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.

Background Little is known about how breastfeeding rates are affected by drugs routinely administered in labour.Objective To examine a large obstetric data set to investigate potentially modifiable associations between drugs routinely administered in labour and breastfeeding in healthy women and infants.Design Retrospective cohort.Setting The Cardiff (Wales UK) Births Survey.Population A total of 48 366 healthy women delivering healthy singleton babies at term.Methods Analysis of the Cardiff Births Survey.Main outcome measure Association between intrapartum medications and breastfeeding at 48 hours postpartum.Results At 48 hours, 43.3% (20 933/48 366) women were not breastfeeding. Regression analysis confirmed previously reported associations of lower breastfeeding rates with certain demographic indicators, epidural analgesia, intramuscular opioid analgesia and ergometrine. Novel associations were detected with oxytocin alone or in combination with ergometrine administered for prevention of postpartum haemorrhage (PPH), which were associated with reductions of 6-8%, (intramuscular oxytocin OR 0.75, 95% CI 0.61-0.91, intravenous oxytocin OR 0.68, 95% CI 0.57-0.82, oxytocin/ergometrine OR 0.77, 95% CI 0.65-0.91), and prostaglandins administered for induction of labour. The associations were maintained when subgroups, such as primiparous women, women whose labours were neither induced nor augmented, and women not receiving epidural analgesia were considered.Conclusion Prospective studies on drugs in labour are needed to investigate potential causative associations between intrapartum medications and breastfeeding. Such studies will delineate the optimum balance between breastfeeding and maternal health, most importantly the risk of PPH.

BackgroundQualitative research methods are increasingly used within clinical trials to address broader research questions than can be addressed by quantitative methods alone. These methods enable health professionals, service users, and other stakeholders to contribute their views and experiences to evaluation of healthcare treatments, interventions, or policies, and influence the design of trials. Qualitative data often contribute information that is better able to reform policy or influence design.MethodsHealth services researchers, including trialists, clinicians, and qualitative researchers, worked collaboratively to develop a comprehensive portfolio of standard operating procedures (SOPs) for the West Wales Organisation for Rigorous Trials in Health (WWORTH), a clinical trials unit (CTU) at Swansea University, which has recently achieved registration with the UK Clinical Research Collaboration (UKCRC). Although the UKCRC requires a total of 25 SOPs from registered CTUs, WWORTH chose to add an additional qualitative-methods SOP (QM-SOP).ResultsThe qualitative methods SOP (QM-SOP) defines good practice in designing and implementing qualitative components of trials, while allowing flexibility of approach and method. Its basic principles are that: qualitative researchers should be contributors from the start of trials with qualitative potential; the qualitative component should have clear aims; and the main study publication should report on the qualitative component.ConclusionsWe recommend that CTUs consider developing a QM-SOP to enhance the conduct of quantitative trials by adding qualitative data and analysis. We judge that this improves the value of quantitative trials, and contributes to the future development of multi-method trials.

IntroductionPreventable adverse effects of medicines often pass unnoticed, but lead to real harm.InterventionNurse-led monitoring using the structured Adverse Drug Reaction (ADRe) Profile identifies and addresses adverse effects of mental health medicines.ObjectivesThis study investigated the implementation and clinical impact of ADRe, and barriers to and facilitators of sustained utilisation in routine practice.MethodsAdministration of ADRe was observed for 30 residents prescribed mental health medicines in ten care homes. The study pharmacist reviewed completed ADRes against medication records. Policy context was explored in 30 interviews with service users, nurse managers and strategic leads in Wales.ResultsResidents were aged 60–95, and prescribed 1–17 (median 9 [interquartile range (IQR) 7–13]) medicines. ADRe identified a median of 18 [IQR 11.5–23] problems per resident and nurses made 2 [1–2] changes to care per resident. For example: falls were reported for 9 residents, and care was modified for 5; pain was identified in 8 residents, and alleviated for 7; all 6 residents recognised as dyspnoeic were referred to prescribers. Nurses referred 17 of 30 residents to prescribers. Pharmacists recommended review for all 30. Doubts about administering ADRe, sometimes expressed by people who had not yet used it, diminished as it became familiar. ADRe was needed to bridge communication between resident, nurses and prescribers. When barriers of time, complacency, and doctors’ non-availability were overcome, reporting with ADRe made prescribers more likely to heed nurses’ concerns regarding residents’ welfare. Clinical gains were facilitated by one-to-one time, staff-resident relationships, and unification of documentation.ImplicationsTo our knowledge, ADRe is the only instrument that brings a full account of patients’ problems to medication reviews. This juxtaposition of signs and symptoms against prescriptions facilitates dose adjustments and de-prescribing and leads to: reduced pain and sedation; early identification of problems linked to ADRs, such as falls; and timely medication reviews e.g. for dyspnoea.