An Introduction to European Market Access
Prepared for:
Seminar Public Health and Primary Care, Imperial College
Prepared by:
Professor Deborah Saltman
Page 1
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Pharmaceutical Products
Company
Heath Economics
Research Medical and Outcomes Marketing Manufacturing Sales
Research
Pre regulatory and Post regulatory and
reimbursement reimbursement
Regulatory Reimbursem
approval ent approval
HTA Page 2
Pricing Reimbursement and Market Access
• Paying for pharmaceutical products varies
from country to country
• All involve an assessment of safety,
efficacy and cost effectiveness
• Some involve more clinician and
consumer input than others
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What is required by these agencies?
Proof of efficacy and safety
Usually from clinical trials
Assessment of cost effectiveness
Usually by comparing with current standard of care
• Where this is not available other means must be
used eg
• What clinicians are doing in practice eg treatment
patterns questionnaires
• What patients and consumers would choose eg
utility studies
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Market access framework for the UK
The UK P&R process can be slow; HTA agencies may recommend
against access regardless of regulatory approval.
Source: PRMA Insights: Pricing and Reimbursement Success in NSCLC 2nd edition, 2012 Page 5
Market access framework for France
Taking effect in 2016, a new regulatory body, the National Agency for
the Safety of Medicines and Healthcare Products is likely to require
data from active comparator trials.
Source: PRMA Insights: Pricing and Reimbursement Success in NSCLC 2nd edition, 2012 Page 6
P&R landscape: France
Products will be awarded an ASMR and an SMR rating; ASMR 4 (parity) or ASMR 5
(EU reference pricing for product) would mean no price premium vs existing
products.
Decision-making process ASMR decision criteria Key trends
• SMR rating is based on 1. Innovative product of • ASMR ratings are getting lower
severity of the disease: significant therapeutic benefit • SMR ratings are increasingly
• major 2. Product of therapeutic benefit being used to deny or restrict
• important in terms of efficacy and/or reimbursement
• moderate reduction in side-effect profile • Importance of incremental
• minor 3. Existing product where clinical benefit (better efficacy
equivalent pharmaceuticals or better safety profile, as
• insufficient to justify
exist; moderate improvement evidenced in relevant clinical
reimbursement
in terms of efficacy and/or trials) will increase
• ASMR (incremental benefit
reduction in side-effect profile • Innovative technologies will
vs SOC) is rated between 1
4. Minor improvement in terms of require pharmacoeconomic
and 5:
efficacy and/or utility studies showing that they
• major (1)
5. No improvement but still provide cost-savings and
• important (2) improve disease management
granted recommendations to
• moderate (3) be listed • Patient stratification is
• minor (4) becoming increasingly
• none (5) important to limit budget
impact
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Premium pricing
The potential for premium pricing has become more challenging in
France as the necessary ASMR ratings are being awarded less often.
HAS has recently advocated replacing the ASMR and SMR ratings with
a single index of “therapeutic benefit”.
Annual split of innovation ratings, 2007–2010
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Note: HAS does not report the number of ASMR 5 ratings that are given.
Market access framework for Germany
Under AMNOG, the process in Germany has become more challenging;
few companies have emerged with positive results.
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Market access framework for Spain
The process in Spain is split across three levels (national, regional,
and local). A formal requirement for cost-effectiveness has been
introduced at the national level; highly innovative, expensive drugs
are increasingly assessed at the regional level.
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Market access framework for Italy
The role of pharmacoeconomic studies at both national and local
levels is becoming clearer and more important.
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EU M5 payors and HTA authorities
Key payors in the EU M5 are represented by their HTA agencies;
these are the most dominant payors globally.
Country Key agencies Details
• Clinical and cost-effectiveness are assessed
• NICE • Cost-effectiveness is assessed using QALYs; the key
• SMC threshold is about £30,000 per QALY
UK
• AWMSG • The SMC reviews all new products before launch (it
is typically the first formal HTA to be completed)
• A dossier is submitted to the TC after marketing
authorization. TC strongly prefers head-to-head
data
• TC • Incremental therapeutic benefit (ASMR) is assessed
and the reimbursed population is identified.
• CEPS
• Prices are negotiated with CEPS on the basis of the
France • HAS ASMR and SMR ratings, and may include price–
volume agreements with payback clauses
• HAS is typically responsible for developing
treatment and prescribing guidelines
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EU M5 payors/HTA authorities
Country Key agencies Details
• Free pricing applies for the first 12 months; the
• G-BA price is negotiated after the benefit assessment
Germany • IQWiG • The AMNOG legislation introduced in 2011 requires
submission of a benefit dossier to the G-BA
• A file is submitted to AIFA
• Products are reimbursed on Class H or A list
• AIFA • Budget impact and head-to-head data are important
• UVEF • Risk-sharing agreements are extensively used,
Italy
particularly in oncology
• Regional autonomy: UVEF is responsible for HTAs in
the Veneto region
• Central HTA agency assesses clinical profile and
daily cost
• Ministry of Health
• HTAs occur mostly at the regional level, with
• Regional HTA increasing use of cost-effectiveness and
Spain agencies coordination at the hospital level
• Cost-effectiveness is likely to be required in future
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Stakeholder influence by country
National and regional authorities exert different levels of influence on
market access. Addressing only national stakeholder needs may be inadequate in
some countries.
High influence
Some influence
Low influence
National level
Regional level
Local level
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Across Europe, market access terms are becoming more restrictive
Key market access themes Comment
• Meaningful clinical differentiation against an active
and relevant comparator eg head-to-head
• May be significantly smaller than the
• Growing importance of subpopulations
regulatory population
• Formal cost-effectiveness
• Growing importance of cost-effectiveness
requirements at launch
• Emergence of more complex
• Critical importance of HRQoL
composite endpoints
• Increased use of risk-sharing agreements
• Regional stakeholders importance • Make independant decisions
• Lifecycle market access requirements
• On-going re-assessments
Source: PRMA Consulting, 2012 Page 15
Key EU M5 submission requirements
Work stream Comments
Therapeutic • Prefer hard efficacy endpoints; however, surrogate
benefit endpoints if supported by guidelines/KOLs
• Cost per QALY gained is preferred ICER. UK threshold
CE modeling usually £30,000 but rises to £50,000 for EoL
treatments
Budget impact • Price–volume agreements or caps in some countries
modeling • Clear ability to define the eligible patient population
• Utilities are used
HRQoL data • HRQoL data may have an impact particularly in
chronic diseases and EoL considerations
Head-to-head
• Establishing the SOC or comparator important
data vs SOC
Real-world
observational • Real-world data may help achieve market access
data
• Innovation is a key factor in P&R and can have a
Innovation
significant impact on price
Key requirement Nice to have Not required
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Note: EoL refers to standard of care considerations around the end of life.
Same data, different access
Similar data sets can result in very different reimbursement decisions.
Product Clinical data P&R outcomes
(indication)
Avastin
Avastin + IFL offers a 4.7 month Not recommended by NICE or SMC
median improvement in OS vs IFL
(mCRC)
+ placebo (20.3 vs 15.6 months)
Reimbursed (ASMR 2)
Not recommended by NICE or SMC
Sorafenib offers a 3 month median
Nexavar
improvement in PFS vs placebo
(RCC)
(24 vs 12 weeks) Reimbursed (ASMR 2)
Reimbursed with a mandatory discount (50%
for first 2 cycles)
Not recommended by NICE or SMC
Nexavar Sorafenib offers a 2.8 month
(HCC) median improvement in OS vs
placebo (10.7 vs 7.9 months) Reimbursed (ASMR 4)
Reimbursed with a mandatory discount (50%
for first 2 cycles)
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Increasing use of risk-sharing agreements
Particularly in oncology.
• Avastin (in NSCLC, CRC, BC, RCC):
• Different types of risk-sharing 50% reimbursed for the first three
agreement are used: cycles; 100% reimbursed for cycles
4–14; cost of subsequent cycles
• Risk sharing (rebate) – borne by manufacturer
reimbursement of drug cost for
non-responders • Sutent (in mRCC): first course of
treatment is free
• Cost sharing (discount) –
discounted drug price • Torisel (in mRCC): total
reimbursement limited to 8 packs
• Payment by results (rebate) – (~2 months of therapy); additional
reimbursement of first cycles for cost is paid back by the manufacturer
non-responders if the patient discontinues treatment
during this period
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Focus of HTA critiques
Across HTAs the areas of consistent criticism were the survival data,
utility data, and choice of active comparators.
Key areas of HTA critique across countries:
Comparators Survival data Eligible PRO/Utility
population data
SMC
NICE
TC
IQWiG
Source: HAS – TC Opinion on Yervoy, Dec. 2011 Page 19
An Introduction to European Market Access
Prepared for:
Seminar Public Health and Primary Care, Imperial College
Prepared by:
Professor Deborah Saltman
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