title: Patient-reported outcome (PRO) assessment in clinical trials: a systematic review of guidance for trial protocol writers.
abstract: BACKGROUND
  Evidence suggests there are inconsistencies in patient-reported outcome (PRO) assessment and reporting in clinical trials, which may limit the use of these data to inform patient care. For trials with a PRO endpoint, routine inclusion of key PRO information in the protocol may help improve trial conduct and the reporting and appraisal of PRO results; however, it is currently unclear exactly what PRO-specific information should be included. The aim of this review was to summarize the current PRO-specific guidance for clinical trial protocol developers.
  
  
  RESULTS
  We searched the MEDLINE, EMBASE, CINHAL and Cochrane Library databases (inception to February 2013) for PRO-specific guidance regarding trial protocol development. Further guidance documents were identified via Google, Google scholar, requests to members of the UK Clinical Research Collaboration registered clinical trials units and international experts. Two independent investigators undertook title/abstract screening, full text review and data extraction, with a third involved in the event of disagreement. 21,175 citations were screened and 54 met the inclusion criteria. Guidance documents were difficult to access: electronic database searches identified just 8 documents, with the remaining 46 sourced elsewhere (5 from citation tracking, 27 from hand searching, 7 from the grey literature review and 7 from experts). 162 unique PRO-specific protocol recommendations were extracted from included documents. A further 10 PRO recommendations were identified relating to supporting trial documentation. Only 5/162 (3%) recommendations appeared in ≥50% of guidance documents reviewed, indicating a lack of consistency.
  
  
  CONCLUSIONS
  PRO-specific protocol guidelines were difficult to access, lacked consistency and may be challenging to implement in practice. There is a need to develop easily accessible consensus-driven PRO protocol guidance. Guidance should be aimed at ensuring key PRO information is routinely included in appropriate trial protocols, in order to facilitate rigorous collection/reporting of PRO data, to effectively inform patient care.
authors.affiliation: Primary Care and Clinical Sciences, University of Birmingham, Birmingham, United Kingdom; MRC Midland Hub for Trials Methodology Research, Birmingham, United Kingdom.
authors.forename: Melanie
authors.initials: M
authors.lastname: Calvert
authors.affiliation: Primary Care and Clinical Sciences, University of Birmingham, Birmingham, United Kingdom; School of Sport, Exercise & Rehabilitation, 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: 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: Psycho-oncology Co-operative Research Group, University of Sydney, Sydney, Australia.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Mercieca-Bebber
authors.affiliation: Medicine. Ethics, Society and History, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Ives
authors.affiliation: MRC Midland Hub for Trials Methodology Research, Birmingham, United Kingdom; Medicine. Ethics, Society and History, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Heather
authors.initials: H
authors.lastname: Draper
authors.affiliation: Queens University, Kingston, Ontario, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Brundage
authors.affiliation: MRC 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: Psycho-oncology Co-operative Research Group, University of Sydney, Sydney, Australia.
authors.forename: Madeleine
authors.initials: M
authors.lastname: King
mesh_terms: D002985:Clinical Protocols / Q000592:standards; D002986:Clinical Trials as Topic; D006801:Humans; D063868:Patient Outcome Assessment; D012107:Research Design; D057566:Self Report; D000078202:Systematic Reviews as Topic; D015201:Meta-Analysis as Topic