title: Design and methods of a postmarketing pharmacoepidemiology study assessing long-term safety of Prolia® (denosumab) for the treatment of postmenopausal osteoporosis.
abstract: OBJECTIVE
  To describe the rationale and methods for a prospective, open-cohort study assessing the long-term safety of Prolia(®) for treatment of postmenopausal osteoporosis (PMO) in postmarketing settings.
  
  
  METHODS
  Data will be derived from United States Medicare, United Healthcare, and Nordic (Denmark, Sweden, Norway) national registries. Observation will begin on the date of first Prolia(®) regulatory approval (May 26, 2010) and continue for 10 years. Women with PMO will be identified by postmenopausal age, osteoporosis diagnosis, osteoporotic fracture, or osteoporosis treatment. Exposure to Prolia(®) and bisphosphonates will be updated during follow-up; exposure cohorts will be defined based on patient-years during which patients are on- or post-treatment. Nine adverse events (AEs) will be assessed based on diagnosis codes: osteonecrosis of the jaw (ONJ), atypical femoral fracture (AFF), fracture healing complications, hypocalcemia, infection, dermatologic AEs, acute pancreatitis, hypersensitivity, and new primary malignancy. Medical review will confirm selected potential cases of ONJ and AFF. Incidence rates (IRs) of AEs will be described overall and for exposure cohorts; multivariate Cox proportional hazard regression models will compare IRs of AEs across exposure cohorts. Utilization patterns of Prolia(®) for approved, and unapproved indications will be described.
  
  
  CONCLUSIONS
  This study is based on comprehensive preliminary research and considers methodological challenges specific to the study population. The integrated data systems used in this regulatory committed program can serve as a powerful data resource to assess diverse and rare AEs over time.
authors.affiliation: Center for Observational Research, Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Xue
authors.forename: Haijun
authors.initials: H
authors.lastname: Ma
authors.forename: Catherine
authors.initials: C
authors.lastname: Stehman-Breen
authors.forename: Christine
authors.initials: C
authors.lastname: Haller
authors.forename: Leonid
authors.initials: L
authors.lastname: Katz
authors.forename: Rachel B
authors.initials: RB
authors.lastname: Wagman
authors.forename: Cathy W
authors.initials: CW
authors.lastname: Critchlow
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D000069448:Denosumab; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000453:epidemiology; D012307:Risk Factors; D012449:Safety; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D000069448:Denosumab
keywords: Prolia® (denosumab); database; pharmacoepidemiology; pharmacoepidemiology methods; pharmacovigilance; postmarketing drug safety; postmenopausal osteoporosis