title: Analysis of endpoints used in marketing authorisations versus value assessments of oncology medicines in Germany.
abstract: OBJECTIVE
  In Germany, a mandatory early benefit assessment (EBA) by the Federal Joint Committee (G-BA) is required for reimbursement of new marketing-authorised medicines. Additional benefit is based on patient-relevant endpoints in mortality, morbidity and health-related quality of life (HRQoL). We aimed to compare endpoints and related benefit categories used in marketing authorisation to those considered by G-BA in the field of oncology.
  
  
  METHODS
  We evaluated EBAs in oncology commencing prior to 31 December 2013. Endpoints for the appropriate medicines, derived from European Medicines Agency's (EMA) Summary of Product Characteristics (SPC), manufacturers' value dossiers and G-BA decisions, were grouped into the three benefit categories.
  
  
  RESULTS
  Of 23 oncology medicines evaluated, primary clinical trial endpoints were included in only 12 G-BA value decisions. Mortality endpoints were generally accepted by EMA and G-BA. However, G-BA excluded 80% of (co-)primary morbidity endpoints. Only 5 SPCs reported HRQoL instruments. G-BA accepted applied instruments in 15 medicines, but the manufacturers' analyses only in 5 medicines, of which 2 indicated an additional benefit.
  
  
  CONCLUSIONS
  Mortality endpoints are accepted by EMA and G-BA. EMA accepted well established and clinically relevant morbidity endpoints (e.g. progression-free survival and response rate), which were mostly excluded by G-BA from their value decisions. The applicability of methods used for benefit assessments to HRQoL differs from the mortality and morbidity categories, and requires further clarification.
authors.affiliation: Roche Pharma AG, Grenzach-Wyhlen, Germany; Medical School of Hanover, Hanover, Germany. Electronic address: joerg.ruof@roche.com.
authors.forename: Jörg
authors.initials: J
authors.lastname: Ruof
authors.affiliation: Roche Pharma AG, Grenzach-Wyhlen, Germany.
authors.forename: Dietrich
authors.initials: D
authors.lastname: Knoerzer
authors.affiliation: Roche Pharma AG, Grenzach-Wyhlen, Germany.
authors.forename: Anja-Alexandra
authors.initials: AA
authors.lastname: Dünne
authors.affiliation: German Association of Research-based Pharmaceutical Companies (vfa), Berlin, Germany; Department of Public Health, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Charalabos-Markos
authors.initials: CM
authors.lastname: Dintsios
authors.affiliation: Roche Pharma AG, Grenzach-Wyhlen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Staab
authors.affiliation: Medical School of Hanover, Hanover, Germany.
authors.forename: Friedrich Wilhelm
authors.initials: FW
authors.lastname: Schwartz
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017277:Drug Approval / Q000379:methods / Q000706:statistics & numerical data*; D005858:Germany; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D011788:Quality of Life; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents
keywords: (Early) benefit assessment; Health-related quality of life; Morbidity; Mortality; Oncology; Patient-relevant endpoints