.portaltransparencia.gov.br/despesasdiarias/empenho?documento=250005000012015NE801493http://hepcasia.com/wp-content/uploads/2016/03/31-Jan-2016-Indian-generic-sofosbuvir.pdf

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Sofosbuvir prices:1. Canada (Quebec): http://www.ramq.gouv.qc.ca/SiteCollectionDocuments/liste_med/liste_med_2016_10_03_fr.pdf2. France: http://www.medecinsdumonde.org/actualites/presse/2016/09/29/mdm-soppose-au-brevet-sur-le-sovaldir-decision-le-5-octobre-20163. Germany: medizinfuchs.de4. Spain: http://politica.elpais.com/politica/2016/04/05/actualidad/1459873421_480033.html?id_externo_rsoc=TW_CC6. UK: British National Formulary 20167. Brazil: http://www.portaltransparencia.gov.br/despesasdiarias/empenho?documento=250005000012015NE8014938. Australia: Based on total annual government expenditure (AU$200 million) and 40,000 treated in 20169. 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)

http://www.medecinsdumonde.org/actualites/presse/2016/09/29/mdm-soppose-au-brevet-sur-le-sovaldir-decision-le-5-octobre-2016http://www.portaltransparencia.gov.br/despesasdiarias/empenho?documento=250005000012015NE801493http://hepcasia.com/wp-content/uploads/2016/03/31-Jan-2016-Indian-generic-sofosbuvir.pdf

Swiss Hepatitis Strategy Network

09/07/2019 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

Swiss Hepatitis Strategy Materials

09/07/2019 24

Website

Publications

Strategy papers

Hepatitis C – what do I know today?

09/07/2019 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.

Example: Myeloma Patients Europe (MPE)

Myeloma Patients Europe is an umbrella organisationrepresenting 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

09/07/2019 26

Slide courtesy MPE

Example: Myeloma Patients Europe (MPE) – CEE region

09/07/2019 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

MPE Access survey 2017 – 2018 Does country have at least one of the ESMO recommended treatments per specific phase?

09/07/2019 28

Country C

Average time between onset and diagnosis

Overall rating of diagnosis standards

Column

a3

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

Co

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 6812Switzerland 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 6347Sweden 1 No data Yes Yes Yes No Yes Yes Yes No data 8,2 8,2 5219Netherlands 2 7 Yes Yes Yes Yes Yes Yes Yes 8 6,9 7 5202Germany 2 9 Yes Yes Yes Yes Yes Yes Yes 9 8,7 7,6 5182Austria 1 8 Yes Yes Yes Yes Yes Yes Yes 8 6,4 6,2 5039Denmark 2 7 Yes Yes Yes Yes Yes Yes Yes 9 6,5 6,5 4782Finland Don't know 9 Yes Yes Yes Yes Yes Yes Yes 9 8,5 8 3701United Kingdom (England) 2 7 Yes No Yes Yes No Yes Yes 8 10,1 10,6 3377United Kingdom (Scotland) 2 7 Yes No Yes Yes Yes Yes Yes 8 10,1 10,6 3377Italy 1 8 Yes Yes Yes Yes Yes Yes Yes 9 10,2 8,6 3239Malta 1 9 Yes Yes Yes Yes Yes Yes Yes 7 6,9 7,1 3072Spain 1 8 Yes Yes Yes Yes Yes Yes Yes 9 7 6,7 2966Slovenia 2 10 Yes Yes Yes Yes Yes Yes Yes 10 7 6,7 2698Israel 3 7 Yes Yes Yes Yes Yes Yes Yes 9 2599Slovak Rep. 3 7 Yes Yes Yes Yes Yes Yes No 5 6,8 8 2179Czech Republic 2 7 Yes No Yes Yes Yes Yes Yes 7 5,3 5,4 2146Cyprus 1 7 Yes No Yes Yes Yes Yes No 6 4,8 6,5 2062Russia 3 7 Yes Yes Yes Yes Yes Yes Yes 9 1836Hungary 2 8 Yes No Yes Yes Yes Only for specific

situationsYes 6 4,6 4,6 1827

Lithuania 2 8 Yes No Yes Yes Yes Yes Yes 8 6,2 6,1 1718Bulgaria 3 8 Yes No Yes Yes No Yes Yes 7 2,3 2,1 1399Serbia 2 9 Yes No Yes Yes Yes Yes Yes 8 1312Romania 2 3 Yes No Yes Yes No Yes Yes 3 3,3 3,4 1079Latvia 2 7 Yes No Yes No No Yes No 5 5,2 5 940Macedonia 2 5 No No Yes No No Yes Yes 4 851

Slide courtesy MPE

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

09/07/2019 29

Slide courtesy MPE

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

09/07/2019 30

Slide courtesy MPE

Resources

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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

https://www.eupati.eu/what-is-the-toolbox/http://www.euro.who.int/en/publications/abstracts/medicines-reimbursement-policies-in-europehttps://www.eurordis.org/news/rare-disease-community-calls-radical-change-improve-patients-access-medicineshttps://www.eurordis.org/publication/early-access-medicines-europe-compassionate-use-become-reality

Access to treatment & care differences within EUEnvironmentDifferences within EU – why?Reimbursement – few rules to followDifferences – pharmaceutical expenditure & utilisation Differences – health systems financing modelDifferences – health systems financing modelDifferences – pricing and reimbursementScope of price regulation outpatient sectorPractice of external reference pricingKey criteria for reimbursementHIV – a lot went wellSlide Number 13A key moment in the history of HIVHepatitis C – the silent epidemicHepatitis C – what made it so different from HIV?Hepatitis C – what made it so different from HIV? - 2Hepatitis C – how did health systems react?Hepatitis C – how did health systems react?Slide Number 20Slide Number 21Slide Number 22Swiss Hepatitis Strategy NetworkSwiss Hepatitis Strategy MaterialsHepatitis C – what do I know today?Example: Myeloma Patients Europe (MPE)Example: Myeloma Patients Europe (MPE) – CEE region�MPE Access survey 2017 – 2018 �Does country have at least one of the ESMO recommended treatments per specific phase?�Role of European umbrellas in accessIdentify access challenges & develop solutionsResources