Recommendations for clinical research in children presenting to primary care out-of-hours services: a randomised controlled trial with parallel cohort study

BACKGROUND: Research in primary care is essential, but recruiting children in this setting can be complex and may cause selection bias. Challenges surrounding informed consent, particularly in an acute clinical setting, can undermine feasibility. The off-protocol use of an intervention nearing implementation has become common in pragmatic randomised controlled trials (RCTs) set in primary care. AIM: To describe how the informed consent procedure affects study inclusion and to assess how off-protocol medication prescribing affects participant selection in a paediatric RCT. DESIGN & SETTING: A pragmatic RCT evaluating the cost-effectiveness of oral ondansetron in children diagnosed with acute gastroenteritis (AGE) in primary care out-of-hours services and a parallel cohort study. METHOD: Consecutive children aged 6 months to 6 years attending primary care out-of-hours services with AGE were evaluated to assess the feasibility of obtaining informed consent, the off-protocol use of ondansetron, and other inclusion and exclusion criteria. RESULTS: The RCT's feasibility was reduced by the informed consent procedure because 39.0% (n = 325/834) of children were accompanied by only one parent. GPs prescribed ondansetron off-protocol to 34 children (4.1%) of which 19 children were eligible for the RCT. RCT-eligible children included in the parallel cohort study had fewer risk factors for dehydration than children in the RCT despite similar dehydration assessments by GPs. CONCLUSION: The informed consent procedure and off-protocol use of study medication affect the inclusion rate, but had little effect on selection. A parallel cohort study alongside the RCT can help evaluate selection bias, and a pilot study can reveal potential barriers to inclusion.