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Headline
Evolving IT security and electronic record requirements hampered platform function resulting in poor recruitment and early trial closure, and the authors make recommendations about electronic platforms for primary care research.
Abstract
Background:
Acute otitis media is a painful infection of the middle ear that is commonly seen in children. In some children, the eardrum spontaneously bursts, discharging visible pus (otorrhoea) into the outer ear.
Objective:
To compare the clinical effectiveness of immediate topical antibiotics or delayed oral antibiotics with the clinical effectiveness of immediate oral antibiotics in reducing symptom duration in children presenting to primary care with acute otitis media with discharge and the economic impact of the alternative strategies.
Design:
This was a pragmatic, three-arm, individually randomised (stratified by age < 2 vs. ≥ 2 years), non-inferiority, open-label trial, with economic and qualitative evaluations, supported by a health-record-integrated electronic trial platform [TRANSFoRm (Translational Research and Patient Safety in Europe)] with an internal pilot.
Setting:
A total of 44 English general practices.
Participants:
Children aged ≥ 12 months and < 16 years whose parents (or carers) were seeking medical care for unilateral otorrhoea (ear discharge) following recent-onset (≤ 7 days) acute otitis media.
Interventions:
(1) Immediate ciprofloxacin (0.3%) solution, four drops given three times daily for 7 days, or (2) delayed ‘dose-by-age’ amoxicillin suspension given three times daily (clarithromycin twice daily if the child was penicillin allergic) for 7 days, with structured delaying advice. All parents were given standardised information regarding symptom management (paracetamol/ibuprofen/fluids) and advice to complete the course.
Comparator:
Immediate ‘dose-by-age’ oral amoxicillin given three times daily (or clarithromycin given twice daily) for 7 days. Parents received standardised symptom management advice along with advice to complete the course.
Main outcome measure:
Time from randomisation to the first day on which all symptoms (pain, fever, being unwell, sleep disturbance, otorrhoea and episodes of distress/crying) were rated ‘no’ or ‘very slight’ problem (without need for analgesia).
Methods:
Participants were recruited from routine primary care appointments. The planned sample size was 399 children. Follow-up used parent-completed validated symptom diaries.
Results:
Delays in software deployment and configuration led to small recruitment numbers and trial closure at the end of the internal pilot. Twenty-two children (median age 5 years; 62% boys) were randomised: five, seven and 10 to immediate oral, delayed oral and immediate topical antibiotics, respectively. All children received prescriptions as randomised. Seven (32%) children fully adhered to the treatment as allocated. Symptom duration data were available for 17 (77%) children. The median (interquartile range) number of days until symptom resolution in the immediate oral, delayed oral and immediate topical antibiotic arms was 6 (4–9), 4 (3–7) and 4 (3–6), respectively. Comparative analyses were not conducted because of small numbers. There were no serious adverse events and six reports of new or worsening symptoms. Qualitative clinician interviews showed that the trial question was important. When the platform functioned as intended, it was liked. However, staff reported malfunctioning software for long periods, resulting in missed recruitment opportunities. Troubleshooting the software placed significant burdens on staff.
Limitations:
The over-riding weakness was the failure to recruit enough children.
Conclusions:
We were unable to answer the main research question because of a failure to reach the required sample size. Our experience of running an electronic platform-supported trial in primary care has highlighted challenges from which we have drawn recommendations for the National Institute for Health Research (NIHR) and the research community. These should be considered before such a platform is used again.
Trial registration:
Current Controlled Trials ISRCTN12873692 and EudraCT 2017-003635-10.
Funding:
This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 67. See the NIHR Journals Library website for further project information.
Contents
About the Series
Declared competing interests of authors: Alastair D Hay is a member of the Efficacy and Mechanism Evaluation (EME) Funding Committee (2019–present), is a National Institute for Health Research (NIHR) Senior Investigator (NIHR200151) and is a member of the National Institute for Health and Care Excellence Common Infections Committee. Vibhore Prasad is a NIHR Academic Clinical Lecturer in General Practice (2019–present). Paul Little was a member of the NIHR Journals Library Board while Director of the Programme Grants for Applied Research (PGfAR) programme (2013–18). Anne Schilder is Director of the NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London Hearing Theme (London, UK) and is the National Specialty Lead of the NIHR Clinical Research Network Ear, Nose and Throat (ENT); in these roles, Anne Schilder advises companies in the hearing field on the design and delivery of clinical trials. Her evidENT research team at the University College London Ear Institute (London, UK) receives support from various funders, including NIHR, the European Union (EU) Horizon 2020 (Brussels, Belgium) and the Wellcome Trust (London, UK). Roderick Venekamp reports grants from the Netherlands Organisation for Health Research and Development (ZonMw; The Hague, the Netherlands) during the conduct of the study.
Article history
The research reported in this issue of the journal was funded by the HTA programme as project number 16/85/01. The contractual start date was in January 2018. The draft report began editorial review in September 2020 and was accepted for publication in June 2021. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.
Last reviewed: September 2020; Accepted: June 2021.
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Joint lead authors
- NLM CatalogRelated NLM Catalog Entries
- Immediate oral versus immediate topical versus delayed oral antibiotics for chil...Immediate oral versus immediate topical versus delayed oral antibiotics for children with acute otitis media with discharge: the REST three-arm non-inferiority electronic platform-supported RCT
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