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

BackgroundThe 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.Methods and ResultsThis 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.ConclusionsPotential 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.Trial RegistrationThis 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.

Probiotics in the prevention of eczema: a randomised controlled trial

“…Details of the recruitment process are described elsewhere 16. Women with known adverse conditions likely to affect them, the fetus, or the outcome of the pregnancy, were excluded.…”

Final year nursing students self-reported understanding of the relevance of bioscience

“…External validity is also jeopardised by missing data for 20 respondents that limited the interpretation of data and therefore the conclusions reached which has implications for implementation of the study findings. Although it was possible to describe demographic characteristics of nonrespondents from available student records, this was not done thereby increasing the potential for volunteer bias (Jordan et al, 2013).…”

Selective serotonin reuptake inhibitor prescribing before, during and after pregnancy: a population‐based study in six European regions

“…SSRI prescribing was recorded independently by the prescriber or pharmacist, and so ascertainment was not reliant on maternal involvement, which can result in potential recall and selection biases. 31,32 The shared data extraction protocol ensured that the study results were as comparable as possible across databases. However, differences did exist between healthcare systems and the type of data available for research.…”