title: Standardisation of information submitted to an endpoint committee for cause of death assignment in a cancer screening trial – lessons learnt from CAP (Cluster randomised triAl of PSA testing for Prostate cancer).
abstract: BACKGROUND
  In cancer screening trials where the primary outcome is target cancer-specific mortality, the unbiased determination of underlying cause of death (UCD) is crucial. To minimise bias, the UCD should be independently verified by expert reviewers, blinded to death certificate data and trial arm. We investigated whether standardising the information submitted for UCD assignment in a population-based randomised controlled trial of prostate-specific antigen (PSA) testing for prostate cancer reduced the reviewers' ability to correctly guess the trial arm.
  
  
  METHODS
  Over 550 General Practitioner (GP) practices (>415,000 men aged 50-69 years) were cluster-randomised to PSA testing (intervention arm) or the National Health Service (NHS) prostate cancer risk management programme (control arm) between 2001 and 2007. Assignment of UCD was by independent reviews of researcher-written clinical vignettes that masked trial arm and death certificate information. A period of time after the process began (the initial phase), we analysed whether the reviewers could correctly identify trial arm from the vignettes, and the reasons for their choice. This feedback led to further standardisation of information (second phase), after which we re-assessed the extent of correct identification of trial arm.
  
  
  RESULTS
  1099 assessments of 509 vignettes were completed by January 2014. In the initial phase (n = 510 assessments), reviewers were unsure of trial arm in 33% of intervention and 30% of control arm assessments and were influenced by symptoms at diagnosis, PSA test result and study-specific criteria. In the second phase (n = 589), the respective proportions of uncertainty were 45% and 48%. The percentage of cases whereby reviewers were unable to determine the trial arm was greater following the standardisation of information provided in the vignettes. The chances of a correct guess and an incorrect guess were equalised in each arm, following further standardisation.
  
  
  CONCLUSIONS
  It is possible to mask trial arm from cause of death reviewers, by using their feedback to standardise the information submitted to them.
  
  
  BACKGROUND
  ISRCTN92187251.
authors.affiliation: School of Social and Community Medicine, University of Bristol, based at Royal Hallamshire Hospital, Sheffield, S10 2JF, UK. naomi.williams@sth.nhs.uk.
authors.forename: Naomi J
authors.initials: NJ
authors.lastname: Williams
authors.affiliation: School of Social and Community Medicine, University of Bristol, Canynge Hall, Bristol, BS8 2PS, UK. liz.hill@bristol.ac.uk.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Hill
authors.affiliation: School of Social and Community Medicine, University of Bristol, based at Freeman Hospital, High Heaton, Newcastle-upon-Tyne, NE7 7DN, UK. siawyein.Ng@nuth.nhs.uk.
authors.forename: Siaw Yein
authors.initials: SY
authors.lastname: Ng
authors.affiliation: School of Social and Community Medicine, University of Bristol, Canynge Hall, Bristol, BS8 2PS, UK. richard.martin@bristol.ac.uk.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Martin
authors.affiliation: School of Social and Community Medicine, University of Bristol, Canynge Hall, Bristol, BS8 2PS, UK. chris.metcalfe@bristol.ac.uk.
authors.forename: Chris
authors.initials: C
authors.lastname: Metcalfe
authors.affiliation: School of Social and Community Medicine, University of Bristol, Canynge Hall, Bristol, BS8 2PS, UK. jenny.donovan@bristol.ac.uk.
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Donovan
authors.affiliation: Royal United Hospital, Bath, BA1 3NG, UK. simonevans47@hotmail.com.
authors.forename: Simon
authors.initials: S
authors.lastname: Evans
authors.affiliation: Department of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK. hughes_laura@outlook.com.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Hughes
authors.affiliation: School of Social and Community Medicine, University of Bristol, Canynge Hall, Bristol, BS8 2PS, UK. charlotte.davies@bristol.ac.uk.
authors.forename: Charlotte F
authors.initials: CF
authors.lastname: Davies
authors.affiliation: Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK. charlotte.davies@bristol.ac.uk.
authors.forename: Freddie C
authors.initials: FC
authors.lastname: Hamdy
authors.affiliation: Department of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK. den22@cam.ac.uk.
authors.forename: David E
authors.initials: DE
authors.lastname: Neal
authors.affiliation: School of Social and Community Medicine, University of Bristol, Canynge Hall, Bristol, BS8 2PS, UK. emma.turner@bristol.ac.uk.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Turner
mesh_terms: D000368:Aged; D002423:Cause of Death; D003362:Cost-Benefit Analysis; D055088:Early Detection of Cancer / Q000191:economics / Q000379:methods*; D058005:General Practitioners / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000191:economics / Q000379:methods*; D008499:Medical Records / Q000592:standards / Q000706:statistics & numerical data*; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000517:prevention & control; D012015:Reference Standards; D012107:Research Design; D006113:United Kingdom
chemical_list: D017430:Prostate-Specific Antigen