Table of Contents

7 EXECUTIVE SUMMARY
7 Accelerating access to medicines
7 Health technology assessment harmonization
7 Key national developments in health technology assessment
8 External reference pricing
8 Managed entry agreements
8 Price resistance: Sovaldi case study
8 Postmarketing cost containment
9 Off-label prescribing
9 Outlook
10 ACCELERATING ACCESS TO MEDICINES
10 Earlier access to medicines is a priority for the EU and its member states
10 Creation of the Expert Group on Safe and Timely Access to Medicines for Patients
11 Established approaches to accelerated assessment
15 Adaptive pathways: a new initiative to expedite access to innovative medicines
21 National initiatives to accelerate access to medicines
23 Bibliography
27 HEALTH TECHNOLOGY ASSESSMENT HARMONIZATION
27 European initiatives to harmonize health technology assessment
31 Multi-HTA early dialogues
33 Parallel scientific advice
35 EUnetHTA’s HTA Core Model
37 Rapid relative effectiveness assessment
40 The HTA Network calls for closer cooperation in HTA
42 Bibliography
45 KEY NATIONAL DEVELOPMENTS IN HEALTH TECHNOLOGY ASSESSMENT
47 France: the increasing importance of health economic evaluation
50 Germany: industry dissatisfaction with AMNOG continues
58 Italy: national and regional governments re-affirm commitment to HTA
60 Spain: therapeutic positioning reports have yet to streamline HTA processes
62 UK: NICE advocates limited methodological change, but establishes a new Office for Market
Access and will play a key role in the Cancer Drugs Fund
66 Bibliography
71 PRICING AND REIMBURSEMENT DELAYS
71 Pricing and reimbursement delays pose a persistent problem for drug manufacturers, patients,
and politicians
73 Bibliography
74 EXTERNAL REFERENCE PRICING
74 External referencing pricing is common in Europe, but systems vary widely
80 Manufacturers seek to minimize the impact of ERP by careful launch sequencing, offering
discounts, or even withdrawing drugs in some circumstances
81 Industry calls for more moderate use of ERP are likely to have limited success
81 Has ERP had its day?
82 Bibliography
84 MANAGED ENTRY AGREEMENTS
84 Uncertainty around drug effectiveness drives the use of managed entry agreements
85 The managed entry environment in leading European markets
89 Patterns of managed entry in Europe
91 Payer and manufacturer perspectives on MEAs
92 The growth of electronic health records and EU collaboration on disease registries will boost
MEAs
93 Bibliography
95 PRICE RESISTANCE: SOVALDI CASE STUDY
95 Will Sovaldi be a watershed?
96 International charities seek to challenge Sovaldi’s intellectual property protection and
expedite the launch of generics
96 Proposals for international collaboration on pricing and procurement
100 National policies on access to Sovaldi
108 Sovaldi’s legacy for pharmaceutical pricing
109 Bibliography
115 POSTMARKETING COST CONTAINMENT
115 Austerity hits southern European pharmaceutical markets hard
120 Parallel trade – an increasingly complex pattern of imports and exports
121 Generics – a tried and true method of cutting costs
124 Biosimilars – a new front in the war on pharmaceutical expenditure
128 Cost-containment pressures are set to intensify
130 Bibliography
133 OFF-LABEL PRESCRIBING
133 Off-label prescribing for economic reasons: Avastin in the spotlight
133 France: new legislation allows off-label use for economic reasons
135 Germany: a court upholds the legality of contracts for off-label prescribing
135 Italy: the government has fined manufacturers and changed the law to allow off-label
prescribing to cut costs
136 Spain: autonomous communities contemplate off-label prescribing
137 UK: the government resists stakeholder demands for off-label prescribing on economic
grounds
139 Bibliography
142 Taking a (very) long-term perspective on the role of pharmaceuticals in changing healthcare
systems
144 Bibliography
145 APPENDIX
145 About the author
145 Scope
145 Methodology142 OUTLOOK
LIST OF FIGURES

17 Figure 1: Pros and cons of adaptive pathways for pharmaceutical manufacturers
31 Figure 2: EUnetHTA early-dialogue process
33 Figure 3: The SEED process
34 Figure 4: Steps in the parallel scientific advice process
36 Figure 5: Applicability of HTA Core Model domains to rapid REA and full HTA
38 Figure 6: Key challenges and success factors in the use of EUnetHTA’s HTA Core Model and/or
guidelines for cross-border rapid REAs
59 Figure 7: Key measures and potential impact of the Health Pact on the pharmaceutical
industry in Italy
71 Figure 8: Pricing and reimbursement delays in selected European markets, 2007–09 and
2010–13
89 Figure 9: Summary of findings – three studies of MEAs
126 Figure 10: Biosimilar penetration in select European markets, 2013
127 Figure 11: Percentage change in weighted average list price of biologics subject to biosimilar
competition, by product class and country, 2006–13

LIST OF TABLES

12 Table 1: EU regulatory initiatives to accelerate access to new medicines
15 Table 2: Comparison of key features of conventional and adaptive approaches to drug
development
28 Table 3: European initiatives and pilot projects aimed at fostering HTA harmonization and
collaboration
45 Table 4: Recent national HTA and reimbursement policies in Europe
51 Table 5: First four years of AMNOG: G-BA determinations of level of additional benefit for
drugs assessed
52 Table 6: First four years of AMNOG: G-BA’s reasons for determining that certain drugs offered
no additional benefit
75 Table 7: External reference pricing in Europe
84 Table 8: Key characteristics of commonly used managed entry agreements
115 Table 9: Key healthcare spending reduction policies implemented by European Economic Area
countries (plus Switzerland) since 2008
118 Table 10: Reforms implemented by European Economic Area countries (plus Switzerland) since
the beginning of the financial crisis of 2008