title: Content validity and clinical meaningfulness of the HFMSE in spinal muscular atrophy.
abstract: BACKGROUND
  Reports on the clinical meaningfulness of outcome measures in spinal muscular atrophy (SMA) are rare. In this two-part study, our aim was to explore patients' and caregivers' views on the clinical relevance of the Hammersmith Functional Motor Scale Expanded- (HFMSE).
  
  
  METHODS
  First, we used focus groups including SMA patients and caregivers to explore their views on the clinical relevance of the individual activities included in the HFMSE. Then we asked caregivers to comment on the clinical relevance of possible changes of HFMSE scores over time. As functional data of individual patients were available, some of the questions were tailored according to their functional level on the HFMSE.
  
  
  RESULTS
  Part 1: Sixty-three individuals participated in the focus groups. This included 30 caregivers, 25 patients and 8 professionals who facilitated the discussion. The caregivers provided a comparison to activities of daily living for each of the HFMSE items. Part 2: One hundred and forty-nine caregivers agreed to complete the questionnaire: in response to a general question, 72% of the caregivers would consider taking part in a clinical trial if the treatment was expected to slow down deterioration, 88% if it would stop deterioration and 97% if the treatment was expected to produce an improvement. Caregivers were informed of the first three items that their child could not achieve on the HFMSE. In response 75% indicated a willingness to take part in a clinical trial if they could achieve at least one of these abilities, 89% if they could achieve two, and 100% if they could achieve more than 2.
  
  
  CONCLUSIONS
  Our findings support the use of the HFMSE as a key outcome measure in SMA clinical trials because the individual items and the detected changes have clear content validity and clinical meaningfulness for patients and their caregivers.
authors.affiliation: Pediatric Neurology, Catholic University, Largo Gemelli 8, 00168, Rome, Italy.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Pera
authors.affiliation: Pediatric Neurology, Catholic University, Largo Gemelli 8, 00168, Rome, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Coratti
authors.affiliation: Pediatric Neurology, Catholic University, Largo Gemelli 8, 00168, Rome, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Forcina
authors.affiliation: Pediatric Neurology, Catholic University, Largo Gemelli 8, 00168, Rome, Italy.
authors.forename: Elena S
authors.initials: ES
authors.lastname: Mazzone
authors.affiliation: Dubowitz Neuromuscular Centre, UCL Institute of Child Health & Great Ormond Street Hospital, London, UK.
authors.forename: Mariacristina
authors.initials: M
authors.lastname: Scoto
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Montes
authors.affiliation: Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Pasternak
authors.affiliation: John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle University, Newcastle, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Mayhew
authors.affiliation: Department of Clinical and Experimental Medicine and Nemo Sud Clinical Center, University of Messina, Messina, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Messina
authors.affiliation: Department of Clinical and Experimental Medicine and Nemo Sud Clinical Center, University of Messina, Messina, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Sframeli
authors.affiliation: Dubowitz Neuromuscular Centre, UCL Institute of Child Health & Great Ormond Street Hospital, London, UK.
authors.forename: Marion
authors.initials: M
authors.lastname: Main
authors.affiliation: John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle University, Newcastle, UK.
authors.forename: Robert Muni
authors.initials: RM
authors.lastname: Lofra
authors.affiliation: Stanford University, Palo Alto, CA, USA.
authors.forename: Tina
authors.initials: T
authors.lastname: Duong
authors.affiliation: Dubowitz Neuromuscular Centre, UCL Institute of Child Health & Great Ormond Street Hospital, London, UK.
authors.forename: Danielle
authors.initials: D
authors.lastname: Ramsey
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Sally
authors.initials: S
authors.lastname: Dunaway
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Salazar
authors.affiliation: Pediatric Neurology, Catholic University, Largo Gemelli 8, 00168, Rome, Italy.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Fanelli
authors.affiliation: Nemours Children's Hospital, University of Central Florida College of Medicine, Orlando, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Civitello
authors.affiliation: Pediatric Neurology, Catholic University, Largo Gemelli 8, 00168, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: de Sanctis
authors.affiliation: Pediatric Neurology, Catholic University, Largo Gemelli 8, 00168, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Antonaci
authors.affiliation: Pediatric Neurology, Catholic University, Largo Gemelli 8, 00168, Rome, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Lapenta
authors.affiliation: Pediatric Neurology, Catholic University, Largo Gemelli 8, 00168, Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Lucibello
authors.affiliation: Pediatric Neurology, Catholic University, Largo Gemelli 8, 00168, Rome, Italy.
authors.forename: Marika
authors.initials: M
authors.lastname: Pane
authors.affiliation: Stanford University, Palo Alto, CA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Day
authors.affiliation: Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Basil T
authors.initials: BT
authors.lastname: Darras
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Darryl C
authors.initials: DC
authors.lastname: De Vivo
authors.affiliation: Dubowitz Neuromuscular Centre, UCL Institute of Child Health & Great Ormond Street Hospital, London, UK.
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
authors.affiliation: Nemours Children's Hospital, University of Central Florida College of Medicine, Orlando, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Finkel
authors.affiliation: Pediatric Neurology, Catholic University, Largo Gemelli 8, 00168, Rome, Italy. eumercuri@gmail.com.
authors.forename: Eugenio
authors.identifier: http://orcid.org/0000-0002-9851-5365
authors.initials: E
authors.lastname: Mercuri
mesh_terms: D000203:Activities of Daily Living; D000293:Adolescent; D000328:Adult; D017028:Caregivers / Q000523:psychology; D002648:Child; D005260:Female; D017144:Focus Groups; D006801:Humans; D008297:Male; D009134:Muscular Atrophy, Spinal / Q000523:psychology*; D017063:Outcome Assessment, Health Care; D010361:Patients / Q000523:psychology; D012720:Severity of Illness Index; D014897:Spinal Muscular Atrophies of Childhood / Q000523:psychology*; D055815:Young Adult
keywords: Carers; Clinical trials; Quality of life; Spinal muscular atrophy