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

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.

Appendicitis is usually treated with an operation to remove the appendix. But we have learned, from other research, that some children with appendicitis may not need an operation, and could be treated with antibiotics instead. To find out how these two different treatments compare with one another, we need to do a big study. First, though, we need to see if doing that kind of study would even be possible (or 'feasible'). We carried out a feasibility study that had several parts. First, we did a small study with children who had appendicitis, whereby children were randomly allocated to have either antibiotics or an operation, with an equal chance of having either treatment. Second, we asked parents and health-care staff about why they wanted, or did not want, to take part in that small study. This helped us to understand how to make a bigger future study as acceptable as possible to children, families and surgeons. Third, we asked parents, patients and surgeons what they think are the most important things ­ or 'outcomes' ­ we should look at in future research on children who have appendicitis. From that, we developed a list of outcomes that should be included in our future big study, so we can be certain that the research we do is likely to help parents and surgeons. Overall, we established that a future big study is feasible and we have plenty of information to help us with how to plan it best, so that it has the greatest possible chance of success. We were also guided in all of these steps of the research by a group of parents, children and young people, some of whom had appendicitis and some of whom did not.

Adding emollient bath additives to standard eczema management for children with eczema: the BATHE RCT.

BACKGROUND: Childhood eczema is very common. Treatment often includes emollient bath additives, despite there being little evidence of their effectiveness. OBJECTIVES: To determine the clinical effectiveness and cost-effectiveness of emollient bath additives in the management of childhood eczema. DESIGN: Pragmatic, randomised, open-label, multicentre superiority trial with two parallel groups. SETTING: Ninety-six general practices in Wales, the west of England and southern England. Invitation by personal letter or opportunistically. PARTICIPANTS: Children aged between 12 months and 12 years fulfilling the UK Diagnostic Criteria for Atopic Eczema. Children with inactive or very mild eczema (a score of ≤ 5 on the Nottingham Eczema Severity Scale) were excluded, as were children who bathed less than once per week or whose parents/carers were not prepared to accept randomisation. INTERVENTIONS: The intervention group were prescribed bath additives by their usual clinical team and were asked to use them regularly for 12 months. The control group were asked to use no bath additives for 12 months. Both groups continued standard eczema management, including regular leave-on emollients and topical corticosteroids (TCSs) when required. MAIN OUTCOME MEASURES: The primary outcome was eczema control measured by Patient Oriented Eczema Measure [POEM, 0 (clear) to 28 (severe)] weekly for 16 weeks. The secondary outcomes were eczema severity over 1 year (4-weekly POEM), number of eczema exacerbations, disease-specific quality of life (QoL) (Dermatitis Family Impact Questionnaire), generic QoL (Child Health Utility-9 Dimensions) and type and quantity of topical steroid/calcineurin inhibitors prescribed. Children were randomised (1 : 1) using online software to either bath additives plus standard eczema care or standard eczema care alone, stratified by recruiting centre, and there was open-label blinding. RESULTS: From December 2014 to May 2016, 482 children were randomised: 51% were female, 84% were white and the mean age was 5 years (n = 264 in the intervention group, n = 218 in the control group). Reported adherence to randomised treatment allocation was > 92% in both groups, with 76.7% of participants completing at least 12 (80%) of the first 16 weekly questionnaires for the primary outcome. Baseline POEM score was 9.5 [standard deviation (SD) 5.7] in the bath additives group and 10.1 (SD 5.8) in the no bath additives group. Average POEM score over the first 16 weeks was 7.5 (SD 6.0) in the bath additives group and 8.4 (SD 6.0) in the no bath additives group, with no statistically significant difference between the groups. After controlling for baseline severity and confounders (ethnicity, TCS use, soap substitute use) and allowing for clustering of participants within centres and responses within participants over time, POEM scores in the no bath additive group were 0.41 points higher than in the bath additive group (95% confidence interval -0.27 to 1.10), which is well below the published minimal clinically important difference of 3 points. There was no difference between groups in secondary outcomes or in adverse effects such as redness, stinging or slipping. LIMITATIONS: Simple randomisation resulted in an imbalance in baseline group size, although baseline characteristics were well balanced between groups. CONCLUSION: This trial found no evidence of clinical benefit of including emollient bath additives in the standard management of childhood eczema. FUTURE WORK: Further research is required on optimal regimens of leave-on emollients and the use of emollients as soap substitutes. TRIAL REGISTRATION: Current Controlled Trials ISRCTN84102309. FUNDING: This project was funded by the NIHR Health Technology Assessment Programme and will be published in full in Health Technology Assessment; Vol. 22, No. 57. See the NIHR Journals Library website for further project information.

Emollient bath additives for the treatment of childhood eczema (BATHE): multicentre pragmatic parallel group randomised controlled trial of clinical and cost effectiveness.

OBJECTIVES: To determine the clinical effectiveness and cost effectiveness of including emollient bath additives in the management of eczema in children. DESIGN: Pragmatic randomised open label superiority trial with two parallel groups. SETTING: 96 general practices in Wales and western and southern England. PARTICIPANTS: 483 children aged 1 to 11 years, fulfilling UK diagnostic criteria for atopic dermatitis. Children with very mild eczema and children who bathed less than once weekly were excluded. INTERVENTIONS: Participants in the intervention group were prescribed emollient bath additives by their usual clinical team to be used regularly for 12 months. The control group were asked to use no bath additives for 12 months. Both groups continued with standard eczema management, including leave-on emollients, and caregivers were given standardised advice on how to wash participants. MAIN OUTCOME MEASURES: The primary outcome was eczema control measured by the patient oriented eczema measure (POEM, scores 0-7 mild, 8-16 moderate, 17-28 severe) weekly for 16 weeks. Secondary outcomes were eczema severity over one year (monthly POEM score from baseline to 52 weeks), number of eczema exacerbations resulting in primary healthcare consultation, disease specific quality of life (dermatitis family impact), generic quality of life (child health utility-9D), utilisation of resources, and type and quantity of topical corticosteroid or topical calcineurin inhibitors prescribed. RESULTS: 483 children were randomised and one child was withdrawn, leaving 482 children in the trial: 51% were girls (244/482), 84% were of white ethnicity (447/470), and the mean age was 5 years. 96% (461/482) of participants completed at least one post-baseline POEM, so were included in the analysis, and 77% (370/482) completed questionnaires for more than 80% of the time points for the primary outcome (12/16 weekly questionnaires to 16 weeks). The mean baseline POEM score was 9.5 (SD 5.7) in the bath additives group and 10.1 (SD 5.8) in the no bath additives group. The mean POEM score over the 16 week period was 7.5 (SD. 6.0) in the bath additives group and 8.4 (SD 6.0) in the no bath additives group. No statistically significant difference was found in weekly POEM scores between groups over 16 weeks. After controlling for baseline severity and confounders (ethnicity, topical corticosteroid use, soap substitute use) and allowing for clustering of participants within centres and responses within participants over time, POEM scores in the no bath additives group were 0.41 points higher than in the bath additives group (95% confidence interval -0.27 to 1.10), below the published minimal clinically important difference for POEM of 3 points. The groups did not differ in secondary outcomes, economic outcomes, or adverse effects. CONCLUSIONS: This trial found no evidence of clinical benefit from including emollient bath additives in the standard management of eczema in children. Further research is needed into optimal regimens for leave-on emollient and soap substitutes. TRIAL REGISTRATION: Current Controlled Trials ISRCTN84102309.

Experiential or Material Purchases? Social Class Determines Purchase Happiness.

Which should people buy to make themselves happy: experiences or material goods? The answer depends in part on the level of resources already available in their lives. Across multiple studies using a range of methodologies, we found that individuals of higher social class, whose abundant resources make it possible to focus on self-development and self-expression, were made happier by experiential over material purchases. No such experiential advantage emerged for individuals of lower social class, whose lesser resources engender concern with resource management and wise use of limited finances. Instead, lower-class individuals were made happier from material purchases or were equally happy from experiential and material purchases.

CONTRACT Study - CONservative TReatment of Appendicitis in Children (feasibility): study protocol for a randomised controlled Trial.

BACKGROUND: Currently, the routine treatment for acute appendicitis in the United Kingdom is an appendicectomy. However, there is increasing scientific interest and research into non-operative treatment of appendicitis in adults and children. While a number of studies have investigated non-operative treatment of appendicitis in adults, this research cannot be applied to the paediatric population. Ultimately, we aim to perform a UK-based multicentre randomised controlled trial (RCT) to test the clinical and cost effectiveness of non-operative treatment of acute uncomplicated appendicitis in children, as compared with appendicectomy. First, we will undertake a feasibility study to assess the feasibility of performing such a trial. METHODS/DESIGN: The study involves a feasibility RCT with a nested qualitative research to optimise recruitment as well as a health economic substudy. Children (aged 4-15 years inclusive) diagnosed with acute uncomplicated appendicitis that would normally be treated with an appendicectomy are eligible for the RCT. Exclusion criteria include clinical/radiological suspicion of perforated appendicitis, appendix mass or previous non-operative treatment of appendicitis. Participants will be randomised into one of two arms. Participants in the intervention arm are treated with antibiotics and regular clinical assessment to ensure clinical improvement. Participants in the control arm will receive appendicectomy. Randomisation will be minimised by age, sex, duration of symptoms and centre. Children and families who are approached for the RCT will be invited to participate in the embedded qualitative substudy, which includes recording of recruitment consultants and subsequent interviews with participants and non-participants and their families and recruiters. Analyses of these will inform interventions to optimise recruitment. The main study outcomes include recruitment rate (primary outcome), identification of strategies to optimise recruitment, performance of trial treatment pathways, clinical outcomes and safety of non-operative treatment. We have involved children, young people and parents in study design and delivery. DISCUSSION: In this study we will explore the feasibility of performing a full efficacy RCT comparing non-operative treatment with appendicectomy in children with acute uncomplicated appendicitis. Factors determining success of the present study include recruitment rate, safety of non-operative treatment and adequate interest in the future RCT. Ultimately this feasibility study will form the foundation of the main RCT and reinforce its design. TRIAL REGISTRATION: ISRCTN15830435 . Registered on 8 February 2017.

What are the main inefficiencies in trial conduct: a survey of UKCRC registered clinical trials units in the UK.

BACKGROUND: The UK Clinical Research Collaboration (UKCRC) registered Clinical Trials Units (CTUs) Network aims to support high-quality, efficient and sustainable clinical trials research in the UK. To better understand the challenges in efficient trial conduct, and to help prioritise tackling these challenges, we surveyed CTU staff. The aim was to identify important inefficiencies during two key stages of the trial conduct life cycle: (i) from grant award to first participant, (ii) from first participant to reporting of final results. METHODS: Respondents were asked to list their top three inefficiencies from grant award to recruitment of the first participant, and from recruitment of the first participant to publication of results. Free text space allowed respondents to explain why they thought these were important. The survey was constructed using SurveyMonkey and circulated to the 45 registered CTUs in May 2013. Respondents were asked to name their unit and job title, but were otherwise anonymous. Free-text responses were coded into broad categories. RESULTS: There were 43 respondents from 25 CTUs. The top inefficiency between grant award and recruitment of first participant was reported as obtaining research and development (R&D) approvals by 23 respondents (53%), contracts by 22 (51%), and other approvals by 13 (30%). The top inefficiency from recruitment of first participant to publication of results was failure to meet recruitment targets, reported by 19 (44%) respondents. A common comment was that this reflected overoptimistic or inaccurate estimates of recruitment at site. Data management, including case report form design and delays in resolving data queries with sites, was reported as an important inefficiency by 11 (26%) respondents, and preparation and submission for publication by 9 (21%). CONCLUSIONS: Recommendations for improving the efficiency of trial conduct within the CTUs network include: further reducing unnecessary bureaucracy in approvals and contracting; improving training for site staff; realistic recruitment targets and appropriate feasibility; developing training across the network; improving the working relationships between chief investigators and units; encouraging funders to release sufficient funding to allow prompt recruitment of trial staff; and encouraging more research into how to improve the efficiency and quality of trial conduct.

Timing of surgical intervention for developmental dysplasia of the hip: a randomised controlled trial (Hip 'Op).

BACKGROUND: Developmental dysplasia of the hip (DDH) is a very common congenital disorder, and late-presenting cases often require surgical treatment. Surgical reduction of the hip may be complicated by avascular necrosis (AVN), which occurs as a result of interruption to the femoral head blood supply during treatment and can result in long-term problems. Some surgeons delay surgical treatment until the ossific nucleus (ON) has developed, whereas others believe that the earlier the reduction is performed, the better the result. Currently there is no definitive evidence to support either strategy. OBJECTIVES: To determine, in children aged 12 weeks to 13 months, whether or not delayed surgical treatment of a congenitally dislocated hip reduces the incidence of AVN at 5 years of age. The main clinical outcome measures were incidence of AVN and the need for a secondary surgical procedure during 5 years' follow-up. In addition, to perform (1) a qualitative evaluation of the adopted strategy and (2) a health economic analysis based on NHS and societal costs. DESIGN: Phase III, unmasked, randomised controlled trial with qualitative and health economics analyses. Participants were randomised 1 : 1 to undergo either early or delayed surgery. SETTING: Paediatric orthopaedic surgical centres in the UK. PARTICIPANTS: Children aged 12 weeks to 13 months with DDH, either newly diagnosed or following failed splintage, and who required surgery. We had a target recruitment of 636 children. INTERVENTIONS: Surgical reduction of the hip performed as per the timing allocated at randomisation. MAIN OUTCOME MEASURES: Primary outcome - incidence of AVN at 5 years of age (according to the Kalamchi and MacEwen classification). Secondary outcomes - need for secondary surgery, presence or absence of the ON at the time of primary treatment, quality of life for the main carer and child, and a health economics and qualitative analysis. RESULTS: The trial closed early after reaching < 5% of the recruitment target. Fourteen patients were randomised to early treatment and 15 to delayed treatment. Implementation of rescue strategies did not improve recruitment. No primary outcome data were collected, and no meaningful conclusions could be made from the small number of non-qualitative secondary outcome data. The qualitative work generated rich data around three key themes: (1) access to, and experiences of, primary and secondary care; (2) the impact of surgery on family life; and (3) participants' experiences of being in the trial. LIMITATIONS: Overoptimistic estimates of numbers of eligible patients seen at recruiting centres during the planning of the trial, as well as an overestimation of the recruitment rate, may have also contributed to unrealistic expectations on achievable patient numbers. FUTURE WORK: There may be scope for investigation using routinely available data. CONCLUSIONS: Hip 'Op has highlighted the importance of accurate advance information on numbers of available eligible patients, as well as support from all participating investigators when conducting surgical research. Despite substantial consultation with parents of children in the planning stage, the level of non-participation experienced during recruitment was much higher than anticipated. The qualitative work has emphasised the need for appropriate advice and robust support for parents regarding the 'real-life' aspects of managing children with DDH. TRIAL REGISTRATION: Current Controlled Trials ISRCTN76958754. 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. 21, No. 63. See the NIHR Journals Library website for further project information.