title: Cost-effectiveness of First-line Chronic Lymphocytic Leukemia Treatments When Full-dose Fludarabine Is Unsuitable.
abstract: OBJECTIVE
  The cost-effectiveness of first-line chronic lymphocytic leukemia treatments was assessed among patients unsuitable for full doses of fludarabine.
  
  
  METHODS
  The study's key outcome was the life-time incremental cost-effectiveness ratio (ICER) (euro/quality-adjusted life-year [QALY] gained) with an annual 3% discounting. A probabilistic Markov model with 3 health states (progression-free, progression, and death) was developed. Survival time was modeled based on age-matched clinical data by using appropriate survival distributions. Each health state was assigned an EuroQoL-5D-3L quality-of-life estimate and Finnish payer costs according to treatment received, and Binet stage of disease; severe adverse events and treatment inconvenience were also included. Six approaches considered the risk and value of key outcomes: cost-effectiveness efficiency frontiers; Bayesian treatment ranking (BTR) rated the lowest ICERs and best QALY gains; the cost-effectiveness acceptability frontier demonstrated optimal treatment; expected value of perfect information; and the cost-benefit assessment (CBA), a type of clinical value analysis, increased the clinical interpretation and appeal of modeled outcomes by including both relative and absolute (impact investment [benefit obtained with a fixed limited budget]) benefit assessments.
  
  
  RESULTS
  The ICERs compared with chlorambucil varied from €29,334 with obinutuzumab + chlorambucil to €82,159 with ofatumumab + chlorambucil. Based on the BTR of ICERs versus chlorambucil, obinutuzumab + chlorambucil was the most cost-effective with 93% probability; rituximab + chlorambucil was the second most cost-effective (73%); and rituximab + bendamustine was the third most cost-effective (65%). The ICERs of obinutuzumab + chlorambucil were €20,038, €11,556, and €15,586 compared with rituximab + chlorambucil, rituximab + bendamustine, and ofatumumab + chlorambucil. Obinutuzumab + chlorambucil was the most cost-effective treatment, with 54% and 99% probability at €30,000 and €50,000/QALY gained, respectively. The corresponding expected values of perfect information were €1438 and €44 per patient. Based on the BTR of QALYs gained, obinutuzumab + chlorambucil was the most effective, with 100% probability; rituximab + chlorambucil was the second most effective (56%); and rituximab + bendamustine was the third most effective treatment (81%). Results were robust in sensitivity analyses. For obinutuzumab + chlorambucil, the CBA demonstrated the best clinical value-to-cost-effectiveness relation and the longest time progression-free with a limited budget.
  
  
  CONCLUSIONS
  The mean results were sensitive to large changes in time horizon, indirect comparison hazard ratios, survival distributions, and discounting; however, obinutuzumab + chlorambucil provided considerable effectiveness and best value for money among chronic lymphocytic leukemia patients unsuitable to receive full doses of fludarabine. In this case, CBA concurred with the key outcome of the study. However, the CBA cannot fully substitute the key outcome, and further cost-effectiveness studies with different cancer types are needed to assess the validity of a limited CBA.
authors.affiliation: ESiOR Oy, Kuopio, Finland. Electronic address: erkki.soini@esior.fi.
authors.forename: Erkki
authors.initials: E
authors.lastname: Soini
authors.affiliation: Roche Oy, Espoo, Finland.
authors.forename: Anne
authors.initials: A
authors.lastname: Hautala
authors.affiliation: Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center, and University of Helsinki, Helsinki, Finland.
authors.forename: Eira
authors.initials: E
authors.lastname: Poikonen
authors.affiliation: F. Hoffmann-La Roche Ltd, Pharmaceuticals Division, Basel, Switzerland.
authors.forename: Ursula
authors.initials: U
authors.lastname: Becker
authors.affiliation: Roche Oy, Espoo, Finland.
authors.forename: Mira
authors.initials: M
authors.lastname: Kyttälä
authors.affiliation: ESiOR Oy, Kuopio, Finland.
authors.forename: Janne
authors.initials: J
authors.lastname: Martikainen
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000191:economics* / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000191:economics* / Q000627:therapeutic use*; D001499:Bayes Theorem; D002699:Chlorambucil / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use; D000075202:Contraindications; D003362:Cost-Benefit Analysis; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D014740:Vidarabine / Q000031:analogs & derivatives*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D002699:Chlorambucil; D014740:Vidarabine; C024352:fludarabine
keywords: bendamustine; chronic lymphocytic leukemia; economic evaluation; obinutuzumab; ofatumumab; rituximab