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Aims: Scoliosis is a lateral curvature of the spine with associated rotation, often causing distress due to appearance. For some curves, there is good evidence to support the use of a spinal brace, worn for 20 to 24 hours a day to minimize the curve, making it as straight as possible during growth, preventing progression. Compliance can be poor due to appearance and comfort. A night-time brace, worn for eight to 12 hours, can achieve higher levels of curve correction while patients are supine, and could be preferable for patients, but evidence of efficacy is limited. This is the protocol for a randomized controlled trial of ‘full-time bracing’ versus ‘night-time bracing’ in adolescent idiopathic scoliosis (AIS). Methods: UK paediatric spine clinics will recruit 780 participants aged ten to 15 years-old with AIS, Risser stage 0, 1, or 2, and curve size (Cobb angle) 20° to 40° with apex at or below T7. Patients are randomly allocated 1:1, to either full-time or night-time bracing. A qualitative sub-study will explore communication and experiences of families in terms of bracing and research. Patient and Public Involvement & Engagement informed study design and will assist with aspects of trial delivery and dissemination. Discussion: The primary outcome is ‘treatment failure’ (Cobb angle progression to 50° or more before skeletal maturity); skeletal maturity is at Risser stage 4 in females and 5 in males, or ‘treatment success’ (Cobb angle less than 50° at skeletal maturity). The comparison is on a non-inferiority basis (non-inferiority margin 11%). Participants are followed up every six months while in brace, and at one and two years after skeletal maturity. Secondary outcomes include the Scoliosis Research Society 22 questionnaire and measures of quality of life, psychological effects of bracing, adherence, anxiety and depression, sleep, satisfaction, and educational attainment. All data will be collected through the British Spine Registry. Cite this article: Bone Jt Open 2023;4(11):873–880.

Some text in this abstract has been reproduced from Lindsay J, Din S, Hawkey C, Hind D, Irving P, Lobo A, et al. OFR-9 An RCT of autologous stem-cell transplantation in treatment refractory Crohn’s disease (low-intensity therapy evaluation): ASTIClite. Gut 2021;70(Suppl. 4):A4. Background Treatment-refractory Crohn’s disease is characterised by chronic symptoms, poor quality of life and high costs to the NHS, and through days of work lost by patients. A previous trial of autologous haematopoietic stem cell transplant (HSCT) failed its end point of medication-free clinical remission for 3 months with no evidence of disease activity, and reported high toxicity. Subsequent studies suggest that HSCT achieves complete mucosal healing in 50% of patients, and that toxicity likely relates to the cyclophosphamide dose. Objectives The primary objective was to assess the efficacy of HSCTlite (HSCT with low-dose cyclophosphamide) compared with standard care for inducing regression of intestinal ulceration in patients with refractory Crohn’s disease at week 48. Secondary objectives included the assessment of disease activity, quality of life and regimen safety. Mechanistic objectives included immune reconstitution after HSCTlite. Design Two-arm, parallel-group randomised controlled trial with a 2 : 1 (intervention : control) allocation ratio. Setting Nine NHS trusts (eight trusts were recruitment sites; one trust was a treatment-only site). Participants Adults with treatment-refractory Crohn’s disease, for whom surgery was inappropriate or who had declined surgery. Interventions The intervention treatment was HSCTlite using cyclophosphamide, and the control was any current available treatment for Crohn’s disease, apart from stem cell transplantation. Main outcomes The primary outcome was treatment success at week 48 [mucosal healing (Simple Endoscopic Score for Crohn’s Disease ulcer subscore of 0) without surgery or death], assessed by central readers blinded to allocation and timing of assessment. Key secondary outcomes were clinical remission, Simple Endoscopic Score for Crohn’s Disease scores at week 48, change in Crohn’s Disease Activity Index scores and safety. Results The trial was halted owing to Suspected unexpected serious adverse events that took place after randomising 23 patients (HSCTlite arm, n = 13; usual-care arm, n = 10). Ten out of the 13 patients randomised to the HSCTlite arm received the intervention and nine (one death) reached the 48-week follow-up. In the usual-care arm 9 out of the 10 patients randomised reached the 48-week follow-up (one ineligible). The primary outcome was available for 7 out of 10 HSCTlite patients (including the patient who died) and six out of nine usual-care patients. Absence of endoscopic ulceration without surgery or death was reported in three out of seven (43%) HSCTlite patients, compared with zero out of six (0%) usual-care patients. Centrally read Simple Endoscopic Score for Crohn’s Disease scores [mean (standard deviation)] were 10.8 (6.3) and 10.0 (6.1) at baseline, compared with 2.8 (2.9) and 18.7 (9.1) at week 48, in the HSCT and usual-care arms, respectively. Clinical remission (Crohn’s Disease Activity Index scores of 18.5 kg/m2). Have received a diagnosis of CD using colonoscopy, histology and/or radiology. Have had a disease duration of at least 6 months. Have a disease distribution accessible to endoscopic assessment (jejuno-ileal, ileo-caecal or colonic). Have had active clinical CD activity with impaired quality of life at any time within 3 months prior to randomisation into the trial, as assessed by a gastroenterology clinician. Be refractory or intolerant to azathioprine, mercaptopurine or methotrexate. Be refractory or intolerant to at least two classes of biologic therapy [currently anti-tumour necrosis factor (TNF) therapy, vedolizumab (Entyvio, Takeda UK Limited, London, UK) or ustekinumab (Stelara, Janssen Pharmaceuticals, New Brunswick, NJ, USA)] despite dose optimisation. Be considered unsuitable for surgery or have had surgery declined. Have endoscopic evidence of active disease in screening [Simple Endoscopic Score for Crohn’s Disease (SES-CD) ulcer size subscore of ≥ 2 in at least one segment]. SES-CD will be used as standard for patients with disease in the ileum and/or colon. Should the disease be only proximal to the ileum, the SES-CD would still be used to score the relevant bowel segment. Have undergone a satisfactory European Society for Blood and Marrow Transplantation. Autoimmune Disease Working Party-recommended screening assessment prior to HSCT. Be willing to discontinue all immunosuppressant medication after randomisation if allocated to the HSCT arm. Be, in the opinion of the Trial Management Group (TMG), fit enough to undergo treatment. Participants were ineligible if any of the following conditions were met: Have received a diagnosis of ulcerative colitis or indeterminate colitis. Have no evidence of active CD on screening endoscopic assessment. Have strictures that prevent assessment for endoscopic active disease. Have undrained perianal fistulae (patients with previous perianal disease or perianal disease adequately drained with a seton in situ were eligible). Presence of undrained perianal sepsis on screening pelvic [magnetic resonance imaging (MRI) scan, or computerised tomography (CT) scan if MRI was contraindicated]. Have evidence of intra-abdominal sepsis on abdominal MRI (or CT scan if MRI scan was contraindicated). Have an active or latent mycobacterial infection. Have had prior exposure to hepatitis B virus, hepatitis C virus or human immunodeficiency virus (HIV). Have evidence of an enteric or systemic infection. Be pregnant or breastfeeding, or planning pregnancy within the study duration. The possibility of current pregnancy was to be ruled out with a pregnancy test at the screening assessment. Be unwilling to use adequate contraception (if appropriate) until at least 12 months after the last dose of study drug. Have a contraindication to the use of cyclophosphamide, fludarabine, filgrastim or rabbit anti-thymocyte globulin (Thymoglobulin, Sanofi UK, Reading, UK). Have a significant medical comorbidity that precludes HSCT, as adjudicated by the TMG. Have significant psychiatric comorbidity. Have significant language barriers likely to affect their understanding of the study or their ability to complete outcome questionnaires. Be participating in another interventional clinical trial. Be considered medically unfit for HSCT as defined by any of the following criteria – Renal: creatinine clearance of 6.7 kPa. Forced expiratory volume or forced vital capacity of 1.0 × 109/l for two consecutive days. Participants randomised to the usual-care arm continued with conventional, biologic or nutritional therapy for the management of CD, until the primary end point was assessed. Follow-up Participants were followed up at 8, 14, 24, 32, 40 and 48 weeks. Day 0 of the follow up was the date of stem cell reinfusion for HSCT arm participants and day 49, post randomisation, for usual-care arm participants to align the timelines in both groups. Main outcome measures The primary outcome was treatment success at week 48, defined as mucosal healing [no endoscopic ulceration (SES-CD ulcer subscore of zero, assessed by central readers blind to allocation and time of assessment)] without surgery or death. Key secondary outcomes included clinical remission using the Crohn’s Disease Activity Index (CDAI), the Harvey–Bradshaw Index and patient-reported outcomes; SES-CD at week 48; change in CDAI SES-CD between baseline and week 48; assessment of safety through reports of AEs and SAEs; patient-reported quality of life; and healthcare resource use. Mechanistic outcomes included analysis of re-engraftment. Results The trial was halted because of unexpected SAEs after 23 patients (HSCT arm, n = 13; usual-care arm, n = 10) had been randomised. Patients had advanced disease [mean (standard deviation) CD duration 13.8 (7) years, mean CDAI at baseline 337.5 (182.4)], with 20 (91%) having undergone at least one resection and nine (41%) having a stoma (these figures are calculated based on the 22 participants in the intention-to-treat population, as opposed to the 23 participants randomised). Of the 13 participants randomised to receive HSCTlite, three withdrew before transplantation, 12 reached mobilisation, and 10 went on to receive stem cell reinfusion. Of the 10 usual-care arm participants, eight received medications specifically to treat CD (including biologic therapies and corticosteroids), one underwent surgery for CD (small bowel resection) and one withdrew. All patients contributed to the safety analysis, and 10 patients who completed HSCT and nine patients receiving usual care contributed to the efficacy analyses. The primary outcome using central reading was available for 7 out of 10 HSCT and six out of nine usual-care patients at week 48. Absence of endoscopic ulceration without surgery or death (at 48 weeks) was reported in three out of seven (43%) HSCT patients, compared with zero out of six (0%) usual-care patients. Centrally read SES-CD scores [mean (SD)] were 10.8 (6.3) and 10.0 (6.1) at baseline, compared with 2.8 (2.9) and 18.7 (9.1) at week 48, in the HSCT and usual-care arms, respectively. Centrally read change in SES-CD fell by 6.4 (4.3) in HSCT patients, whereas it increased by 7.5 (3.5) in usual-care patients. Clinical remission (CDAI

Abstract Background At times, clinical case complexity and different types of uncertainty present challenges to less experienced clinicians or the naive application of clinical guidelines where this may not be appropriate. Cognitive task analysis (CTA) methods are used to elicit, document and transfer tacit knowledge about how experts make decisions. Methods We conducted a methodological review to describe the use of CTA methods in understanding expert clinical decision-making. We searched MEDLINE, EMBASE and PsycINFO from inception to 2019 for primary research studies which described the use of CTA methods to understand how qualified clinicians made clinical decisions in real-world clinical settings. Results We included 81 articles (80 unique studies) from 13 countries, published from 1993 to 2019, most commonly from surgical and critical care settings. The most common aims were to understand expert decision-making in particular clinical scenarios, using expert decision-making in the development of training programmes, understanding whether decision support tools were warranted and understanding procedural variability and error identification or reduction. Critical decision method (CDM) and CTA interviews were most frequently used, with hierarchical task analysis, task knowledge structures, think-aloud protocols and other methods less commonly used. Studies used interviews, observation, think-aloud exercises, surveys, focus groups and a range of more CTA-specific methodologies such as the systematic human error reduction and prediction approach. Researchers used CTA methods to investigate routine/typical (n = 64), challenging (n = 13) or more uncommon, rare events and anomalies (n = 3). Conclusions In conclusion, the elicitation of expert tacit knowledge using CTA has seen increasing use in clinical specialties working under challenging time pressures, complexity and uncertainty. CTA methods have great potential in the development, refinement, modification or adaptation of complex interventions, clinical protocols and practice guidelines. Registration PROSPERO ID CRD42019128418 .

Abstract Background STEPWISE is a theory-informed self-management education programme that was co-produced with service users, healthcare professionals and interventionists to support weight loss for people with schizophrenia. We report the process evaluation to inform understanding about the intervention and its effectiveness in a randomised controlled trial (RCT) that evaluated its efficacy. Methods Following the UK Medical Research Council (MRC) Guidelines for developing and evaluating complex interventions, we explored implementation quality. We considered causal mechanisms, unanticipated consequences and contextual factors associated with variation in actual and intended outcomes, and integrated treatment fidelity, using the programme theory and a pipeline logic model. We followed a modified version of Linnan and Steckler’s framework and single case design. Qualitative data from semi-structured telephone interviews with service-users (n = 24), healthcare professionals delivering the intervention (n = 20) and interventionists (n = 7) were triangulated with quantitative process and RCT outcome data and with observations by interventionists, to examine convergence within logic model components. Results Training and course materials were available although lacked co-ordination in some trusts. Healthcare professionals gained knowledge and some contemplated changing their practice to reflect the (facilitative) ‘style’ of delivery. They were often responsible for administrative activities increasing the burden of delivery. Healthcare professionals recognised the need to address antipsychotic-induced weight gain and reported potential value from the intervention (subject to the RCT results). However, some doubted senior management commitment and sustainability post-trial. Service-users found the intervention highly acceptable, especially being in a group of people with similar experiences. Service-users perceived weight loss and lifestyle benefits; however, session attendance varied with 23% (n = 47) attending all group-sessions and 17% (n = 36) attending none. Service-users who lost weight wanted closer monitoring and many healthcare professionals wanted to monitor outcomes (e.g. weight) but it was outside the intervention design. No clinical or cost benefit was demonstrated from the intermediate outcomes (RCT) and any changes in RCT outcomes were not due to the intervention. Conclusions This process evaluation provides a greater understanding of why STEPWISE was unsuccessful in promoting weight loss during the clinical trial. Further research is required to evaluate whether different levels of contact and objective monitoring can support people with schizophrenia to lose weight. Trial registration ISRCTN, ISRCTN19447796. Registered 20 March 2014.

Abstract Background Increasingly, pragmatic randomised controlled trials are being used to evaluate surgical interventions, although they present particular difficulties in regards to recruitment and retention. Methods Procedures and processes related to implementation of a multi-centre pragmatic surgical randomised controlled trial are discussed. In this surgical trial, forecasting of consent rates based on similar trials and micro-costing of study activities with research partners were undertaken and a video was produced targeting recruiting staff with the aim of aiding recruitment. The baseline assessments were reviewed to ensure the timing did not impact on the outcome. Attrition due to procedure waiting time was monitored and data were triangulated for the primary outcome to ensure adequate follow-up data. Results Forecasting and costing ensured that the recruitment window was of adequate length and adequate resource was available for study procedures at multiple clinics in each hospital. Recruiting staff found the recruitment video useful. The comparison of patient-reported data collected prior to randomisation and prior to treatment provided confidence in the baseline data. Knowledge of participant dropout due to delays in treatment meant we were able to increase the recruitment target in a timely fashion, and along with the triangulation of data sources, this ensured adequate follow-up of randomised participants. Conclusions This paper provides a range of evidence-based and experience-based approaches which, collectively, resulted in meeting our study objectives and from which lessons may be transferable. Trial registration ISRCTN, ISRCTN41394716. Registered on 10 May 2012. UKCRN Study ID: 12486.

Abstract Background Good Clinical Practice guidelines issued in 2016 encourage risk-based approaches to monitoring clinical trials. This study compared current risk assessment and monitoring approaches in UK Clinical Trials Units (CTUs) with the published guidance and makes recommendations for risk-based monitoring in pragmatic trials. Methods An online survey of UK Clinical Research Collaboration registered CTUs was administered via email invitation. Forty-nine units were invited, and 23 responded. Respondents were also invited to share copies of risk assessment templates. Results Most CTUs reported using remote combined with on-site monitoring. All reported undertaking a risk assessment for Clinical Trials of Investigational Medicinal Products (CTIMPs) and 21 units did so for non-CTIMPs. Most CTIMP risk assessments used MHRA (Medicines and Healthcare products Regulatory Agency) classifications, although some also employed staff judgement. Almost all units based their monitoring on perceived risk level; this number was higher for CTIMPs (n = 22) than for non-CTIMPs (n = 19). In most cases, monitoring plans were produced. More CTUs revisited risk assessments during trials in CTIMPs (n = 21) than in non-CTIMPs (n = 18). Small numbers of units reviewed the monitoring approach always (n = 4) or sometimes (n = 9) and few used the reflection to guide future monitoring. Conclusions A high proportion of UK CTUs are using risk-based monitoring in the UK, as recommended by guidelines, for both CTIMPs and non-CTIMPs. This has the potential to make trials more efficient and reduce costs. However, there appears to be a lack of reflection on the value of these revised approaches. There may be a benefit in CTUs collaborating nationally to improve processes for reflection and making changes during the life course of a trial.

Abstract Background Intestinal inflammation in Crohn’s disease (CD) is caused by mucosal immune system reactivity to luminal antigen and results in debilitating symptoms, reduced quality of life, impaired work productivity and significant health care costs. Not all patients respond to conventional and biologic therapies, with chronic inflammation ensuing. Although surgical resection may be required, disease frequently returns and surgery may not be an option, or may be declined. Case reports suggest potential benefit after haematopoietic stem cell transplant (HSCT) for patients with refractory CD. The ASTIC trial asked whether HSCT could cure CD. Few patients achieved the primary endpoint of clinical remission for 3 months, off all medication with no evidence of active disease, and there were a high number of adverse events (AEs) and serious adverse events (SAEs), including one patient death. However, beneficial effects were observed in some aspects of disease activity. The ASTIClite trial will investigate these potential benefits and safety using a lower intensity regimen than ASTIC. Methods Ninety-nine participants will be recruited from secondary care IBD centres in the UK into a multicentre, randomised controlled trial (RCT, ASTIClite) and an observational follow-up, and randomised to autologous HSCT versus standard care (ratio 2:1). The primary endpoint is treatment success at week 48, defined as mucosal healing without surgery or death. Secondary endpoints relating to efficacy, safety and mechanistic analyses will be evaluated at week 8, 14, 24, 32, 40 and 48. Long-term safety of the low intensity HSCT regimen forms the primary endpoint for the EBMT follow-up study and will be assessed annually for 4–7 years. Discussion ASTIClite will compare HSCTlite with standard care with respect to safety, efficacy and quality of life, and capture outcomes allowing findings to be generalised to current clinical practice in the UK. It will also provide significant mechanistic insights into the immunological consequences of HSCTlite and its impact on treatment outcomes. The observational follow-up will provide information, which is currently unavailable for this population. Trial registration The ASTIClite RCT was registered on 31st October 2017 (ISRCTN17160440) and the EBMT follow-up study on 19th January 2018 (ISRCTN31981313).

Abstract Background The number of people with diabetes is growing rapidly. Diabetes can cause nerve damage leading to severe pain in the feet, legs and hands, which is known as diabetic peripheral neuropathic pain (DPNP). In the UK, the National Institute for Health and Care Excellence (NICE) recommends amitriptyline, duloxetine, pregabalin or gabapentin as initial treatment for DPNP. If this is not effective, adding one of the other drugs in combination with the first is recommended. NICE points out that these recommendations are not based on robust evidence. The OPTION-DM randomised controlled trial has been designed to address this evidence deficit, with the aims of determining the most clinically beneficial, cost-effective and tolerated treatment pathway for patients with DPNP. Methods/design A multicentre, double-blind, centre-stratified, multi-period crossover study with equal allocation to sequences (1:1:1:1:1:1) of treatment pathways. Three hundred and ninety-two participants will be recruited from secondary care DPNP centres in the UK. There are three treatment pathways: amitriptyline supplemented with pregabalin, pregabalin supplemented with amitriptyline and duloxetine supplemented with pregabalin. All participants will receive all three pathways and randomisation will determine the order in which they are received. The primary outcome is the difference between 7-day average 24-h pain scores on an 11-point NRS scale measured during the final follow-up week of the treatment pathway. Secondary outcomes for efficacy, cost-effectiveness, safety, patient-perceived tolerability and subgroup analysis will be measured at week 6 and week 16 of each pathway. Discussion The study includes direct comparisons of the mainstay treatment for DPNP. This novel study is designed to examine treatment pathways and capture clinically relevant outcomes which will make the results generalisable to current clinical practice. The study will also provide information on health economic outcomes and will include a subgroup study to provide information on whether patient phenotypes predict response to treatment. Trial registration ISRCTN17545443. Registered on 12 September 2016.

Background: Obesity is twice as common in people with schizophrenia as in the general population. The National Institute for Health and Care Excellence guidance recommends that people with psychosis or schizophrenia, especially those taking antipsychotics, be offered a healthy eating and physical activity programme by their mental health care provider. There is insufficient evidence to inform how these lifestyle services should be commissioned. Objectives: To develop a lifestyle intervention for people with first episode psychosis or schizophrenia and to evaluate its clinical effectiveness, cost-effectiveness, delivery and acceptability. Design: A two-arm, analyst-blind, parallel-group, randomised controlled trial, with a 1 : 1 allocation ratio, using web-based randomisation; a mixed-methods process evaluation, including qualitative case study methods and logic modelling; and a cost–utility analysis. Setting: Ten community mental health trusts in England. Participants: People with first episode psychosis, schizophrenia or schizoaffective disorder. Interventions: Intervention group: (1) four 2.5-hour group-based structured lifestyle self-management education sessions, 1 week apart; (2) multimodal fortnightly support contacts; (3) three 2.5-hour group booster sessions at 3-monthly intervals, post core sessions. Control group: usual care assessed through a longitudinal survey. All participants received standard written lifestyle information. Main outcome measures: The primary outcome was change in weight (kg) at 12 months post randomisation. The key secondary outcomes measured at 3 and 12 months included self-reported nutrition (measured with the Dietary Instrument for Nutrition Education questionnaire), objectively measured physical activity measured by accelerometry [GENEActiv (Activinsights, Kimbolton, UK)], biomedical measures, adverse events, patient-reported outcome measures and a health economic assessment. Results: The trial recruited 414 participants (intervention arm: 208 participants; usual care: 206 participants) between 10 March 2015 and 31 March 2016. A total of 341 participants (81.6%) completed the trial. A total of 412 participants were analysed. After 12 months, weight change did not differ between the groups (mean difference 0.0 kg, 95% confidence interval –1.59 to 1.67 kg; p = 0.964); physical activity, dietary intake and biochemical measures were unchanged. Glycated haemoglobin, fasting glucose and lipid profile were unchanged by the intervention. Quality of life, psychiatric symptoms and illness perception did not change during the trial. There were three deaths, but none was related to the intervention. Most adverse events were expected and related to the psychiatric illness. The process evaluation showed that the intervention was acceptable, with participants valuing the opportunity to interact with others facing similar challenges. Session feedback indicated that 87.2% of participants agreed that the sessions had met their needs. Some indicated the desire for more ongoing support. Professionals felt that the intervention was under-resourced and questioned the long-term sustainability within current NHS settings. Professionals would have preferred greater access to participants’ behaviour data to tailor the intervention better. The incremental cost-effectiveness ratio from the health-care perspective is £246,921 per quality-adjusted life-year (QALY) gained and the incremental cost-effectiveness ratio from the societal perspective is £367,543 per QALY gained. Conclusions: Despite the challenges of undertaking clinical research in this population, the trial successfully recruited and retained participants, indicating a high level of interest in weight management interventions; however, the STEPWISE intervention was neither clinically effective nor cost-effective. Further research will be required to define how overweight and obesity in people with schizophrenia should be managed. The trial results suggest that lifestyle programmes for people with schizophrenia may need greater resourcing than for other populations, and interventions that have been shown to be effective in other populations, such as people with diabetes mellitus, are not necessarily effective in people with schizophrenia. Trial registration: Current Controlled Trials ISRCTN19447796. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 65. See the NIHR Journals Library website for further project information.

Background: Optimal surgical intervention for low-grade haemorrhoids is unknown. Rubber band ligation (RBL) is probably the most common intervention. Haemorrhoidal artery ligation (HAL) is a novel alternative that may be more efficacious. Objective: The comparison of HAL with RBL for the treatment of grade II/III haemorrhoids. Design: A multicentre, parallel-group randomised controlled trial. Perspective: UK NHS and Personal Social Services. Setting: 17 NHS Trusts. Participants: Patients aged ≥ 18 years presenting with grade II/III (second- and third-degree) haemorrhoids, including those who have undergone previous RBL. Interventions: HAL with Doppler probe compared with RBL. Outcomes: Primary outcome – recurrence at 1 year post procedure; secondary outcomes – recurrence at 6 weeks; haemorrhoid severity score; European Quality of Life-5 Dimensions, 5-level version (EQ-5D-5L); Vaizey incontinence score; pain assessment; complications; and cost-effectiveness. Results: A total of 370 participants entered the trial. At 1 year post procedure, 30% of the HAL group had evidence of recurrence compared with 49% after RBL [adjusted odds ratio (OR) = 2.23, 95% confidence interval (CI) 1.42 to 3.51; p = 0.0005]. The main reason for the difference was the number of extra procedures required to achieve improvement/cure. If a single HAL is compared with multiple RBLs then only 37.5% recurred in the RBL arm (adjusted OR 1.35, 95% CI 0.85 to 2.15; p = 0.20). Persistence of significant symptoms at 6 weeks was lower in both arms than at 1 year (9% HAL and 29% RBL), suggesting significant deterioration in both groups over the year. Symptom score, EQ-5D-5L and Vaizey score improved in both groups compared with baseline, but there was no difference between interventions. Pain was less severe and of shorter duration in the RBL group; most of the HAL group who had pain had mild to moderate pain, resolving by 3 weeks. Complications were low frequency and not significantly different between groups. It appeared that HAL was not cost-effective compared with RBL. In the base-case analysis, the difference in mean total costs was £1027 higher for HAL. Quality-adjusted life-years (QALYs) were higher for HAL; however, the difference was very small (0.01) resulting in an incremental cost-effectiveness ratio of £104,427 per additional QALY. Conclusions: At 1 year, although HAL resulted in fewer recurrences, recurrence was similar to repeat RBL. Symptom scores, complications, EQ-5D-5L and continence score were no different, and patients had more pain in the early postoperative period after HAL. HAL is more expensive and unlikely to be cost-effective in terms of incremental cost per QALY. Limitations: Blinding of participants and site staff was not possible. Future work: The incidence of recurrence may continue to increase with time. Further follow-up would add to the evidence regarding long-term clinical effectiveness and cost-effectiveness. The polysymptomatic nature of haemorrhoidal disease requires a validated scoring system, and the data from this trial will allow further assessment of validity of such a system. These data add to the literature regarding treatment of grade II/III haemorrhoids. The results dovetail with results from the eTHoS study [Watson AJM, Hudson J, Wood J, Kilonzo M, Brown SR, McDonald A, et al. Comparison of stapled haemorrhoidopexy with traditional excisional surgery for haemorrhoidal disease (eTHoS): a pragmatic, multicentre, randomised controlled trial. Lancet 2016, in press.] comparing stapled haemorrhoidectomy with excisional haemorrhoidectomy. Combined results will allow expansion of analysis, allowing surgeons to tailor their treatment options to individual patients. Trial registration: Current Controlled Trials ISRCTN41394716. Funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 88. See the NIHR Journals Library website for further project information.