Conservative treatment for uncomplicated appendicitis in children: the CONTRACT feasibility study, including feasibility RCT

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.

Parental Knowledge of Appendicitis and Preference for Operative or Non-Operative Treatment at a United Kingdom Children’s Hospital

“…Whether a preference for non-operative treatment remains once comparative data are available remains to be seen. As with any survey, hypothetical choices made by parents may differ from the choices they may make if their child were to actually develop appendicitis, yet our observations in treating patients and through our research confirm significant interest in non-operative treatment [ 13 , 20 ]. We should also note that this work was undertaken prior to the SARS-CoV-2 pandemic, a period during which there was much greater use of non-operative treatment than had previously been the case—certainly within the UK [ 21 ].…”

Core Outcome Sets in Child Health

“…A total of 37 762 articles were retrieved, of which 37 710 were identified from the bibliographic databases and 52 were identified via Google and/or relevant websites. A total of 77 COS fulfilled inclusion criteria (published in 98 articles) (eFigure 1 in the Supplement).…”

“…Of the 74 COS with complete methods reporting, only 6 (8%) met all 12 criteria for COS development (eFigure 4 and eTable 4 in the Supplement). Scope was relatively well reported, with 3 specifications for scope found in 98% or more. On the other hand, the consensus process was generally poorly reported; the scoring process (9a) was reported in 17 COS (23%) and consensus definition (9b) and criteria for including/dropping/adding outcomes (10) were reported in 16 COS (22%), 3 of which need to be described a priori.…”

Conservative antibiotic treatment of pediatric acute uncomplicated appendicitis during the COVID-19 pandemic: a prospective comparative cohort study

“…The CONTRACT feasibility study identified key cost drivers as cost of inpatient ward stay and cost of surgery. The study included outpatient costs up to the 6 months follow-up period and evidenced a significant cost reduction in the non-operative treatment arm as compared to the appendectomy arm ( p < 0.001) [ 18 ]. In the randomized controlled study conducted by Hansson et al there was similarly a significant cost reduction associated with the antibiotic treatment group though limited to only in-hospital costs incurred [ 19 ].…”