title: Detection in blood of autoantibodies to tumour antigens as a case-finding method in lung cancer using the EarlyCDT®-Lung Test (ECLS): study protocol for a randomized controlled trial.
abstract: Lung cancer is the most common cause of cancer related death worldwide. The majority of cases are detected at a late stage when prognosis is poor. The EarlyCDT®-Lung Test detects autoantibodies to abnormal cell surface proteins in the earliest stages of the disease which may allow tumour detection at an earlier stage thus altering prognosis. The primary research question is: Does using the EarlyCDT®-Lung Test to identify those at high risk of lung cancer, followed by X-ray and computed tomography (CT) scanning, reduce the incidence of patients with late-stage lung cancer (III & IV) or unclassified presentation (U) at diagnosis, compared to standard practice?
  
  
  
  A randomised controlled trial of 12 000 participants in areas of Scotland targeting general practices serving patients in the most deprived quintile of the Scottish Index of Multiple Deprivation. Adults aged 50-75 who are at high risk of lung cancer and healthy enough to undergo potentially curative therapy (Performance Status 0-2) are eligible to participate. The intervention is the EarlyCDT®-Lung Test, followed by X-ray and CT in those with a positive result. The comparator is standard clinical practice in the UK. The primary outcome is the difference, after 24 months, between the rates of patients with stage III, IV or unclassified lung cancer at diagnosis. The secondary outcomes include: all-cause mortality; disease specific mortality; a range of morbidity outcomes; cost-effectiveness and measures examining the psychological and behavioural consequences of screening. Participants with a positive test result but for whom the CT scan does not lead to a lung cancer diagnosis will be offered 6 monthly thoracic CTs for 24 months. An initial chest X-ray will be used to determine the speed and the need for contrast in the first screening CT. Participants who are found to have lung cancer will be followed-up to assess both time to diagnosis and stage of disease at diagnosis.
  
  
  
  The study will determine the clinical and cost effectiveness of EarlyCDT®-Lung Test for early lung cancer detection and assess its suitability for a large-scale, accredited screening service. The study will also assess the potential psychological and behavioural harms arising from false positive or false negative results, as well as the potential benefits to patients of true negative EarlyCDT lung test results. A cost-effectiveness model of lung cancer screening based on the results of the EarlyCDT Lung Test study will be developed.
  
  
  
  NCT01925625 . August 19, 2013.
authors.affiliation: Gordon F. Cheesbrough Research Chair & Director of UTOPIAN, Department of Family and Community Medicine University of Toronto, North York General Hospital, 4001 Leslie St LE140, Toronto, ON, M2K 1E1, Canada. Frank.Sullivan@nygh.on.ca.
authors.forename: F M
authors.initials: FM
authors.lastname: Sullivan
authors.affiliation: School of Medicine,, St Andrews University, St Andrews, UK.
authors.forename: Eoghan
authors.initials: E
authors.lastname: Farmer
authors.affiliation: General Practice and Primary Care, Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
authors.forename: Frances S
authors.initials: FS
authors.lastname: Mair
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Shaun
authors.initials: S
authors.lastname: Treweek
authors.affiliation: School of Medicine, Division of Primary Care, Floor 13, Tower Building, University Park, Nottingham, UK.
authors.forename: Denise
authors.initials: D
authors.lastname: Kendrick
authors.affiliation: School of Medicine, University of Central Lancashire, Preston, UK.
authors.forename: Cathy
authors.initials: C
authors.lastname: Jackson
authors.affiliation: Department of Mathematics and Statistics, Livingstone Tower, 26 Richmond Street, Glasgow, G1 1XH, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Robertson
authors.affiliation: Health Economics & Health Technology Assessment, Institute of Health & Wellbeing, University of Glasgow, Glasgow, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Briggs
authors.affiliation: Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
authors.forename: Colin
authors.initials: C
authors.lastname: McCowan
authors.affiliation: School of Medicine, Division of Primary Care, Medical School, Queen's Medical Centre, Nottingham, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Bedford
authors.affiliation: School of Medicine, Division of Primary Care, Medical School, Queen's Medical Centre, Nottingham, UK.
authors.forename: Ben
authors.initials: B
authors.lastname: Young
authors.affiliation: School of Medicine, Division of Primary Care, Floor 13, Tower Building, University Park, Nottingham, UK.
authors.forename: Kavita
authors.initials: K
authors.lastname: Vedhara
authors.affiliation: Clinical Trial Manager, Tayside Clinical Trials Unit, University of Dundee, Dundee, UK.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gallant
authors.affiliation: Senior Clinical Trial Manager, Tayside Clinical Trials Unit, University of Dundee, Dundee, UK.
authors.forename: Roberta
authors.initials: R
authors.lastname: Littleford
authors.affiliation: Graduate Entry Medicine & Health School (GEMS), University of Nottingham, Royal Derby Hospital, Nottingham, UK.
authors.forename: John
authors.initials: J
authors.lastname: Robertson
authors.affiliation: Division of Immunology, School of Life Sciences, Queens Medical Centre, Nottingham, UK.
authors.forename: Herb
authors.initials: H
authors.lastname: Sewell
authors.affiliation: Consultant Physician, NHS Greater Glasgow & Clyde, Glasgow, UK.
authors.forename: Alistair
authors.initials: A
authors.lastname: Dorward
authors.affiliation: The Queen Elizabeth University Hospital Glasgow, 1345 Govan Road, Glasgow, G51 4TF, UK.
authors.forename: Joseph
authors.initials: J
authors.lastname: Sarvesvaran
authors.affiliation: Consultant Respiratory Physician, Ninewells Hospital, Dundee, UK.
authors.forename: Stuart
authors.initials: S
authors.lastname: Schembri
mesh_terms: D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D003362:Cost-Benefit Analysis; D055088:Early Detection of Cancer / Q000191:economics / Q000379:methods*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000276:immunology; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D009367:Neoplasm Staging; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D014057:Tomography, X-Ray Computed; D014965:X-Rays
chemical_list: D001323:Autoantibodies
keywords: Autoantibodies; Biomarker; Early diagnosis; Health economics; Lung cancer; Primary care; RCT; Screening