title: Patient-reported outcomes of pain and physical functioning in neurofibromatosis clinical trials.
abstract: OBJECTIVE
  Tumors and other disease complications of neurofibromatosis (NF) can cause pain and negatively affect physical functioning. To document the clinical benefit of treatment in NF trials targeting these manifestations, patient-reported outcomes (PROs) assessing pain and physical functioning should be included as study endpoints. Currently, there is no consensus on the selection and use of such measures in the NF population. This article presents the recommendations of the PRO group of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration for assessing the domains of pain and physical functioning for NF clinical trials.
  
  
  METHODS
  The REiNS PRO group reviewed and rated existing PRO measures assessing pain intensity, pain interference, and physical functioning using their systematic method. Final recommendations are based primarily on 4 main criteria: patient characteristics, item content, psychometric properties, and feasibility for clinical trials.
  
  
  RESULTS
  The REiNS PRO group chose the Numeric Rating Scale-11 (≥8 years) to assess pain intensity, the Pain Interference Index (6-24 years) and the Patient-Reported Outcome Measurement Information System (PROMIS) Pain Interference Scale (≥18 years) to evaluate pain interference, and the PROMIS Physical Functioning Scale to measure upper extremity function and mobility (≥5 years) for NF clinical trials.
  
  
  CONCLUSIONS
  The REiNS Collaboration currently recommends these PRO measures to assess the domains of pain and physical functioning for NF clinical trials; however, further research is needed to evaluate their use in individuals with NF. A final consensus recommendation for the pain interference measure will be disseminated in a future publication based on findings from additional published research.
authors.affiliation: From the Pediatric Oncology Branch (P.L.W., S.M., A.B.), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Neurology and Cancer Center (V.L.M.), Massachusetts General Hospital, Boston; University of Chicago Pritzker School of Medicine (J.H.T.), IL; Department of Psychological Sciences (S.E.S.), University of Vermont, Burlington; Departments of Neurology and Genetics (A.L.B.), Johns Hopkins University, Baltimore, MD; Children's National Health System & The George Washington School of Medicine (K.W.), Washington, DC; Department of Speech Pathology & Audiology (H.L.T.), California State University, Sacramento; Veteran's Administration Pittsburgh Healthcare System and University of Pittsburgh (K.L.G.), PA; Department of Clinical Neurosciences (C.M.H.), Spectrum Health Medical Group and College of Human Medicine, Michigan State University, East Lansing; Division of Human Genetics (E.S.), Cincinnati Children's Hospital, OH; Department of Public Health Education (W.N.D.), School of Health and Human Sciences, University of North Carolina at Greensboro; and Advocure NF2 Inc. (B.F.), Los Angeles, CA. woltersp@mail.nih.gov.
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Wolters
authors.affiliation: From the Pediatric Oncology Branch (P.L.W., S.M., A.B.), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Neurology and Cancer Center (V.L.M.), Massachusetts General Hospital, Boston; University of Chicago Pritzker School of Medicine (J.H.T.), IL; Department of Psychological Sciences (S.E.S.), University of Vermont, Burlington; Departments of Neurology and Genetics (A.L.B.), Johns Hopkins University, Baltimore, MD; Children's National Health System & The George Washington School of Medicine (K.W.), Washington, DC; Department of Speech Pathology & Audiology (H.L.T.), California State University, Sacramento; Veteran's Administration Pittsburgh Healthcare System and University of Pittsburgh (K.L.G.), PA; Department of Clinical Neurosciences (C.M.H.), Spectrum Health Medical Group and College of Human Medicine, Michigan State University, East Lansing; Division of Human Genetics (E.S.), Cincinnati Children's Hospital, OH; Department of Public Health Education (W.N.D.), School of Health and Human Sciences, University of North Carolina at Greensboro; and Advocure NF2 Inc. (B.F.), Los Angeles, CA.
authors.forename: Staci
authors.initials: S
authors.lastname: Martin
authors.affiliation: From the Pediatric Oncology Branch (P.L.W., S.M., A.B.), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Neurology and Cancer Center (V.L.M.), Massachusetts General Hospital, Boston; University of Chicago Pritzker School of Medicine (J.H.T.), IL; Department of Psychological Sciences (S.E.S.), University of Vermont, Burlington; Departments of Neurology and Genetics (A.L.B.), Johns Hopkins University, Baltimore, MD; Children's National Health System & The George Washington School of Medicine (K.W.), Washington, DC; Department of Speech Pathology & Audiology (H.L.T.), California State University, Sacramento; Veteran's Administration Pittsburgh Healthcare System and University of Pittsburgh (K.L.G.), PA; Department of Clinical Neurosciences (C.M.H.), Spectrum Health Medical Group and College of Human Medicine, Michigan State University, East Lansing; Division of Human Genetics (E.S.), Cincinnati Children's Hospital, OH; Department of Public Health Education (W.N.D.), School of Health and Human Sciences, University of North Carolina at Greensboro; and Advocure NF2 Inc. (B.F.), Los Angeles, CA.
authors.forename: Vanessa L
authors.initials: VL
authors.lastname: Merker
authors.affiliation: From the Pediatric Oncology Branch (P.L.W., S.M., A.B.), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Neurology and Cancer Center (V.L.M.), Massachusetts General Hospital, Boston; University of Chicago Pritzker School of Medicine (J.H.T.), IL; Department of Psychological Sciences (S.E.S.), University of Vermont, Burlington; Departments of Neurology and Genetics (A.L.B.), Johns Hopkins University, Baltimore, MD; Children's National Health System & The George Washington School of Medicine (K.W.), Washington, DC; Department of Speech Pathology & Audiology (H.L.T.), California State University, Sacramento; Veteran's Administration Pittsburgh Healthcare System and University of Pittsburgh (K.L.G.), PA; Department of Clinical Neurosciences (C.M.H.), Spectrum Health Medical Group and College of Human Medicine, Michigan State University, East Lansing; Division of Human Genetics (E.S.), Cincinnati Children's Hospital, OH; Department of Public Health Education (W.N.D.), School of Health and Human Sciences, University of North Carolina at Greensboro; and Advocure NF2 Inc. (B.F.), Los Angeles, CA.
authors.forename: James H
authors.initials: JH
authors.lastname: Tonsgard
authors.affiliation: From the Pediatric Oncology Branch (P.L.W., S.M., A.B.), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Neurology and Cancer Center (V.L.M.), Massachusetts General Hospital, Boston; University of Chicago Pritzker School of Medicine (J.H.T.), IL; Department of Psychological Sciences (S.E.S.), University of Vermont, Burlington; Departments of Neurology and Genetics (A.L.B.), Johns Hopkins University, Baltimore, MD; Children's National Health System & The George Washington School of Medicine (K.W.), Washington, DC; Department of Speech Pathology & Audiology (H.L.T.), California State University, Sacramento; Veteran's Administration Pittsburgh Healthcare System and University of Pittsburgh (K.L.G.), PA; Department of Clinical Neurosciences (C.M.H.), Spectrum Health Medical Group and College of Human Medicine, Michigan State University, East Lansing; Division of Human Genetics (E.S.), Cincinnati Children's Hospital, OH; Department of Public Health Education (W.N.D.), School of Health and Human Sciences, University of North Carolina at Greensboro; and Advocure NF2 Inc. (B.F.), Los Angeles, CA.
authors.forename: Sondra E
authors.initials: SE
authors.lastname: Solomon
authors.affiliation: From the Pediatric Oncology Branch (P.L.W., S.M., A.B.), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Neurology and Cancer Center (V.L.M.), Massachusetts General Hospital, Boston; University of Chicago Pritzker School of Medicine (J.H.T.), IL; Department of Psychological Sciences (S.E.S.), University of Vermont, Burlington; Departments of Neurology and Genetics (A.L.B.), Johns Hopkins University, Baltimore, MD; Children's National Health System & The George Washington School of Medicine (K.W.), Washington, DC; Department of Speech Pathology & Audiology (H.L.T.), California State University, Sacramento; Veteran's Administration Pittsburgh Healthcare System and University of Pittsburgh (K.L.G.), PA; Department of Clinical Neurosciences (C.M.H.), Spectrum Health Medical Group and College of Human Medicine, Michigan State University, East Lansing; Division of Human Genetics (E.S.), Cincinnati Children's Hospital, OH; Department of Public Health Education (W.N.D.), School of Health and Human Sciences, University of North Carolina at Greensboro; and Advocure NF2 Inc. (B.F.), Los Angeles, CA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Baldwin
authors.affiliation: From the Pediatric Oncology Branch (P.L.W., S.M., A.B.), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Neurology and Cancer Center (V.L.M.), Massachusetts General Hospital, Boston; University of Chicago Pritzker School of Medicine (J.H.T.), IL; Department of Psychological Sciences (S.E.S.), University of Vermont, Burlington; Departments of Neurology and Genetics (A.L.B.), Johns Hopkins University, Baltimore, MD; Children's National Health System & The George Washington School of Medicine (K.W.), Washington, DC; Department of Speech Pathology & Audiology (H.L.T.), California State University, Sacramento; Veteran's Administration Pittsburgh Healthcare System and University of Pittsburgh (K.L.G.), PA; Department of Clinical Neurosciences (C.M.H.), Spectrum Health Medical Group and College of Human Medicine, Michigan State University, East Lansing; Division of Human Genetics (E.S.), Cincinnati Children's Hospital, OH; Department of Public Health Education (W.N.D.), School of Health and Human Sciences, University of North Carolina at Greensboro; and Advocure NF2 Inc. (B.F.), Los Angeles, CA.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Bergner
authors.affiliation: From the Pediatric Oncology Branch (P.L.W., S.M., A.B.), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Neurology and Cancer Center (V.L.M.), Massachusetts General Hospital, Boston; University of Chicago Pritzker School of Medicine (J.H.T.), IL; Department of Psychological Sciences (S.E.S.), University of Vermont, Burlington; Departments of Neurology and Genetics (A.L.B.), Johns Hopkins University, Baltimore, MD; Children's National Health System & The George Washington School of Medicine (K.W.), Washington, DC; Department of Speech Pathology & Audiology (H.L.T.), California State University, Sacramento; Veteran's Administration Pittsburgh Healthcare System and University of Pittsburgh (K.L.G.), PA; Department of Clinical Neurosciences (C.M.H.), Spectrum Health Medical Group and College of Human Medicine, Michigan State University, East Lansing; Division of Human Genetics (E.S.), Cincinnati Children's Hospital, OH; Department of Public Health Education (W.N.D.), School of Health and Human Sciences, University of North Carolina at Greensboro; and Advocure NF2 Inc. (B.F.), Los Angeles, CA.
authors.forename: Karin
authors.initials: K
authors.lastname: Walsh
authors.affiliation: From the Pediatric Oncology Branch (P.L.W., S.M., A.B.), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Neurology and Cancer Center (V.L.M.), Massachusetts General Hospital, Boston; University of Chicago Pritzker School of Medicine (J.H.T.), IL; Department of Psychological Sciences (S.E.S.), University of Vermont, Burlington; Departments of Neurology and Genetics (A.L.B.), Johns Hopkins University, Baltimore, MD; Children's National Health System & The George Washington School of Medicine (K.W.), Washington, DC; Department of Speech Pathology & Audiology (H.L.T.), California State University, Sacramento; Veteran's Administration Pittsburgh Healthcare System and University of Pittsburgh (K.L.G.), PA; Department of Clinical Neurosciences (C.M.H.), Spectrum Health Medical Group and College of Human Medicine, Michigan State University, East Lansing; Division of Human Genetics (E.S.), Cincinnati Children's Hospital, OH; Department of Public Health Education (W.N.D.), School of Health and Human Sciences, University of North Carolina at Greensboro; and Advocure NF2 Inc. (B.F.), Los Angeles, CA.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Thompson
authors.affiliation: From the Pediatric Oncology Branch (P.L.W., S.M., A.B.), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Neurology and Cancer Center (V.L.M.), Massachusetts General Hospital, Boston; University of Chicago Pritzker School of Medicine (J.H.T.), IL; Department of Psychological Sciences (S.E.S.), University of Vermont, Burlington; Departments of Neurology and Genetics (A.L.B.), Johns Hopkins University, Baltimore, MD; Children's National Health System & The George Washington School of Medicine (K.W.), Washington, DC; Department of Speech Pathology & Audiology (H.L.T.), California State University, Sacramento; Veteran's Administration Pittsburgh Healthcare System and University of Pittsburgh (K.L.G.), PA; Department of Clinical Neurosciences (C.M.H.), Spectrum Health Medical Group and College of Human Medicine, Michigan State University, East Lansing; Division of Human Genetics (E.S.), Cincinnati Children's Hospital, OH; Department of Public Health Education (W.N.D.), School of Health and Human Sciences, University of North Carolina at Greensboro; and Advocure NF2 Inc. (B.F.), Los Angeles, CA.
authors.forename: Kathy L
authors.initials: KL
authors.lastname: Gardner
authors.affiliation: From the Pediatric Oncology Branch (P.L.W., S.M., A.B.), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Neurology and Cancer Center (V.L.M.), Massachusetts General Hospital, Boston; University of Chicago Pritzker School of Medicine (J.H.T.), IL; Department of Psychological Sciences (S.E.S.), University of Vermont, Burlington; Departments of Neurology and Genetics (A.L.B.), Johns Hopkins University, Baltimore, MD; Children's National Health System & The George Washington School of Medicine (K.W.), Washington, DC; Department of Speech Pathology & Audiology (H.L.T.), California State University, Sacramento; Veteran's Administration Pittsburgh Healthcare System and University of Pittsburgh (K.L.G.), PA; Department of Clinical Neurosciences (C.M.H.), Spectrum Health Medical Group and College of Human Medicine, Michigan State University, East Lansing; Division of Human Genetics (E.S.), Cincinnati Children's Hospital, OH; Department of Public Health Education (W.N.D.), School of Health and Human Sciences, University of North Carolina at Greensboro; and Advocure NF2 Inc. (B.F.), Los Angeles, CA.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Hingtgen
authors.affiliation: From the Pediatric Oncology Branch (P.L.W., S.M., A.B.), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Neurology and Cancer Center (V.L.M.), Massachusetts General Hospital, Boston; University of Chicago Pritzker School of Medicine (J.H.T.), IL; Department of Psychological Sciences (S.E.S.), University of Vermont, Burlington; Departments of Neurology and Genetics (A.L.B.), Johns Hopkins University, Baltimore, MD; Children's National Health System & The George Washington School of Medicine (K.W.), Washington, DC; Department of Speech Pathology & Audiology (H.L.T.), California State University, Sacramento; Veteran's Administration Pittsburgh Healthcare System and University of Pittsburgh (K.L.G.), PA; Department of Clinical Neurosciences (C.M.H.), Spectrum Health Medical Group and College of Human Medicine, Michigan State University, East Lansing; Division of Human Genetics (E.S.), Cincinnati Children's Hospital, OH; Department of Public Health Education (W.N.D.), School of Health and Human Sciences, University of North Carolina at Greensboro; and Advocure NF2 Inc. (B.F.), Los Angeles, CA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Schorry
authors.affiliation: From the Pediatric Oncology Branch (P.L.W., S.M., A.B.), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Neurology and Cancer Center (V.L.M.), Massachusetts General Hospital, Boston; University of Chicago Pritzker School of Medicine (J.H.T.), IL; Department of Psychological Sciences (S.E.S.), University of Vermont, Burlington; Departments of Neurology and Genetics (A.L.B.), Johns Hopkins University, Baltimore, MD; Children's National Health System & The George Washington School of Medicine (K.W.), Washington, DC; Department of Speech Pathology & Audiology (H.L.T.), California State University, Sacramento; Veteran's Administration Pittsburgh Healthcare System and University of Pittsburgh (K.L.G.), PA; Department of Clinical Neurosciences (C.M.H.), Spectrum Health Medical Group and College of Human Medicine, Michigan State University, East Lansing; Division of Human Genetics (E.S.), Cincinnati Children's Hospital, OH; Department of Public Health Education (W.N.D.), School of Health and Human Sciences, University of North Carolina at Greensboro; and Advocure NF2 Inc. (B.F.), Los Angeles, CA.
authors.forename: William N
authors.initials: WN
authors.lastname: Dudley
authors.affiliation: From the Pediatric Oncology Branch (P.L.W., S.M., A.B.), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Neurology and Cancer Center (V.L.M.), Massachusetts General Hospital, Boston; University of Chicago Pritzker School of Medicine (J.H.T.), IL; Department of Psychological Sciences (S.E.S.), University of Vermont, Burlington; Departments of Neurology and Genetics (A.L.B.), Johns Hopkins University, Baltimore, MD; Children's National Health System & The George Washington School of Medicine (K.W.), Washington, DC; Department of Speech Pathology & Audiology (H.L.T.), California State University, Sacramento; Veteran's Administration Pittsburgh Healthcare System and University of Pittsburgh (K.L.G.), PA; Department of Clinical Neurosciences (C.M.H.), Spectrum Health Medical Group and College of Human Medicine, Michigan State University, East Lansing; Division of Human Genetics (E.S.), Cincinnati Children's Hospital, OH; Department of Public Health Education (W.N.D.), School of Health and Human Sciences, University of North Carolina at Greensboro; and Advocure NF2 Inc. (B.F.), Los Angeles, CA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Franklin
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods*; D004185:Disability Evaluation; D006801:Humans; D017253:Neurofibromatoses / Q000503:physiopathology* / Q000628:therapy*; D010146:Pain / Q000503:physiopathology; D010147:Pain Measurement / Q000379:methods*; D000071066:Patient Reported Outcome Measures; D057566:Self Report