title: Systematic evaluation of the patient-reported outcome (PRO) content of clinical trial protocols.
abstract: BACKGROUND
  Qualitative evidence suggests patient-reported outcome (PRO) information is frequently absent from clinical trial protocols, potentially leading to inconsistent PRO data collection and risking bias. Direct evidence regarding PRO trial protocol content is lacking. The aim of this study was to systematically evaluate the PRO-specific content of UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme trial protocols.
  
  
  RESULTS
  We conducted an electronic search of the NIHR HTA programme database (inception to August 2013) for protocols describing a randomised controlled trial including a primary/secondary PRO. Two investigators independently reviewed the content of each protocol, using a specially constructed PRO-specific protocol checklist, alongside the 'Standard Protocol Items: Recommendations for Interventional Trials' (SPIRIT) checklist. Disagreements were resolved through discussion with a third investigator. 75 trial protocols were included in the analysis. Protocols included a mean of 32/51 (63%) SPIRIT recommendations (range 16-41, SD 5.62) and 11/33 (33%) PRO-specific items (range 4-18, SD 3.56). Over half (61%) of the PRO items were incomplete. Protocols containing a primary PRO included slightly more PRO checklist items (mean 14/33 (43%)). PRO protocol content was not associated with general protocol completeness; thus, protocols judged as relatively 'complete' using SPIRIT were still likely to have omitted a large proportion of PRO checklist items.
  
  
  CONCLUSIONS
  The PRO components of HTA clinical trial protocols require improvement. Information on the PRO rationale/hypothesis, data collection methods, training and management was often absent. This low compliance is unsurprising; evidence shows existing PRO guidance for protocol developers remains difficult to access and lacks consistency. Study findings suggest there are a number of PRO protocol checklist items that are not fully addressed by the current SPIRIT statement. We therefore advocate the development of consensus-based supplementary guidelines, aimed at improving the completeness and quality of PRO content in clinical trial protocols.
authors.affiliation: Primary Care and Clinical Sciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Derek
authors.initials: D
authors.lastname: Kyte
authors.affiliation: Primary Care and Clinical Sciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Helen
authors.initials: H
authors.lastname: Duffy
authors.affiliation: The Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Fletcher
authors.affiliation: Department of Global Health and Development, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: Adrian
authors.initials: A
authors.lastname: Gheorghe
authors.affiliation: Quality of Life Office, Psycho-oncology Co-operative Research Group, School of Psychology, University of Sydney, Sydney, Australia.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Mercieca-Bebber
authors.affiliation: Quality of Life Office, Psycho-oncology Co-operative Research Group, School of Psychology, University of Sydney, Sydney, Australia.
authors.forename: Madeleine
authors.initials: M
authors.lastname: King
authors.affiliation: Medicine, Ethics, Society and History, University of Birmingham, Birmingham, United Kingdom; MRC Midland Hub for Trials Methodology Research, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Heather
authors.initials: H
authors.lastname: Draper
authors.affiliation: Medicine, Ethics, Society and History, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Ives
authors.affiliation: Queens University, Kingston, Ontario, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Brundage
authors.affiliation: Medical Research Council ConDuCT II Hub for Trials Methodology Research, School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Jane
authors.initials: J
authors.lastname: Blazeby
authors.affiliation: Primary Care and Clinical Sciences, University of Birmingham, Birmingham, United Kingdom; MRC Midland Hub for Trials Methodology Research, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Melanie
authors.initials: M
authors.lastname: Calvert
mesh_terms: D057189:Checklist; D002986:Clinical Trials as Topic; D016208:Databases, Factual; D019983:Guideline Adherence; D006801:Humans; D063868:Patient Outcome Assessment; D057566:Self Report