title: Volunteer bias in recruitment, retention, and blood sample donation in a randomised controlled trial involving mothers and their children at six months and two years: a longitudinal analysis.
abstract: BACKGROUND
  The vulnerability of clinical trials to volunteer bias is under-reported. Volunteer bias is systematic error due to differences between those who choose to participate in studies and those who do not.
  
  
  RESULTS
  This paper extends the applications of the concept of volunteer bias by using data from a trial of probiotic supplementation for childhood atopy in healthy dyads to explore 1) differences between a) trial participants and aggregated data from publicly available databases b) participants and non-participants as the trial progressed 2) impact on trial findings of weighting data according to deprivation (Townsend) fifths in the sample and target populations. 1) a) Recruits (n = 454) were less deprived than the target population, matched for area of residence and delivery dates (n = 6,893) (mean [SD] deprivation scores 0.09[4.21] and 0.79[4.08], t = 3.44, df = 511, p<0.001). b) i) As the trial progressed, representation of the most deprived decreased. These participants and smokers were less likely to be retained at 6 months (n = 430[95%]) (OR 0.29,0.13-0.67 and 0.20,0.09-0.46), and 2 years (n = 380[84%]) (aOR 0.68,0.50-0.93 and 0.55,0.28-1.09), and consent to infant blood sample donation (n = 220[48%]) (aOR 0.72,0.57-0.92 and 0.43,0.22-0.83). ii) Mothers interested in probiotics or research or reporting infants' adverse events or rashes were more likely to attend research clinics and consent to skin-prick testing. Mothers participating to help children were more likely to consent to infant blood sample donation. 2) In one trial outcome, atopic eczema, the intervention had a positive effect only in the over-represented, least deprived group. Here, data weighting attenuated risk reduction from 6.9%(0.9-13.1%) to 4.6%(-1.4-+10.5%), and OR from 0.40(0.18-0.91) to 0.56(0.26-1.21). Other findings were unchanged.
  
  
  CONCLUSIONS
  Potential for volunteer bias intensified during the trial, due to non-participation of the most deprived and smokers. However, these were not the only predictors of non-participation. Data weighting quantified volunteer bias and modified one important trial outcome.
  
  
  BACKGROUND
  This randomised, double blind, parallel group, placebo controlled trial is registered with the International Standard Randomised Controlled Trials Register, Number (ISRCTN) 26287422. Registered title: Probiotics in the prevention of atopy in infants and children.
authors.affiliation: Department of Nursing, The College of Human and Health Sciences, Swansea University, Singleton Park, Swansea, Wales, United Kingdom. s.e.jordan@swansea.ac.uk
authors.forename: Sue
authors.initials: S
authors.lastname: Jordan
authors.forename: Alan
authors.initials: A
authors.lastname: Watkins
authors.forename: Mel
authors.initials: M
authors.lastname: Storey
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Allen
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Brooks
authors.forename: Iveta
authors.initials: I
authors.lastname: Garaiova
authors.forename: Martin L
authors.initials: ML
authors.lastname: Heaven
authors.forename: Ruth
authors.initials: R
authors.lastname: Jones
authors.forename: Sue F
authors.initials: SF
authors.lastname: Plummer
authors.forename: Ian T
authors.initials: IT
authors.lastname: Russell
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Thornton
authors.forename: Gareth
authors.initials: G
authors.lastname: Morgan
mesh_terms: D000328:Adult; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D009035:Mothers; D010043:Outcome and Process Assessment, Health Care; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D012307:Risk Factors; D015983:Selection Bias; D014838:Volunteers