Recruitment
Paediatric Emergency Research United Kingdom and Ireland (PERUKI), an increasingly well-established network of clinicians, which aims to effectively deliver high-quality trials in paediatric trauma and emergency care, facilitated the delivery of this trial. At the outset of the trial, we were mindful of the seasonality of injuries likely to be encountered, and the overall number of patients screened in the trial was in keeping with the estimated rate of recruitment at the recruitment centres, including this marked seasonal effect. As expected, the rate of recruitment was substantially higher during the summer months, with approximately three times more patients both screened and recruited than during the winter months. The rate of recruitment among the younger group of patients was slower than anticipated, leading to a 3-month extension of the recruitment window. The key reason for this delay was an unanticipated imbalance between the age groups within the study, with the older group (i.e. 8–15 years) screened and recruited at twice the rate of those in the younger group (i.e. 4–7 years). As a result, we recruited considerably more children than planned in the older group.
Among the children who met the inclusion criteria, 20% of those screened were excluded because they did not meet the predetermined eligibility criteria. The majority of these (65%) were made up of children who presented to the recruitment centre > 36 hours after their injury. This exclusion criterion was decided on based on the primary outcome of pain measured at 3 days post randomisation, with the anticipation that children with fractures typically present immediately. It was therefore felt that those presenting > 36 hours after injury would already be approaching the point for which pain was already significantly resolving.
The number of potentially eligible patients presenting at each centre differed considerably, largely because of the size of their catchment populations. The key determinant driving the conversion of ‘screened’ to ‘recruited’ was patient preference. Among families, there was a strong preference for rigid immobilisation, with 252 patients/parents declining to participate for this reason. Conversely, only four families declined to participate because they had a preference for a bandage. Although we were unable to formally explore this preference through qualitative interviews, it was apparent that there was a pre-existing belief among parents and young people that ‘broken bones require immobilisation’. However, clinician preference was uncommon, with only 14 patients excluded based on clinician preference, presumably with their actions informed through evidence and their own experience of the infrequent nature of complications and reattendance with this injury.
The study was delivered almost wholly online; consent forms, case report forms, treatment details, details of complications and details of patient-reported outcomes were collected electronically and added directly to the database. There were relatively few difficulties encountered with consent, with only 29 patients unable to be enrolled because of technical difficulties. The online approach contributed to the study being widely accessible to clinical teams, with more than half of patients recruited outside normal working hours. The online approach also minimised errors within recruitment (i.e. there were few errors of consent or incomplete data fields throughout follow-up) and meant that the study material was easily accessible to all (i.e. through the internet). However, there were challenges in terms of an initial reluctance of some clinical/research teams to move online, a reliance on the availability of a ‘device’ in busy EDs, and inevitable ‘glitches’ that occured throughout the process (i.e. study enrolment was unable to be performed between 00.00 and 01.00, as this was the time that the database server updated, which contributed to some of the technical difficulties encountered).
Overall, 965 of the 1513 (64%) eligible patients were included within the trial. We can be confident that the patients who took part in the trial are broadly representative of those children with an acute torus fracture of the distal radius.
Participants and treatments
In total, 965 patients consented to take part in the trial. The mean age of the participants was slightly higher than previously anticipated, at 9.65 years. This accounted for the imbalance in the recruitment between the two age groups, with recruitment being extended until sufficient primary outcomes were acquired in both groups to reach the sample size (n = 278). Consequently, 300 patients were recruited in the 4–7 years age group, and 665 patients were recruited in the 8–15 years age group. As expected, most injuries were the result of low-energy trauma (75%). The injury was equally common in both sexes in the 4–7 years age group, but in the 8–15 years age group two-thirds of those screened and recruited were male, which reflects previous epidemiological data concerning sex disparities in childhood injuries.56 This difference is believed to be a consequence of behavioural differences in boys and girls that emerge at an early age.57
A total of 489 participants were randomised to the offer of a bandage group and 476 were randomised to the rigid immobilisation group. We anticipated that some patients would cross over following randomisation and, indeed, in the ED, seven patients received rigid immobilisation despite being randomised to the offer of a bandage group, and one received the offer of a bandage despite being randomised to the rigid immobilisation group. The crossovers were mostly driven by family preference, with families changing their mind after randomisation. By the point of the primary outcome (i.e. day 3), 36 patients had received rigid immobilisation despite being randomised to the offer of a bandage group, and one patient had received the offer of a bandage despite being randomised to the rigid immobilisation group. The additional crossovers occurring before day 3 were almost all related to pain. Crossovers after the initial treatment were all unidirectional (i.e. the offer of a bandage changing to rigid immobilisation) because families generally returned for reassurance or an escalation in care. After day 3, an additional 14 children crossed over from the offer of a bandage group to the rigid immobilisation group, such that 50 (10.2%) children randomised to the offer of a bandage group ultimately changed treatment. This imbalance could potentially pose a threat to the integrity of the trial, but, because the number of such crossovers was small in the context of a trial of 965 participants, this is very unlikely to have affected the results. Furthermore, the analysis undertaken considered the result according to both treatment received (PP) and by treatment randomised (ITT).
Although crossovers were generally unidirectional, changes in the immobilisation device occurred in both groups. Twenty-two participants in the rigid immobilisation group had further immobilisation changes after the initial treatment, which included splint changes or escalation in care from a removable splint to plaster cast immobilisation. Furthermore, care was frequently de-escalated at home: by day 3, 69 (14.3%) bandages and four (0.8%) casts had been removed.
Most participants in the rigid immobilisation group (451/476, 95%) were treated with a futura-type splint or similar. A prior study of UK practice found that 40% of hospitals were primarily using casts,58 so the widespread use of futura-type splints in the study suggests either that use of this practice has rapidly increased throughout the UK or that the centres involved in the trial are more innovative than centres not involved in the trial. Most patients in the offer of a bandage group (458/489, 94%) chose to have the bandage applied in the ED. Compliance with the treatments was good. The average duration of treatment use was 7 days in the offer of a bandage group and 18 days in the rigid immobilisation group. At 3 weeks, 37% of the rigid immobilisation group continued to wear the treatment, but only 10% of the offer of a bandage group did.
In terms of the primary outcome measure of pain at 3 days, there were 94.1% complete scores, with follow-up rates broadly similar across age groups and treatment groups. The early primary outcome time point allowed the trial to be efficiently concluded once the number of primary outcomes required to achieve 90% power in each age group of children had been collected.
At 6 weeks, the rate of completion of secondary outcome measures was 90% overall, with a slight discrepancy between age groups, the rate being 92.7% for 4- to 7-year-olds and 88.3% for 8- to 15-year-olds. The high rates of follow-up reflect the success of automated electronic participant follow-up in this patient population.
Of those participants who did not complete the 6 weeks’ follow-up for the trial, five withdrew, with the remaining participants failing to respond to prompts.
Results
Primary outcome
This trial showed equivalence in the Wong–Baker Scale scores at 3 days post randomisation between the offer of a bandage group and the rigid immobilisation group in the management of torus fractures of the distal radius in children aged 4–15 years. Both the ITT analysis (analysis by treatment randomised) and the PP analysis (analysis of participants who received their allocated treatment) confirmed equivalence. Furthermore, the trial was powered to separately assess equivalence in each of the age subgroups, and equivalence was confirmed for both groups.
The number of missing data at the primary end point was very small (approximately 5%); therefore, as per the statistical analysis plan,20 no attempt was made to account for missing data.
Secondary outcomes
In keeping with the primary analysis of pain at 3 days, this trial found no evidence of a difference between the two treatment groups at any of the time points up to the final 6-week follow-up, with the exception of day 1. For the day 1 follow-up, the ITT analysis demonstrated a small but statistically significant difference in pain scores (difference –0.36, 95% CI –0.61 to –0.12) favouring the rigid immobilisation group, but this difference was notably smaller than both the prespecified equivalence margin of 1 point and the minimal clinically important difference of 2 points. This finding was not significant in the PP analysis (difference –0.22, 95% –0.47 to 0.03). Interestingly, the number of participants receiving analgesia was similarly slightly larger in the offer of a bandage group than in the rigid immobilisation group, with approximately 5% more children receiving analgesia at each time point during the first 7 days (day 1, 83% vs. 78%; day 3, 57% vs. 51%; day 7, 25% vs. 23%). The analgesia used was, almost universally, simple ‘over-the-counter’ analgesia.
In keeping with the outcome of pain, the secondary outcomes of upper extremity function or quality of life identified no evidence of a difference between the two treatment groups at any of the time points during follow-up. Parental satisfaction was slightly better (extremely satisfied vs. very satisfied) at day 1 among those treated with a rigid immobilisation than among those receiving the offer of a bandage, but there was no difference at the completion of follow-up.
Although differences did not exist between the treatment groups, there were small differences between the age groups. Children in the older age group generally reported slightly higher pain and poorer quality of life at each time point than those in the younger group, but, conversely, this group also reported more rapid functional recovery. Although this difference is small, it may reflect a difference between self-reporting and proxy reporting, which alters the interpretation of the experience.
School attendance was similar, with participants in both groups, missing an average of 1.5 days of school.
The size of this study allowed particular consideration of complications, of which refracture and worsening deformity requiring intervention are the key concerns of families and clinicians alike. Of the 965 children, none was found to have a worsened deformity. One fracture was identified to have a refracture; the patient was initially randomised to the offer of a bandage group but crossed over to the rigid immobilisation group in week 1 because of pain and was treated with a splint. This patient then experienced refracture at around 3 weeks, following a fall. In total, only eight complications were reported, seven of which related to an alternative type than that originally diagnosed by the treating clinician – all of which were treated with cast immobilisation. Owing to the pragmatic nature of the study, these were not considered protocol deviations, as the treating clinician acted in accordance with their usual practice, and there is subjectivity in making the diagnosis. However, as these alternative fracture patterns inevitably were present from the outset, they amount to errors of radiographical interpretation and, therefore, of study eligibility.
Diagnosis audit
Given the unexpected age distribution of participants (i.e. imbalance between the younger and older patient groups) the FORCE trial TSC recommended that the trial team audit the diagnostic agreement between treating clinicians and reporting radiologists to ensure the validity of the diagnoses. The audit took place when the first 250 patients had been recruited to the trial. The decision was made to use the ‘reporting radiologist’ as a baseline, but it should be noted that the radiologist’s interpretation of the radiograph is also prone to misinterpretation, as there is no clear reference standard to follow.
In total, 12 recruitment centres participated in the audit, contributing 212 fractures. There was agreement between the treating clinician and the reporting radiologist in 85% of cases. Seven per cent of cases were reported by the radiologist to be less severe (i.e. no fracture) and 8% of cases were reported to be more severe (i.e. greenstick, growth plate injury or a complete fracture) than the report by the treating clinician. There was, therefore, broad consistency in the diagnosis of torus fractures, but there was some diagnostic uncertainty. Although, in a few cases, this resulted in crossover between treatment groups, the majority, after review by the treating emergency clinicians, continued to be treated as torus fractures. The absence of worsened deformity, irrespective of the fracture pattern, indicates that the treatment approach is likely to be appropriate even in the presence of diagnostic debate among expert clinicians.
The addition of the posters detailing the inclusion parameters for the trial (see Appendix 3, ) may have improved the diagnostic accuracy beyond that seen in usual care. However, 281 clinicians from 23 recruitment centres recruited patients to the trial, demonstrating the generalisability of the study findings.
Health economic evaluation
The unit cost of treatment was £12.55 higher in the rigid immobilisation group than in the offer of a bandage group, and quality of life was also marginally higher in the rigid immobilisation group (mean 0.0013 QALYs, 95% CI 0.000 to 0.003 QALYs). Based on the base-case analysis, the cost per patient of offer of a bandage was lower than the cost of rigid immobilisation from the NHS and PSS perspective.
At a £30,000 per QALY ceiling ratio, the offer of a bandage was the most cost-effective treatment for treating children with a torus fracture of the distal radius. A significant decrease in cost and small non-significant increase in quality of life combine to provide a positive NMB for the offer of a bandage and better than 95% probability of cost-effectiveness. The findings appeared to be robust when considering sensitivity analyses, although the evidence is less compelling for the older age group (i.e. 8–15 years).
Although missing data are usually an issue in an economic analysis and may introduce bias into the health economics results, the combined level of missingness of cost and outcome data (12.1%) in the FORCE trial was low, enhancing the robustness of findings and similarity between the imputed and complete-case model estimates.
Limitations
Recruiting patients to clinical trials in the context of emergencies is difficult, which is magnified when the patient group involves children. A concern before this trial started was that families and/or clinicians would not be willing to take part. This concern was unfounded regarding the clinicians, who were broadly in equipoise, with only 14 patients not enrolled owing to a clinician preference. However, families had a strong pre-existing preference for rigid immobilisation, with 252 declining to participate from the outset for this reason. This preference continued after randomisation, with seven patients declining to accept the allocated treatment as randomised and immediately changing treatment groups. Given the preference and the inability to blind families to the treatment allocation, it is likely that there was some bias in the reporting of patient-reported outcomes. This bias is likely to amplify the magnitude of the treatment effect, that is to overstate outcomes in the rigid immobilisation group. This is perhaps most evident in reports of patient satisfaction: satisfaction on follow-up day 1 was lower among participants randomised to the offer of a bandage group, despite only a small reduction in reported pain that was well below the minimal clinically important difference. Despite this bias, there was equivalence in the primary outcome and all other clinical outcomes at every time point in the trial.
Although a selection bias could emerge through the initial patient preference in the trial, these numbers are small compared with the size of the trial, and the demographics of those declining to participate in the trial were broadly similar to those included within the trial. Any potential selection bias therefore appears unlikely to affect the external validity of the results.
The exclusion criteria excluded participants in whom the injury had occurred > 36 hours previously. Although this was intended to ensure that the treated participants were recruited at a similar point on the recovery pathway, this does affect the generalisability of the findings to this group of patients. Nevertheless, clinically, it seems unlikely that the results would not equally apply to this patient group.
Research recommendations
Given the findings of this study, a clinical decision tool to determine which children require radiography for wrist injuries would be an important next step. Only fractures that require intervention need undergo radiography; therefore, differentiating these from sprains and torus fractures could be important in preventing overinvestigation and overtreatment of sprains and torus fractures. There is also a need to rationalise interventions for other common injuries in children (e.g. rigid immobilisation and follow-up for ‘toddler’s fractures’ of the tibia).
A future trial may similarly investigate whether or not bandage immobilisation and immediate discharge would be as good as rigid immobilisation and follow-up.
