title: Incorporating development of a patient-reported outcome instrument in a clinical drug development program: examples from a heart failure program.
abstract: BACKGROUND
  Patient-reported outcome (PRO) measures can be used to support label claims if they adhere to US Food & Drug Administration guidance. The process of developing a new PRO measure is expensive and time-consuming. We report the results of qualitative studies to develop new PRO measures for use in clinical trials of omecamtiv mecarbil (a selective, small molecule activator of cardiac myosin) for patients with heart failure (HF), as well as the lessons learned from the development process.
  
  
  METHODS
  Concept elicitation focus groups and individual interviews were conducted with patients with HF to identify concepts for the instrument. Cognitive interviews with HF patients were used to confirm that no essential concepts were missing and to assess patient comprehension of the instrument and items.
  
  
  RESULTS
  During concept elicitation, the most frequently reported HF symptoms were shortness of breath, tiredness, fluid retention, fatigue, dizziness/light-headedness, swelling, weight fluctuation, and trouble sleeping. Two measures were developed based on the concepts: the Heart Failure Symptom Diary (HF-SD) and the Heart Failure Impact Scale (HFIS). Findings from cognitive interviews suggested that the items in the HF-SD and HFIS were relevant and well understood by patients. Multiple iterations of concept elicitation and cognitive interviews were needed based on FDA request for a broader patient population in the qualitative study. Lessons learned from the omecamtiv mecarbil PRO/clinical development program are discussed, including challenges of qualitative studies, patient recruitment, expected and actual timelines, cost, and engagement with various stakeholders.
  
  
  CONCLUSIONS
  Development of a new PRO measure to support a label claim requires significant investment and early planning, as demonstrated by the omecamtiv mecarbil program.
authors.affiliation: Evidera, Metro Building 6th Floor, 1 Butterwick, London, W6 8DL, UK. ingela.wiklund@evidera.com.
authors.forename: Ingela
authors.initials: I
authors.lastname: Wiklund
authors.affiliation: Evidera, Bethesda, MD, USA.
authors.forename: Milena
authors.initials: M
authors.lastname: Anatchkova
authors.affiliation: Evidera, Bethesda, MD, USA.
authors.forename: Hafiz
authors.initials: H
authors.lastname: Oko-Osi
authors.affiliation: Evidera, Metro Building 6th Floor, 1 Butterwick, London, W6 8DL, UK.
authors.forename: Robyn
authors.initials: R
authors.lastname: von Maltzahn
authors.affiliation: Amgen Inc., Thousand Oaks, USA.
authors.forename: Dina
authors.initials: D
authors.lastname: Chau
authors.affiliation: Cytokinetics, Inc., San Francisco, CA, USA.
authors.forename: Fady I
authors.initials: FI
authors.lastname: Malik
authors.affiliation: University of Washington, Seattle, WA, USA.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Patrick
authors.affiliation: University of Missouri, Kansas City, KS, USA.
authors.forename: John
authors.initials: J
authors.lastname: Spertus
authors.affiliation: San Francisco Veterans Affairs Medical Center and University of California San Francisco School of Medicine, San Francisco, CA, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Teerlink
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D024722:Cardiac Myosins; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004244:Dizziness; D004417:Dyspnea; D004487:Edema; D005221:Fatigue; D005260:Female; D017144:Focus Groups; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071066:Patient Reported Outcome Measures; D036301:Qualitative Research; D011788:Quality of Life; D007319:Sleep Initiation and Maintenance Disorders; D014481:United States; D014486:United States Food and Drug Administration; D014508:Urea / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D002317:Cardiovascular Agents; C547293:omecamtiv mecarbil; D014508:Urea; D024722:Cardiac Myosins
keywords: FDA guidance; Heart failure; Instrument development; Omecamtiv mecarbil; Patient-reported outcome; Qualitative research