Accessibility to cancer medicines in Europe - Towards equitable access and fair pricing
Julie Vancoppenolle is a PhD student in the Department of Health Technology & Services Research. (Co)Promotors are prof.dr. W.H. van Harten from the Faculty of Behavioural, Management and Social Science, prof. dr. V.P.R. Retèl from NKI Netherlands Cancer Institute and dr. N. Franzen from the Erasmus University Rotterdam.
Ensuring equitable access to novel cancer medicines remains a key challenge across Europe, as expenditure on cancer treatments continues to rise. Evidence-based interventions are essential for improving affordability while maintaining pharmaceutical innovation, thereby ensuring timely access to safe and effective treatments in Europe. In this dissertation, we examine disparities in access to cancer medicines across Europe from the perspectives of patients, healthcare practitioners, and national authorities. By assessing the current pharmaceutical landscape and proposing recommendations, this dissertation aims to support efforts towards fairer accessibility and pricing of cancer care.
In the first part of this dissertation, we explored disparities in patient access to cancer treatments. Variations in accessibility of novel cancer medicines were assessed, considering different access pathways, indications, and national contexts. In Chapter 2, we presented findings from a cross- sectional survey with hospital pharmacists in nineteen hospitals across six European countries (Hungary, Italy, the Netherlands, Belgium, Switzerland, and France). First patient access to six novel cancer medicines and their indications were collected through hospital databases. Our findings reveal substantial heterogeneity in patient access at hospital level, with specialized hospitals (x̄: -0.9 years; SD: 2.0) more likely to provide access before national reimbursement than general hospitals (x̄: 0.4 years; SD: 2.9). Additionally, we found that combination therapies were generally less accessible than monotherapies, with accessibility varying across hospitals and countries. These findings underscore the need for harmonized national policies that optimize pricing and reimbursement timelines, promote collaboration between health authorities and market authorization holders, and implement harmonized early access programs to stimulate equitable access.
As treatment paradigms evolve, the increasing use of targeted combination therapies (TCTs) introduces new complexities in pricing and reimbursement processes. Existing regulatory frameworks are primarily designed for monotherapies and have been slow to adapt. We explored access to 23 TCTs for advanced melanoma and lung cancer, as reported by 19 specialists from 17 leading cancer institutions in nine European countries (Chapter 3). Our findings highlight country-specific regulatory differences, varying levels of clinical trial implementation, and inconsistent access to combination therapies, particularly when different manufacturers are involved. We emphasize the need for updated regulatory frameworks that better accommodate combination therapies and promote their evidence-based and authorized use.
In the second part of this dissertation, the focus shifts to the pricing aspect of accessibility. Due to confidentially negotiated discounts, actual cancer medicine prices are often unknown, highlighting the need for greater transparency in price reporting. We provide an overview of mechanisms and stakeholders involved in price negotiations as well as pricing and expenditure information at national and hospital level.
Managed entry agreements (MEAs) have become a key instrument in national price negotiations for expensive treatments across European countries. Using desk research and interviews with public negotiators, we examined the mechanisms and stakeholders involved in MEA negotiations to identify trends in reporting practices (Chapter 4). We found that MEA decision-making structures vary across Europe, ranging from single government agencies to multiple negotiating bodies. We demonstrated that MEA implementation has increased substantially since 2016, particularly in Belgium and Norway. Total expenditure reductions varied across countries, ranging from €0.04 billion in Slovakia to €5.68 billion in France. Similarly, reported discounts ranged from 3% to 54%, reflecting differences in scope of MEAs across countries. Differences in legal frameworks, decision-making structures, and definitions hinder cross-country comparisons. As MEAs become more widespread, price transparency continues to decline. We recommend establishing standardized reporting requirements to enhance transparency, accountability, and the effectiveness of MEAs in Europe.
In addition to national negotiations through MEAs, medicine prices can also be (re)negotiated at hospital level. Through structured interviews with hospital staff, we collected and analyzed actual price data and discounts for 15 novel cancer medicines across 23 hospitals in nine European countries (Chapter 5). Our findings reveal substantial pricing disparities, with the highest hospital-level prices observed in France, followed by Serbia, Germany, Hungary, and the Netherlands. In contrast, hospitals in Southern Europe reported the lowest prices. The largest price variation was observed for ribociclib (Difference: 183%), while the smallest variation was observed for daratumumab (Difference: 27%). The fragmentation of price negotiations, coupled with confidential discount agreements, complicated international price comparisons. While hospitals employ various price reduction strategies, these efforts remain inconsistent across Europe. We recommend implementing standardized price reporting guidelines to facilitate informed price negotiations and strengthen hospital collaboration on pricing strategies, ultimately improving negotiation outcomes.
While the cost of cancer care is often debated and analyzed from the perspectives of authorities and payers, we shift the focus in the third part of this dissertation to the patient's perspective. Through the SocioEconomic impact of Cancer (SEC) study, a cross-sectional European study conducted in 25 countries (N=3157), we aimed to explore socio-economic impact and financial toxicity of cancer from the patient perspective (Chapter 6 and 7). A 44-item survey was developed to measure the socio- economic impact following a cancer diagnosis. The primary outcome was the level of financial toxicity, measured by the Financial Index of Toxicity-score (FIT).
In Chapter 6, we focused on patients who were currently undergoing treatment or had received treatment within the past two years were included (N=2507). To identify vulnerable groups, multiple regression analyses were used to investigate the association between the FIT-score, clinical characteristics, and socioeconomic demographics. Next to a significant association of the country of residence, our regression models demonstrated that divorced, self-employed patients who were younger (-0.02; P<0.000), lower educated (0.75; P<0.000) with lower household income (1.21; P<0.000) and children (0.21; P<0.000) at the time of diagnosis reported significantly higher financial toxicity compared to older patients who were married (-0.56; P<0.000), retired (-1.55; P<0.000) or employed (-0.56; P<0.000). We recommend enhancing health insurance coverage, strengthening local support systems, and improving employment protections to reduce the financial burden of a cancer diagnosis, especially for vulnerable groups. Additionally, further research on socio-economic impact and public awareness campaigns should be prioritized to inform evidence-based policies and support initiatives.
As a follow-up study (Chapter 7), we narrowed the focus to adolescents and young adults (AYAs, aged 15-39). A sub-analysis of the SEC-AYA population (N=577) was conducted, alongside a survey of healthcare practitioners (N=41) to contextualize the SEC-AYA data and identify national and local support systems. Our findings from our sub-analysis indicated that 79% of AYAs experienced financial difficulties, while 65% reported income loss. Additionally, 70% took measures to increase financial resources, such as using savings or borrowing money, to cover treatment-related expenses. Furthermore, 40% faced challenges in accessing financial services, including mortgages. Our findings from the survey with the healthcare practitioners revealed that while 54% of them routinely discussed financial difficulties with AYAs, 68% remained unaware of the financial challenges faced by this group. Moreover, existing services for treatment-related income loss, work reintegration, and financial support were often not tailored specifically to AYAs. Our findings highlight the importance of expanding support mechanisms, not only for AYAs but also for other vulnerable patient populations.
In the last part of this dissertation, the considerations from previous chapters are discussed, leading to the formulation of recommendations and future research (Chapter 8):
- Establish harmonized EU-wide regulations for pre-registered access to ensure equitable implementation across Member States, with clear eligibility criteria, transparent oversight to prevent misuse in pricing negotiations, and stricter guidelines requiring strong benefit-risk profiles and substantial evidence, ultimately reducing disparities and promoting safe and timely access.
- Further research is required to evaluate the effectiveness of market entry agreements across Europe. More (aggregated) harmonized reporting mechanisms are essential to facilitate the assessment of effectiveness of market entry agreements, allowing for cross-country comparisons.
- Real-world evidence collected through early access programs and managed entry agreements should complement clinical trial data in health technology assessments, and assist in price (re)negotiations determining a fair price based on the real world efficacy of a medicine.
- External reference pricing should be discontinued as a baseline for price negotiations, as it incentivizes artificial pricing, strategic market launches and delays patient access.
- Further research is needed to determine the optimal level and format of price transparency to stimulate affordability and equity while safeguarding competition and increase market efficiency, ensuring medicine availability across product types, maintaining the EU’s attractiveness.
- Develop an improved, validated instrument to identify vulnerable cancer patients, adaptable across national and international contexts allowing for cross-country comparison in Europe. Use the data to create evidence-based policies and interventions that reduce the socio-economic impact of cancer and provide targeted support to vulnerable patient populations. Assign a dedicated stakeholder in each facility to connect patients with the necessary financial and social resources and supporting organizations.
