Surgical fixation compared with cast immobilisation for adults with a bicortical fracture of the scaphoid waist: the SWIFFT RCT

Fixation

Immediate surgical fixation may avoid the need to immobilise the wrist in a cast and could accelerate return to function, work and sport;16 however, this method requires the person to have an operation and be exposed to surgical risks. The fracture is fixed with a standard Conformité Européenne (CE)-marked headless screw generating compression at the fracture site but avoiding the pressure effects of the screw head on articular cartilage. This can be done either percutaneously or in open surgery. 17–19 The surgical techniques for this method are well described and are now standard. 20–22 These screws did not change during the recruitment period for this study. Some surgeons use splintage for the first few weeks after surgery.

Cast treatment

The usual treatment is immobilisation in a below-elbow cast for 6–10 weeks, followed by mobilisation. The type of below elbow cast used does not affect union rate. 8 The 10–12% of patients who develop non-union [as seen on radiographs and/or computed tomography (CT) scans] usually have urgent surgical fixation. This is the current standard non-operative pathway. 3

Displaced fractures

A scaphoid fracture is considered displaced if there is a step or gap of ≥1 mm. 38 Angulation and rotation between fragments are more difficult to assess. A systematic review reported that non-union occurs in around 18% of displaced fractures39 and that, when treated in a cast, the relative risk of non-union between undisplaced and displaced fractures is 4.4 [95% confidence interval (CI) 2.3 to 8.7]. 39 At present, the evidence of the treatment of displaced fractures is weak and recommendations are based on case series. 40 When the displacement is > 2 mm, clinicians consider the fracture so unstable that they usually recommend early reduction and fixation.

Increase in surgical activity

Despite insufficient evidence, there is an increasing trend41 to immediately fix scaphoid fracture rather than to immobilise in a cast for 6 weeks and fix only the 10–12% that fail to unite. 3 This current trend to fix fractures may be attributed to short-term benefits, but concerns remain about the lack of evidence on the long-term benefits and additional risks of surgery, such as malunion, infection, implant-related problems and avascular necrosis.

Hospital Episode Statistics for NHS hospitals in England recorded a two-third increase in acute scaphoid fracture fixations between 2007/8 and 2009/10 (1534, 1720 and 2582 in 2007/8, 2008/9 and 2009/10, respectively), before this study was commissioned. The rate of surgical fixation42 rose very slightly from 37% to 41% from 2007/8 to 2008/9 but then increased sharply to 62% in 2009/10. This trend of an increasing intervention rate emphasised the need for this study.

Economic aspects

There is also a lack of information on the economic aspects43 of this injury and its treatment. One study used a decision-analytic model43 and utility scores were obtained from 50 medical students. This study concluded that early fixation provided more quality-adjusted life-years (QALYs) and consumed fewer economic resources than cast treatment. However, a different view has also been suggested,44,45 namely that cast treatment is economically less costly. This conclusion came from studies of both non-randomised (95 patients) and randomised evidence (52 patients), based on a comparison of direct and indirect costs in patients who had their fracture treated in a cast or had it fixed.

What do patients feel and experience?

There is little published evidence on patients’ experiences and preferences after a scaphoid fracture. Understanding our patients’ priorities helps efficient patient-centred clinical decision-making. We know little about patients’ experience of their recovery and the impact that the injury and treatment have on them. We also have a poor understanding of the issues pertinent to recruiting participants in surgical clinical trials. 46,47

Five-year review

The long-term consequences of cast immobilisation and internal fixation have not been adequately determined in RCTs. The consolidation of partial union of the fracture has not been investigated, nor has the progression of carpal malalignment or the development of arthritis. Although this report focuses on outcomes at 52 weeks, the study will investigate function, impairment and arthritis at 5 years. 48

Inclusion criteria

Patients were eligible for the trial if they:

• were skeletally mature and aged ≥ 16 years

• presented at a participating site within 2 weeks of their injury and within which time it was feasible to have surgery

• had a clear, unequivocal bicortical fracture of the scaphoid waist seen on a series of plain radiographs of the scaphoid that:

  1. – did not involve the proximal pole (the proximal 20% of the scaphoid) and

  2. – included minimally displaced fractures with a step or gap of ≤ 2 mm on any radiographic view.

Exclusion criteria

Patients were excluded from the trial if:

• their fracture had > 2-mm displacement, as these fractures are likely to be unstable and require surgical intervention

• they had a concurrent wrist fracture in the opposite limb

• they had a trans-scaphoid perilunate dislocation

• they had multiple injuries in the same limb

• they lacked the mental capacity to comply with treatment or data collection

• they were pregnant, because radiation exposure would be contraindicated

• they were not resident in the trauma catchment area of a participating site to allow follow-up.

Cast treatment followed by surgical fixation if there is confirmed non-union

The control treatment was non-operative, with wrist immobilisation in a below-elbow cast for 6–10 weeks, followed by mobilisation. The below-elbow cast could include the thumb or not, as this does not affect union rate. 8 Early CT was obtained if plain radiographs at 6–12 weeks raised any suspicion of non-union. If non-union was confirmed on radiographs and/or CT scans, urgent surgical fixation was expected to be performed and was encouraged by the trial team, which monitored this with the completion of the 6- and 12-week treatment confirmation forms (see Report Supplementary Materials 1 and 2). The surgical procedure to treat a non-union and postoperative care were similar to the surgical arm of this trial. Cast immobilisation, identification and confirmation of non-union at 6–12 weeks, and immediate surgical fixation of confirmed non-union is the current standard non-operative pathway. 3 We anticipated that most, if not all, fixation of confirmed non-union would occur by around 12 weeks.

Surgical fixation

Surgical treatment was by percutaneous or open surgical fixation depending on the surgeon’s preferred technique. Standard CE-marked headless compression screws18,52 were used to avoid the pressure effects of the screw head on articular cartilage. These are standard surgical techniques. 20–22 The type of implant used was not restricted, but the screw used was recorded (see Report Supplementary Material 3). The surgical approach or the postoperative care was not specified and was instead left to clinical discretion, as it was expected that most surgeons would use some splintage for the first few weeks after surgery. The application of a plaster cast or splint following surgery, and its duration, was recorded. At each recruiting site, it was agreed which surgeons would fix the scaphoid fractures and that surgeons would use techniques with which they were familiar to avoid learning-curve problems.

Rehabilitation

All participants randomised into the two groups received standardised, written physiotherapy advice detailing the exercises they needed to perform for rehabilitation following their injury (see Report Supplementary Material 4). All participants were advised to move their shoulder, elbow and finger joints fully within the limits of their comfort. Those participants treated in a cast performed range-of-movement exercises at the wrist as soon as their plaster cast was removed at the 6-week follow-up appointment as long as there were no concerns regarding bone union. Those participants who had the fracture fixed began their wrist exercises as soon as comfort permitted, if they did not have a plaster cast, or as soon as the cast was removed. Any other rehabilitation input beyond the written information sheet (including a formal referral to physiotherapy) was the decision of the treating clinicians. A record of any additional rehabilitation input (including the reason for referral and number of appointments) was recorded at the 52-week hospital visit.

Primary outcome

The primary outcome and end point for the trial was the PRWE total score at 52 weeks from randomisation. The PRWE was completed at baseline for the time before and after injury, and at 6, 12, 26 and 52 weeks, and will be completed 5 years after randomisation. The PRWE is a 15-item questionnaire that is completed by the participant. It is a brief, reliable and valid instrument for assessing wrist pain and disability. 50,53 Scoring for all the questions is on a 10-point ordered scale, ranging from ‘no pain’ or ‘no difficultly’ (0) to ‘worst ever pain’ or ‘unable to do’ (10). A total score can be computed on a scale of 0–100 (0 = no disability), as well as two non-overlapping subscales (pain and function), which are weighted equally. The PRWE score was chosen as the primary outcome because patient-reported functional outcomes are favoured for decision-making and it allows the assessment of both wrist pain and function.

Two small RCTs3,18 of patients with scaphoid fractures have demonstrated that there is little change in objective and subjective outcomes between 26 and 52 weeks. In the case of the 10–12% of patients who are treated initially in cast but do not heal, surgery should be performed between 6 and 12 weeks after randomisation. Therefore, if assessed at 26 weeks, this would leave only 14–20 weeks for healing and recovery to take place. To allow all patients the time to heal from surgery and to stabilise after any complications, 52 weeks was chosen as the primary end point.

Secondary outcomes

The secondary outcomes were health-related quality of life (HRQoL), bone union, range of movement and grip strength, return to work and unpaid recreational activities, and complications.

Recruitment

Site and patient recruitment was presented. The characteristics of the population of patients who were screened, ineligible and eligible, stratified by consent, were summarised. The flow of participants through the trial was presented in a Consolidated Standards of Reporting Trials (CONSORT) diagram.

Baseline characteristics of randomised participants

Baseline participant characteristics and fracture details were summarised descriptively overall and by randomised group, both ‘as randomised’ and ‘as analysed’, comparing the groups as included in the primary outcome analysis model (i.e. with full data for the baseline covariates and valid PRWE data for at least one post-randomisation time point). No formal statistical comparisons were undertaken on baseline data.

Follow-up

For each time point, the number of participant questionnaires sent and returned, with median [interquartile range (IQR)] days to completion and return, was presented by treatment group and overall. The number of questionnaires completed at home, over the telephone or in the hospital was reported. Return rates for hospital forms were tabulated by randomised group and time point.

Hospital visits

Participants were asked to attend a hospital follow-up visit at 6, 12 and 52 weeks post randomisation. Baseline participant characteristics and fracture details were summarised descriptively overall and by randomised group according to whether or not participants attended the hospital visit at each time point.

Compliance with random allocation and treatment received

The treatment received by participants in the two groups was summarised, with reasons given for any treatment crossover.

Primary outcome (Patient-Rated Wrist Evaluation) analysis

The PRWE was assessed at baseline (pre and post injury, prior to randomisation) and at 6, 12, 26 and 52 weeks post randomisation. The PRWE total score is a value between 0 and 100, where a higher score indicates worse pain and functioning. The score is computed by scoring the two subscales out of 50 (pain = sum of items 1–5; function = sum of items 6–15 divided by two) and summing them, so that pain and function problems are weighted equally. If there was up to one missing item in each subscale, then the missing item was replaced by the mean of the completed items within that subscale. 49 If two consecutive responses (between 0 and 10) to a particular item were selected, then the higher of the two (the worse response) was taken for analysis. Other ambiguous responses were treated as missing. If more than one item was missing in either subscale, then a score for that subscale, or for the total, could not be calculated.

The number and percentage of participants with valid and partial PRWE data were reported by randomised group and time point. Baseline participant characteristics and fracture details were summarised descriptively overall and by randomised group according to whether or not participants had valid PRWE outcome data at each post-randomisation time point. Total PRWE scores were summarised by time point according to whether or not participants had valid data for (1) all post-randomisation time points, (2) at least one, but not all, post-randomisation time points or (3) no post-randomisation time points. PRWE scores (subscales and total) were summarised descriptively by treatment group and overall.

Total PRWE scores were compared between the two groups using a covariance pattern, mixed-effect linear regression model incorporating all post-randomisation time points. Treatment group, time point, a treatment-by-time interaction, participant age at randomisation, baseline fracture displacement and dominance of injured hand were included as fixed effects, and participant was included as a random effect (repeated observations per participant). Fracture displacement was used as a stratification factor in the randomisation; however, there were several instances in which the wrong displacement category was used in the randomisation. Such stratification errors were identified when there was a discrepancy between the data provided at randomisation and the data recorded on the study eligibility form. If the randomisation data were incorrect, a file note was raised and the trial statistician was notified; if the data on the study eligibility form were incorrect, the form was amended. The displacement used in the randomisation was the variable included in the primary analysis, but the errors were discussed. The primary model was not adjusted for baseline total PRWE, as, in this young population, we expected pre-injury PRWE score to be low and have little variability and post-injury PRWE score to be confounded, as patients would most likely be in a plaster cast.

An unstructured covariance pattern for the correlation between the observations for a participant over time was specified in the final model based on Akaike information criterion (AIC)77 (smaller value preferred).

An estimate of the difference between treatment groups in total PRWE score was extracted from the repeated measures model for each time point, and overall, with a 95% CI and p-value. The primary end point was the treatment effect estimate at 52 weeks. Estimates for the treatment effect at other time points (6, 12 and 26 weeks) and overall served as secondary outcomes. This repeated-measures approach is more efficient and parsimonious than conducting separate linear regressions for each time point, and also allows for the ‘overall’ (across the whole 52 weeks) effect to be investigated using the same model. The analysis takes advantage of the extra information provided at, and the correlation between, all post-randomisation time points. The standard errors for treatment effects at individual time points were calculated using information from all time points and were hence more robust and accurate than standard errors calculated from separate analyses at each time point. An additional advantage of the mixed model approach is that the presence of missing data across time points does not cause a problem under the assumption that they are missing at random. For the estimates at a single time point, say at 52 weeks, it is primarily the observations at that time point that determine the treatment effect and power; however, owing to the covariance between the post-randomisation time points, greater power and precision is obtained than that from a comparison using only the 52-week data. 78

Model assumptions were checked as follows: the normality of the standardised residuals was checked using a quantile–quantile plot and homoscedasticity was assessed by means of a scatterplot of the standardised residuals against fitted values.

Sensitivity analyses

Secondary analysis

Design of patient questionnaires and hospital case report forms

The patient questionnaires and hospital CRFs were designed using TeleForm software (version 10; Cardiff Software, Cambridge, UK). Specification CRFs were populated with variable names and appropriate scoring. To maximise data quality, when hospital CRFs were returned to YTU, key variables required for the statistical analysis were reviewed for completion and accuracy by a trial co-ordinator/research data administrator who resolved any queries with the research nurse at the site. The hospital sites were reimbursed according to a payment schedule for the completion of CRFs and provision of research imaging up to a total of £430.30. This was agreed between each trust and trial sponsor using a Clinical Trial Agreement. No checks regarding the data quality of the postal questionnaires were made on immediate return to YTU. A trial co-ordinator did, however, as a duty of care, check if a participant had responded with the extreme answers to the following: questions 4a, 4b, 6a and 6b of the SF-12 and the final EQ-5D-3L question. The trial co-ordinator also checked free-text responses to see if the participant could be at harm. When this occurred, the PI and research nurse at the recruiting site were notified by e-mail.

After this initial check, all postal questionnaires and hospital CRFs were prepared for scanning by a research data administrator using the TeleForm software. When a form would not scan, the data were manually entered. When a form was scanned, the data were then verified depending on what TeleForm identified as requiring correction. The verified data were then temporarily held in the download database and available for second checking. This involved each hard copy of all forms being compared against the entry stored in the download database and correcting the electronic data as necessary. All data were scanned, downloaded and second checked in the validate database. The automated data validation was undertaken by the data manager who applied predetermined rules to check for agreed variables to see if the data were recorded correctly. Data that had been validated were then held in the survey database and were available on a formal request from the trial statistician and health economist.

Strategies to follow up patients

Participants at the 6-, 12-, 26- and 52-week follow-ups were notified by post to expect the questionnaire (see Report Supplementary Material 15) 2 weeks before it was due. Reminder letters were sent 2 and 4 weeks after the due letter was sent out. When there was no response to reminder letters, a trial co-ordinator at YTU contacted participants by telephone, who were invited to provide answers for, as a minimum, the primary outcome (PRWE) and EQ-5D-3L. At 52 weeks only (the primary time point for the study), in addition to the telephone call at 6 weeks, a letter was sent to non-responding participants requesting that they complete the PRWE only. At 26 weeks, if participants did not attend a hospital appointment, an unconditional incentive of £5 was included with the postal questionnaire. At 52 weeks, a £40 payment was made to participants who attended the clinic. For the final 11 months of the follow-up period of the study, participants were also offered up to £40 to cover their travel expenses, or more if this was agreed with the trial team. The participants could complete the follow-up questionnaires during the clinic visits.

Various techniques were used to minimise loss to follow-up. This included regular participant newsletters, which publicised the progress of the study on the trial website (www.swifft.co.uk). A trial ‘tagline’ was placed on postal envelopes sent to participants to highlight the importance of their involvement in the research (i.e. ‘SWIFFT Study: Patients helping to improve healthcare through research’). As the return of postal questionnaires can be improved when participants are included in a prize draw,87 anyone who returned their questionnaire at 26 weeks could win an iPad^® (Apple Inc., Cupertino, CA, USA) worth £500. Participants who attended their hospital clinic appointment at 52 weeks were also entered into a prize draw to win an iPad worth £500. If, at 52 weeks, it was difficult to arrange the hospital appointment, a letter was sent from the hospital to the participant along with a leaflet to encourage their attendance. Other strategies to collect follow-up data on participants who did not return their questionnaire or attend clinics included using a participating hospital’s Picture Archiving Communication System (PACS) for the local area/region to retrieve imaging of patients; accessing Summary Care Records to view participants’ addresses and/or the general practitioner (GP) they were registered with to help contact them; and asking a participant’s GP if they have had an operation on their scaphoid fracture.

A trial participant could withdraw from the study at any time for any reason, but any data collected up to that point was used in the analysis. A participant could withdraw from all data collection, or from postal questionnaire collection or hospital data collection only, which was recorded using a change in status form (see Report Supplementary Material 16).

Data management for the review of imaging

The forms used to capture assessments of the scaphoid fracture and conduct measurements on the imaging collected were created using the ‘Design’ module in Formic Fusion^® software (5.5.1; Formic Limited, Middlesex, UK) and include the SWIFFT master radiograph form, SWIFFT baseline CT form and SWIFFT 52-week CT form.

Once completed by reviewers, variables within each form were checked visually for completeness and for whether or not measurements were within an expected range. Completed forms were then scanned using the Formic ‘Capture & Process’ module and responses were reviewed. The Formic scanning software flagged hand-written text and those checkboxes with no mark or more than one mark; these were manually corrected to reflect the entry on the form. The scanned image of the form was also held within the database to permit independent verification. Once exported to the ‘SWIFFT logging database’ (Microsoft Access^®, Microsoft Corporation, Redmond, WA, USA), the data then went through a final electronic check to ensure all measurements were within the limits assigned by the chief investigator and to check for errors in measurements (e.g. cm instead of mm). The data were then checked for these rules in Stata v15 and potential problems were flagged and checked by each reviewer.

Data from the three reviewers were assessed and any classification conflicts on fracture displacement at baseline and state of the union at 52 weeks were identified and resolved in ‘conflict resolution meetings’ using specific forms (SWIFFT conflict CT form, SWIFFT conflict radiograph form and SWIFFT 52-week inter-observer conflict forms), which were used when conflicts were resolved. Predefined agreement rules were used to generate the final data based on all three reviewers’ assessments.

All conflicts identified were reviewed by all reviewers at face-to-face/teleconference meetings. All reviewers looked at the images together and a collective decision was made and recorded. From the 439 baseline radiographs reviewed, 106 were taken back to a conflict meeting. Of the 431 CT images reviewed at baseline, 155 were taken back to a conflict meeting to agree displacement thresholds. These baseline conflicts were reviewed over 26 meetings between September 2013 and February 2018. At 52 weeks, 297 radiographs and 292 CT scans were reviewed. All radiographs and CT scans at 52 weeks that were classified as a ‘non-union’ by any one reviewer were brought back to the conflict resolution meeting for confirmation. Of both radiographs and CT scans, only 17 were taken back to three conflict meetings to agree the state of the union.

Finally, the reviewers also agreed the cases that did not have an identifiable fracture on baseline radiographs (one) and CT scans (five). There were also a total of 52 conflicts identified on the categorical data at baseline. For baseline radiographs, 15 conflicts were identified from the categorical classification of the orientation of the fracture line. These were reviewed by all reviewers and were resolved. For baseline CT scans, 37 conflicts were identified involving the fracture line (27) and fracture location (10). All of these were reviewed at a conflict meeting in January 2018 and all were resolved.

Ethics committee approval and any changes to the project protocol

SWIFFT was approved by Derby Research Ethics Committee – East Midlands on 21 May 2013 (REC reference 13/EM/0154). NHS permission was given by the research and development department of each participating site. A summary of the changes made to the protocol since the original REC approval are listed in Appendix 2. The trial protocol was published in BMC Musculoskeletal Disorders. 48

Trial Management Group

The day-to-day management of the trial was overseen by the TMG, which met on a quarterly basis. A representative of the sponsor attended when available. These meetings monitored the progress as regards recruitment (e.g. enrolment, consent and eligibility), allocation to study groups, adherence of the trial interventions to the protocol, retention of trial participants, monitoring of (S)AEs and reasons for participant withdrawal. The review of progress was undertaken at the level of the participating site and, as necessary, feedback was given to the PI and research nurses at each site.

Trial Steering Committee

A TSC was appointed by the funding body to provide overall supervision of the trial and to advise on its continuation. Membership is listed in the Acknowledgements.

Data Monitoring Committee

The DMC was appointed by the funding body with access to the unblinded comparative data as provided by a statistician at YTU who was independent of the trial team. The DMC monitored the data and notified the TSC of whether or not there were any ethical or safety reasons why the trial should not continue. Membership is listed in the Acknowledgements.

Site recruitment

In our original protocol, we estimated that we would need 17 sites to recruit patients into SWIFFT. The number of sites was increased to meet the slightly lower than planned recruitment rate. Forty sites were approached to take part in SWIFFT between May 2013 and March 2015 and, in total, 34 sites were set up and opened to recruitment, the last of which commenced screening/recruitment in June 2015. Thirty-three sites screened at least one patient and 31 sites recruited at least one participant (median 10, range 1–61). Two of the three sites that did not recruit any participants screened one and two patients, respectively, one of which was eligible but non-consenting. The lead site, Leicester Royal Infirmary within the University Hospitals of Leicester NHS Trust, recruited the highest number of patients of all sites (n = 61). Table 1 presents the number of patients recruited by each site, ordered by when each site was set up to recruit (Leicester first), with sites identified at trust level. One hospital from each trust took part in SWIFFT. All sites agreed to recruit an average of one patient per month, but only two sites achieved this.

Patient recruitment

Our required sample size was 438 participants, which we aimed to achieve by the end of March 2016; however, recruitment was slightly slower than anticipated in the final few months and we agreed with the trial sponsor, the trial funder and the REC (February 2016) to extend recruitment beyond March 2016 until the 438 patients had been recruited.

The first participant was randomised on 23 July 2013. As of 31 July 2016, 439 patients had been enrolled in the trial and sites were notified that recruitment should cease; thus, patients were recruited over 37 months. Figures 3 and 4 demonstrate our final recruitment figures.

FIGURE 3.

Recruitment into SWIFFT by month.

FIGURE 4.

Recruitment targets of participants into SWIFFT.

Characteristics of screened patients

A total of 1047 patients who met the inclusion criteria (aged 16 years or over and skeletally mature, presenting within 2 weeks of injury with a radiologically confirmed clear and bicortical fracture of the scaphoid waist that does not include the proximal pole) were assessed for participation in the trial from July 2013 to July 2016, of which 775 (74.0%) were eligible and 439 (41.9%) were eligible and consenting, the latter all being randomised. The number of participants screened per site ranged from 1 to 133 (median 23) and the percentage of screened participants who were eligible per site ranged from 0 to 100% (median 83.3%). Table 2 displays the characteristics of the different populations. Eligible patients tended to be younger and were more likely to be male and have a displaced fracture than ineligible patients. There were no marked differences between consenting and non-consenting patients in gender, age or time since injury; however, there was an indication that consenting patients were more likely to have a displaced fracture than non-consenting patients. The numbers of patients for whom each type of radiograph was used to determine eligibility, along with the percentage of those screened, are as follows: elongated scaphoid view (n = 910, 86.9%), posterior–anterior view (n = 1024, 97.8%), 45° semisupine view (n = 610, 58.3%), lateral view (n = 1017, 97.1%) and 45° semiprone view (n = 834, 79.7%). Screened patients had a median of four scaphoid radiographic views taken.

Reasons for exclusion

A total of 272 (26.0%) of the 1047 patients screened were ineligible for the trial for one or more reasons (Table 3). Twenty-nine of these should strictly never have been screened for participation in the trial, as they did not fulfil the inclusion criteria: their injury was more than 2 weeks old (n = 15), they did not have a radiologically confirmed bicortical fracture (n = 7), their fracture included the proximal pole (n = 6) or they were skeletally immature (n = 1). A further 156 patients failed at least one of the exclusion criteria, most commonly having a concurrent other injury in the same limb (n = 70). The remaining 87 were ineligible for other reasons: the site did not think it was feasible for the patient’s surgery (if allocated) to be scheduled within 2 weeks from presentation (n = 30), the patient was not approached about study (e.g. they presented at the weekend when there was no clinician available to confirm eligibility) (n = 21), the patient was deemed to be unsuitable for surgery (n = 16), the fracture was seen on radiography but not on the subsequent CT scan (n = 8) or other miscellaneous/unknown reasons (n = 12).

Patient consent

The percentage of eligible patients who consented to take part in the trial varied in the 31 sites that recruited a patient from 13.9% to 100% (median 63.2%). A reason was provided for 325 of the 336 (96.7%) patients who did not consent to the study, despite being eligible: patient had a preference for non-operative treatment (n = 206), patient had a preference for surgery (n = 40), patient was unable to commit to follow-ups (n = 24), patient did not want to take part in research and/or was unhappy with the concept of random treatment allocation (n = 13), consent was not given in time to allow surgery (if allocated) to be conducted within 2 weeks of presentation at A&E or another clinic (n = 13), patient circumstances did not allow for surgery (if allocated) to be conducted within 2 weeks of presentation at A&E or another clinic (e.g. planned holiday or exams) (n = 7) and other miscellaneous reasons (e.g. patient trying to become pregnant, patient having multiple comorbidities, etc.) (n = 22).

Treatment preference data were collected for 320 of the 336 eligible but non-consenting patients: 30 (9.4%) had no treatment preference, 57 (17.8%) had a preference for surgery and 233 (72.8%) preferred not to have surgery. A response to the treatment that the surgeon advised the patient to have was provided for 325 patients: no surgery (n = 191, 58.8%), surgery (n = 32, 9.9%) and uncertain (n = 102, 31.4%). The agreed treatment for 328 of these patients was recorded: surgery (n = 45, 13.7%) and no surgery (n = 283, 86.3%).

In total, the median time spent obtaining consent from each participant to participate in the trial was 20 minutes. In general, approximately 10 more minutes were spent with participants who went on to be randomised than those who did not [randomised: mean [standard deviation (SD)] = 31.6 minutes (18.9 minutes), median = 30 minutes; not randomised: mean (SD) = 19.5 minutes (12.7 minutes), median = 20 minutes].

Participant flow

The flow of patients through the trial is summarised in a CONSORT flow diagram in Figure 5. Of the 439 randomised participants, 408 (92.9%) were eligible for inclusion in the primary analysis model (surgery arm: 203/219, 92.7%; non-surgery arm: 205/220, 93.2%). The trial was designed to allow for 20% attrition.

FIGURE 5.

The SWIFFT CONSORT flow diagram. Modified from Lancet, vol. 396, Dias JJ, Brealey SD, Fairhurst C, Amirfeyz R, Bhowal B, Blewitt N, et al. , Surgery versus cast immobilisation for adults with a bicortical fracture of the scaphoid waist (SWIFFT): a pragmatic, multicentre, open-label, randomised superiority trial, pp. 390–401,89 Copyright (2020), with permission from Elsevier.

Modified from Lancet, vol. 396, Dias JJ, Brealey SD, Fairhurst C, Amirfeyz R, Bhowal B, Blewitt N, et al. , Surgery versus cast immobilisation for adults with a bicortical fracture of the scaphoid waist (SWIFFT): a pragmatic, multicentre, open-label, randomised superiority trial, pp. 390–401,89 Copyright (2020), with permission from Elsevier.

Participant questionnaires

In total, follow-up participant questionnaires were returned for 359 (81.8%), 349 (79.5%), 313 (71.3%) and 364 (82.9%) of the 439 randomised participants at 6, 12, 26 and 52 weeks, respectively (Table 6). Return rates were lower in the plaster cast group at all time points, except at 6 weeks, when they were similar between the two groups.

The participant questionnaires were primarily returned by post (50% or more at each time point). At 6, 12 and 52 weeks, when participants were invited to attend a hospital visit, there was the opportunity to complete the questionnaire in clinic. This occurred in 46.0%, 41.6% and 34.3% of cases at weeks 6, 12 and 52, respectively. Questionnaire data were completed by telephone as a last resort for hard-to-reach participants in 84 instances.

The numbers of days from the date that the questionnaire was due (e.g. the 6-week questionnaire was due 42 days after randomisation) to the completion of the questionnaire as recorded by the patient (‘Days to complete’) and the return of the questionnaire to the YTU (‘Days to return’) are presented in Table 6. If the questionnaire was completed/returned before the due date (i.e. if it was completed during a clinic visit rather than having been posted by the YTU on the due date), the number of days was recorded as zero. Medians and IQRs are presented, as the data had a right-skewed distribution because most patients completed and returned their forms promptly. There was no obvious difference between the two groups in time to completion or time to return.

Hospital data collection forms

The return of hospital forms is summarised in Table 7. Treatment confirmation forms were collected at 6 and 12 weeks post randomisation; at least one treatment confirmation form was completed for all but one participant (who was allocated to surgery but withdrew on the day of randomisation). A complications form was completed for over 84% of the randomised participants at each of the 6-, 12- and 52-week time points. Wrist range of movement and grip strength forms were received for 389 (88.6%), 336 (76.5%) and 309 (70.4%) participants at 6, 12 and 52 weeks, respectively. At 52 weeks, there appears to be a difference in the percentage of grip and range forms returned between the two groups (surgery, 74.4%; plaster cast, 66.4%), otherwise there are no obvious differences between the two groups in the return rates of hospital forms. The return of treatment confirmation and complications forms was higher than for the grip and range forms, as completion of these forms did not require the participant to attend the hospital visit.

Patient withdrawals

Five participants (surgery, n = 2; plaster cast, n = 3) withdrew from hospital follow-up but agreed to continue completing participant questionnaires; three of these were before the 6-week visit (no hospital visits attended) and two were following the 6-week visit (12- and 26-week visits not attended). The reasons provided were work commitments (surgery, n = 1; plaster cast, n = 1), the participant moved away from the trial catchment area (surgery, n = 1), the participant was too ill to commit to extra hospital visits (plaster cast, n = 1) and the participant sought further opinions at an alternative hospital, with surgical fixation and follow-ups completed there instead of at the recruiting site (plaster cast, n = 1).

A further 14 participants were withdrawn completely from the trial; eight before the 6-week time point (surgery, n = 5; plaster cast, n = 3), two between the 6- and 12-week time points (surgery, n = 2), one between 12 and 26 weeks (plaster cast, n = 1) and three between 26 and 52 weeks (plaster cast, n = 3). The reasons for these withdrawals were the participant no longer wanted to take part in the study, for example was too busy or was sick of the questionnaires (surgery, n = 2; plaster cast, n = 3); no fracture present on the CT scan (surgery, n = 4; plaster cast, n = 1); the participant was unhappy with their treatment allocation (surgery, n = 1; plaster cast, n = 2); and the participant emigrated (plaster cast, n = 1).

Allocated to receive surgery

Of the 219 patients allocated to surgery, 188 (85.8%) received treatment as allocated (Table 8). Surgery took place, on average, 10.2 days (median 11 days, range 3–20 days) after injury, 9.5 days (median 10 days, range 1–20 days) after presenting at A&E or another clinic and 4.5 days (median 5 days, range 0–15 days) after randomisation. Of the 188 participants who underwent surgery, 39 (20.7%) received routine treatment (i.e. surgery and no subsequent plaster cast or splint), 141 (75%) had further routine treatment with a plaster cast or splint only after surgery (not recorded as being due to a treatment failure) and 8 (4.3%) had at least one other surgery within the 12 months (seven had one other surgery and one had two).

The reasons for repeat surgeries (for the seven patients with only one extra surgery within 12 months of randomisation) were removal of the screw due to (1) protrusion (n = 3), (2) experiencing pain and poor flexion of wrist (n = 1) or (3) the scaphoid screw breaching the cortex of the scaphoid at the capitate articulation owing to mispositioning of the screw (n = 1); revision surgery owing to pain/prominent metal work (n = 1); or persistent non-union (n = 1). For the participant who underwent two further surgeries, the first was to remove the screw and perform iliac bone graft/k-wire stabilisation owing to non-union of the scaphoid fracture; the second was for persistent non-union.

The remaining 31 (14.2%) participants allocated to receive surgery were treated non-surgically. It should be noted that the participant with no treatment confirmation form was allocated to the surgery group but withdrew on the day of randomisation and provided no follow-up data. However, one of the reasons provided for withdrawal was that the participant wanted conservative treatment; therefore, this patient is assumed not to have received surgery. The reasons for participants being treated non-surgically are as follows: no fracture was observed on the CT scan subsequent to randomisation (n = 10), the participant’s choice was not to have surgery (n = 9), the participant did not have a bicortical scaphoid waist fracture [n = 8; these fractures were instead described as a waist plus distal pole fracture (n = 2), a radial styloid fracture (n = 1), a unicortical fracture (n = 1), a lunate fracture (n = 1), a Y-shaped waist fracture involving the tubercle (n = 1), an associated scaphoid tubercle fracture (n = 1) and an incomplete fracture (n = 1)]; and other reasons [n = 4; the surgeon felt that surgery was inappropriate/unnecessary following a review of the CT scan but no further information is available (n = 2), no appropriate time for surgery was available for either the surgeon or the patient (n = 1) and the patient was admitted to hospital with pericarditis (n = 1)]. Of these, 30 received a plaster cast and/or splint following randomisation, while one did not receive any treatment because the treating clinician deemed that their subsequent CT scan indicated no injury (see Table 8).

Following randomisation, 41 participants did not report wearing any plaster cast/splint and 65 were reported to be wearing only a splint (for a median of 40 days post randomisation, range 4–97 days – although the upper range may not be accurate, as the final date of splint wearing was often not recorded/known and the splint may have been worn for longer than the 12-week reporting period of the treatment confirmation forms). Of the remaining 113 participants, 29 had a cast (with thumb incorporated) for a median of 21 days (range 2–60 days) following randomisation [of whom two then had a cast (with thumb free) applied for a median of 37 days] and 84 had a cast (with thumb free) for a median of 18 days (range 1–63 days) following randomisation [of whom two then had a cast (with thumb incorporated) for a median of 9 days]. Overall, 103/219 (47.0%) participants allocated to the surgery group were still in a plaster cast or splint 6 weeks post randomisation and 13 (5.9%) still had a cast or splint at 12 weeks.

Allocated to receive plaster cast intervention

Of the 220 patients allocated to not receive immediate surgical fixation, the majority (n = 195, 88.6%) were treated conservatively and did not receive surgery (Table 9), although two of these were considered for surgical fixation owing to non-union. Six (2.7%) participants immediately crossed over to surgery following randomisation with no cast applied before this, for the following reasons: participant choice (n = 4), the CT scan showed displacement (n = 1) and the radiographs were reviewed again at a later date and displacement was judged to be > 2 mm (n = 1). For these six participants, surgery took place, on average, 13.5 days (median 12 days, range 5–32 days) after injury, 12.8 days (median 11.5 days, range – 31 days) after presenting at A&E or another clinic and 8.8 days (median 8.5 days, range 0–24 days) after randomisation. None of these six participants underwent further surgery within 12 months from randomisation.

One (0.5%) participant had a plaster cast applied but received surgery 29 days after randomisation owing to treatment failure, as their fracture was displacing with the plaster cast. This participant received a revision surgery to remove the screw 3 months after initial fixation.

One (0.5%) participant received surgery within 6 months of randomisation at a non-participating hospital to fix what the treating surgeon deemed to be a historic fracture. This was noted by the participant on a participant questionnaire. Limited information is available for this participant, as they withdrew from hospital follow-up at their recruiting site.

The remaining 17 (7.7%) participants received surgery as part of their expected treatment pathway when the treating surgeon judged that the bone had failed to unite with conservative treatment. Sixteen of these received only one surgery in the 12 months following randomisation and one received three surgeries (the second one for persistent non-union and the third to remove the wires from the second operation). The initial surgery took place, on average, 159.0 days (median 161 days, range 68–358 days) after injury, 157.0 days (median 156 days, range 67–358 days) after presenting at A&E or another clinic and 151.6 days (median 153 days, range 61–350 days) after randomisation. Fourteen participants met the protocol definition of the control condition by receiving early surgical fixation of their fractures following detection of persistent non-union after plaster cast management (defined here as surgery within 6 months of randomisation, although only five had their surgery within 12 weeks), while three had delayed surgical fixation, one of whom opted to attend a private hospital for their fixation, as they were told there would be a 4- to 5-month wait for surgery at the treating centre.

There were two participants who were deemed to have a suspected non-union at 12 weeks and for whom surgical fixation was recommended, but who did not receive surgery. These participants did not fully comply with the anticipated control condition for the trial. The limited information we have about these participants is as follows: for one, the operation was scheduled but then delayed and the participant self-discharged after waiting and declined all further treatment, including offers of surgery; for the second, it was the surgeon’s decision not to operate.

Following randomisation, two participants did not report wearing any plaster cast/splint and two were reported to be wearing only a splint (for a median of 44 days post randomisation). Of the remaining 216 participants, 45 had a cast (with thumb incorporated) for a median of 42 days (range 7–84 days) following randomisation [of which eight then had a cast (with thumb free) for a median of 25 days (range 14–42 days)] and 171 had a cast (with thumb free) for a median of 42 days (range 7–98 days) following randomisation [of which five then had a cast (with thumb incorporated) for a median of 44 days (range 12–69 days)]. Overall, 187/220 (85.0%) participants allocated to the plaster cast group were still in a plaster cast or splint 6 weeks post randomisation and 47 (21.4%) still had a cast or splint at 12 weeks.

Surgical fixation details

A surgery form was received for 210 of the 213 participants in the trial who received surgical fixation of their fracture (surgery group, n = 187/188, 99.5%; plaster cast group, n = 23/25, 92.0%). Surgery was performed by 102 surgeons across 30 sites. Each surgeon performed between one and six operations (median 1). Details of the operation, for initial surgical fixation procedures only, are provided in Table 10. Surgery lasted a median of 55 minutes (range 15–140 minutes) with a mean (SD) of 2 (0.9) surgeons in attendance. Most commonly, the main operating surgeon was a consultant (n = 39, 66.2%), followed by a specialist trainee (n = 49, 23.3%) and a staff grade/associate specialist (n = 22, 10.5%). When the main operating surgeon was a specialist trainee, an assisting consultant was recorded as being present in 33 of 49 (67.4%) surgeries. Acutrak^® screws (Acumed LLC, Hillsboro, OR, USA) were the most frequently used type and a second screw was used for two (1.0%) participants. There were no reported intraoperative complications and most participants (n = 113, 53.8%) were treated with a plaster cast postoperatively.

Primary outcome (Patient-Rated Wrist Evaluation) analysis

The PRWE (pre and post injury) was assessed at baseline and at 6, 12, 26 and 52 weeks post randomisation. The PRWE total score is a value between 0 and 100, where a higher score indicates worse pain and functioning. The pain and function subscale scores are each out of a maximum of 50 (50 being the worst score). The trial was powered to detect an effect size of 0.3 (assuming a SD of 20); this is equivalent to a difference in total PRWE score of 6 points.

Primary end point analysis

There was no evidence of a difference in PRWE score between the surgery and plaster cast groups at the 52-week time point, with an adjusted mean difference of –2.1 in favour of the surgery group (95% CI –5.8 to 1.6; p = 0.27).

This result was extracted from a multilevel model in which participant was treated as a random effect and observations over time (6, 12, 26 and 52 weeks) were nested within participant. The effect of randomised treatment group was assessed while adjusting for time, group-by-time interaction, age, fracture displacement and hand dominance. The predicted means and associated 95% CIs for each group and time point are presented in Table 11 and displayed in Figure 6.

FIGURE 6.

Adjusted mean PRWE scores (with 95% CIs) over time by randomised group for primary analysis. Modified from Lancet, vol. 396, Dias JJ, Brealey SD, Fairhurst C, Amirfeyz R, Bhowal B, Blewitt N, et al. , Surgery versus cast immobilisation for adults with a bicortical fracture of the scaphoid waist (SWIFFT): a pragmatic, multicentre, open-label, randomised superiority trial, pp. 390–401,89 Copyright (2020), with permission from Elsevier.

Modified from Lancet, vol. 396, Dias JJ, Brealey SD, Fairhurst C, Amirfeyz R, Bhowal B, Blewitt N, et al. , Surgery versus cast immobilisation for adults with a bicortical fracture of the scaphoid waist (SWIFFT): a pragmatic, multicentre, open-label, randomised superiority trial, pp. 390–401,89 Copyright (2020), with permission from Elsevier.

Different covariance structures were applied to the model. An unstructured pattern that models all variances and covariances separately resulted in the lowest AIC and so was used in the final model.

Diagnostics of model fit revealed that the standardised residuals demonstrated only a minor deviation from normality and were uniform against fitted values; therefore, analyses were carried out on untransformed values. Model coefficients for the covariates with 95% CIs are provided as the software output in Appendix 4 to aid understanding of the fitted model.

Valid data

The primary analysis included data from 408 patients (surgery, n = 203; plaster cast, n = 205) with a valid PRWE score for at least one follow-up time point and complete baseline covariates. A valid response is defined here as sufficient data (maximum of one missing PRWE item in each of the two subscales) to allow the calculation of the total score. The number of participants with valid PRWE data at each time point is presented by randomised group in Table 12, with reasons for missing data.

The percentage of randomised participants with valid PRWE data ranged from 68.8% (26 weeks) to 82.5% (52 weeks) for the post-randomisation time points. Overall, 408 participants (surgery, n = 203, 92.7%; plaster cast, n = 205, 93.2%) had valid PRWE data for at least one post-randomisation time point and so were included in the primary analysis model.

Demographic and injury characteristics at baseline for participants who provided valid PRWE data at each time point are presented by randomised group in Appendix 3, Tables 52–55.

Overall, 249 patients (56.7%) had a valid PRWE response at all post-randomisation follow-up time points (complete responders: surgery, n = 130, 59.4%; plaster cast, n = 119, 54.1%) and a further 159 patients (intermittent responders: surgery, n = 73, 33.3%; plaster cast, n = 86, 39.1%) had a valid PRWE response at one or more, but not all, post-randomisation time points. Table 13 provides the descriptive PRWE total scores for complete and intermittent responders and the baseline PRWE scores for those who had no valid post-randomisation PRWE data. Complete responders had, on average, better PRWE outcomes (lower mean scores) than intermittent responders pre injury and at 52 weeks post randomisation, but had similar outcomes at baseline (post injury) and at 6, 12 and 26 weeks post randomisation.

Descriptive Patient-Rated Wrist Evaluation statistics

Total mean PRWE scores pre injury and at enrolment (post injury) were similar between the two groups (Table 14). Total mean PRWE scores improved (decreased) over time following injury in both groups, but were higher (worse) in the plaster cast group than in the surgery group at all post-randomisation time points except at 26 weeks. At 52 weeks, the unadjusted mean difference was –2.8 points (95% CI –6.5 to 1.0 points) favouring the surgery group.

Patient-Rated Wrist Evaluation at the secondary time points

Adjusted PRWE means and group differences for the primary analysis model are presented in Table 11 and displayed in Figure 6. The analysis showed a statistically significant difference between treatment groups at week 12 (p = 0.01) and a borderline result at week 6 (p = 0.06) but not at week 26 (p = 0.89) or at the primary end point of 52 weeks (p = 0.27). There was no overall effect of treatment group (difference of 3.0 points in favour of the surgery group; p = 0.07). Although statistically significant, the mean difference observed at 12 weeks was lower than our minimum clinically important difference of 6 points, although the confidence interval does include this difference.

Missing data

Adjusted PRWE means and group differences for the separate linear regression analysis models, for each time point, run on the multiply imputed data set are presented in Table 15. Analyses showed very similar results to the primary analysis, that is, a statistically significant difference between treatment groups at weeks 6 (p = 0.049) and 12 (p = 0.01) but not at week 26 (p = 0.93) or the primary end point of 52 weeks (p = 0.28). The adjusted mean difference at 52 weeks was –2.0 (95% CI –5.7 to 1.6) in favour of the surgery group. Although separate linear regressions were performed for these analyses, as opposed to a repeated measures model, there is no estimate for the overall treatment effect over time.

Handling multisite data

Adjusted PRWE means and group differences are presented in Table 15 for the analysis in which the primary outcome model also included site as a random effect (within which participants were nested). An unstructured covariance pattern was specified for this model. The analysis showed no statistically significant differences between treatment groups post randomisation, except at week 12 (p = 0.01). The adjusted mean difference at 52 weeks was –1.9 (95% CI –5.6 to 1.8). There was no overall effect of treatment group (difference of 2.8 points in favour of the surgery group; p = 0.09).

Timing of data collection

The primary analysis model was repeated including only data collected 1 week either side of the 6-week time point (surgery, n = 118; plaster cast, n = 112), 2 weeks either side of the 12-week time point (surgery, n = 121; plaster cast, n = 108), 6 weeks either side of the 26-week time point (surgery, n = 133; plaster cast, n = 128) and 8 weeks either side of the 52-week time point (surgery, n = 170; plaster cast, n = 155). A total of 380 participants were included in this analysis (190 in each group).

Adjusted PRWE means and group differences for the model as specified above are presented in Table 15. The analysis showed no statistically significant differences between treatment groups post randomisation, except at week 12 (p = 0.01). The adjusted mean difference at 52 weeks is in this population was –3.1 (95% CI –6.7 to 0.6). There was no overall effect of treatment group (difference of 2.4 points in favour of the surgery group; p = 0.16).

Post hoc sensitivity analysis including smoking status

Smoking status (yes/no) was included as a covariate in the primary analysis model in a sensitivity check, as this factor was found to be imbalanced by chance at baseline (smokers: 33% in the surgery group, 26% in the plaster cast group) and thought to be associated with poorer bone healing and complications. The analysis showed similar results to the primary analysis, that is, a statistically significant difference between treatment groups at week 12 (p = 0.01), but at not at week 26 (p = 0.67) or the primary end point of 52 weeks (p = 0.14). Week 6 was now statistically significant at the 5% level (p = 0.03). However, there was evidence of an overall effect of treatment group (difference of 3.6 points in favour of the surgery group; p = 0.03). The magnitude of the effect at 52 weeks increased compared with the primary analysis (from 2.1 to 2.8 points in favour of the surgery group) and the 95% CI includes the minimum clinically important difference of 6 points (see Table 15).

Displacement and lack of fracture as assessed by independent review of baseline imaging data

The randomisation for the trial was stratified by presence (or not) of displacement of a scaphoid fracture (< 1 mm or 1–2 mm inclusive) as seen on the plain radiographic views taken at baseline and used by the treating clinician to determine eligibility (although the discrepancies discussed in Chapter 3, Baseline characteristics of randomised participants, should be noted). This judgement of displacement is included as a covariate in the primary analysis model. The extent of fracture displacement was also subsequently assessed and agreed on by three independent raters who reviewed all available participant baseline imaging data (CT scans and radiographs) throughout the trial.

Baseline radiographic images were available and reviewed for all but one participant (in the surgery arm). Baseline CT images were available and reviewed for 431 participants (surgery, n = 214, 97.3%; plaster cast, n = 217, 99.1%). Both baseline and CT images were reviewed for 431 (98.2%) participants, radiographs were reviewed for only seven participants (1.6%) and neither were reviewed for one participant (0.2%). The maximum fracture displacement, in millimetres, observed on either the CT or the radiographic images was identified and used to categorise the participant’s fracture displacement as < 1 mm, 1–2 mm inclusive or > 2 mm. Overall, 213 (81.6%) of the 261 fractures that were deemed by the treating clinician to not be displaced at baseline were classified as not displaced (< 1 mm) on review, 39 (14.9%) were classified as displaced 1–2 mm, eight (3.1%) were classified as displaced > 2 mm and one (0.4%) was missing (see Appendix 3, Table 56). Of the 178 fractures that were deemed to be displaced (1–2 mm) by the treating clinician at baseline, 112 (62.9%) were classified as not displaced (< 1 mm) on review, 47 (26.4%) were classified as displaced 1–2 mm and 19 (10.7%) were classified as displaced > 2 mm.

The primary analysis model was rerun, replacing displacement as used in the randomisation as a covariate with the variable indicating the extent of displacement agreed by the three raters (see Table 15) providing very similar results to the primary analysis (see Table 11).

Consensus was reached between the three raters that displacement of the fracture was > 2 mm, based on their assessment of the baseline radiography/CT scans, for 27 (6.2%) randomised participants. A fracture could be seen on radiographic imaging for all but one of the 438 participants (n = 437, 99.8%) for whom these data were available and on CT imaging for 426 (98.8%) of 431 participants. In five participants no fracture could be seen on the CT scan, but in four of these participants the fracture could be seen on the radiographic images; thus, consensus was reached between the three raters that only one participant did not actually have a fracture (participant allocated to surgery group). Sensitivity analyses of the primary outcome model were conducted that excluded these participants (see Table 15).

The quality of the radiographic imaging in the participant who was deemed not to have a fracture was considered to be ‘good’. In the five cases in which a fracture could not be seen on CT images, the quality of the images was deemed to be ‘good’ in three cases and ‘fair’ in the other two.

In addition, for patients for whom raters thought there was no fracture on the CT scan, later images were reviewed for evidence of bone healing to confirm whether there had been a fracture. For the participant for whom the baseline radiographic images also indicated there was no fracture, this was confirmed in all other images. In the four others, the radiographic images indicated a fracture: one only had baseline images, so later images could not be reviewed; one had only baseline and 52-week images and, at 52 weeks, the fracture was interpreted as having united; one had baseline, 6-week and 52-week images and in all subsequent images the fracture was considered to be united; and one had only 6-week images, in which the fracture was considered to have united. However, union cannot be said to confirm that a fracture was initially present.

Complier-average causal effect analysis

The CACE analysis considers the effect of receiving early surgical fixation compared with no surgical fixation of the fracture, and as such does not account for the ‘partial’ compliers in the plaster cast group [i.e. the two participants for whom surgery was considered for non-union after a period of plaster cast management, and the three participants who received delayed surgical fixation (6 months after randomisation) of their non-united fracture]. We have considered these a pragmatic aspect of the ‘control’ condition. Six (2.7%) participants in the plaster cast group crossed over to the surgery group and received immediate surgical fixation of their fractures (contamination), while 31 (14.2%) participants in the surgery group did not receive surgery but instead were managed conservatively (non-compliance). The CACE estimate of the treatment effect with adjustment for non-compliance and contamination is a difference of –3.1 (95% CI –7.3 to 1.1; p = 0.15) in 52-week total PRWE score. This difference is in favour of the surgery group and is larger than the ITT treatment effect estimate at 52 weeks, demonstrating a greater, but not statistically significant, benefit of surgery among participants who complied with their treatment allocation. The 95% CI is –7.3 to 1.1; therefore, we cannot rule out a clinically meaningful difference or no effect.

Patient preference for treatment

The first subgroup analysis was undertaken to test the hypothesis that participants who expressed a preference for surgery at baseline would benefit more from surgery than participants who expressed a preference against surgery or who had no particular treatment preference.

Descriptive summary statistics for the PRWE total score are presented in Appendix 3, Table 57, and displayed in Appendix 3, Figure 14, by treatment group stratified by baseline treatment preference. No notable differences between the two groups are observed at any time point within the subgroup who did not express a treatment preference at baseline. Unadjusted mean scores are lower (better) in the surgery group at all time points, except 26 weeks in the subgroup who expressed a preference for surgery. In the subgroup who preferred no surgery, unadjusted mean scores are lower (better) in the surgery group at all time points, except baseline (post injury) in the subgroup who expressed a preference for surgery, and the differences between the groups are larger at 6, 12 and 26 weeks than in the subgroup with a preference for surgery.

No significant interaction was observed between randomised allocation and treatment preference (surgery group and preference for surgery, p = 0.54; surgery group and preference for no surgery, p = 0.65). At 52 weeks, the adjusted mean difference in total PRWE score between the surgery and plaster cast groups was –0.9 (95% CI –6.0 to 4.2; p = 0.72) in the no preference subgroup, –3.0 (95% CI –8.2 to 2.2; p = 0.25) in the surgery preference subgroup and –4.2 (95% CI –17.2 to 8.9; p = 0.53) in the no-surgery preference subgroup.

Fracture displacement (randomisation)

The second subgroup analysis tested the hypothesis that patients with a displaced fracture at baseline would benefit more from surgery than those with a non-displaced fracture. The relationship between fracture displacement (as stratified on in the randomisation) and randomised group in terms of PRWE is illustrated in Appendix 3, Table 58 and Figure 15. Overall, participants with a displaced fracture tended to have higher post-randomisation PRWE scores than those with no or minimal displacement, and scores in the surgery group were lower than in the plaster cast group at 6, 12, 26 and 52 weeks for this subgroup. There was no statistically significant interaction effect (p = 0.35); at 52 weeks, the adjusted mean difference between the surgery and plaster cast groups was –0.8 (95% CI –5.4 to 3.8; p = 0.73) in the no displacement subgroup and –4.0 (95% CI –9.3 to 1.4; p = 0.15) in the displaced subgroup, both favouring the surgery group.

Fracture displacement (study eligibility form)

A third subgroup analysis tested the same hypothesis as above using displacement as recorded on the study eligibility form. The relationship between fracture displacement (as recorded on the study eligibility form) and randomised group in terms of PRWE is illustrated in Appendix 3, Table 59 and Figure 16. Overall, participants with a displaced fracture tended to have higher post-randomisation PRWE scores than those with no or minimal displacement, and scores in the surgery group were lower than in the plaster cast group at 6, 12, and 52 weeks for this subgroup. There was no statistically significant interaction effect (p = 0.70); at 52 weeks, the adjusted mean difference between the surgery and plaster cast groups was –1.6 (95% CI –6.1 to 3.0; p = 0.50) in the no displacement subgroup and –2.9 (95% CI –8.4 to 2.6; p = 0.30) in the displaced subgroup, both favouring the surgery group.

Surgery patients for whom the screw caused cartilage damage

A total of 188 (85.8%) participants allocated to the surgery group received treatment as allocated. For 142 (75.5%) of these, CT images at 52 weeks were assessed by three independent raters for surgical screw penetration. No screw penetration was observed for 49 (34.5%) participants. The extent of the penetration was measured for the remaining 93 participants (mean 1.6 mm, SD 0.95 mm, range 0.2–4.7 mm), and was categorised as minor (< 1 mm), which is unlikely to have an effect on articular cartilage (n = 25/93, 26.9%); moderate (1–2 mm inclusive), which will probably have an effect on cartilage, causing damage (n = 44, 47.3%); or severe (> 2 mm), which will definitely cause lasting damage to articular cartilage (n = 24, 25.8%). Descriptive summaries of baseline participant and fracture data and PRWE scores for these participants, stratified by whether or not the surgical screw used was too long and caused cartilage damage (none plus minor versus moderate plus severe) as determined on the CT scans, are provided in Appendix 3, Tables 58–60. Participants with displaced fractures at baseline were less likely to suffer from cartilage damage caused by the screw. At 52 weeks, those who did not have significant surgical screw protrusion tended to perform better on the PRWE (total unadjusted mean: 8.9 versus 10.8).

Plaster cast patients who required surgery for non-union

Of the 220 participants allocated to the plaster cast group, six crossed over to receive immediate surgical fixation while, of the remaining 214, 19 (8.9%) were deemed to require surgical fixation of a non-united fracture following plaster cast management (although two participants did not receive the surgery, see Allocated to receive plaster cast intervention). Descriptive summaries of baseline participant and fracture data and PRWE scores for the 214 plaster cast participants stratified by whether or not they needed surgery owing to non-union are presented in Appendix 3, Tables 60–62. Participants with displaced fractures at baseline were more likely to require surgery for non-union than those with < 1-mm displacement. Other risk factors include being female and a smoker. In addition, those that required surgery had had their injuries for slightly longer at enrolment to the trial than those who did not require surgery (median: 6 versus 4 days). At 52 weeks, those who did not require surgery for non-union tended to perform better on the PRWE (total unadjusted mean: 12.8 vs. 29.1).

Feasibility requirements

There were two feasibility requirements for this trial: (1) that a CT scan was performed within 2 weeks (14 days) of a patient’s injury (and before surgery if this occurred earlier) and (2) for patients in the surgery arm, that surgery was performed within 2 weeks of presentation to A&E or another clinic.

The majority of participants had a CT scan within 2 weeks of their injury (and before surgery if this was earlier) (surgery group, n = 216, 98.6%; plaster cast group, n = 196, 89.1%; see Appendix 3, Tables 63–65). Three participants in the surgery group did not meet this feasibility requirement: two crossed over treatment and received neither a CT scan nor surgery and one had their CT scan 15 days after their injury, but this was before their surgery which occurred 5 days later. Twenty-four participants in the plaster cast group did not meet this feasibility requirement: five received routine treatment and did not receive a CT scan; one immediately crossed over to surgery, which took place 7 days after injury, but did not receive a CT scan; and 18 had their CT scan between 15 and 47 days after injury (three of whom received surgery at a later date as part of their further routine treatment for non-union).

Among participants allocated to the surgery group, 182 (83.1%) had surgical fixation of their fracture within 14 days of presenting at A&E or another clinic. Of the remaining 37 participants, 31 did not receive surgery and six had their surgery between 15 and 20 days after presentation (see Appendix 3, Tables 63–65). A linear regression for the surgery arm indicated that time from injury to surgery in days may be predictive of PRWE score at 52 weeks, such that a 1-day delay in surgery is associated with a 0.78-point increase in PRWE score (95% CI –0.01 to 1.57; p = 0.054).

Patient-Rated Wrist Evaluation subscales: pain and function

The PRWE subscale scores for pain and function are summarised in Table 14. Adjusted PRWE pain and function subscale means and group differences are presented in Table 16 and displayed in Appendix 3, Figure 17. The pain subscale analysis included data from 409 participants (surgery, n = 203, 92.7%; plaster cast, n = 206, 93.6%) and the function analysis included data from 408 participants (surgery, n = 203, 92.7%; plaster cast, n = 205, 93.2%). The analysis of the pain subscale showed no statistically significant difference between treatment groups overall or at any individual post-randomisation time point. The adjusted mean difference at 52 weeks was –1.1 (95% CI –3.3 to 1.0) in favour of the surgery group. However, a statistically significant difference in function subscale score, favouring the surgery group, was seen at 6 and 12 weeks. This difference did not persist to 26 or 52 weeks, but there is an overall statistically significant difference between the two groups over time.

Short Form questionnaire 12-items: physical and mental health component scores

Mean mental component summary (MCS) and physical component summary (PCS) scores of the SF-12 improved (increased) over time following randomisation in both groups (except between 26 and 52 weeks in PCS in the plaster cast arm) (Table 17). At 52 weeks, the unadjusted mean difference in MCS was –1.1 points (95% CI –3.2 to 1.0 points) favouring the plaster cast group, but in PCS was 1.8 points (95% CI 0.2 to 3.3 points) favouring the surgery group.

Adjusted SF-12 means and group differences for the models are presented in Table 17 and displayed in Appendix 3, Figure 18. Both analysis models included data from 408 participants (surgery, n = 202, 92.2%; plaster cast, n = 206, 93.6%). The analysis of the MCS subscale showed no statistically significant difference between treatment groups overall or at any individual post-randomisation time point. The adjusted mean difference at 52 weeks was –1.2 (95% CI –3.3 to 0.8) in favour of the plaster cast group. However, a statistically significant difference in PCS subscale score, favouring the surgery group, was seen at 12 and 52 weeks, but not at 6 or 26 weeks or overall (p = 0.08). The adjusted mean difference at 52 weeks was 1.6 (95% CI 0.2 to 3.1) in favour of the surgery group.

Wrist range of movement and grip strength: affected wrist

Measures of wrist range of movement and grip strength for the affected wrist are presented in Table 18. Similar mean values were observed across these variables in the two groups at baseline. These were assessed at hospital visits at baseline and at 6, 12 and 52 weeks post randomisation.

Union

Assessment of union via radiographs was possible for 188 (85.8%) participants in the surgery group and 201 (91.4%) participants in the plaster cast group at 6 weeks, of whom 13 (6.9%) and 32 (15.9%), respectively, displayed non-union or only slight union (Table 20). At week 12, radiographic images were available for assessment of union for fewer participants than at 6 weeks: 169 (77.2%) in the surgery group and 163 (74.1%) in the plaster cast arm. A lower proportion of those reviewed were graded as having non-union or slight union at this time point than at 6 weeks in both groups (surgery, n = 7, 4.1%; plaster cast, n = 23, 14.1%).

The proportion of participants assessed for union decreased at each time point in both groups. At 52 weeks, the grading of union was based on CT images or on radiographic images when CT was not available and was assessed for 314 participants (surgery, n = 164, 74.9%; plaster cast, n = 150, 68.2%), of whom 13 (4.1%) were deemed to have non-union or only slight union of their fracture (surgery, n = 4, 2.4%; plaster cast, n = 9, 6.0%). Furthermore, in Table 20, the percentages are calculated using a denominator that includes participants with missing data. There is a substantial number of participants with missing data (28.5% overall at 52 weeks), which may underestimate the proportion of participants with union.

The 52-week PRWE scores, where available, are summarised for the two groups according to whether or not the participants had imaging available for union assessment at 52 weeks (see Table 20). Overall, there is little difference in the mean PRWE scores of those who attended and did not attend imaging (12.7 vs. 13.2, respectively); however, there are differences between the two randomised groups. In the surgery group, participants who did not attend imaging tended to have higher (worse) scores than those who did attend imaging (mean 16.4 vs. 10.6, respectively) and so were perhaps less likely to have full union of their fractures. However, the trend reverses in the plaster cast group, with those not attending imaging having lower (better) scores and so more likely to have better union.

Participants in the surgery group were less likely than those in the plaster cast group to have non-union or only slight union of their fracture at 52 weeks, but this difference was not statistically significant in a logistic regression model adjusting for age, fracture displacement and hand dominance [odds ratio (OR) 0.40, 95% CI 0.12 to 1.33; p = 0.13). Similarly, results following multiple imputation of the union variables at 6, 12 and 52 weeks indicated that the likelihood of participants having non-union or only slight union of their fracture at 52 weeks was lower for participants allocated to the surgery group than for those in the plaster cast group (OR 0.51, 95% CI 0.17 to 1.57), but this difference was not statistically significant (p = 0.24). In the surgery group, 4 out of 219 participants were deemed to have non-union or slight union at 52 weeks (1.8%), compared with 9 out of 220 in the plaster cast group (4.1%). Based on these figures, the increase in the number of participants who need to be offered surgery compared with the number offered plaster cast management (followed by fixation of fractures that fail to unite with cast immobilisation) to prevent one extra non-union or slight union at 52 weeks is 44 [number needed to treat (NNT)]. However, data are missing in over a quarter of participants, and this calculation, by default, assumes that all those in whom data are missing experience at least partial union. At the other extreme, assuming that all those in whom data are missing experience slight union or non-union, the NNT is 11. For non-union alone, the NNT is 73 and 12 in the first and second scenario, respectively.

The one participant in the plaster cast group whose fracture was assessed at 52 weeks by three raters as showing non-union underwent surgical fixation the day after randomisation, then wore a splint for 2 weeks; no concerns about non-union were raised and recorded in the treatment confirmation form at 6 or 12 weeks. One of the four participants in the plaster cast group whose fractures were assessed as showing non-union had surgery to fix non-union 3 months after randomisation, a further surgery for persistent non-union 6 months after that and surgery a month later to remove the wires from the second operation. The remaining three participants received routine treatment with a plaster cast and were not offered surgery; for two of them, this was because non-union was not suspected by the treating clinician on review of radiography, while the third did not attend for radiography at 6 or 12 weeks.

Malunion

Malunion was determined by calculating the ratio of the scaphoid height to length, using thresholds of both 0.6 and 0.7 (Table 21). By default, more participants are classified as having malunion using the 0.6 threshold than 0.7. Considering those with non-missing data only, at 6 weeks, 175 (93.6%) participants in the surgery group and 180 (90.0%) participants in the plaster cast group had malunion based on the 0.6 threshold. At 0.7, the figures are 52 (27.8%) and 51 (25.5%), respectively. Malunion at both thresholds remained reasonably steady in both groups at 6, 12 and 52 weeks, as determined from radiographic images. However, at 52 weeks, based on CT scans, the rate of malunion dramatically decreased to 60 (38.29%) participants in the surgery group and 45 (33.3%) participants in the plaster cast group at the 0.6 threshold, and to seven (4.5%) and seven (5.2%), respectively, at 0.7.

Complications

At least one surgical complication, up to and including 52 weeks post randomisation, was experienced by 31 (14.2%) participants randomised to the surgery group and by three (1.4%) participants in the plaster cast group. The most common surgical complication was screw protrusion (Table 22), reported for 10 participants in the surgery group and one in the plaster cast group at 6, 12 or 52 weeks. A nerve event (of any kind) was reported for one participant in the plaster cast group (hypoaesthesia at 52 weeks) and for 10 unique participants in the surgery group. Table 22 presents only complications that were reported for at least one participant throughout the course of the study; however, we also explicitly asked about the following surgical complications, of which none were reported: superficial division of radial nerve, vessel events and avascular necrosis.

At least one issue relating to the plaster cast, up to and including 52 weeks, was reported for five (2.3%) participants randomised to the surgery group and for 40 (18.2%) participants in the plaster cast group (Table 23). The most commonly reported issue was that the cast caused soreness (this was generally minor rubbing of the skin), reported for three surgery participants and 23 plaster cast participants at 6 or 12 weeks.

At least one medical complication, up to 52 weeks, was reported for four (1.8%) participants randomised to the surgery group and for five (2.3%) participants in the plaster cast group. These were either a chest infection or another issue (gastric upset, depression or tenderness of the affected wrist; Table 24). We also explicitly asked about the following medical complications, of which none were reported: myocardial infarction, stroke, deep vein thrombosis requiring treatment and pulmonary embolism requiring treatment.

There was no evidence of a difference between the two groups in the likelihood of participants experiencing at least one surgical, medical or cast complication (as recorded on the complications form, with details in Tables 22–24) up to 52 weeks [surgery group, n = 39, 17.8%; plaster cast group, n = 51, 23.2% (OR 0.72, 95% CI 0.45 to 1.15; p = 0.17)]. We must be careful not to overinterpret this finding to mean that the likelihood of experiencing a surgical, cast or medical complication is similar in both groups. Cast complications were observed more frequently among the plaster cast group and surgical complications were observed more frequently among the surgery group. Complications related to the plaster cast tended to be relatively minor and would not result in ongoing problems (see Table 23). However, surgery-related complications are more severe and are more likely to have potentially long-lasting consequences for the individual (see Table 22). As an example, Table 23 shows that, in the plaster cast group, half (30 of 58 events) of the complications were due to the cast being broken, soft or tight, and, in the statistical analysis of the complications, are given the same importance as CRPS or an infection. Non-union symptoms (n = 8) were recorded as AEs or complications, even when this was an expected part of the control pathway and when non-union had been identified. There are also some discrepancies between the reporting of events on the complications form and on the AEs form. For example, the AEs form logs three participants as having CRPS, but the complications form records only two. The three raters’ review of the imaging identified further complications that were not accounted for in the AE or complications forms, particularly after surgery. This could have been influenced by whether or not the problem had been recognised, by the surgeon’s decision on whether or not this needed to be reported or by whether or not the complication was identified on imaging done solely for research purposes and hence was not available to clinicians. The logistic regression included complications from the hospital forms only and did not include those from other data sources (i.e. AE reporting or imaging).

Cases when two out of the three raters agreed that there was a complication on a review of imaging data are reported by randomised group and time point in Table 25.

Osteoarthritis (OA) was detected at baseline on either radiographic or CT images for 25 (11.4%) participants in the surgery group and 31 (14.1%) participants in the plaster cast group. OA was more likely to be detected on CT images than in plain radiographic views. Of these 25 participants in the surgery group, 23 had radiographic or CT imaging at 52 weeks and 17 were seen to have OA on either of these. OA was detected for a further 28 participants at 52 weeks in the surgery group. Of the 31 participants in the plaster cast group with OA at baseline, 22 had radiographic or CT imaging at 52 weeks and 20 were seen to have OA on either of these. OA was detected for a further 22 participants at 52 weeks in the plaster cast group.

Penetration of the screw (used during surgical fixation) of the radioscaphoid joint (RSJ), the scaphotrapezium joint (STJ) or another joint was reported for a total of 104 unique participants at 6, 12 or 52 weeks (surgery, n = 94, 42.9%; plaster cast, n = 10, 4.6%). At 52 weeks, the CT scans of 80 participants in the surgery group were reported to show screw penetration in one or more joints (RSJ, n = 44/80, 55.0%; STJ, n = 48/80, 60.0%; another joint, n = 19/80, 23.8%. For the plaster cast group, of which a smaller proportion underwent surgery, the CT scans of nine participants were reported to show screw penetration in one or more joints (RSJ, n = 4/9, 44.4%; STJ, n = 6/9, 66.7%; another joint, n = 0/9, 0.0%). On CT scans at 52 weeks, the maximum screw protrusion was measured and seen to be, on average, 1.7 mm (SD 0.9 mm, range 0.4–4.7 mm) and was similar in both groups. Overall, maximum screw protrusion was categorised as < 1 mm (20.7%), 1–2 mm (52.4%) or > 2 mm (26.8%).

Lucency was assessed based on each of these categories on follow-up radiographic images (worst of each view available) and the 52-week CT scan (worst of each of three MPRs available) agreed by three observers using agreement rules. This was considered only when an implant was present. In the surgery group, serious lucency (1–2 mm) was observed on radiography for only one participant at 6 weeks, for two participants (including the one at 6 weeks) at 12 weeks and for four participants (including the one at 12 weeks who did not display lucency at 6 weeks) at 52 weeks. No serious lucency was observed on radiographs for any participant in the plaster cast group.

The prevalence of avascular necrosis (which is also known as osteonecrosis) is summarised for the two groups in Table 25; prevalence appears to be similar in both groups at baseline but, at later time points, the plaster cast group has a higher proportion of more significant cases of avascular necrosis.

Adverse events

At least one non-serious AE was reported for 24 (11.0%) participants in the surgery group and for 29 (13.2%) participants in the plaster cast group (difference of –2.2%, 95% CI –8.3% to 3.9%; Table 26). Of those who experienced at least one event, most reported only one event (surgery group, n = 19, 79.2%; plaster cast group, n = 23, 79.3%) but participants reported up to three events each. In total, 30 events were reported for participants in the surgery group and 36 events were reported for participants in the plaster cast group, of which, respectively, 24 (80.0%) and four (11.1%) were related to receiving anaesthesia and/or surgery, three (3.0%) and 23 (63.9%) were related to cast treatment and three (3.0%) and nine (25.0%) were other events. Sixteen events (surgery group, n = 5, 16.7%; plaster cast group, n = 11, 30.6%) were deemed to be unexpected by the reporting clinician.

Three SAEs were reported among three (1.4%) participants in the surgery group (Table 27). All three were related to anaesthesia and/or surgery and two were deemed to be unexpected at the time of reporting.

Agreement analysis

Descriptive analyses of the agreement between the three independent raters on review of radiographic and CT imaging are presented in Appendix 5.

Participant use of home exercises to care for wrist

When entered into the study, participants should have been provided with written advice about home exercises to perform to care for their wrist. Participants were asked on the 12-week participant questionnaire how they found doing these exercises. Responses to these questions are provided in Appendix 3, Table 66. Of those who provided a response to the question, 151/176 (85.8%) in the surgery group and 123/155 (79.4%) in the plaster cast group reported that they found the exercises very or quite useful. Among those who performed the exercises, the exercises were reported to have been performed on a median of 41 days (range 1–168 days) in the surgery group and on a median of 35 days (range 2–137 days) in the plaster cast group. On the 52-week complication form, data were collected on whether or not the participant was referred for physiotherapy for the treatment of their wrist injury during the previous year. Approximately twice as many participants allocated to the surgery group had been referred for physiotherapy (n = 58, 26.5%) as in the plaster cast group (n = 30, 13.6%).

Participant perceptions of their wrist and treatment preference at 52 weeks

On the 52-week questionnaire, participants were asked about the state of their wrist at present in comparison with a year ago (see Appendix 3, Table 67). Of those who provided a response to the question, a very similar proportion in the two groups reported that their wrist felt much or slightly better (surgery group, n = 166/181, 91.7%; plaster cast group, n = 156/174, 89.7%). Participants were also asked, based on their experiences of the treatment received as part of the trial, if they were to again injure their wrist to the same extent as they did 52 weeks ago, which treatment they would prefer. Of those who provided a response to the question, in the surgery group, three-quarters reported that they would have surgery again (n = 137/181, 75.7%), 36 (19.9%) participants did not have a preference and eight (4.4%) participants reported that they would not have surgery. In the plaster cast group, there was a reasonably equal split among the three categories (surgery, n = 59/175, 33.7%; no preference, n = 68, 38.9%; no surgery, n = 48, 27.4%).

Quality of life: EuroQol-5 Dimensions, three-level version

The EQ-5D-3L is a validated questionnaire to assess the generic health status or QoL of a patient, consisting of questions covering five dimensions of health: mobility, self-care, usual activity, pain/discomfort and anxiety/depression. 90 It is the most widely used means of consistently estimating the general health of a patient and is used by the National Institute for Health and Care excellence (NICE) as its preferred measure. 91 While other disease-specific questionnaires are available, such as the PRWE, they do not allow for comparison across disease areas and they cannot be used to determine the optimal allocation of limited NHS resources. A score of 0 is equivalent to death and 1 represents perfect health; negative scores are considered worse than death. Under the UK preference weighting, achievable scores range from –0.594 (worst response across all five dimensions) to 1 (best responses).

The responses to EQ-5D-3L questionnaires were collected at baseline and then at 6, 12, 26 and 52 weeks after randomisation. In this section, the combined EQ-5D-3L scores using the preference weighting are presented, such that each patient who completed a questionnaire at each time point has a single EQ-5D-3L QoL ‘score’ given to them based on their responses to the questionnaire. These scores are carried forward to the missing data analysis discussed later in this section and the within-trial analyses.

After having imputed for any missing questionnaires (see later section), the QoL scores are combined to estimate a score for the patient across the full within-trial period, using the equation below, where t_i is the time in days at which questionnaire ‘i’ was conducted and QoL_i is the QoL score reported at time ‘i’:

This combined QoL score is used to inform the regression analysis conducted to estimate the impact of patient characteristics, including treatment allocation, on QoL.

Resource use and unit costs

Costs to the NHS are considered in two ways: those reported by clinical staff and those reported by patients at 6, 12, 26 and 52 weeks during the trial (see the trial CRFs in Report Supplementary Material 15). As the trial did not directly seek to report the costs of care, but instead reported the frequency of various interactions and care provision, all elements reported have to be linked with an appropriate unit cost to estimate total costs. We assumed that all interactions with the NHS were captured by the trial CRFs.

Relevant resource use is reported from the time of randomisation into the trial and does not include the cost of initial presentation with the injury or the care that might have occurred prior to the randomly allocated treatment, typically immobilisation with a cast or splint. Randomisation should ensure that these initial treatment options and costs are balanced between the two groups.

For the purpose of the costing of the within-trial analysis, only those interactions reported as being related to the patient’s wrist are included. Unrelated interactions reported by the patients should not affect the incremental cost, but risk introducing bias if patients had high cost but completely unrelated health care. An investigation into the level of NHS and PSS interactions for reasons other than the wrist injury confirmed that there was no statistically significant difference between the randomised group (mean number of interactions: 5.65 for plaster immobilisation, 5.91 for surgical fixation; p = 0.828).

The unit costs associated with each component of the within-trial analysis are presented in Table 28.

Patient-reported costs are estimated at 6, 12, 26 and 52 weeks for the purpose of the missing data analysis, and treatment and imaging costs are estimated for the full within-trial period.

After imputation for patient-reported costs at the four time points and imaging costs, costs are combined into an estimate of the total patient-level cost for the within-trial period.

Patient-reported medications, aids and out-of-pocket costs such as private health care related to the initial injury are excluded from this analysis. In the case of medications, all reported cases were identified as being low-cost painkillers, which either cost less than the patient prescription cost or could have been purchased by patients over the counter. Aids are not routinely provided to patients on the NHS, as reflected by the trial data, and as such reflect a private cost that, alongside out-of-pocket costs, fall outside the NHS and PSS perspective taken in this chapter.

Missing data

Missing data were imputed across the patient-reported questionnaires related to QoL and resource use in addition to imaging. Using the framework described by Faria et al.,94 the missing data were assumed to be missing at random. Imputation was conducted across all nine cost and QoL variables identified as having missing data (i.e. costs at 6, 12, 26 and 52 weeks and QoL at baseline and at 6, 12, 26 and 52 weeks). Consistent with the missing data approach outlined in the PRWE analysis in the previous chapter, these missing variables were assumed to be correlated to each other as well as to treatment allocation, age at randomisation, whether or not the patient’s dominant hand was fractured and displacement of the fracture. The number of imputations was set equal to the proportion of missing values in the variable with the largest level of missingness, presented in Results in this chapter. Imputation was conducted using the ‘ICE’ multiple imputation package in Stata and reporting using the ‘MIM’ package. 95,96

Impact of lost employment and unpaid activities

In addition to considering the costs to the NHS and PSS and the QoL of patients, this within-trial analysis reports the impact of treatment allocation on days of lost employment and unpaid activities. The method of this analysis is reported in Appendix 6, Impact of lost employment and unpaid activities.

Systematic review of existing cost-effectiveness evidence

A literature review was conducted to determine if previous economic evaluations had sufficiently determined the cost-effectiveness of surgical fixation versus plaster cast immobilisation for bicortical, minimally displaced fractures of the scaphoid waist in adults. A secondary aim of the search was to determine if previous mathematical models could be adapted to estimate the long-term cost-effectiveness, and thus remove the need to construct a de novo mathematical model. Full details and results of the search strategy and results are given in Appendix 6, Systematic review of previous cost-effectiveness studies.

The review found no suitably robust cost-effectiveness analysis. Therefore, we determined that a de novo mathematical model was required to investigate the long-term cost-effectiveness of surgical fixation compared with cast immobilisation.

Cost-effectiveness analysis: analytical methods and model inputs

This section details the scope of the de novo extrapolated model and provides details on its structure, the base-case inputs and the scenarios considered.

Model structure

The model itself has two components: (1) a short-term decision model, which characterises the first 52 weeks after initial presentation, consistent with the SWIFFT period; and (2) a long-term element, over which the implications of the treatment and union status on long-term outcomes and costs are considered. These two components are presented separately below for clarity but are intricately linked.

The model takes as a starting point the time at which a treatment decision is made, such that patients have already experienced the injury and attended hospital for their initial assessment. As a result, the nature of the fracture is known and the patient has been identified as within this population.

Short-term decision model

Covering the first year since treatment, the short-term element closely matches the within-trial analysis by drawing directly from the findings of SWIFFT, with the additional treatment pathways of no treatment and primary cast immobilisation only. Figure 7 provides an overview of the short-term element of the model through this 52-week period, from the treatment decision to the 52-week time point, at which point patients enter the long-term ‘Markov’ model, symbolised by the ‘M’ in the figure. The key features of each treatment arm in the short-term element are as follows:

• No treatment – after having been identified as within the population considered in this analysis, all patients receive no active treatment (i.e. neither cast nor surgery). As a result, no short-term treatment costs are incurred, but patients are assumed in the base-case analysis to never achieve union of the fracture. While it is expected that some untreated fractures would unite, as the literature provides examples of such cases,99,100 it is not possible to estimate this as a proportion of all cases and, as such, the base case assumes no cases of union. This assumption is explored in a later scenario.

• Cast immobilisation only – primary cast immobilisation is assumed to be the only treatment available to patients, such that all are initially immobilised in a cast but, should the fracture fail to unite, no subsequent surgery is available. Treatment characteristics and rates of union are drawn directly from the SWIFFT primary cast immobilisation arm, but all those offered post-cast surgery for non-union are assumed to remain as non-unions.

• Cast immobilisation with immediate surgery for non-union – this treatment arm is consistent with the cast-only arm, except that patients who fail to achieve union are offered surgical fixation (like in SWIFFT), a proportion of whom will opt for it. The patients who failed to achieve union with the cast and chose to not have surgery are assumed to end the short-term component while still having non-union, while patients who opted for surgical fixation can achieve union or non-union at a rate determined by SWIFFT results.

• Primary surgery – like the surgery group of SWIFFT, patients are treated with surgical fixation as their primary treatment; many patients initially receive a cast, which is then removed and surgery is performed. After surgery, patients can achieve union or non-union. A small proportion determined by SWIFFT have multiple rounds of surgery if the primary surgery is unsuccessful or there are complications. Furthermore, most patients are provided with a cast after surgery as part of routine therapy.

All cost and QoL impacts that occur within this first year are included in the estimates presented later in this section. Mortality within the first year is not explicitly modelled, as scaphoid-related death is not expected to occur and the primary population is young, with no related or unrelated deaths observed in SWIFFT.

FIGURE 7.

Schematic of the short-term element of the economic evaluation model.

Long-term Markov model

The long-term cost and health outcomes extrapolated beyond the 52-week short-term model are estimated using two Markov models, presented in Figures 8 and 9. In a Markov model, patients reside in one out of a set of mutually exclusive health states at particular points in time. 101 During discrete time intervals, these patients can either remain in a particular health state or move to a separate health state, typically because they have experienced a particular clinical event.

FIGURE 8.

Long-term Markov model for successful union.

FIGURE 9.

Long-term Markov model for non-union.

As shown in Figures 8 and 9, the Markov model that patients enter is dependent on their union status at the end of the short-term decision model, with patients who achieve union entering the model outlined in Figure 8 and non-union patients entering the model outlined in Figure 9. This is consistent with the very different long-term clinical expectations associated with the two groups, as discussed in Chapter 1, with union patients likely to regain usual health and function, but those with non-union likely to have long-term health concerns.

The treatment pathway that a patient experienced to get to their union status is informative to their rate of transition through the model. In other words, while a patient’s prior treatment is assumed to not affect the set of long-term health states they can achieve, it does affect the likelihood with which they achieve them.

Patients achieving successful union at the end of the short-term element are placed into one of two starting states in the union Markov model: ‘no OA or other AEs’ or ‘no OA but long-term AEs’. This distinction is made because of the prevailing evidence that a number of patients experience lifelong symptomatic AEs associated with the original injury and treatment that are not related to the development of OA. Specifically, Lindström and Nyström102 reported the presence of pain and weakness not associated with OA in their long-term follow-up study of patients treated with cast immobilisation. Limitations in the available evidence on the long-term transitions necessitated the assumption that these patients represent a separate group from those who will go on to develop OA.

Patients who experience permanent long-term symptomatic AEs without OA remain in this state until they die of other causes, as the treatment or related events are unlikely to cause death. We also assumed that these non-OA AEs are fixed for the patient’s remaining lifetime, with all time-limited AEs being resolved within the short-term element of the model (i.e. within a year of injury).

Patients who enter the long-term model in an AE-free state (i.e. no OA or other AEs) can similarly stay in this state until they die of other causes, or they may develop OA, which is modelled as being either symptomatic or non-symptomatic, again informed by the literature. As is discussed later, limitations in the data mean we are unable to model the potential development of OA from non-symptomatic to symptomatic, or the potential for different levels of symptomatic presentation. From each of the OA states, patients stay in that state until they die of other causes.

The dearth of evidence relating to the development and transition between AEs in this population necessitated the assumption that patients do not transit between the three AE states. As a result, the analysis assumes that patients experience at most only one lifelong AE. As there is no difference in the cost and no utility difference between the two symptomatic states, discussed later in this section, and the asymptomatic OA state is based on long-term observational data, this model assumption does not affect the result of the analysis.

In contrast, patients who end the short-term element in a non-union state are modelled based on their risk of developing SNAC, as shown in Figure 9. As discussed in Chapter 1, SNAC represents a SAE that results from non-union, whereby the proximal carpal row can no longer stabilise the distal carpal row, and hence the wrist. The resulting abnormal loading leads to carpal collapse, cartilage degeneration and arthritis. Owing to a dearth of evidence relating to the natural history of events associated with non-union, we were not able to model separate states reflecting the development of OA and other symptoms within the non-union Markov model. Patients in this Markov model enter in the ‘no SNAC’ state and throughout their lifetime face a risk of progressing to SNAC or dying from unrelated causes. As with OA in the union Markov model, SNAC is modelled as being a binary disease state, but, unlike OA, is assumed to always be symptomatic as a result of the severity of the condition. Owing to the challenging nature of treating SNAC, and the lifetime implications even if treatment is successful, patients are modelled as remaining in the SNAC state for the rest of their life if it develops. Unlike the union model, patients are not modelled as separately having non-OA-related long-term symptoms and non-symptomatic OA. This assumption is the result of the observation by Dias et al. 103 that almost all patients (9 of 10) had pain or stiffness after a mean of 2.1 years. Therefore, our base-case model assumes that all non-union patients had some QoL decrement, incorporating a range of AEs including low-grade OA and non-OA AEs.

Model inputs

Much of the evidence defining the patient cohort and the short-term element is sourced directly from SWIFFT. As SWIFFT currently has only 52 weeks of patient follow-up, all long-term model inputs are informed by the wider literature.

Consistent with SWIFFT, the base-case patient cohort is modelled as being 33 years old, with 84% being male. A patient’s age is assumed to affect only the rate of mortality, as, while there is likely to be a correlation between age and OA and other AEs, there was insufficient evidence to incorporate such a correlation. Similarly, the gender mix affects only the mortality rate.

Scenario analyses

To develop the mathematical model into the form presented above, a number of simplifying assumptions and interpretations of the available evidence were necessary, as is true of all mathematical models. 97 While the assumptions made in the base-case analysis are considered to be the most reasonable, given the evidence available, it is important to test the impact of different approaches on the results of the analysis. A number of scenarios, detailed in Appendix 6, Extrapolated model scenario analyses, have been constructed to conduct these tests; as far as possible, other sources of evidence are used to inform the scenarios.

Within-trial analysis: results

In this section, we present the results of the within-trial analysis. This section is structured around four different scenarios relating to an ITT or per-protocol analysis and whether a complete-case approach or after multiple imputation approach is taken. The ITT analysis is presented as the base case and the summary statistics relating to QoL and costs are reported only for this analysis. The majority of within-trial analyses results are presented in Appendix 6, Within-trial analysis results, with the focus here on the regression analyses conducted across the QoL and cost outcomes.

Extrapolated model: results

In this section, the results of the extrapolated mathematical model are reported. First, we report the headline cost-effectiveness results (i.e. the expected costs, QALYs and resultant ICER and NHB), alongside a consideration of how the NHB accumulates over time. We then go on to consider the decision uncertainty present in the decision model. This is reported in two ways: the probability of each of the four strategies being cost-effective at a given cost-effectiveness threshold represented by the cost-effectiveness acceptability curve (CEAC) and a series of scenario analyses exploring the impact of structural uncertainty on the result.