title: A note on the design of cancer screening trials.
abstract: OBJECTIVE
  To investigate the consequences of different cancer screening trial designs and follow-up options for accuracy of the estimate of the effect of screening on disease-specific mortality.
  
  
  METHODS
  We consider a randomized trial of breast cancer screening with a screening phase in which the intervention group is offered screening and the control group is not, and optional further follow-up after this screening phase. Postulating a lead time effect similar to that observed in breast cancer screening trials, we calculate the observed relative risk of disease-specific mortality and compare this with the true relative risk, for four design options: (1) no follow-up beyond the screening phase, ie. the screening phase and the observation period are identical; (2) follow-up continuing beyond the screening phase, all cancer-specific deaths counted, including those diagnosed after the screening phase; (3) follow-up continuing beyond the screening phase, but with only deaths from cancers diagnosed during the screening phase included; and (4) follow-up continuing beyond the screening phase, a single screen of the control group conducted at the end of the screening phase, and only deaths from cancers diagnosed during the screening phase in both arms up to completion of the single control screen included.
  
  
  RESULTS
  All designs in which follow-up for mortality continues beyond the screening phase incurred a bias against screening. The design in which the control group undergoes a single screen at the end of the screening phase was least biased in the example used.
  
  
  CONCLUSIONS
  The expedient of a single screen of the control group at the end of the screening phase has acceptable accuracy, but is still slightly conservatively biased.
authors.affiliation: Professor of Cancer Screening, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK s.w.duffy@qmul.ac.uk.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Duffy
authors.affiliation: Senior Director, Cancer Screening, American Cancer Society Inc, 250 Williams St, Atlanta GA 30303, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Smith
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008403:Mass Screening; D016032:Randomized Controlled Trials as Topic
keywords: Cancer screening; follow-up; trial design