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

PLoS One. 2013 Jul 9;8(7):e67912. doi: 10.1371/journal.pone.0067912. Print 2013.

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.

Methods and 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.

Trial registration: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Longitudinal Studies
  • Male
  • Mothers
  • Outcome and Process Assessment, Health Care
  • Randomized Controlled Trials as Topic*
  • Research Design*
  • Risk Factors
  • Selection Bias*
  • Volunteers*

Associated data

  • ISRCTN/ISRCTN26287422

Grant support

The project was supported by the Knowledge Exploitation Fund, Collaborative Industrial Research (project number HE09 COL 1002), Welsh Development Agency, United Kingdom (UK) and Cultech Limited, Unit 3, Christchurch Rd, Baglan Industrial Park, Port Talbot, SA12 7BZ, UK. Cultech Ltd. UK part funded the trial and provided the probiotic and matching placebo, and generated the random allocation sequence. Sue Plummer is a Director of Cultech and advised on study design and contributed to the final report. The sponsors were not involved in data collection, analysis or interpretation of the findings. The Knowledge Exploitation Fund had no involvement in the conduct of the trial. The funders had no role in data collection and analysis, decision to publish, or preparation of the manuscript. Dr. Sue Plummer proposed the product to be researched and commented on the study design. Dr. Sue Plummer and Dr. Iveta Garaiova commented on the manuscript prepared by Sue Jordan to ensure clarity. No changes to the findings were either suggested or made.