title: Impact on mortality and cancer incidence rates of using random invitation from population registers for recruitment to trials.
abstract: BACKGROUND
  Participants in trials evaluating preventive interventions such as screening are on average healthier than the general population. To decrease this 'healthy volunteer effect' (HVE) women were randomly invited from population registers to participate in the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and not allowed to self refer. This report assesses the extent of the HVE still prevalent in UKCTOCS and considers how certain shortfalls in mortality and incidence can be related to differences in socioeconomic status.
  
  
  METHODS
  Between 2001 and 2005, 202 638 postmenopausal women joined the trial out of 1 243 312 women randomly invited from local health authority registers. The cohort was flagged for deaths and cancer registrations and mean follow up at censoring was 5.55 years for mortality, and 2.58 years for cancer incidence. Overall and cause-specific Standardised Mortality Ratios (SMRs) and Standardised Incidence Ratios (SIRs) were calculated based on national mortality (2005) and cancer incidence (2006) statistics. The Index of Multiple Deprivation (IMD 2007) was used to assess the link between socioeconomic status and mortality/cancer incidence, and differences between the invited and recruited populations.
  
  
  RESULTS
  The SMR for all trial participants was 37%. By subgroup, the SMRs were higher for: younger age groups, extremes of BMI distribution and with each increasing year in trial. There was a clear trend between lower socioeconomic status and increased mortality but less pronounced with incidence. While the invited population had higher mean IMD scores (more deprived) than the national average, those who joined the trial were less deprived.
  
  
  CONCLUSIONS
  Recruitment to screening trials through invitation from population registers does not prevent a pronounced HVE on mortality. The impact on cancer incidence is much smaller. Similar shortfalls can be expected in other screening RCTs and it maybe prudent to use the various mortality and incidence rates presented as guides for calculating event rates and power in RCTs involving women.
authors.affiliation: Gynaecological Oncology, EGA Institute for Women's Health, University College London, London, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Burnell
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Gentry-Maharaj
authors.forename: Andy
authors.initials: A
authors.lastname: Ryan
authors.forename: Sophia
authors.initials: S
authors.lastname: Apostolidou
authors.forename: Mariam
authors.initials: M
authors.lastname: Habib
authors.forename: Jatinderpal
authors.initials: J
authors.lastname: Kalsi
authors.forename: Steven
authors.initials: S
authors.lastname: Skates
authors.forename: Mahesh
authors.initials: M
authors.lastname: Parmar
authors.forename: Mourad W
authors.initials: MW
authors.lastname: Seif
authors.forename: Nazar N
authors.initials: NN
authors.lastname: Amso
authors.forename: Keith
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authors.lastname: Godfrey
authors.forename: David
authors.initials: D
authors.lastname: Oram
authors.forename: Jonathan
authors.initials: J
authors.lastname: Herod
authors.forename: Karin
authors.initials: K
authors.lastname: Williamson
authors.forename: Howard
authors.initials: H
authors.lastname: Jenkins
authors.forename: Tim
authors.initials: T
authors.lastname: Mould
authors.forename: Robert
authors.initials: R
authors.lastname: Woolas
authors.forename: John
authors.initials: J
authors.lastname: Murdoch
authors.forename: Stephen
authors.initials: S
authors.lastname: Dobbs
authors.forename: Simon
authors.initials: S
authors.lastname: Leeson
authors.forename: Derek
authors.initials: D
authors.lastname: Cruickshank
authors.forename: Stuart
authors.initials: S
authors.lastname: Campbell
authors.forename: Lesley
authors.initials: L
authors.lastname: Fallowfield
authors.forename: Ian
authors.initials: I
authors.lastname: Jacobs
authors.forename: Usha
authors.initials: U
authors.lastname: Menon
mesh_terms: D000367:Age Factors; D000368:Aged; D015992:Body Mass Index; D005260:Female; D006801:Humans; D015994:Incidence; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality / Q000517:prevention & control; D018579:Patient Selection; D017698:Postmenopause; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D012959:Socioeconomic Factors; D013997:Time Factors; D006113:United Kingdom / Q000453:epidemiology