Time to reimbursement of novel anticancer drugs in Europe: a case study of seven European countries

Abstract

Background: Time to reimbursement (TTR) of new anticancer medicines differs between countries and contributes to unequal access. We aimed to investigate TTR of new anticancer medicines and explore factors influencing the reimbursement process in seven high-income European countries.

Materials and methods: We carried out a retrospective case study of anticancer medicines with European Union Market Access (EU-MA) and a positive Committee for Medicinal Products for Human Use opinion from 2016 until 2021 with subsequent national reimbursement approval (NRA). The National Health Technology Assessment (HTA) and reimbursement websites of Germany, France, UK, the Netherlands, Belgium, Norway and Switzerland were used to identify TTR, defined as time from EU-MA to NRA. Additionally, we investigated medication-, country-, indication- and pharma-related factors potentially influencing TTR.

Results: Thirty-five medicines were identified for which TTR ranged from -81 days to 2320 days (median 407 days). At data cut-off, 16 (46%) were reimbursed in all seven countries. Overall, the shortest TTR was in Germany (median 3 days, all medicines reimbursed <5 days). The time limit for reimbursement of 180 days stated by the Council of European Communities after the EU-MA (EU Transparency Directive) was met for 100% of included medicines in Germany, 51% in France, 29% in the UK and the Netherlands, 14% in Switzerland, 6% in Norway and 3% in Belgium. The TTR was significantly different between countries (P < 0.001). In multivariate analysis, factors associated with shorter TTR were higher gross domestic product (GDP), absence of a pre-assessment procedure and submission by a big pharmaceutical company.

Conclusions: TTR of anticancer medicines varies significantly between seven high-income European countries and leads to inequality in access. Among explored medication-, country-, indication- and pharma-related factors we found that a high GDP, the absence of a pre-assessment procedure and submission by big pharmaceutical companies were associated with shorter TTR.

Keywords: anticancer medicines; drug access; inequality; regulatory approval; reimbursement.

Figure 1

Kaplan–Meyer curve of time to reimbursement in seven high-income European countries in days. mTTR GE = 3 days, FR = 142 days UK = 265 days, NL = 345 days, NO = 628 days, CH = 689 days, BE = 742 days (mTTR and IQR specifically for each country see Table 1, Supplementary Appendix 3, available at https://doi.org/10.1016/j.esmoop.2023.101208). The dotted vertical line at 180 days indicates the Council of European Communities stated time limit for reimbursement of 180 days after EU-MA. The EU Transparency Directive reimbursement time limit of 180 days was met 100% (n = 35) in Germany, 51% (n = 16) in France, 29% (n = 10) in the UK and the Netherlands, 14% (n = 5) in Switzerland, 6% (n = 2) in Norway and 3% (n = 1) in Belgium. GE, Germany; FR, France; UK, the United Kingdom; NL, the Netherlands; NO, Norway; CH, Switzerland; BE, Belgium; IQR, interquartile range; mTTR, median time to reimbursement.

Figure 2

Scatter dot plot of time to national reimbursement from EU-MA per reimbursed new anticancer medicine in the different countries. Median (bar) and interquartile range (error bars, red) displayed. Statistically significant differences exist (tested with Mann–Whitney U tests) and after Bonferroni correction for multiple testing are indicated with an asterisk and described hereafter. GE-UK P < 0.001∗; GE-FR P < 0.001∗; GE-NL P < 0.001∗; GE-NO P < 0.001∗; GE-CH P < 0.001∗; GE-BE P < 0.001∗; FR-NO P < 0.001∗; FR-CH P < 0.001∗; FR-BE P < 0.001∗; UK-NO P = 0.006; UK-CH P = 0.009; BE P < 0.001∗; NL-NO P = 0.004; NL-CH P = 0.006; NL-BE P < 0.001∗. All statistical test results are described in Supplementary Appendix 2, available at https://doi.org/10.1016/j.esmoop.2023.101208. GE, Germany; FR, France; UK, United Kingdom; NL, the Netherlands; NO, Norway; CH, Switzerland; BE, Belgium.

Figure 3

Univariate and multivariate analysis of the different factors. HR, 95% CI and IQR are displayed, together with Kaplan–Meyer curves for reimbursement over time and the different factors. In the Kaplan–Meyer curves, the two medicines registered in Switzerland before EMA-MA were set at 0 days to create the figure. For the factor Country (panels A and B), countries were sorted based on mTTR. In panel 3E, pre-assessment graft seems invisible because it overlaps the y-axis. Three drugs were not assessed by ESMO and no ESMO-MCBS score was available; these three medicines were omitted in the analysis of this factor.CI, confidence interval; ESMO-MCBS, European Society Medical Oncology-Magnitude of Clinical Benefit Scale; HR, hazard ratio; IQR, interquartile range; mTTR, median time to reimbursement.

Figure 4

Time to national reimbursement (TTR) from EU-MA per reimbursed new anticancer medicine in the different countries (GE, Germany; FR, France; UK, United Kingdom; NL, The Netherlands; NO, Norway; CH, Switzerland; BE, Belgium) within the specified sub-categories. Median (bar) and IQR (error bars) are displayed for panels A, B, D, E, F. 95% confidence interval is displayed for panel C (dotted line). Significant differences after correction for multiple testing are displayed (∗) only in categories orphan status (for NO, P = 0.005∗) and company size (for CH, P < 0.001∗ and BE, P = 0.0044∗). Moreover, linear regression showed association between TTR and GDP and can be described in the linear function TTR = −0.0002119xGDP + 727.2 with a good fit (R² = 0.8427; P = 0.0035). All statistical test results are described in Supplementary Appendix 2, available at https://doi.org/10.1016/j.esmoop.2023.101208. AA, accelerated approval; CMA, conditional marketing authorization; ESMO-MCBS, European Society Medical Oncology-Magnitude of Clinical Benefit Scale; GDP, gross domestic product; HR, hazard ratio; IQR, interquartile range.