title: An exploratory analysis of the factors leading to delays in cancer drug reimbursement in the European Union: the trastuzumab case.
abstract: BACKGROUND
  The European Union (EU) has adopted a common procedure for granting marketing authorisation for cancer drugs. Nevertheless, pricing and reimbursement decisions are a competency of EU national governments, and their policies are diverse. We aimed to evaluate the time for trastuzumab reimbursement approval and its association to health expenditure, to health policy performance, to the availability of cost-effectiveness studies and to breast cancer outcome.
  
  
  METHODS
  Breast cancer outcome was estimated by the mortality/incidence (M/I) ratio. Trastuzumab reimbursement approval dates were provided by Roche. Spearman's rank correlation and Wilcoxon rank-sum test were used to evaluate associations and/or differences between the variables studied. Additional analyses were made by grouping countries according to compliance to the 180 day timeframe stipulated in the EU 89/105/EEC Directive for drug pricing and reimbursement.
  
  
  RESULTS
  A statistically significant inverse and strong correlation between breast cancer M/I ratio and health expenditure (r(s)=-0.730, p<0.001) and health policy performance (r(s)=-0.711, p<0.001) was found, meaning the better the score and the higher the expenditure, the fewer patients died after a breast cancer diagnosis. Factors associated with trastuzumab faster reimbursement and compliance to the 89/105/EEC Directive were better health policy score, higher health expenditure and availability of cost-effectiveness studies.
  
  
  CONCLUSIONS
  Higher health policy scores and health expenditure are associated with faster reimbursement of trastuzumab and better breast cancer outcome. Although the study design does not allow inference of causal associations, a marked difference is observed between Eastern and Western Europe, with long delays and increased breast cancer mortality identified in Eastern European countries.
authors.affiliation: Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Boulevard de Waterloo 121 (7th Floor), 1000 Brussels, Belgium.
authors.forename: Felipe
authors.initials: F
authors.lastname: Ades
authors.affiliation: Research Center of Epidemiology, Biostatistics and Clinical Research, School of Public Health, Université Libre de Bruxelles, Campus Erasme - CP598, Route de Lennik 808, 1070 Brussels, Belgium.
authors.forename: Chistelle
authors.initials: C
authors.lastname: Senterre
authors.affiliation: Breast International Group Headquarters (BIG-aisbl), Brussels, Belgium.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Zardavas
authors.affiliation: Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Boulevard de Waterloo 121 (7th Floor), 1000 Brussels, Belgium.
authors.forename: Evandro
authors.initials: E
authors.lastname: de Azambuja
authors.affiliation: Department of Medical Oncology, Hirslanden Clinic Aarau, Schänisweg, 5001 Aarau, Switzerland.
authors.forename: Razvan
authors.initials: R
authors.lastname: Popescu
authors.affiliation: Research Center of Social Approaches of Health, School of Public Health, Université Libre de Bruxelles, Campus Erasme - CP 596, Route de Lennik, 808, 1070 Brussels, Belgium.
authors.forename: Florence
authors.initials: F
authors.lastname: Parent
authors.affiliation: Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Boulevard de Waterloo 121 (7th Floor), 1000 Brussels, Belgium. Electronic address: martine.piccart@bordet.be.
authors.forename: Martine
authors.initials: M
authors.lastname: Piccart
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000191:economics* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000191:economics* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000191:economics*; D017024:Chemotherapy, Adjuvant / Q000191:economics; D003362:Cost-Benefit Analysis; D017277:Drug Approval / Q000191:economics; D005062:European Union / Q000191:economics; D005260:Female; D005102:Health Expenditures / Q000706:statistics & numerical data; D006291:Health Policy / Q000191:economics; D006801:Humans; D009362:Neoplasm Metastasis; D012051:Reimbursement Mechanisms; D013997:Time Factors; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068878:Trastuzumab
keywords: Breast cancer; Drug reimbursement; European Union; Health expenditure; Health policy; Trastuzumab