title: Is the raised volume rapid thoracic compression technique ready for use in clinical trials in infants with cystic fibrosis?
abstract: The European Cystic Fibrosis Society Clinical Trial Network (ECFS-CTN) has established a Standardization Committee to undertake a rigorous evaluation of promising outcome measures with regard to use in multicentre clinical trials in cystic fibrosis (CF). The aim of this article is to present a review of literature on clinimetric properties of the infant raised-volume rapid thoracic compression (RVRTC) technique in the context of CF, to summarise the consensus amongst the group on feasibility and answer key questions regarding the promotion of this technique to surrogate endpoint status.
  
  
  METHODS
  A literature search (from 1985 onwards) identified 20 papers that met inclusion criteria of RVRTC use in infants with CF. Data were extracted and tabulated regarding repeatability, validity, correlation with other outcome measures, responsiveness and reference values. A working group discussed the tables and answered 4 key questions.
  
  
  RESULTS
  Overall, RVRTC in particular forced expiratory volume in 0.5s, showed good clinimetric properties despite presence of individual variability. Few studies showed a relationship between RVRTC and inflammation and infection, and to date, data remains limited regarding the responsiveness of RVRTC after an intervention. Concerns were raised regarding feasibility in multi-centre studies and availability of reference values.
  
  
  CONCLUSIONS
  The ECFS-CTN Working Group considers that RVRTC cannot be used as a primary outcome in clinical trials in infants with CF before universal standardization of this measurement is achieved and implementation of inter-institutional networking is in place. We advise its use currently in phase I/II trials and as a secondary endpoint in phase III studies. We emphasise the need for (1) more short-term variability and longitudinal 'natural history' studies, and (2) robust reference values for commercially available devices.
authors.affiliation: Pediatric Functional Exploration Unit, University Hospital of Montpellier, UMR CNRS 9214-INSERM U1046, Université Montpellier, France. Electronic address: s-matecki@chu-montpellier.fr.
authors.forename: Stefan
authors.initials: S
authors.lastname: Matecki
authors.affiliation: Centre for Health and Rehabilitation Technologies (CHaRT), Institute for Nursing and Health Research, University of Ulster, Newtownabbey, UK; Northern Ireland Adult Cystic Fibrosis Centre, Belfast Health and Social Care Trust, Belfast, UK.
authors.forename: Lisa
authors.initials: L
authors.lastname: Kent
authors.affiliation: Pediatric Pulmonology, University Hospitals Leuven and KU Leuven, Leuven, Belgium.
authors.forename: Kris
authors.initials: K
authors.lastname: de Boeck
authors.affiliation: Centre de Compétences de la Mucoviscidose, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Le Bourgeois
authors.affiliation: Department of Paediatrics, J.W. Goethe-Universität Frankfurt, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zielen
authors.affiliation: Cystic Fibrosis Centre, Pediatric Department, Meyer Children's Hospital, Florence, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Braggion
authors.affiliation: Department of Paediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, The Netherlands.
authors.forename: H G M
authors.initials: HG
authors.lastname: Arets
authors.affiliation: Centre for Health and Rehabilitation Technologies (CHaRT), Institute for Nursing and Health Research, University of Ulster, Newtownabbey, UK; Northern Ireland Adult Cystic Fibrosis Centre, Belfast Health and Social Care Trust, Belfast, UK.
authors.forename: Judy
authors.initials: J
authors.lastname: Bradley
authors.affiliation: Cystic Fibrosis Pediatric Centre, Indianapolis, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Davis
authors.affiliation: Centre de Compétences de la Mucoviscidose, Hôpital Necker-Enfants Malades, Paris, France; Université Paris Descartes, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Sermet
authors.affiliation: Centre de Référence de la Mucoviscidose, Lyon, France; Université Claude Bernard Lyon 1, Lyon, UMR5558, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Reix
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods / Q000592:standards; D003550:Cystic Fibrosis / Q000175:diagnosis*; D005060:Europe; D006801:Humans; D007223:Infant; D017063:Outcome Assessment, Health Care / Q000379:methods; D062072:Patient Acuity; D012129:Respiratory Function Tests / Q000379:methods / Q000592:standards; D012955:Societies, Medical
keywords: Clinical trials; Clinimetric properties; Cystic fibrosis; Infant pulmonary function; Raised volume rapid thoracic compression; Surrogate outcome