title: Patient-reported outcome labeling claims and measurement approach for metastatic castration-resistant prostate cancer treatments in the United States and European Union.
abstract: BACKGROUND
  Metastatic castration-resistant prostate cancer (mCRPC) and its treatment significantly affect health-related quality of life (HRQOL). Our objectives were to evaluate and compare patient-reported outcome (PRO) claims granted by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for 5 recently approved mCRPC treatments and to examine key characteristics, development, and measurement properties of the PRO measures supporting these claims against current regulatory standards.
  
  
  METHODS
  Five products approved for treatment of mCRPC by the FDA and the EMA (2010-2013) were examined: enzalutamide, abiraterone, sipuleucel-T, cabazitaxel, and radium Ra 223 dichloride. United States (US) drug approval packages and European Public Assessment Reports were reviewed. PRO claims in the US labels and European Summaries of Product Characteristics and supporting measures were identified. For PRO measures supporting claims, a targeted literature review was conducted to identify information on key characteristics and measurement properties; this information was compared against FDA PRO guidance criteria.
  
  
  RESULTS
  Nine PRO "claims" were granted across 4 of 5 products reviewed. The EMA granted more claims (7 claims-4 for pain, 3 for HRQOL) than the FDA (2 claims, both for pain). The Brief Pain Inventory-Short Form (BPI-SF) worst pain item supported most pain claims and was the only measure supporting US claims. EMA pain claims were supported by BPI-SF worst pain (n = 2) and average pain (n = 1) items and the McGill Pain Questionnaire Present Pain Intensity component (n = 1). EMA HRQOL claims were supported by the Functional Assessment of Cancer Therapy-Prostate Module (n = 2) and the EuroQol 5 Dimensions with visual analogue scale (n = 1). Pain and prostate cancer-specific HRQOL measures supporting claims met US regulatory standards for construct validity, reliability, and responsiveness; these properties were strongest for the BPI-SF worst pain item. Only the BPI-SF worst pain item has documented content validity in mCRPC.
  
  
  CONCLUSIONS
  PRO label claims were commonly granted across the mCRPC products reviewed. Among the measures reviewed, only the BPI-SF worst pain item supported US label claims. The BPI-SF worst pain item is recommended for pain assessment for the evaluation of new mCRPC treatments.
authors.affiliation: RTI Health Solutions, 3005 Boardwalk Drive, Suite 105, Ann Arbor 48108, MI, USA. mclark@rti.org.
authors.forename: Marci J
authors.initials: MJ
authors.lastname: Clark
authors.forename: Nimanee
authors.initials: N
authors.lastname: Harris
authors.forename: Ingolf
authors.initials: I
authors.lastname: Griebsch
authors.forename: Dagmar
authors.initials: D
authors.lastname: Kaschinski
authors.forename: Catherine
authors.initials: C
authors.lastname: Copley-Merriman
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004348:Drug Labeling; D005062:European Union; D006305:Health Status Indicators; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010146:Pain / Q000209:etiology; D010147:Pain Measurement; D063868:Patient Outcome Assessment; D064129:Prostatic Neoplasms, Castration-Resistant / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D011594:Psychometrics; D011788:Quality of Life; D015203:Reproducibility of Results; D057566:Self Report; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000970:Antineoplastic Agents