Does HubBLe spell trouble for HAL?
Authors: Simon P Bach, Nicola S Fearnhead
Journal: The Lancet (2016)

Tens of thousands of surgical procedures are performed every year in the UK to resolve symptoms of anal bleeding and prolapse caused by haemorrhoids.1Hospital Episode StatisticsAdmitted patient care, England 2012–13: procedures and interventions. Main Procedures and Interventions.http://www.hscic.gov.uk/catalogue/PUB12566/hosp-epis-stat-admi-proc-2012-13-tab.xlsxDate: 2013Google Scholar A steady stream of novel therapeutic approaches may promise more convenient, comfortable, and ultimately effective treatment for this common complaint, but innovation is generally associated with increased cost and complexity compared with standard outpatient rubber band ligation (RBL). New surgical devices require systematic evaluation to support development of effective patient pathways that make efficient use of precious health-care resources.2NICEGuide to the processes of technology appraisal.https://www.nice.org.uk/article/pmg19Date: 2014Google Scholar Haemorrhoidal artery ligation (HAL) uses Doppler equipped proctoscopy to pinpoint branches of the haemorrhoidal artery that supply blood to haemorrhoids. These feeding vessels are sutured to inhibit further bleeding, while a second stitch firmly fixes the pile within the anal canal to prevent prolapse. Advocates of HAL suggest that it is much more effective than standard RBL as a first-line treatment of haemorrhoids, justifying the increased cost and use of general or spinal anaesthesia.3Pucher PH Sodergren MH Lord AC Darzi A Ziprin P Clinical outcome following Doppler-guided haemorrhoidal artery ligation: a systematic review.Colorectal Dis. 2013; 15: e284-e294Crossref PubMed Scopus (63) Google Scholar, 4Liu H Yang C Chen B Wu J He H Clinical outcomes of Doppler-guided haemorrhoidal artery ligation: a meta-analysis.Int J Clin Exp Med. 2015; 8: 4932-4939PubMed Google Scholar To our knowledge, no randomised controlled trials have compared HAL with RBL until now. In The Lancet, Steven Brown and colleagues5Brown SR Tiernan JP Watson AJM et al.Haemorrhoidal artery ligation versus rubber band ligation for the management of symptomatic second-degree and third-degree haemorrhoids (HubBLe): a multicentre, open-label, randomised controlled trial.Lancet. 2016; (published online May 25.)http://dx.doi.org/10.1016/S0140-6736(16)30584-0Google Scholar present HubBLe, a randomised, non-blinded, multicentre, phase 3 study comparing standard RBL versus HAL for first-line or selected second-line treatment of symptomatic haemorrhoids that prolapse and bleed following defecation (ie, grades II and III). This is a clinically relevant patient population that constitutes a large proportion of the surgical workload. Individuals with a history of haemorrhoid surgery or repeated outpatient treatments in the preceding 3 years were excluded. Recurrence of haemorrhoids or haemorrhoidal symptoms at 12 months constituted the primary endpoint. This composite assessment was based on the presence of any one of the following: (1) patients reporting "unchanged or worse" symptoms, rather than "cured or improved", during a telephone assessment, (2) further therapy being administered, or (3) symptoms suggestive of haemorrhoids being recorded in the medical notes and verified by two investigators blinded to treatment allocation. The study was powered to detect a 50% reduction in haemorrhoid recurrence at 12 months, from 30% with RBL to 15% with HAL. Secondary endpoints assessed at 6 weeks and 12 months included symptom severity score, pain score, surgical complications, further treatment, and health state utility using EQ-5D. Between September, 2012, and May, 2014, 372 patients entered the study, of whom 340 received treatment. Assessment of the primary outcome was possible in 337 patients using 256 patient-reported outcomes, 236 GP forms, and 337 consultant reports. Groups were generally well balanced with marginally more severe haemorrhoids allocated to HAL, and more previously treated patients allocated to RBL. The major finding of this study was that haemorrhoid recurrence at 12 months was significantly lower following HAL (48 [30%] of 161 patients) than following RBL (87 [49%] of 176 patients). Actual recurrence rates were much higher than predicted, possibly reflecting use of a sensitive patient-reported outcome. Further analysis of the composite primary endpoint revealed that this treatment effect was accounted for by patients receiving multiple RBL who were classified as having recurred. In our opinion, patients frequently require a course of RBL to achieve optimal symptom control, and the investigators might have inadvertently designated residual haemorrhoids as recurrences. Evaluation of patient-reported dissatisfaction at 12 months revealed no difference between RBL and HAL (29%), suggesting that multiple RBL had similar effectiveness than did HAL from the patients' perspectives. Surprisingly, HAL was associated with increased pain and a persistent reduction in EQ-5D compared with RBL, contrary to the widely held belief that it represents a painless approach to management of haemorrhoids.6Simillis C Thoukididou SN Slesser AA Rasheed S Tan E Tekkis PP Systematic review and network meta-analysis comparing clinical outcomes and effectiveness of surgical treatments for haemorrhoids.Br J Surg. 2015; 102: 1603-1618Crossref PubMed Scopus (123) Google Scholar Costs were also higher. The HubBLe trial will undoubtedly change practice within the UK and other health-care systems with finite resources. It is unique in directly comparing first-line haemorrhoidal interventions considered of most utility by colorectal surgeons and most acceptable by patients.7Shanmugam V Thaha MA Rabindranath KS Campbell KL Steele RJ Loudon MA Rubber band ligation versus excisional haemorrhoidectomy for haemorrhoids.Cochrane Database Syst Rev. 2005; 3: CD005034PubMed Google Scholar, 8Sajid MS Parampalli U Whitehouse P Sains P McFall MR Baig MK A systematic review comparing transanal haemorrhoidal de-arterialisation to stapled haemorrhoidopexy in the management of haemorrhoidal disease.Tech Coloproctol. 2012; 16: 1-8Crossref PubMed Scopus (55) Google Scholar This study has provided valuable information about the natural history of haemorrhoidal symptoms following treatment, and established a "course" of banding as a real, safe, and more cost-effective means of alleviating prolapse and bleeding in the majority of patients. The National Institute for Health and Care Excellence (NICE) will probably wish to update their recommendations on HAL.9NICE interventional procedure guidance [IPG342].https://www.nice.org.uk/guidance/ipg342Date: 2010Google Scholar The HubBLe study can help establish realistic patient expectations and provide a framework for counselling patients. This study has been a trend setter in selecting patient-reported outcomes as the primary endpoint. In context, patient-reported outcomes are now widely used, although this development is recent.10Speight J Barendse SM FDA guidance on patient reported outcomes.BMJ. 2010; 340: c2921Crossref PubMed Scopus (111) Google Scholar Use of a patient-centric qualitative endpoint is underpinned by the high-quality health economics model applied in HubBLe. The role of HAL, which has become widely accepted as a safe intervention for grade II–III haemorrhoids, will need re-evaluation. However, HAL might find a niche role as second-line treatment for patients who relapse following a course of RBL and do not wish to have excisional haemorrhoidectomy. SPB has provided consulting services and advice on product development and testing to Ethicon Inc, which manufactures and markets medical devices, but in fields outside the work discussed here. NSF reports a travel grant from Obsidian Health (Pty) Ltd, which markets haemorrhoidal artery ligation (HAL) equipment in South Africa. Neither SPB nor NSF has any past, current, or planned involvement in development of competing devices to HAL. Both authors work in hospitals that recruited patients to the HubBLe trial but neither recruited patients to the study nor had access to outcome data either locally or centrally before publication. Haemorrhoidal artery ligation versus rubber band ligation for the management of symptomatic second-degree and third-degree haemorrhoids (HubBLe): a multicentre, open-label, randomised controlled trialAlthough recurrence after HAL was lower than a single RBL, HAL was more painful than RBL. The difference in recurrence was due to the need for repeat bandings in the RBL group. Patients (and health commissioners) might prefer such a course of RBL to the more invasive HAL. Full-Text PDF Open Access