LUGANO, Switzerland – Access to cancer medicines is highly unequal across Europe both for new drugs in development because of uneven access to clinical trials and for currently approved drugs due to huge disparities in healthcare spending by different countries, according to results from studies presented at ESMO 2020. (1, 2)
Countries in Western Europe run a higher number of clinical trials for novel cancer treatments than countries in Eastern and Central Europe, showed an analysis of clinical trials active in different countries (1) that indicated large differences in access to new treatments in development for cancer patients depending on where they live.
“Our study gives us proof of what we previously suspected, that there is a huge asymmetry in the number of clinical trials for cancer treatments in different countries,” said study co-author Dr Teresa Amaral, from University Hospital Tubingen, Germany.
“Having access to clinical trials confers several benefits to cancer patients. It means they can potentially access novel therapies earlier during the trial phase rather than having to wait for licensing and reimbursement,” she explained. “Also, all trial participants benefit from the regular follow-up and monitoring involved in taking part in a clinical study.”
The researchers searched the Clinicaltrials.gov database for interventional clinical trials in adults with tumours between 2009 and 2019. Analysing the number of trials in 34 European countries revealed huge differences. Albania had the lowest number of active clinical trials for cancer (0.14 clinical trials per 100 000 population) while Belgium had the highest number (11.06 per 100 000).
Further results showed that the total number of oncology clinical trials performed in European countries increased by 33% between 2010 and 2018, with a much greater increase in early phase trials (61% increase in phase I-II trials) than late-phase trials (7% increase in phase II-III trials).
Amaral suggested that this might be due to a shift in clinical trial design: “There is no longer a clear progression from first-in-human studies to phase 1, phase 2 and then much larger phase 3 trials. Instead we tend to have more trials in earlier phases, namely phase II, which might expand to later phases.”
The increase in early phase trials was again asymmetrical and the growth rate depended on the baseline number of trials. “Countries need to have the necessary infrastructure and expertise to conduct trials of any type, including early phase trials.”
“A higher number of phase I trials is a sign of more active research going on in a particular country, with the appropriate infrastructure and necessary incentives to conduct clinical trials,” said Thomas Cerny, Professor of medical oncology at the University of Berne, Switzerland and member of the ESMO Principles of Clinical Trials and Systemic Therapy Faculty. "And the only way to develop new cancer drugs is to be able to put patients into clinical trials,” he added.
“The difference in the number of clinical trials per head of population, with more trials in wealthier countries, means access to clinical trials and innovative drugs is just not possible for cancer patients living in many less wealthy countries.” Although the study is descriptive, he considered it made best use of the available data to evaluate differences in clinical trial availability in different countries.
He added: “Clinical studies require a solid infrastructure in terms of personnel and equipment, and this depends on a country’s overall financial situation. These requirements are increasing so the gap in clinical trial capacity is not likely to reduce soon.”
“There is still a lot to do to increase access to clinical trials for cancer patients in different countries,” agreed Amaral. “The voluntary harmonisation procedure, in which trial sponsors can submit trial documentation to several countries at the same time, has streamlined the process and reduced the approval time for trials. But more is needed to increase access to clinical trials in countries where the number of trials is currently low.” The research group is currently exploring the reasons for the asymmetry to inform potential solutions.
A health economics analysis also reported at ESMO 2020 showed that wealthier European countries spent ten times as much as poorer countries per inhabitant on cancer medicines in 2018, following a similar pattern to that seen for clinical trials. (2)
“There was a huge difference in spending on cancer medicines,” said lead author Dr Nils Wilking, from the Karolinska Instituet, Stockholm, Sweden. “We found that inequalities are mainly related to countries’ economic strength and not to the disease burden of cancer.”
The researchers estimated cancer-specific health expenditure for 31 countries (EU-27 plus Iceland, Norway, Switzerland and the UK) using national figures for 2018. Results showed the top spenders on cancer medicines were Austria, Germany and Switzerland (Euros 90 to 108 per capita) while the lowest spenders were the Czech Republic, Latvia and Poland (Euros 13 to 16). The largest differences in spending between countries were seen for immuno-oncology drugs.
“There are two main factors accounting for the differences in spending on cancer medicines: one is shortage of money and the other is drugs not being approved for use by some healthcare systems,” suggested Wilking. He noted that, although the study did not consider data at the individual patient level, the difference observed in access to cancer medicines would affect patient outcomes.
Cerny commented: “It is difficult to assess the real costs in any country because systems vary in different countries and there are many hidden costs not reflected in the databases used. But the study essentially shows the more a country has to spend, the more its inhabitants have access to cancer medicines.”
Considering how to widen access to cancer medicines, Wilking suggested: “We need a model in which we incentivise innovation of valuable medicines through outcome-based payment models and consider a disease area and what a society is able to pay for treatment.” He added: “The work of health technology assessment organisations has been important and a critical scrutiny and evaluation of new drugs should always be applied.”
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References
- Abstract LBA66_PR ‘Disparities in access to oncology clinical trials in Europe in the period 2009-2019’ will be presented by Ana Carneiro during the Proffered paper session “Public Policy” on Monday, 21 September 2020, 14:25-16:05 CEST. Annals of Oncology, Volume 31 Supplement 4, September 2020
- Abstract 1588MO_PR ‘A comparative study on costs of cancer and access to medicines in Europe’ will be presented by Niels Wilking during the Mini Oral session “Public Policy” available on demand as of Friday, 18 September at 09:00 CEST. Annals of Oncology, Volume 31 Supplement 4, September 2020
A. Carneiro1, T.M.S. Amaral2, M. Brandao3, M. Scheffler4, K. Bol5, R. Ferrara6, M. Jalving7, G. Lo Russo8, I. Marquez-Rodas9, A. Matikas10, L. Mezquita11, G. Morgan12, C.E. Onesti13, S. Pilotto14, E. Saloustros15, D. Trapani16
1Department of Clinical Sciences Lund, Oncology, Lund University, Skane University Hospital, Lund, Sweden, 2Dermatooncology Center, University Hospital Tubingen, Tuebingen, PT, Germany, 3Clinical Trial Support Unit, Institute Jules Bordet, Brussels, Belgium, 4Lung Cancer Group Cologne, Department I of Internal Medicine, Uniklinik Köln, Cologne, Germany, 5Medical Oncology Department, Herlev Hospital - National Center for Cancer Immune Therapy, Herlev, Denmark, 6Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy, 7Department of Medical Oncology, University Medical Center Groningen, Groningen, Netherlands, 8Dipartimento Oncologia Toraco-Polmonare, Istituto Nazionale dei Tumori di Milano - Fondazione IRCCS, Milan, Italy, 9Medical Oncology, Hospital General Universitario Gregorio Marañon - Fundación Investigación Biomedica, Madrid, Spain, 10Oncology-Pathology Department, Karolinska University Hospital-Solna, Stockholm, Sweden, 11Medical Oncology Department, Hospital Clinic y Provincial de Barcelona, Barcelona, Spain, 12Oncology, Skane University Hospital, Lund, Sweden, 13Medical Oncology department, Centre Hospitalier Universitaire Sart Tilman, Liège, Belgium, 14Section of Oncology, Department of Medicine, University of Verona School of Medicine and Verona University Hospital Trust, Verona, Italy, 15Department of Oncology, University Hospital of Larissa, Larissa, Greece, 16IRCCS, Istituto Europeo di Oncologia, Milan, Italy
Background: Clinical trials are essential for advancing cancer treatment. Yet, there is limited data on their distribution and access in Europe. To ascertain the extent of potential inequalities in access to clinical trials in Europe, we compared their distribution among European countries.
Methods: The Clinicaltrials.gov database was searched for interventional clinical trials in adults with neoplasms. Available data from phase I-III trials between 06/2009 to 06/2019 in Europe were retrieved. We considered the number of clinical trials registered in each country and one “trial-entry” was defined as one trial/country.
Results: In total, 18454 trial-entries were identified, of which 12% were phase I, 10% phase I/II, 32% phase II, 2% phase II/III and 44% phase III; 74% were industry-sponsored, 15% were academic and 11% were an academic/industry partnership. The number of trials per country varied from 2.48 in Central/Eastern Europe to 5.33/100 000 inhabitants in Northern Europe. The proportion of phase I-II trials was higher in the Southern and Western regions (13-15%) compared to Central/Eastern and Northern regions (4-9%). The number of trial-entries/100 000 inhabitants/country ranged from 0.14 (Albania) to 10.7 (Belgium). Between 2010 and 2018, the total number of trials per country in Europe increased by 33%. The increase in early-phase trials was larger (phase I-II, 61%) than in late-phase trials (phase II-III, 7%). Portugal, Ireland, Finland, Greece and Norway registered the largest percentage increase in early-phase trials, while Ireland, Spain, Norway, Italy and Belgium led the largest percentage increase in late-phase trials. Five countries dominated in terms of an increase in the absolute number of total trial-entries in both early- and late-phase trials: Spain (90/40), France (45/16), UK (45/13), Italy (38/19) and Belgium (35/12). During this period there was no significant variation in the distribution of industry and academic sponsored trials but an increase in industry/academic partnerships was observed (≈ 8%).
Conclusions: The number of clinical trials varies greatly among European regions resulting in potential asymmetries in patients' access to clinical trials. The disparities in access to oncology trials need to be addressed by all the stakeholders.
Legal entity responsible for the study: The authors
Funding: Has not received any funding
Disclosure: T.M.S. Amaral: Honoraria (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Travel/Accommodation/Expenses: BMS; Honoraria (self): Pierre Fabre; Honoraria (self): CeCaVa.
M. Brandao: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche/GNE.
M. Scheffler: Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim, AMGEN, AstraZeneca, BMS, Roche, Pfizer, Takeda; Research grant/Funding (self): AMGEN, Dracen.
R. Ferrara: Advisory/Consultancy: MSD.
M. Jalving: Advisory/Consultancy: MERCK, BMS, NOVARTIS, PIERRE FABRE, TESARO, ASTRA ZENECA; Research grant/Funding (self): BMS, ABBVIE, MERCK, CRISTAL THERAPEUTICS.
G. Lo Russo: Advisory/Consultancy: MSD, BMS, ASTRAZENECA; Travel/Accommodation/Expenses: BMS, ROCHE.
I. Marquez-Rodas: Advisory/Consultancy: BMS, MSD, NOVARTIS, ROCHE, PIERRE FABRE, AMGEN, ASTRA ZENECA, REGENERON, SANOFI, HIGHLIGHT THERAPEUTICS, INCYTE, GSK.
L. Mezquita: Research grant/Funding (self): Bristol-Myers Squibb, Boehringer Ingelheim; Non-remunerated activity/ies, Lectures and educational activities: Bristol-Myers Squibb, Tecnofarma, AstraZeneca, Roche; Advisory/Consultancy: Roche Diagnostics, Roche; Travel/Accommodation/Expenses: Bristol-Myers Squibb, Roche; Research grant/Funding (self), International Mentorship Program : AstraZeneca.
S. Pilotto: Advisory/Consultancy, Speaker Bureau/Expert testimony: Astra-Zeneca, Eli-Lilly, BMS, Boehringer Ingelheim, MSD and Roche.
E. Saloustros: Advisory/Consultancy: Pfizer, AstraZeneca, Roche; Speaker Bureau/Expert testimony: Pfizer, AstraZeneca, Roche, Amgen, BMS.
All other authors have declared no conflicts of interest.
N. Wilking1, G. Brådvik2, P. Lindgren3, C. Svedman2, B. Jönsson4, T. Hofmarcher5
1Oncology and pathology, Karolinska Institutet, Stockholm, Sweden, 2The Swedish Institute for Health Economics, Lund, Sweden, 3Karolinska Institutet, The Swedish Institute for Health Economics, Lund, Sweden, 4Economics, Stockholm School of Economics, Stockholm, Sweden, 5Lund University, The Swedish Institute for Health Economics, Lund, Sweden
Background: Costs and value of new cancer treatments are often causing headlines without being discussed in a larger context. This study estimates the cost of cancer and access to medicines in Europe in 2018 and extends a previous analysis for 1995–2014.
Methods: Cancer-specific health expenditure for 31 countries (EU-27 plus Iceland, Norway, Switzerland, and the UK) were derived from national estimates. Data on cancer drug sales were obtained from IQVIA. Productivity loss from premature mortality was estimated from data from Eurostat and the WHO. Productivity loss from morbidity and informal care costs were estimated based on previous studies.
Results: The total cost of cancer was €199 billion in 2018. Total costs ranged from €160 per capita in Romania to €578 in Switzerland (after adjustment for price differentials). Health expenditure on cancer care were €103 billion, of which €32 billion were spent on cancer drugs. Informal care costs were €26 billion. The total productivity loss was €70 billion, composed of €50 billion from premature mortality and €20 billion from morbidity. Patient access to cancer medicines was much greater in wealthier than poorer countries in 2018, in terms of value and volume. The top spenders were Austria, Germany, and Switzerland (€92 to €108 per capita), whereas Czech Republic, Latvia, and Poland spent the least (€13 to €16). The largest country differences were seen in immuno-oncology medicines. Between 1995 and 2018, cancer incidence increased by 50% in Europe, but cancer mortality increased only by 20%. Health spending on cancer doubled from €52 billion to €103 billion (in 2018 prices and exchange rates), but the share of cancer care on the total health expenditure remained stable at around 4–7%. A shift from treatment in inpatient care to ambulatory care has likely saved costs. Expenditure on cancer medicines tripled from €10 billion to €32 billion between 2005 and 2018 (excluding confidential rebates). Productivity loss from premature mortality decreased over time, linked to mortality reductions in working-age patients.
Conclusions: There are large and persistent country differences in spending on cancer care, access to new cancer medicines and outcomes in Europe. Inequalities are mainly related to countries’ economic strength and not to the disease burden of cancer.
Legal entity responsible for the study: The Swedish Institute for Health Economics, Lund, Sweden
Funding: European Federation of Pharmaceutical Industries and Associations (EFPIA), Brussels, Belgium (unrestricted grant)
Disclosure: N. Wilking: Advisory/Consultancy, This study has been supported by an unrestricted grant from EFPIA: Bayer, BMS, EFPIA,Eisai, Oasmia, Roche, Sanofi,.
G. Brådvik: Advisory/Consultancy, IHE conducts research and evaluations for a large number of for-profit health care companies: IHE and EFPIA (unrestricited grant).
P. Lindgren: Advisory/Consultancy, IHE conducts research and evaluations for a large number of for-profit health care companies: IHE and EFPIA (unrestricted grant).
C. Svedman: Advisory/Consultancy, IHE conducts research and evaluations for a large number of for-profit health care companies: IHE and EFPIA (unrestricted grant).
B. Jönsson: Advisory/Consultancy, IHE and EFPIA (unrestricted grant): Bayer, BMS, AZ, Allergan, Celgene, Jansen, Takeda, Vifor, Pfizer, Novartis.
T. Hofmarcher: Advisory/Consultancy, IHE conducts research and evaluations for a large number of for-profit health care companies: IHE and EFPIA (unrestricted grant).