title: Development of the Flu-PRO: a patient-reported outcome (PRO) instrument to evaluate symptoms of influenza.
abstract: BACKGROUND
  To develop content validity of a comprehensive patient-reported outcome (PRO) measure following current best scientific methodology to standardize assessment of influenza (flu) symptoms in clinical research.
  
  
  METHODS
  Stage I (Concept Elicitation): 1:1 telephone interviews with influenza-positive adults (≥18 years) in the US and Mexico within 7 days of diagnosis. Participants described symptom type, character, severity, and duration. Content analysis identified themes and developed the draft Flu-PRO instrument. Stage II (Cognitive Interviewing): The Flu-PRO was administered to a unique set of influenza-positive adults within 14 days of diagnosis; telephone interviews addressed completeness, respondent interpretation of items and ease of use.
  
  
  RESULTS
  Samples: Stage I: N = 46 adults (16 US, 30 Mexico); mean (SD) age: 38 (19), 39 (14) years; % female: 56%, 73%; race: 69% White, 97% Mestizo. Stage II: N = 34 adults (12 US, 22 Mexico); age: 37 (14), 39 (11) years; % female: 50%, 50%; race: 58% White, 100% Mestizo.
  
  
  METHODS
  Symptoms identified by >50%: coughing, weak or tired, throat symptoms, congestion, headache, weakness, sweating, chills, general discomfort, runny nose, chest (trouble breathing), difficulty sleeping, and body aches or pains. No new content was uncovered during Stage II; participants easily understood the instrument.
  
  
  CONCLUSIONS
  Results show the 37-item Flu-PRO is a content valid measure of influenza symptoms in adults with a confirmed diagnosis of influenza. Research is underway to evaluate the suitability of the instrument for children and adolescents. This work can form the basis for future quantitative tests of reliability, validity, and responsiveness to evaluate the measurement properties of Flu-PRO for use in clinical trials and epidemiology studies.
authors.affiliation: Clinical Monitoring and Research Program, Clinical Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702 in support of the Collaborative Clinical Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA. john.powers@nih.gov.|, 5601 Fishers Lane, Room 4D50, Rockville, MD, 20852, USA. john.powers@nih.gov.
authors.forename: John H
authors.initials: JH
authors.lastname: Powers
authors.affiliation: Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. mlga08@gmail.com.
authors.forename: M Lourdes
authors.initials: ML
authors.lastname: Guerrero
authors.affiliation: Evidera, Bethesda, MD, USA. nancy.leidy@evidera.com.
authors.forename: Nancy Kline
authors.initials: NK
authors.lastname: Leidy
authors.affiliation: Infectious Disease Clinical Research Program, Uniformed Services University, Bethesda, MD, USA. mary.p.fairchok.ctr@mail.mil.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA. mary.p.fairchok.ctr@mail.mil.|Madigan Army Medical Center, Tacoma, WA, USA. mary.p.fairchok.ctr@mail.mil.
authors.forename: Mary P
authors.initials: MP
authors.lastname: Fairchok
authors.affiliation: Clinical Monitoring and Research Program, Clinical Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702 in support of the Collaborative Clinical Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA. arosenberg@mail.nih.gov.
authors.forename: Alice
authors.initials: A
authors.lastname: Rosenberg
authors.affiliation: Instituto Nacional de Enfermedades Infecciosas, Mexico City, Mexico. andreshernandez57@gmail.com.
authors.forename: Andrés
authors.initials: A
authors.lastname: Hernández
authors.affiliation: Evidera, Bethesda, MD, USA. sonja.stringer@evidera.com.
authors.forename: Sonja
authors.initials: S
authors.lastname: Stringer
authors.affiliation: Madigan Army Medical Center, Tacoma, WA, USA. christina.m.schofield2.civ@mail.mil.
authors.forename: Christina
authors.initials: C
authors.lastname: Schofield
authors.affiliation: Hospital General Dr. Manuel Gea González, Mexico City, Mexico. rozu76@hotmail.com.
authors.forename: Patricia
authors.initials: P
authors.lastname: Rodríguez-Zulueta
authors.affiliation: Evidera, Bethesda, MD, USA. katherine.kim@evidera.com.
authors.forename: Katherine
authors.initials: K
authors.lastname: Kim
authors.affiliation: San Antonio Health System, San Antonio, TX, USA. patrick.j.danaher6.mil@mail.mil.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Danaher
authors.affiliation: Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. hilda.ortega.innsz@gmail.com.
authors.forename: Hilda
authors.initials: H
authors.lastname: Ortega-Gallegos
authors.affiliation: Evidera, Bethesda, MD, USA. elizabeth.bacci@evidera.com.
authors.forename: Elizabeth Dansie
authors.initials: ED
authors.lastname: Bacci
authors.affiliation: Camp Lejeune, Jacksonville, NC, USA. nathaniel.stepp@med.navy.mil.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Stepp
authors.affiliation: Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. galindofraga@yahoo.com.
authors.forename: Arturo
authors.initials: A
authors.lastname: Galindo-Fraga
authors.affiliation: Naval Medical Center Portsmouth, Portsmouth, VA, USA. Kristina.j.stclair.mil@mail.mil.
authors.forename: Kristina
authors.initials: K
authors.lastname: St Clair
authors.affiliation: Walter Reed National Military Medical Center, Bethesda, MD, USA. michael.rajnik@usuhs.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Rajnik
authors.affiliation: Naval Health Research Center, San Diego, CA, USA. erin.mcdonough@med.navy.mil.
authors.forename: Erin A
authors.initials: EA
authors.lastname: McDonough
authors.affiliation: Infectious Disease Clinical Research Program, Uniformed Services University, Bethesda, MD, USA. michelande.ridore@gmail.com.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA. michelande.ridore@gmail.com.
authors.forename: Michelande
authors.initials: M
authors.lastname: Ridoré
authors.affiliation: Naval Medical Center San Diego, San Diego, CA, USA. john.arnold@med.navy.mil.
authors.forename: John C
authors.initials: JC
authors.lastname: Arnold
authors.affiliation: Infectious Disease Clinical Research Program, Uniformed Services University, Bethesda, MD, USA. emillar@idcrp.org.|Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA. emillar@idcrp.org.
authors.forename: Eugene V
authors.initials: EV
authors.lastname: Millar
authors.affiliation: Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. gmrps@servidor.unam.mx.
authors.forename: Guillermo M
authors.initials: GM
authors.lastname: Ruiz-Palacios
mesh_terms: D000328:Adult; D003371:Cough; D005260:Female; D006261:Headache; D006801:Humans; D007251:Influenza, Human / Q000503:physiopathology*; D008297:Male; D008800:Mexico; D010146:Pain; D063868:Patient Outcome Assessment; D015203:Reproducibility of Results; D011795:Surveys and Questionnaires