Abstract
Background
Although non-operative treatment is known to be effective for the treatment of uncomplicated acute appendicitis in children, randomised trial data comparing important outcomes of non-operative treatment with those of appendicectomy are lacking.
Objectives
The objectives were to ascertain the feasibility of conducting a multicentre randomised controlled trial comparing the clinical effectiveness and cost-effectiveness of a non-operative treatment pathway with appendicectomy for the treatment of uncomplicated acute appendicitis in children.
Design
This was a mixed-methods study, which included a feasibility randomised controlled trial, embedded and parallel qualitative and survey studies, a parallel health economic feasibility study and the development of a core outcome set.
Setting
This study was set in three specialist NHS paediatric surgical units in England.
Participants
Children (aged 4–15 years) clinically diagnosed with uncomplicated acute appendicitis participated in the feasibility randomised controlled trial. Children, their families, recruiting clinicians and other health-care professionals involved in caring for children with appendicitis took part in the qualitative study. UK specialist paediatric surgeons took part in the survey. Specialist paediatric surgeons, adult general surgeons who treat children, and children and young people who previously had appendicitis, along with their families, took part in the development of the core outcome set.
Interventions
Participants in the feasibility randomised controlled trial were randomised to a non-operative treatment pathway (broad-spectrum antibiotics and active observation) or appendicectomy.
Main outcome measures
The primary outcome measure was the proportion of eligible patients recruited to the feasibility trial.
Data sources
Data were sourced from NHS case notes, questionnaire responses, transcribed audio-recordings of recruitment discussions and qualitative interviews.
Results
Overall, 50% (95% confidence interval 40% to 59%) of 115 eligible patients approached about the trial agreed to participate and were randomised. There was high acceptance of randomisation and good adherence to trial procedures and follow-up (follow-up rates of 89%, 85% and 85% at 6 weeks, 3 months and 6 months, respectively). More participants had perforated appendicitis than had been anticipated. Qualitative work enabled us to communicate about the trial effectively with patients and families, to design and deliver bespoke training to optimise recruitment and to understand how to optimise the design and delivery of a future trial. The health economic study indicated that the main cost drivers are the ward stay cost and the cost of the operation; it has also informed quality-of-life assessment methods for future work. A core outcome set for the treatment of uncomplicated acute appendicitis in children and young people was developed, containing 14 outcomes. There is adequate surgeon interest to justify proceeding to an effectiveness trial, with 51% of those surveyed expressing a willingness to recruit with an unchanged trial protocol.
Limitations
Because the feasibility randomised controlled trial was performed in only three centres, successful recruitment across a larger number of sites cannot be guaranteed. However, the qualitative work has informed a bespoke training package to facilitate this. Although survey results suggest adequate clinician interest to make a larger trial possible, actual participation may differ, and equipoise may have changed over time.
Conclusions
A future effectiveness trial is feasible, following limited additional preparation, to establish appropriate outcome measures and case identification. It is recommended to include a limited package of qualitative work to optimise recruitment, in particular at new centres.
Future work
Prior to proceeding to an effectiveness trial, there is a need to develop a robust method for distinguishing children with uncomplicated acute appendicitis from those with more advanced appendicitis, and to reach agreement on a primary outcome measure and effect size that is acceptable to all stakeholder groups involved.
Trial registration
Current Controlled Trials ISRCTN15830435.
Funding
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 10. See the NIHR Journals Library website for further project information.
•Interventions
Participants in the feasibility RCT were randomised to a non-operative treatment pathway (broadspectrum antibiotics and active observation) or appendicectomy.
•Main outcome measures
Primary outcome measure was the proportion of eligible patients recruited to the feasibility trial.
•Data sources
NHS casenotes, questionnaire responses, transcribed audio recordings of recruitment discussions and qualitative interviews
•Results
Overall, 50% (95%CI 40-59) of 115 eligible participants approached about the trial agreed to participate and were randomised. There was high acceptance of randomisation and good adherence to trial procedures and follow-up (follow rates of 89%, 85% and 85% at six weeks, three months and six months respectively). More participants had perforated appendicitis than had been anticipated. Qualitative work enabled us to: communicate about the trial effectively with patients and families; design and deliver bespoke training to optimise recruitment; and understand how to optimise design and delivery of a future trial. The health economic study, indicated that the main cost drivers are the ward stay cost and the cost of the operation, and has informed quality of life assessment methods for future work. A core outcome set for the treatment of uncomplicated acute appendicitis in children and young people was developed, containing 14 outcomes. There is adequate surgeon interest to justify proceeding to an effectiveness trial with 51% of those surveyed expressing a willingness to recruit with an unchanged trial protocol.
•Limitations
Since the feasibility RCT was only performed in three centres we cannot guarantee successful recruitment across a larger number of sites. However, our qualitative work has informed a bespoke training package to facilitate this. Although survey results suggest adequate clinician interest to make a larger trial possible, actual participation may differ, and equipoise may have moved over time.
•Conclusions
A future effectiveness trial is feasible following limited additional preparation to establish appropriate outcome measures and case identification. We recommend a limited package of qualitative work be included to optimise recruitment at new centres in particular.
•Future work
Prior to proceeding to an effectiveness trial we need to: develop a robust method for distinguishing children with uncomplicated acute appendicitis from those with more advanced appendicitis; reach agreement on a primary outcome measure and effect size that is acceptable to all stakeholder groups involved.
Although non-operative treatment is known to be effective for the treatment of uncomplicated acute appendicitis in children, randomised trial data comparing important outcomes of non-operative treatment with those of appendicectomy are lacking.
Objectives
The objectives were to ascertain the feasibility of conducting a multicentre randomised controlled trial comparing the clinical effectiveness and cost-effectiveness of a non-operative treatment pathway with appendicectomy for the treatment of uncomplicated acute appendicitis in children.
Design
This was a mixed-methods study, which included a feasibility randomised controlled trial, embedded and parallel qualitative and survey studies, a parallel health economic feasibility study and the development of a core outcome set.
Setting
This study was set in three specialist NHS paediatric surgical units in England.
Participants
Children (aged 4–15 years) clinically diagnosed with uncomplicated acute appendicitis participated in the feasibility randomised controlled trial. Children, their families, recruiting clinicians and other health-care professionals involved in caring for children with appendicitis took part in the qualitative study. UK specialist paediatric surgeons took part in the survey. Specialist paediatric surgeons, adult general surgeons who treat children, and children and young people who previously had appendicitis, along with their families, took part in the development of the core outcome set.
Interventions
Participants in the feasibility randomised controlled trial were randomised to a non-operative treatment pathway (broad-spectrum antibiotics and active observation) or appendicectomy.
Main outcome measures
The primary outcome measure was the proportion of eligible patients recruited to the feasibility trial.
Data sources
Data were sourced from NHS case notes, questionnaire responses, transcribed audio-recordings of recruitment discussions and qualitative interviews.
Results
Overall, 50% (95% confidence interval 40% to 59%) of 115 eligible patients approached about the trial agreed to participate and were randomised. There was high acceptance of randomisation and good adherence to trial procedures and follow-up (follow-up rates of 89%, 85% and 85% at 6 weeks, 3 months and 6 months, respectively). More participants had perforated appendicitis than had been anticipated. Qualitative work enabled us to communicate about the trial effectively with patients and families, to design and deliver bespoke training to optimise recruitment and to understand how to optimise the design and delivery of a future trial. The health economic study indicated that the main cost drivers are the ward stay cost and the cost of the operation; it has also informed quality-of-life assessment methods for future work. A core outcome set for the treatment of uncomplicated acute appendicitis in children and young people was developed, containing 14 outcomes. There is adequate surgeon interest to justify proceeding to an effectiveness trial, with 51% of those surveyed expressing a willingness to recruit with an unchanged trial protocol.
Limitations
Because the feasibility randomised controlled trial was performed in only three centres, successful recruitment across a larger number of sites cannot be guaranteed. However, the qualitative work has informed a bespoke training package to facilitate this. Although survey results suggest adequate clinician interest to make a larger trial possible, actual participation may differ, and equipoise may have changed over time.
Conclusions
A future effectiveness trial is feasible, following limited additional preparation, to establish appropriate outcome measures and case identification. It is recommended to include a limited package of qualitative work to optimise recruitment, in particular at new centres.
Future work
Prior to proceeding to an effectiveness trial, there is a need to develop a robust method for distinguishing children with uncomplicated acute appendicitis from those with more advanced appendicitis, and to reach agreement on a primary outcome measure and effect size that is acceptable to all stakeholder groups involved.
Trial registration
Current Controlled Trials ISRCTN15830435.
Funding
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 10. See the NIHR Journals Library website for further project information.
•Interventions
Participants in the feasibility RCT were randomised to a non-operative treatment pathway (broadspectrum antibiotics and active observation) or appendicectomy.
•Main outcome measures
Primary outcome measure was the proportion of eligible patients recruited to the feasibility trial.
•Data sources
NHS casenotes, questionnaire responses, transcribed audio recordings of recruitment discussions and qualitative interviews
•Results
Overall, 50% (95%CI 40-59) of 115 eligible participants approached about the trial agreed to participate and were randomised. There was high acceptance of randomisation and good adherence to trial procedures and follow-up (follow rates of 89%, 85% and 85% at six weeks, three months and six months respectively). More participants had perforated appendicitis than had been anticipated. Qualitative work enabled us to: communicate about the trial effectively with patients and families; design and deliver bespoke training to optimise recruitment; and understand how to optimise design and delivery of a future trial. The health economic study, indicated that the main cost drivers are the ward stay cost and the cost of the operation, and has informed quality of life assessment methods for future work. A core outcome set for the treatment of uncomplicated acute appendicitis in children and young people was developed, containing 14 outcomes. There is adequate surgeon interest to justify proceeding to an effectiveness trial with 51% of those surveyed expressing a willingness to recruit with an unchanged trial protocol.
•Limitations
Since the feasibility RCT was only performed in three centres we cannot guarantee successful recruitment across a larger number of sites. However, our qualitative work has informed a bespoke training package to facilitate this. Although survey results suggest adequate clinician interest to make a larger trial possible, actual participation may differ, and equipoise may have moved over time.
•Conclusions
A future effectiveness trial is feasible following limited additional preparation to establish appropriate outcome measures and case identification. We recommend a limited package of qualitative work be included to optimise recruitment at new centres in particular.
•Future work
Prior to proceeding to an effectiveness trial we need to: develop a robust method for distinguishing children with uncomplicated acute appendicitis from those with more advanced appendicitis; reach agreement on a primary outcome measure and effect size that is acceptable to all stakeholder groups involved.
| Original language | English |
|---|---|
| Pages (from-to) | 1-228 |
| Number of pages | 228 |
| Journal | Health Technology Assessment |
| Volume | 25 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 1 Feb 2021 |
Bibliographical note
Funding Information:The research reported in this issue of the journal was funded by the HTA programme as project number 14/192/90. The contractual start date was in July 2016. The draft report began editorial review in January 2019 and was accepted for publication in December 2019. 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.
Funding Information:
This report presents independent research funded by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, NETSCC, the HTA programme or the Department of Health and Social Care. If there are verbatim quotations included in this publication the views and opinions expressed by the interviewees are those of the interviewees and do not necessarily reflect those of the authors, those of the NHS, the NIHR, NETSCC, the HTA programme or the Department of Health and Social Care.
Funding Information:
Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 10. See the NIHR Journals Library website for further project information.
Publisher Copyright:
© 2021 Hall et al.