An Overview of Cross-Border Collaborations on Healthcare

An Overview of Cross-Border Collaborations on Healthcare Technology Assessment, Pricing Negotiation, and Procurement By Thomas Quirk, Yan Xue, Ph.D., Eleanor Berry, DPhil, and Kathryn Acheson, DPhil

White Paper

An Overview of Cross-Border Collaborations on Healthcare Technology Assessment, Pricing Negotiation, and Procurement

In our previous paper, we discussed assessment (HTA) and price nego- and negotiation, and increase capacity several trends shaping the European tiations for RWE collection. However, biophar- market access landscape. Here, we 2. Increased official or unofficial price ma companies could also face greater explore recent cross border collabora- referencing pricing pressure as countries share tions in more detail. While the recent 3. EU-wide initiatives e.g., HTA har- information and boost their negotiat- COVID response highlighted many monization, evidence generation ing power. challenges, payers are making (slow) requirements, real world evidence In this paper, we outline some progress on a range of ongoing or (RWE) cross-border initiatives of interest, planned initiatives: From the biopharma industry’s per- their progress to date, their likely fu- 1. Small groups of countries conduct- spective, these initiatives could deliver ture impact, and potential implications ing joint healthcare technology streamlined consultation, submission for biopharma.

Table 1: Overview of Cross-Border Initiatives

Potential level of impact over the next 1-3 years: Low Medium High

Name Geography Scope / Focus Areas Potential Impact on Biophar- ma Product Strategy (next 1 - 3 years) Active, Ongoing Initiatives EUnetHTA EU HTA harmonization EU-wide impact, but limited change from current state anticipated Beneluxa Belgium, Luxembourg, Nether- Price negotiation and horizon Proof-of-concept; potential lands, Austria, and Ireland scanning. to expand to other countries; HTA in development provides a public benchmark on price discount/payment terms Nordic Pharmaceutical Forum Nordics (Denmark, Sweden, Tenders, HTA. High feasibility but limited and FiNoSE Norway, Finland and Iceland) Price negotiation in develop- geography ment Baltic Partnership Agreement Estonia, Latvia and Lithuania Joint procurement, currently Limited scope / geography focused on vaccines Initiatives in Development EU Regulation on HTA EU Joint HTA assessment for High potential impact, but the drugs submitted for a central final regulation (if approved) will marketing authorization likely allow member states sub- stantial flexibility, and reduce the likelihood of a fully aligned approach across states

An Overview of Cross-Border Collaborations on HTA, Pricing Negotiation, and Procurement

EC Pharmaceutical Strategy EU Information exchange, pricing, High potential impact but many cost-effectiveness, payment, hurdles and long implementa- procurement tion timelines EMA Strategy EU Evidence generation Moderate feasibility and EU- wide impact but limited to evidence generation Additional Initiatives to Watch Visegrád Group Poland, the Czech Republic, Information exchange, price Limited geography Hungary, Slovakia (the V4) and negotiations, HTA Lithuania Valletta Declaration Cyprus, Greece, Italy, Malta, Horizon scanning, informa- Affects 30% of EU population Portugal, Spain, Croatia, Ireland, tion sharing (focused on price if implemented; potentially Romania, and Slovenia transparency), price negotiation significant impact on pricing and HTA IHSI Netherlands, Belgium, Ire- Information on medicines and Limited scope land, Denmark, Luxembourg, horizon scanning Norway, Portugal, Sweden and Switzerland RWE4Decisions EU RWE collection, RWE to inform High feasibility, impact on RWE decision making Unofficial Price Referencing Referencing HE Models from All Benchmark for price negotia- Easy to adopt and impactful for Other Countries tions price negotiations

Active, Ongoing Initiatives

There are numerous ongoing initia- in providing early consultations to What’s next?: EUnetHTA was due tives in Europe, covering a range of pharma companies on their clinical to finish its mandate in 2020 with no access topics from cooperation on programs as well as joint relative effi- official announcement yet on future pricing to HTA standardization. The cacy assessments of medical prod- plans. It is possible that joint early scope of these initiatives also varies, ucts, developing these assessments consultations to provide clinical devel- from EU-wide to small groups of coun- with countries who opt in. opment advice will continue. However, tries voluntarily coming together. joint assessments of medical products Recent news: EUnetHTA is currently are likely to remain advisory and lim- in its 3rd and final joint action,2 Joint ited in scope.5 EUnetHTA1 Action 3 (JA3). JA3 aims to build on EUnetHTA’s work to date and “ulti- About: An EU-wide initiative, EUnetH- mately develop and disseminate [a] The Beneluxa Initiative6 TA was set up in 2006 to “connect Europe-wide actionable product, in public national HTA agencies, research the form of Joint Assessments in both About: Launched in 2015 by Belgium, institutions and health ministries, Pharmaceuticals and Other Technolo- Luxembourg and the Netherlands, 3 enabling an effective exchange of gies.” JA3 includes a plan for facilitat- the Beneluxa Initiative now includes information and support for policy ing national implementation to help Austria and Ireland, with interest decisions by Member States”. Basi- make the joint assessments usable in from other parties.7 The initiative has 4 cally, its goal is to develop harmonized a real-world setting. instigated a number of joint actions. HTA processes. It has also been active These include a successful joint price

An Overview of Cross-Border Collaborations on HTA, Pricing Negotiation, and Procurement

negotiation for Spinraza in 2018 and cost-effectiveness in the assessment which they plan to follow with a joint establishment of a joint horizon scan- of medicines 2) robust clinical evi- price negotiation.16 ning initiative. dence for decision makers in a timely manner. What’s next?: The Nordic Pharmaceu- Recent news: In May 2020, the Publication of the evaluation out- tical Forum and FiNoSe have worked Beneluxa Initiative announced that comes, as well as public statements on their first joint tendering and HTA Belgium, Ireland and the Netherlands on price discounts, pay-for-perfor- assessments. Future joint tenders are will undertake a joint HTA assessment mance, and payment terms also pro- being considered, and the Forum is of Zolgensma.8 In May 2021, the joint vide an easily available benchmark for planning to take lessons learned from assessment was finally published, other countries to reference for their their first tender forward.17 with Zorginstituut Nederland (ZIN) own negotiations. publicly recommending a “pay-for- performance” agreement and 50% The Baltic Partnership price-cut. ZIN also recommended a The Nordic Pharmaceutical Agreement joint price negotiation with Belgium Forum11,12 and FiNoSe13 and Ireland.9 About: In 2012 Estonia, Latvia and About: The Nordic Pharmaceutical Fo- Lithuania set up the Baltic Partnership What’s next?: Beneluxa has dem- rum was set up in 2015, with the aim Agreement for joint procurement of onstrated success in joint price and of expanding the purchasing power of medicines and medical devices.18 Their HTA negotiations, and further joint the smaller nordic countries, including current focus is on vaccines.19 assessments on three more gene joint procurement.14 FiNoSe was set therapies have been planned. While up in 2018 to pilot joint evaluation of Recent news: In 2017, the first suc- the pilots have been lengthy, future innovative therapies, with an aligned cessful joint tender took place be- assessments are likely to increase HTA approach and evidence require- tween Estonia and Latvia, to purchase in speed as the joint methodology is ments. the rotavirus vaccine. In 2018, Latvia established. and Lithuania jointly purchased pneu- Success of the Beneluxa initiative Recent news: In 2019 the first joint mococcal vaccines.20 could attract other countries to par- tender for certain hospital products ticipate. It has already reached out to took place through the Nordic Pharma- What’s next?: The Baltic procure- other international initiatives, such as ceutical Forum, with the agreements ment initiative has achieved success the Nordic Pharmaceutical Forum, for coming into effect in 2020.15 In 2019 with some joint procurements. The collaboration.10 Their joint statement FiNoSe conducted its first joint health frequency and scope of future joint ac- outlines initial aim in examining 1) economic assessment (of Zynteglo®) tions will be interesting to watch.

Initiatives in Development

The European Commission (EC), Eu- would require joint clinical assess- ropean Medicines Agency (EMA), and ment for drugs submitted for a central Heads of Medicines Agencies (HMA) EU Regulation on HTA marketing authorisation.21 However, it published strategies in 2020 that aim has taken three years for the proposal to promote and facilitate EU-wide The EU regulation on HTA is a recent to move into negotiations between cooperation. The EC is also still in the example of lengthy negotiations within the European Parliament and Council. process of negotiating an EU-wide the EU. Proposed by the EC in 2018 The original regulation has also been regulation on HTA. (see our European market access adapted to increase flexibility for landscape paper), this legislation member states and reduce its abil-

An Overview of Cross-Border Collaborations on HTA, Pricing Negotiation, and Procurement

ity to ensure a common approach.22 effectiveness, payment, procurement agencies to support further collabora- Moreover, even if agreement is policies and affordability−including tion with and between HTAs across reached, the requirements would only of cancer treatment.”24 The strategy Europe, as well as information shar- be phased in over an eight-year period, also supports a pan-European HTA, ing and transparency across borders with cancer therapies the first to be through the EU regulation on HTA. The in general. Strategic goals include slated for joint assessments. strategy has been adopted by the EC working with HTA bodies and payers and includes plans for legislative and on evidence generation, including pre- non-legislative action. planning of post-licencing evidence generation. The strategy also indicates EC Pharmaceutical Strategy that the EU regulation on HTA would 23 for Europe support the strategic objectives of the European Medicines Agen- EMA and HMA. As part of this strategy, the EC pro- cies Network Strategy to While these strategies and regula- poses EU-level cooperation on pricing 202525 tion could result in major changes for and reimbursement, with “payers the pharma industry, they will likely to exchange information on sustain- Part of this strategy indicates the take many years to implement and able health systems, pricing, cost- intention of the European medicines need to overcome significant hurdles.

Additional Initiatives to Watch

Beyond the initiatives described of the first memorandum. gotiations. However, it has not yet above, there are many other cross- performed any joint assessments or border collaborations related to market What’s next?: FaAP is looking to set negotiations.31 access. We describe a few examples up pilot negotiations,28 but does not below. appear to have initiated any yet. What’s next?: It remains to be seen how successful the collaboration will be, though it has taken a strong

29 stance on price transparency and is The Visegrád Group - “Fair and The Valletta Declaration looking for ways to achieve this across 26 Affordable Pricing” FaAP borders. About: Initiated in 2017, the Valletta About: Set up in 2016/2017, FaAP now Declaration has now been joined by includes Poland, the Czech Repub- 10 European countries, primarily in the lic, Hungary, Slovakia (the V4), and south and east (Cyprus, Greece, Italy, International Horizon Scanning Lithuania. FaAP plans to focus on the Malta, Portugal, Spain, Croatia, Ireland, Initiative (IHSI)32 exchange of information on pricing Romania, and Slovenia), making up and reimbursement, joint price nego- over 30% of the EU population.30 The About: Initiated by the Beneluxa initia- tiations, and joint HTA assessments group is interested in horizon scan- tive in 2019, IHSI aims to develop a (specifically of high-cost treatments).27 ning, sharing information on pricing, database that brings together publicly joint negotiations and joint HTA as- available information on medicines to Recent news: The Ministers of Health sessments. provide member states (Netherlands, for each country signed a memoran- Belgium, Ireland, Denmark, Luxem- dum of understanding in 2017, and Recent news: The group has identi- bourg, Norway, Portugal, Sweden and then again in 2019 following expiration fied target treatments for joint ne- Switzerland), payers, and regulators

An Overview of Cross-Border Collaborations on HTA, Pricing Negotiation, and Procurement

insights on upcoming treatments that make use of it remains to be seen. real-world data (RWD) can be collect- will support their decision making. ed for highly innovative technologies – when, by whom and how – in order

Recent news: The IHSI began the 34 to generate real-world evidence (RWE) tender process to find a third-party to RWE4Decisions that informs decisions by healthcare build their database in early 2020. Se- systems, clinicians and patients.” About: Initiated by the Belgian Na- lection of a partner is expected in Q2 tional Institute of Health and Disability 2021, with the first datasets available What’s next?: RWE4Decisions is Insurance in 2020, RWE4Decisions in early 2022.33 aiming to drive policy changes at the brings together European policy-mak- European and national levels. We will ers, HTA bodies, payers, regulatory What’s next?: The impact of the data- explore RWE and potential implica- agencies, patient groups, academics, base and whether member states will tions for biopharma in a future article. clinicians, and industry to “agree what

Unofficial Price Referencing

Referencing HE Models from ing joint HTA and price negotiations: Other Countries Biopharma companies should Implications for the a. Prepare for the need to provide About: Health Economics models, Biopharma Industry greater support (e.g., access / especially those published by leading health economics expertise, local HTA agencies (e.g., NICE), provide Cross-border changes in Europe could data generation) from global or a benchmark for other countries to bring both benefits and challenges for regional offices. calibrate their own price expectations. biopharma companies, from increased b. Enable knowledge and best Payers in France and Germany for ex- price transparency that impacts ne- practice sharing among affiliates ample, have both reported leveraging gotiations to joint HTA assessments engaging or likely to engage with NICE models during price negotiations that could streamline processes and cross-border initiatives (e.g., learn with biopharma. alter evidence requirements. While from the Beneluxa experiences some changes, especially those at a to date and consider what inter- Recent news: Publication of the EU-wide level, will take a long time nal adaptations are needed). Zolgensma evaluation by the Beneluxa to implement, other initiatives (e.g., 2. Increased official or unofficial price initiative and public statements by ZIN Beneluxa) are demonstrating early referencing: Biopharma companies on price expectations now provide success and establishing a precedent should additional benchmarks for smaller EU for other countries interested in joining a. Monitor for the need to adjust countries interested in a benchmark or following. launch sequencing. closer to their own health system and Publication of joint evaluation b. Conduct scenario planning and budget needs. results—and public statements on establish contingency plans for price discounts and payment require- IRP What’s next?: While “official” initia- ments—are likely to support other c. Develop a proactive plan for tives take significant time and effort countries in their price negotiations, managed entry agreements that to progress, adoption of unofficial regardless of whether they participate speaks to the value of the prod- price referencing faces few barriers to directly in a cross-border collaboration. uct (we will explore this topic in implementation. With the increasing Below, we provide a short outline of more detail in a later publication). number of ATMPs coming to market, potential implications for biopharma 3. EU-wide initiatives e.g., HTA har- we expect payers to increasingly companies. monization, evidence generation leverage these methods to manage requirements: budgets. 1. Small groups of countries conduct- a. While changes are longer-term

An Overview of Cross-Border Collaborations on HTA, Pricing Negotiation, and Procurement

and likely to be phased in, policy- RWE) should also facilitate the ly, and leveraging the cross-functional level engagement via industry eventual adoption of broader HTA team’s expertise to address access bodies such as the EFPIA are alignment. challenges are critical to the success important to ensure a two-way of products and portfolios. In future dialogue and that biopharma con- Overall, per evidence requirements articles, we will continue to explore cerns are heard. and price- or budget-impact sensitivity these challenges and opportunities, b. Working to establish standards are both evolving. Proactively incorpo- and what market access functions can for—and improve the quality of— rating payer evidence needs from the do to maximize value for patients, pay- individual types of evidence (e.g., start, developing access solutions ear- ers and biopharma companies.

Acronyms

EC European Commission HMA Heads of Medicines Agencies RWD Real World Data EMA European Medicines Agency HTA Health Technology Assessment RWE Real World Evidence FaAP Fair and Affordable Pricing IHSI International Horizon Scanning Initiative

References

1 https://www.eunethta.eu/eunethta-project-2006-2008/ 2 https://www.efpia.eu/media/361736/cra-efpia-learnings-from-the-first-three-eunethta-joint-action-3-assessments-final-report.pdf 3 https://eunethta.foleon.com/eunethta-winter-2021/winter-2021/eunethta-overview/ 4 https://eunethta.eu/ja3-archive/work-package-7-national-implementation-and-impact/ 5 Kanavos, P., Angelis, A. & Drummond, M. An EU-wide approach to HTA: An irrelevant development or an opportunity not to be missed?. Eur J Health Econ 20, 329–332 (2019). https://doi.org/10.1007/s10198-019-01037-2 6 https://beneluxa.org/collaboration 7 https://pharmaboardroom.com/articles/cross-country-collaborations-in-europe-the-future-of-pricing-access-negotiations/ 8 https://beneluxa.org/news3 9 https://www.zorginstituutnederland.nl/actueel/nieuws/2021/05/07/medicijn-zolgensma-voor-zeldzame-spierziekte-sma-alleen-in-basispakket-na-prijson- derhandeling 10 https://amgros.dk/media/3160/statement-beneluxa-og-nordisk-laegemiddelforum.pdf 11 https://amgros.dk/en/about-amgros/cooperation-partners/international-cooperation/ 12 https://www.infarmed.pt/documents/15786/2835945/Flemming%2bSonne%2b_Abs.pdf/522ce638-2712-46db-ac4e-5a01549610f7 13 https://www.tlv.se/in-english/international-collaboration/finose---a-nordic-cooperation.html 14 https://pharmaboardroom.com/articles/cross-country-collaborations-in-europe-the-future-of-pricing-access-negotiations/ 15 https://amgros.dk/en/knowledge-and-analyses/articles/all-the-agreements-in-the-first-joint-nordic-tendering-procedure-are-in-place/ 16 https://pharmaboardroom.com/articles/cross-country-collaborations-in-europe-the-future-of-pricing-access-negotiations/ 17 https://amgros.dk/en/knowledge-and-analyses/articles/all-the-agreements-in-the-first-joint-nordic-tendering-procedure-are-in-place/ 18 “How can voluntary cross-border collaboration in public procurement improve access to health technologies in Europe?” Policy Brief, No. 21. Espín J, Rovira J, Calleja Aet al., European Observatory on Health Systems and Policies; 2016. https://www.ncbi.nlm.nih.gov/books/NBK464528/ 19 https://amgros.dk/en/knowledge-and-analyses/articles/all-the-agreements-in-the-first-joint-nordic-tendering-procedure-are-in-place/ 20 https://www.baltictimes.com/latvia_to_purchase_vaccines_jointly_with_baltic_neighbors/ 21 https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A52018PC0051 22 https://www.efpia.eu/news-events/the-efpia-view/statements-press-releases/efpia-statement-in-response-to-the-council-compromise-agreement-on- the-commission-proposal-for-a-regulation-on-health-technology-assessment/ 23 https://ec.europa.eu/commission/presscorner/detail/en/ip_20_2173 24 https://ec.europa.eu/health/human-use/strategy/affordable_medicines_en 25 https://www.ema.europa.eu/en/documents/report/european-union-medicines-agencies-network-strategy-2025-protecting-public-health-time-rapid- change_en.pdf#page=17&zoom=100,0,0 26 https://www.gov.pl/web/zdrowie/faap 27 Cross-country collaborations to improve access to medicines and vaccines in the WHO European Region. Copenhagen: WHO; 2020 (https://www. euro.who.int/en/publications/abstracts/cross-country-collaborations-to-improve-access-to-medicines-and-vaccines-in-the-who-european-region-2020) 28 Cross-country collaborations to improve access to medicines and vaccines in the WHO European Region. Copenhagen: WHO; 2020 (https://www. euro.who.int/en/publications/abstracts/cross-country-collaborations-to-improve-access-to-medicines-and-vaccines-in-the-who-european-region-2020) 29 https://timesofmalta.com/articles/view/10-eu-countries-fighting-for-better-deals-on-medicine-prices.721318 30 Cross-country collaborations to improve access to medicines and vaccines in the WHO European Region. Copenhagen: WHO; 2020 (https://www. euro.who.int/en/publications/abstracts/cross-country-collaborations-to-improve-access-to-medicines-and-vaccines-in-the-who-european-region-2020) 31 https://pharmaboardroom.com/articles/cross-country-collaborations-in-europe-the-future-of-pricing-access-negotiations/ 32 https://ihsi-health.org/mission/ 33 https://ihsi-health.org/tender/ 34 https://rwe4decisions.com/about-us/

New Ideas. Better Results.

Blue Matter is a consulting firm serving the life sciences industry. We strive to bring a new approach to consulting with original ideas that deliver a meaningful impact.

This paper authored by Thomas Quirk Yan Xue, Ph.D. Eleanor Berry, DPhil Kathryn Acheson, DPhil

San Francisco London Berlin [email protected] [email protected] [email protected] 400 Oyster Point Blvd. 6th Floor Potsdamer Platz - Suite 309 75 Farringdon Road Kemperplatz 1 South San Francisco, CA 94080 London EC1M 3JY Berlin Mitte, 10785 650-754-6817 UK Germany

New York Zurich [email protected] [email protected] 575 Lexington Avenue Walchestrasse 9 Suite 24A 8006 Zurich New York, NY 10022 Switzerland www.bluematterconsulting.com