Europe's "postcode lottery" - the challenge of central authorisation versus national access to medicines - By David Torstensson and Meir Pugatch

 
Europe's "postcode lottery" - the challenge of central authorisation versus national access to medicines - By David Torstensson and Meir Pugatch
Europe’s “postcode lottery” – the challenge of
        central authorisation versus national access to
        medicines

                                                      1

By David Torstensson and Meir Pugatch
Europe's "postcode lottery" - the challenge of central authorisation versus national access to medicines - By David Torstensson and Meir Pugatch
Europe’s “postcode lottery” – the challenge
of central authorisation versus national
access to medicines

By David Torstensson and Meir Pugatch

© Stockholm Network 2009. The views expressed in this publication are those
of the authors and do not necessarily represent the corporate view of the
Stockholm Network or those of its member think tanks.

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Foreword
The Stockholm Network’s health and welfare programme was set up to examine the issue of
healthcare system reform from the point of view of consumers of healthcare. Our vision is of a
sustainable, consumer-driven health system which pools risk, draws in investment and attracts
sufficient funding from a variety of sources to make high quality treatment available to all.

In this context, our overall research programme asks the following types of questions: Do European
health systems work better or less well than in other countries? Would market-oriented policies lead
to better outcomes than government-led ones and, if so, why? Do European policies encourage
innovation and give patients access to the most cutting edge medicines and treatments?

Turning to the last of these questions, this paper examines in detail the state of the European
pharmaceutical market as a whole and asks what impact European regulatory structures are having on
patients’ ability to access medicines promptly. Is there a gap between the theory and practice
regarding when patients in different EU member states can get hold of the medicines they need and, if
so, what can be done to speed up the process?

This paper attempts to shed some light and provide some answers to these important questions
about Europe’s current and future state of health.

                                                                                                   3
Executive Summary
This paper looks at two important regulatory and budgetary aspects linked to the issue of access to
medicines in Europe. The first aspect concerns the approval process of a new medicine or treatment
– the difference between the time it takes to approve a medicine for use by the European Medicines
Agency (EMEA) and the time when patients may be able to purchase this medicine in their respective
countries. The second aspect deals with the time it takes national authorities to reach a decision
about the reimbursement status of different medicines and treatments, once they have been
authorised for market use.

Accordingly, the paper focus on two empirical questions: Are there significant differences in the time
it takes after a medicine is approved for market by the EMEA and the date when it actually becomes
reimbursed and thus fully available to most Europeans? And what has been the effect of many EU
countries’ policies relating to the cost of pharmaceuticals on the actual availability of medicines and
treatments to patients?

By looking at a sample of 40 medicines in two EU Member States, Denmark and Sweden, this paper
has found that there exists a significant time delay between the approval of a medicine for market
through the European Centralised Procedure of EMEA and the time when that medicine becomes
available to many European patients through reimbursement. For Sweden and Denmark the results of
this sample are not encouraging. The averages range from a high of 331.1 and 397.8 days respectively
for each country to a low of 199 and 261. Even at the lowest range this is still a time lag of close to
nine months for Denmark and over six months for Sweden.

In addition, this paper has found that there are large variations between individual Member States
regarding when a specific medicine or therapeutic class of medicines and treatments become
reimbursable and thus accessible to the majority of patients. For instance, Swedes have to wait
considerably less to receive reimbursement for Oncologics and Cancer-related treatments than their
Danish counterparts. For the seven medicines sampled in this therapeutic class, Swedes had to wait an
average of 159.6 days, whereas in Denmark a reimbursement decision took almost 200 days longer at
348.3 days. The opposite can be said for Antipsychotics and Antidepressants. For these medicines the
Danish approval process took on average 241.1 days, whereas in Sweden the process reached almost
a full year at 337 days. These discrepancies are so large that one can talk of a ‘postcode lottery’: a
patient’s national address within the EU determines when they can access a particular medicine or
treatment, rather than when it was first approved by EMEA.

By comparing the date of EU-wide market approval of a medicine or treatment through the European
Medicines Agency (EMEA) with the date on which the medicine is first reimbursed in an individual
Member State this paper finds that that Europe still has a long way to go before having a "single
pharmaceutical market".

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1. Introduction
Much has been discussed in the academic literature with regard to different policies that aim to
increase access to medicines in different countries. Yet (and as will be discussed later in this paper)
such discussions tend to focus on different policies that both aim to reduce the price of a given
medicine (so called cost containment) and to expedite the introduction of cheaper alternatives, most
commonly via the introduction of generic medicines.

The underlying rationale behind such policies is that by reducing the amount of spending on a given
medicine (or medicines) it would be possible to use these savings to finance additional medicines and
healthcare technologies in general.

In national systems where the financing of medicines is based (in large or in part) on the public purse
(i.e on national reimbursement mechanisms) it is certainly legitimate to consider and discuss the
rationale, logic and purpose of such cost-containment models.

However, this does not mean that other questions concerning access should be sidelined. In this
context, and not least in Europe, one may ask the following questions:

         Is the access to a given medicine affected by the actual availability of that medicine in a given
         country?

         Is the access to a given medicine affected by the decision about whether to reimburse this
         medicine in that country?

The answer to both of these questions is, of course, yes. However, these questions are not only
theoretical. In fact, they are very real.

Since its inception in the mid 1990s the European Medicines Agency (EMEA) and its precursor have
increased the efficiency and speed at which medicines and pharmaceutical treatments are brought to
market. Most patients, policymakers, and other stakeholders would agree that EMEA’s Centralised
Procedure of medicine authorisation has proven to be a success.

But in Western Europe, where so much of healthcare is either publicly funded or provided, obtaining
regulatory approval for bringing a new medicine to market is only the first stage in bringing that
medicine to the patient. For patients to gain actual, practical access to a newly EMEA-approved
medicine or treatment, in most EU Member States that medicine must also be approved for
reimbursement by a national medicines regulator.

                                                                                                        5
Therefore, while the overall effect of EMEA has been to centralise and improve the market
authorisation process, reimbursement decisions still vary across Europe from medicine to medicine
and country to country. Consequently, while a medicine or treatment may have received market
approval for EU Member States at the same time, individual reimbursement policies still determine
when, and if, patients will be able to access new medicines and treatments.

In this context this paper compares the date of approval of a pharmaceutical medicine by EMEA’s
marketing authorisation authority with the date on which the same medicine is eligible for
reimbursement.

However, in order to obtain a better understanding of this comparison it is important to first outline
(in brief) how European healthcare systems review and approve new medicines for market use, as
well as how different countries determine the pricing and reimbursement of such medicines.

This paper consists of two sections. Section 1, Pharmaceuticals and European Health Care Systems,
outlines some facts about how Europe’s health care systems and pharmaceutical policy are organised
both at a centralised EU level, and at the level of the individual Member State. It focuses on
pharmaceutical policy and specifically on how medicines are approved for market, how they are
priced, and how reimbursement levels are set. The aim of this section is not to detail all variations in
policy and implementation of public health and medicines policy across all Member States, but to
highlight some of the major important trends and policies of recent years. The purpose is to broadly
describe how pharmaceutical policy works and how policymakers have attempted to grapple with the
rise in health care spending by, amongst other things, limiting expenditure on pharmaceuticals.

Section 2, Market Authorisation and Reimbursement, compares EMEA’s market authorisation date for
a sample of 20 medicines versus the date of reimbursement in two sample EU countries: Sweden and
Denmark. The purpose of this section is to provide some real data on the relationship between these
two dates: Is there a significant time lag between when a medicine is approved for sale and use and
when it is reimbursed? Are there variations in when a medicine can first become reimbursed between
these two countries?

Overall this paper asks two simple questions: Are there significant differences in time when a
medicine is approved for market by EMEA and when it becomes reimbursed and thus fully available to
most Europeans? And what has been the effect of reimbursement policies on the availability of
medicines and pharmaceutical treatments to patients across Europe?

2. Pharmaceuticals and European Health
Care Systems
                                                                                                      6
Pharmaceutical medicines and treatments are a big part of European health care and medical
treatment. In fact, Europeans are almost as keen in their use of pharmaceuticals as the biggest market
in the world: North America. According to the latest estimates from the health consultancy IMS
Health, the total unaudited and audited pharmaceutical market for Europe in 2008 was $247.5billion.1
(This is in comparison to the North American market which was valued at $311.8billion.) Since in
many of Europe’s biggest health care markets governments are the main purchasers of care, much of
this expenditure comes either directly or indirectly from the public purse. For example, the UK’s
National Health Service (a publicly provided and funded health service) is one of the biggest
purchasers of medicines in the world. This is an important point and helps to explain why many of the
policies European countries have historically adopted to curb health care spending focus, among other
things, on cutting medicine spending.

These policies are not, and have never been, uniform across the European continent. Instead, they
vary from country to country and in their overall impact on each individual country’s health system’s
standard of care. In Germany, for example, policymakers have historically maintained their
commitment to cut the perceived rising costs of pharmaceutical medicines through reference pricing,
price freezes, across the board reductions on non-referenced priced as well as referenced-priced
medicines, and the imposition of rebates on manufacturers.2 Many other countries have similar aims,
but different policies. For example, both Ireland and Spain have systems of rebates whereby a portion
of sales made by a manufacturer are returned to the institutional purchaser.3 And, in the UK,
medicine expenditure is contained through a system of profit control of branded pharmaceuticals.4
Before outlining in more detail what the most common policies are and how they have been
implemented across the EU, it is worth describing some of the basic facts about how Europeans
access their medicines.

The regulation of the pharmaceutical medicines market: marketing authorisation and
reimbursement
For a pharmaceutical medicine or treatment to become available within the EU it must go through a
process of market authorisation. This process is meant to test and ensure the safety of the treatment
and is a prerequisite to the bringing to market of a new medicine. For EU Member States, EU
legislation defines three main procedures for the marketing authorisation of medicines: the
Centralised procedure, the Mutual Recognition and Decentralised procedures, and National
procedures.

1
  IMS, ‘Total Unaudited and Audited Global Pharmaceutical Market by Region’, IMS Health Market Prognosis, March 2009. See:
http://www.imshealth.com/portal/site/imshealth/menuitem.a46c6d4df3db4b3d88f611019418c22a/?vgnextoid=cec0977ccedc0210
VgnVCM100000ed152ca2RCRD&cpsextcurrchannel=1
2
  ‘Reference Pricing of Pharmaceuticals for Medicare: Evidence from Germany, The Netherlands and New Zealand’, Patricia M.
Danzon and Jonathan D. Ketcham, National Bureau of Economic Research, Working Paper 10007, September 2003 and Valérie
Paris and Elizabeth Docteur, Pharmaceutical Pricing and Reimbursement Policies in Germany, OECD, 2008:22
3
  Jaime Espin and Joan Rovira, “Analysis of differences and commonalties in pricing and reimbursement systems in Europe”, A paper
funded by DG Enterprise and Industry of the European Commission, p. 29.
4
  Ibid. p. 30.

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The Centralised procedure for authorising biotechnology-derived and high-technology medicines is
laid out in Regulation (EEC) No 726/2004. This procedure, which came into operation in 1995, allows
applicants to obtain a marketing authorisation that is valid throughout the EU. It is compulsory for
medicinal products manufactured using biotechnological processes, for orphan medicinal products
and for human products containing a new active substance which was not authorised in the
Community before 20 May 2004 (date of entry into force of Regulation (EC) No 726/2004) and which
are intended for the treatment of AIDS, cancer, neurodegenerative disorder or diabetes.5 The
Centralised procedure is optional for any other products containing new active substances not
authorised in the Community before 20 May 2004 or for products which constitute a significant
therapeutic, scientific or technical innovation or for which a Community authorisation is in the
interests of patients’ health at the Community level. When a company wishes to place on the market
a medicinal product that is eligible for the Centralised procedure, it sends an application directly to
EMEA, to be assessed by the Committee for Medicinal Products for Human Use (CHMP). The
procedure results in a Commission decision, which is binding on all EU Member States, to authorise
the product. Centrally-authorised products may be marketed in all Member States.

For a medicinal product to be eligible for the Mutual Recognition procedure it already needs to have
obtained a marketing authorisation in one Member State. The mutual recognition procedure is based
on the principle of the mutual recognition by EU Member States of their respective national marketing
authorisations. An application for mutual recognition may be addressed to one or more Member
States. The applications submitted must be identical and all Member States must be notified of them.
As soon as one Member State decides to evaluate the medicinal product (at which point it becomes
the “Reference Member State”), it notifies this decision to other Member States (which then become
the “Concerned Member States”), to whom applications have also been submitted. Concerned
Member States will then suspend their own evaluations, and await the Reference Member State’s
decision on the product. Should any Member State refuse to recognise the original national
authorisation, on the grounds of potential serious risk to public health, the issue will be referred to
the coordination group. Within a timeframe of 60 days, Member States shall, within the coordination
group, make all efforts to reach a consensus. In case this fails, the procedure is submitted to the
appropriate EMEA group for arbitration. The opinion of the EMEA Committee is then forwarded to
the Commission. The Commission will then decide on granting or refusing a marketing authorisation
valid in all member states.

The Decentralised procedure applies for medicinal products which have not received a marketing
authorisation in any EU Member State at the time of application and are not required to apply under
the Centralised procedure. The Decentralised procedure is also based on recognition by national
authorities of a first assessment performed by one Member State. An identical application for
marketing authorisation is submitted simultaneously to the competent authorities of the Reference

5
  An orphan medicine or medicinal product is a medicine developed for very rare diseases. Within the EU there exist a number
of incentives to encourage the development of such orphan medicines. See:
http://www.emea.europa.eu/htms/human/orphans/intro.htm

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Member State and of the Concerned Member States. The following steps are identical to the Mutual
Recognition procedure.

Finally, there are the national procedures. A manufacturer may seek marketing authorisation for some
of its products in only one Member State, provided that the product does not meet the criteria for
obligatory Centralised procedure. This may be a first step for a Mutual Recognition procedure. In this
case national authorities have to abide by transparency rules and make public any relevant reports and
reasoning for the decision. The national procedure is specifically relevant for manufacturers of generic
medicines, as expiring dates of patents may be different from one country to another.

Thanks to the European Union and the EMEA-based Centralised procedure medical technologies and
pharmaceuticals are all more easily bought and sold within the EU than they were 15-20 years ago.
EMEA now provides a highly sophisticated and respected market authorisation authority. However,
the streamlining and improved efficiency and coordination of marketing authorisation has not
eliminated time lags and discrepancies in when EU citizens gain actual access to new pharmaceutical
medicines and treatments. The EU has not become a true single market for pharmaceuticals – quite
the contrary. As mentioned above, individual countries still apply different rules and have different
systems of pricing, medicine reimbursement, distribution and funding. Some countries, like the United
Kingdom, apply a very thorough Health Technology Assessment process in order to decide on
reimbursement policies for expensive medicines and treatments. Other countries use various systems
of reference pricing and comparative pricing.6 Indeed, within this area of policymaking, each individual
Member State wields its own authority. Reimbursement policy is not an EU competency nor is it likely
to become one in the short or medium term. The result is that Member States have highly complex
and different regulatory regimes in place for the supervision and reimbursement of pharmaceutical
medicines and health care technologies.

Reimbursement and pricing policies in Europe – an outline of common practices
While reimbursement and pricing policies differ substantially in how they have been formulated and
implemented within the EU, there are broad similarities in the kinds of overall strategies that are
used. Indeed, a major 2004 study of pricing and reimbursement policies within the EU (funded by the
European Commission and Austrian federal government) concluded that while there existed, in effect,
27 different systems of pharmaceutical pricing and reimbursement policies there were also many
shared characteristics.7 The countries surveyed included all 27 EU Member States (except Romania
and Spain) as well as Norway and Turkey. The survey found that 24 of the 27 countries studied
controlled the price of pharmaceuticals. Pharmacy remuneration and profits were found to be
regulated in all 27 countries. All countries had reimbursement lists or national formularies, either

6
  Reference Pricing refers to the practice of clustering medical and pharmaceutical products with similar therapeutic effects into
groups. A reference price is then set based on the median or minimum price of the cluster. This concept will be discussed in
more detail below.
7
  Sabine Vogler (Lead author), Pharmaceutical Pricing and Reimbursement Information, Report, Vienna, June 2008, Commissioned
by European Commission, Directorate General Health and Consumer Protection and Austrian Federal Ministry of Health,
Family and Youth.

                                                                                                                                9
positive or negative, that is, describing either which medicines are to be reimbursed (a positive list) or
those that are not to be reimbursed (a negative list). Some 18 of the 27 countries had in place
systems of reference pricing; that is, setting a maximum reimbursement amount for a group of
pharmaceuticals that have been defined as being interchangeable. Using international price referencing
or comparison was even more popular with 22 countries having adopted this.8 (Reference pricing will
be discussed in more detail below.)

As these examples illustrate, the most common forms of determining the amount of public resources
to be spent on pharmaceuticals are either through pricing or reimbursement policies. The most direct
form of controlling prices is that of statutory pricing, whereby the authorities of each individual
country set and directly control the price for a medicine either through setting the ex-factory price,
the wholesale price or the pharmacy retail price. Out of the 27 countries studied by the EU
Commission in the above cited EU-funded study, 18 had direct price controls in place.9 In a few of
these countries, such as Italy and France, prices were set in negotiation with the pharmaceutical
industry, but in the majority prices were set directly by the relevant authority. In most countries free
pricing was allowed for pharmaceuticals which were not eligible for reimbursement and often sold
over the counter.10

Internal and external reference pricing
When setting prices and reimbursement levels for medicines, reimbursement and pricing authorities
often compare their prices to a basket of external and/or internal prices. This process is referred to
as reference pricing and is widely used in some form in most EU Member States. External reference
pricing compares and sets a price for a medicine or a reimbursement level based on the price and
reimbursement level of other countries, normally those deemed to be of a similar size and socio-
economic make-up. This is sometimes referred to as international reference pricing and
benchmarking.11 In Greece, for example, the price for branded pharmaceutical products is the average
of the three lowest prices among EU Member States. In Italy, for medicines where generics are
available, prices are set at the lowest medicine price of all the EU Member States, while for medicines
where no generics are available, prices are set at the average cost of all the EU Member States.

Internal reference pricing is the process whereby prices and reimbursement amounts are set in
comparison to a basket of what is deemed to be similar medicines. This may or may not include
generic medicines. Similarity between medicines is determined either by similarity in the active
substance employed by the medicine or by therapeutic similarity. This latter comparison (that of
therapeutic similarity) is a relatively new way of referencing and has widened the comparisons to
medicines that do not necessarily employ the same active substance or ingredient.12 Therapeutic

8
  Ibid. IX-X
9
  Ibid. XVI-XVII
10
   Ibid. XVI
11
   Ibid. XVIII
12
   Ibid. XX

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similarity largely leaves it up to the medical and/or reimbursement authority to decide what is
considered to be of therapeutic equivalence. Of those Member States that employ internal reference
pricing most base their comparisons on active substances, but Germany, the Netherlands and the
Czech Republic also use comparisons of therapeutic similarity.13

Often the basket of medicines used in both internal and external reference pricing and the setting of
reimbursement limits include comparisons to generic medicines. In Denmark, for example,
reimbursement amounts are set in relation to the cheapest existing and therapeutically equivalent
generic medicine. Patients can top up the difference between the generic substitute and another
medicine but the reimbursable amount will only be the equivalent of the generic. Similarly, in
Germany reference pricing can take the form of so-called ‘jumbo groups’, whereby both patented and
generic medicines are included in the reference group.

HTA and evidence-based medicine evaluation
Many European countries have also moved into the field of Health Technology Assessment (HTA).
HTA is an evaluation of new medicines and pharmaceutical treatments which usually, though not
always, involves a cost-benefit analysis. Based on this HTA assessment the relevant medical or
reimbursement body can make a recommendation on whether or not a medicine should be
reimbursed and at what percentage. These recommendations can either be binding (that is they
become actually policy) or merely act as guidance to the relevant reimbursement and health
authorities who retain the ultimate decision-making power. A few examples of EU countries that are,
or are beginning to make, wide-spread use of HTA evaluations and cost analysis in their
reimbursement and pricing decisions include the Netherlands, the UK, France, Germany, and Sweden.
In many of these countries the relevant HTA body plays a key role in directly setting reimbursement
prices and policy on medicine pricing. For example, the Swedish Dental and Pharmaceuticals Benefits
Agency, TLV, (Tandvårds- och Läkemedelesförmånsverket) is charged by the Swedish government to
examine whether or not a pharmaceutical medicine or dental treatment should be subsidised by the
public sector.14 Similarly, the cost effectiveness analysis and subsequent guidelines issued by the UK’s
National Institute for Health and Clinical Excellence (NICE) are largely binding. And from the summer
of 2009, the German national HTA body, the Institute for Quality and Efficiency in Health Care
(IQWiG), will also be performing cost-effectiveness analysis.

Section Summary
The rising demand and cost of health care is a key challenge for most, if not all, EU countries. The
combination of an ageing population and an increasing demand for high-quality, high-cost care means
that the long-term financial pressure on mainly publicly funded systems of care is immense. In most
EU states policies have focused on limiting and reducing expenditure on pharmaceutical medicines by
imposing and setting pricing and reimbursement limits and restrictions.

13
     Ibid.
14
     See: ‘Om TLV’, http://www.tlv.se/tlv/

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Having outlined how many of these policies work, the purpose of the following section is to present
some concrete data which helps illuminate the relationship between these policies and the actual
availability of medicines. The following section will show how reimbursement policies have restricted
the speed and rate at which Europeans can access new pharmaceutical medicines and medical
treatments.

3. Market Approval and Reimbursement –
An Empirical Analysis of Two Countries
Since the mid 1990s, Europe has developed something akin to a "one-stop shop" when it comes to
the authorisation of medicines through EMEA’s centralised market authorisation procedure, yet
reimbursement policies are set in each individual country. Measuring the differences between the
market approval date and the date on which reimbursement is approved shows the effect of this
policy on European patients’ access to medicines.

Aims and methodology
The purpose of this section is to use publicly available information and perform a simple comparison:
to compare the date a medicine is approved for market by EMEA against the date when that medicine
becomes available to most potential users, that is, the date when it becomes reimbursable in a given
EU Member State. The methodology used is one of simple comparison between these two dates.
Differences between the two dates (market approval versus reimbursement) were measured in days.

Points of comparisons
Two variables were chosen for the date comparison: a pharmaceutical medicine or treatment
approved by EMEA and an individual EU Member State. The table below outlines the 40 medicines
that were used in the comparison and groups them according to therapeutic class. These medicines
were randomly selected from an initial sample of 280 medicines to provide as broad a sample as
possible. They include seven different therapeutic categories: Oncologics, Antiviral and Viral
Vaccinces,     Antipsychotics   and    Antidepressants,   Antidiabetics,   Cardiovascular   medicines,
Immunosuppressive medicines, Biphosphonates, and a more general ‘Other’ category. As well as
blockbuster medicines, such as Enbrel (a medicine used to treat autoimmune diseases such as
arthritis), more specialised and less widely used medicines and treatments were also included in the
sample.

                                      Table 1: Medicine Sample
     Therapeutic Class                     Medicine Name                     Active Ingredient
             Oncologics                        Revlimid                        Lenalditomide

                                                                                                   12
Sprycel                      Dasatinib
                                          Tarceva                      Erlotinib
                                           Sutent                  Sunitinib malate
                                          Velcade                    Bortezomib
                                          Onsenal                     Celecoxib
                                         Lysodren                      Mitotane
Antivirals and Viral Vaccines              Sebivo                    Telbivudine
                                          Reyataz                 Stazanavir sulphate
                                          Prezista                    Darunavir
     Antipsychotics and                    Abilify                   Aripiprazole
      Antidepressants
                                          Azilect                     Rasagiline
                                           Lyrica                     Pregabalin
                                         Zonegran                    Zonisamide
                                         Diacomit                     Stiripentol
                                           Invega                    Paliperidone
                                         Yentreve              Duloxetine hydrochloride
       Antidiabetics                       Apidra                   Insulin glulisine
                                         Avandamet             Metformin, rosiglitazone
                                          Januvia                      Sitagliptin
                                           Lantus                   Insulin glargine
                                          Levemir                   Insulin detemir
                                           Galvus                 Galvus vildagliptin
  Cardiovascular medicines               Procoralan                   Ivabradine
                                           Xolair                    Omalizumab
                                          Ganfort                Bimatoprost/timolol
Immunosuppressive Medicines                Enbrel                     Etanercept
                                          Raptiva                     Efalizumab
                                Thalidomide Pharmion/Celgene         Thalidomide
                                          Tysabri                    Natalizumab
      Biphosphonates                      Aclasta                  Zoledronic acid
                                         Fosavance                 Alendronic acid
                                         Bondronat                 Ibandronic acid
          Others                          Protelos                Strontium ranelate
                                          Stalevo                Levodopa, carbidopa,
                                                                     entacapone
                                           Xagrid                     Anagrelide
                                          Neupro                      Rotigotine
                                          Advagraf                    Tacrolimus

                                                                                          13
Advate                                   Octocog alfa
                                                            Noxafil                                  Posaconazole

The two EU Member States compared were Denmark and Sweden. Initially, the country sample was
much larger, including six countries from across the EU (Sweden, Denmark, Germany, Spain, France,
and the Netherlands) but due to a lack of reliable and available data only the results from Sweden and
Denmark qualified for the final sample.15

During the course of the data collection it was found that the health care systems in both Sweden and
Denmark share important characteristics which actually lend themselves to this paper. Firstly, both
countries have highly centralised pricing and reimbursement policies centred on the Swedish Dental
and Pharmaceuticals Benefits Agency, TLV, and the Danish Medicines Agency (Laegemiddelstyrelsen).
Both these agencies are responsible for setting reimbursement decisions for all medicines used within
the publicly provided and managed health care system. Secondly, both countries have a relatively open
and transparent system of setting reimbursement policy, making most of the relevant information
accessible to the public. Finally, both countries are relatively similar in terms of both political and
socio-economic make-up. This fact makes it less difficult to attribute differences in reimbursement
policy to reasons other than actual policy and funding disagreements.

Results
The following two tables outline how the EMEA approval dates compare with the date of
reimbursement for the sample of 40 medicines in Denmark and Sweden.

                                                           Table 2:
            Reimbursement and Market Authorisation Approval Dates for Denmark
      Medicines                    Date of EMEA                 Date of Reimbursement                  Difference in Days
                                                 16                                 17
                                     Approval                            Approval
       Revlimid
                                     14/06/2007                         03/12/2007                              172
        Sprycel
                                     20/11/2006                         18/12/2006                               28
       Tarceva
                                     19/09/2005                         19/06/2006                              273
        Sutent
                                     19/07/2006                         25/09/2006                               68
       Velcade
                                     26/04/2004                         19/06/2006                              784
       Onsenal
                                     17/10/2003                         13/09/2004                              331

15
   Only four out of the six countries originally surveyed had information readily available about some aspects of their respective
reimbursement rates and standards; Spain and Germany were the exceptions. Yet where information regarding reimbursement
levels and the decision to reimburse were available it was not always accompanied by a time line or notice of initial
reimbursement date. This may be caused by many countries having in the last few years begun to give HTA evaluations a more
prominent role in their reimbursement decisions. Both France and Germany are examples of this. This lack of transparency is
worrying and should concern any public official working towards greater public insight and scrutiny of existing pharmaceutical
pricing and reimbursement policies across Europe.
16
   All dates collected from the European Medicines Agency website: http://www.emea.europa.eu/home.htm
17
   All dates for reimbursement for Denmark were collected from the Danish Medicines Agency website:
http://www.medicinpriser.dk/Default.aspx

                                                                                                                              14
Lysodren
                            28/04/2004                 19/06/2006                     782
      Sebivo
                            24/04/2007                 22/10/2007                     181
      Reyataz
                            02/03/2004                 19/06/2006                     839
      Prezista
                            12/02/2007                 12/03/2007                      28
      Abilify
                            04/06/2004                 05/07/2004                      32
      Azilect
                            21/02/2005                 15/08/2005                     176
      Lyrica
                            06/07/2004                 25/10/2004                     111
     Zonegran
                            10/03/2005                 13/03/2006                     368
     Diacomit
                            04/01/2007                 04/05/2009                     850
      Invega
                            25/06/2007                 22/10/2007                     119
     Yentreve
                            11/08/2004                 13/09/2004                      32
      Apidra
                            27/09/2004                 29/08/2005                     336
    Avandamet
                            20/10/2003                 24/11/2003                      34
      Januvia
                            21/03/2007                 23/04/2007                      32
      Lantus
                            09/06/2000                 24/05/2004                    1444
     Levemir
                            01/06/2004                 30/08/2004                      89
      Galvus
                            26/09/2007                 21/04/2008                     207
    Procoralan
                            25/10/2005                 24/04/2006                     180
      Xolair
                            25/10/2005                 19/06/2006                     236
     Ganfort
                            19/05/2006                 29/01/2007                     255
      Enbrel
                            03/02/2005                 18/07/2005                    1990
      Raptiva
                            20/09/2004                 18/07/2005                     302
   Thalidomide
Pharmion/Celgene
                            16/04/2008                 25/08/2008                     131
      Tysabri
                            27/06/2006                 31/07/2006                      34
      Aclasta
                            15/04/2005                 19/06/2006                     430
    Fosavance
                            24/08/2005                 26/09/2005                      32
    Bondronat
                            25/06/1996                 15/03/2004                    2818
     Protelos
                            21/09/2004                 20/12/2004                      90
      Stalevo
                            17/10/2003                 24/11/2003                      38
      Xagrid
                            16/11/2004                 19/06/2006                     580
     Neupro
                            15/02/2006                 09/10/2006                     236
     Advagraf
                            23/04/2007                 08/10/2007                     168
      Advate
                            02/03/2004                 19/06/2006                     839
      Noxafil
                            25/10/2005                 19/06/2006                     237

These figures show a significant time lag between the date of EMEA approval of a medicine for market
and the day from which that medicine becomes reimbursable. For the 40 medicines in this sample the
average delay was 397.8 days. Biphosphonates and Immunosuppressive Medicines are the two

                                                                                                 15
therapeutic classes for which reimbursement decisions took the longest at 1093.3 and 614.25 days
respectively.18 Cardiovascular medicines and Antipsychotics and Antidepressants were the quickest to
be approved at 223.7 and 241.1 days respectively. The longest delays were 2818 for Bondronat, 1990
days for Enbrel, and 1444 days for Lantus. The medicines Sprycel, Abilify and Fosavance were
approved the most quickly at around 30 days. Discounting the significant time delay taken for the
reimbursement approvals of Lantus, Bondronat and Enbrel and any possible statistical skewing that
these three will have had on the overall sample, the average delay was still close to nine months at
261 days.19

As can be seen from the table below, the numbers of days between EMEA’s marketing authorisation
and reimbursement approval in Sweden are very similar to Denmark.

                                                         Table 3:
            Reimbursement and Market Authorisation Approval Dates for Sweden
      Medicines                   Date of EMEA                Date of Reimbursement                 Difference in Days
                                               20                                 21
                                    Approval                          Approval
       Revlimid
                                    14/06/2007                        14/03/2008                             274
       Sprycel
                                    20/11/2006                        03/03/2007                             103
       Tarceva
                                    19/09/2005                        29/10/2005                              40
        Sutent
                                    19/07/2006                        21/11/2006                             124
       Velcade
                                    26/04/2004                        07/10/2004                             164
       Onsenal
                                    17/10/2003                        02/07/2004                             258
      Lysodren
                                    28/04/2004                        29/09/2004                             154
        Sebivo
                                    24/04/2007                        01/12/2007                             221
       Reyataz
                                    02/03/2004                        25/05/2004                              84
       Prezista
                                    12/02/2007                        29/03/2007                              45
        Abilify
                                    04/06/2004                        10/06/2004                              6
        Azilect
                                    21/02/2005                        17/05/2006                             450
        Lyrica
                                    06/07/2004                        02/02/2005                             211
      Zonegran
                                    10/03/2005                        22/12/2005                             287
      Diacomit
                                    04/01/2007                        27/05/2009                             873
        Invega
                                    25/06/2007                        09/09/2008                             441
      Yentreve
                                    11/08/2004                        10/11/2004                              91
        Apidra
                                    27/09/2004                        01/12/2004                              65

18
   It should be noted that both of these categories contain one or several medicines which weigh down the averages
considerably.
19
   The delay in reimbursement for both Enbrel and Lantus are probably caused by the long delay in national approval for market
by the Danish Medicines Agency. For these two medicines the difference between the EMEA approval date and the national
approval date the delay was 1911 and 1544 days respectively.
20
   All dates collected from the European Medicines Agency website: http://www.emea.europa.eu/home.htm
21
   All dates for reimbursement for Denmark were collected from the Danish Medicines Agency website:
http://www.medicinpriser.dk/Default.aspx

                                                                                                                          16
Avandamet
                                   20/10/2003                        27/02/2004                            130
        Januvia
                                   21/03/2007                        06/06/2007                             77
        Lantus
                                   09/06/2000                        01/06/2003                           1087
       Levemir
                                   01/06/2004                        07/10/2004                            128
        Galvus
                                   26/09/2007                        09/09/2008                            348
     Procoralan
                                   25/10/2005                            N/A                               N/A
        Xolair
                                   25/10/2005                        08/03/2006                            134
       Ganfort
                                   19/05/2006                        24/10/2006                            157
        Enbrel
                                   03/02/2005                        14/02/2005                           1838
       Raptiva
                                   20/09/2004                        22/12/2004                             93
     Thalidomide
 Pharmion/Celgene
                                   16/04/2008                        19/12/2008                            247
       Tysabri
                                   27/06/2006                        23/12/2006                            179
       Aclasta
                                   15/04/2005                        09/09/2005                            147
      Fosavance
                                   24/08/2005                        09/05/2006                            258
     Bondronat
                                   25/06/1996                        17/03/2004                           2820
       Protelos
                                   21/09/2004                        28/05/2005                            249
       Stalevo
                                   17/10/2003                        15/11/2003                             29
        Xagrid
                                   16/11/2004                        26/02/2005                            102
       Neupro
                                   15/02/2006                        20/11/2007                            643
      Advagraf
                                   23/04/2007                        02/10/2007                            192
       Advate
                                   02/03/2004                        04/05/2004                             63
       Noxafil
                                   25/10/2005                        03/02/2006                            101

The data for Sweden (as in Denmark) shows significant lags in time between the date of EMEA market
approval of a medicine and the date from which it is first reimbursed. For the 40 medicines sampled
the average time lag was 331.1 days, with the longest medicine reimbursement approval taking 1838
days for Enbrel and 2820 for Bondronat. The shortest amount of time was spent on approving Abilify
and Stalevo at 6 and 29 days respectively. The therapeutic classes for which reimbursement took the
longest are Immunosuppressive medicines and Biphosphonates at 589.25 and 1075 days respectively.22
At the other end of the spectrum, Oncologics and Antivirals and Viral Vaccines were the two
therapeutic classes which took the least amount of time at 159.6 and 116.7 days on average.
Discounting the significant time delay taken for the reimbursement approvals of Lantus, Bondronat
and Enbrel and any possible statistical skewing that these three will have had on the overall sample,
the average delay was still close to seven months at 199 days.

Summary

22
  It should be noted that both of these categories contain one or several medicines which weigh down the averages
considerably.

                                                                                                                    17
From this sample of medicines and countries one can conclude that there exist significant time delays
between the approval of a medicine for market through the European Centralised Procedure of
EMEA and the time from which that medicine becomes available to many European patients. For
Sweden and Denmark the results of this sample are not encouraging. The averages range from a high
of 331.1 and 397.8 days respectively for each country to a low of 199 and 261 days. Even at the
lowest range this is still a time lag of close to nine months for Denmark and over 6 months for
Sweden. These findings have serious implications for policy makers - and even more so for European
patients waiting for treatment.

Final considerations
By comparing the difference in time from when a medicine first becomes authorised for use with the
time when it first becomes reimbursable this paper highlights two important findings.

Firstly, there is visible gap between the time when a medicine is first approved for market use and the
time it take national authorities to reach a decision about the reimbursement (or non-
reimbursement) of that medicine.

Secondly, this paper illustrates the variation that exists within the EU regarding reimbursement
decisions on specific medicines. As the above data sample and comparison between Sweden and
Denmark shows, there are substantial differences in when a patient can receive reimbursement for a
medicine depending on which side of the Skagerrak, Kattegat and Baltic Sea they live on. For example,
in Sweden, Abilify was reimbursable 6 days after it was approved for market by EMEA. In Denmark
the amount of time was 32 days. Similarly, Swedes who wanted to get their prescriptions for Tarceva
reimbursed only had to wait 40 days after EMEA approval, whereas Danes had to wait a full 273 days.
Similar examples can be found of a reverse relationship with Danish reimbursement decisions
preceding Swedish ones. For instance, in Denmark patients could receive reimbursement for
Avandamet within 34 days of EMEA approval whereas Swedes had to wait 130 days. Similarly, for
Sprycel, Danes only had to wait 28 days whereas Swedes waited a full 103 days. Similarly, when
comparing therapeutic classes, Swedes have to wait considerably less for Oncologics and Cancer-
related treatments than their Danish counterparts. For the seven medicines sampled in this
therapeutic class Swedes had to wait an average of 159.6 days whereas in Denmark a reimbursement
decision took almost 200 days longer at 348.3 days. The opposite can be said for Antipsychotics and
Antidepressants. For these medicines the Danish approval process took on average 241.1 days,
whereas in Sweden the process reached almost a full year at 337 days.

The above data may, or may not, be a reflection of wider trends either for Denmark’s and Sweden’s
reimbursement policies or for the rest of the EU. Still, these discrepancies are so large (at least in the
case of Sweden and Denmark) that one can legitimately speak of a postcode lottery within the EU.

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With regard to the broader policy implications of these findings, most health care stakeholders would
agree that, since its inception, EMEA has worked well and provided Europe with a quicker and more
effective market approval process than that which preceded it. Yet if the time lag for reimbursement
decisions is so substantial and varies as much as the findings from Denmark and Sweden suggest, the
goal of a "single European market" is still very far off.

What can be done about this? Unfortunately, there is no simple answer. The EU-wide focus on strict
reimbursement policies and cost-benefit evaluation of medicines, by definition, means that there will
be some delay between a medicine being approved for market and the date when it can be
reimbursed by a publicly funded health care system. Certainly, there are inefficiencies in the current
system but they are individual and are determined by the specific characteristics of the structure and
functioning of a given country’s system of care. Drastically reducing the time lag between market
authorisation and reimbursement is possible but necessitates a shift in policy thinking, including the
shift towards more collaborative models between the state and private entities. Complementing the
existing publicly defined reimbursement policies with a system of private insurance could remove a
burden both for patients as well as public reimbursement authorities. But judging from current trends,
further privatisation of health care in Europe is probably still viewed as politically unacceptable by
many voters and therefore off the cards for most political parties. It looks like most European patients
currently have no choice but to keep on waiting or, if they have the means, to make provision for
their own future healthcare

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