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

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

Sue Jordan  1 , Alan Watkins, Mel Storey, Steven J Allen, Caroline J Brooks, Iveta Garaiova, Martin L Heaven, Ruth Jones, Sue F Plummer, Ian T Russell, Catherine A Thornton, Gareth Morgan
Affiliations

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

Sue Jordan et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: S. Jordan, S. J. Allen, C. A. Thornton, A. Watkins, R. Jones, I. Russell, C. J. Brooks, M. L. Heaven, and G. Morgan declare no conflicts of interest. M. Storey received financial support from Cultech Ltd. I. Garaiova is a Senior Research Manager and S. F. Plummer is the Managing Director, Obsidian Research Ltd. The affiliations of two authors and the commercial funding, along with any other relevant declarations relating to employment, products in development does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials, as detailed in the online guide for authors. The product in the trial was not commercially available at the time of the trial.

Figures

Figure 1
Figure 1. Participant Flow Diagram for observation study to 6 month contact point.
Figure 2
Figure 2. Participant Flow Diagram for observation study to 2 year contact point.
Figure 3
Figure 3. Proportion in each deprivation (Townsend) fifth in the population and each stage of the trial.
Figure 4
Figure 4. Proportion of participants from ONS Category 3 at each stage of the trial.
Figure 5
Figure 5. Comparison of proportion of smokers at each stage of the trial.
Figure 6
Figure 6. Women lost to follow up at 6 months compared with the whole sample.
See this image and copyright information in PMC

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