This is a repository copy of Management of adults with primary frozen shoulder in secondary care (UK FROST) : a multicentre, pragmatic, three-arm, superiority randomised clinical trial. White Rose Research Online URL for this paper: https://eprints.whiterose.ac.uk/161540/ Version: Accepted Version Article: (2020) Management of adults with primary frozen shoulder in secondary care (UK FROST) : a multicentre, pragmatic, three-arm, superiority randomised clinical trial. The Lancet. pp. 977-989. ISSN 0140-6736 https://doi.org/10.1016/S0140-6736(20)31965-6 Reuse This article is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs (CC BY-NC-ND) licence. This licence only allows you to download this work and share it with others as long as you credit the authors, but you can’t change the article in any way or use it commercially. 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Title Management of adults with primary frozen shoulder in secondary care: the UK FROST randomised controlled trial with economic evaluation Keywords Frozen shoulder; Physiotherapy; Manipulation under anaesthesia; Arthroscopic capsular release; Randomised controlled trial Author list Stephen Brealey1, Matthew Northgraves1, Lucksy Kottam2, Ada Keding1, Belen Corbacho1, Lorna Goodchild3, Cynthia Srikesevan4, Saleema Rex1, Charalambos Charalambous5, Nigel Hanchard6, Alison Armstrong7, Andrew Brooksbank8, Andrew Carr4, Cushla Cooper4, Joseph Dias7, Ioana Donnelly8, Catherine Hewitt1, Sarah Lamb4, Catriona McDaid1, Gerry Richardson9, Sara Rodgers1, Emma Sharp8, Sally Spencer10, David Torgerson1, Francine Toye11, Amar Rangan1,2,4 1 York Trials Unit, ARRC Building, Department of Health Sciences, University of York, York, Y010 5DD, UK 2 The James Cook University Hospital, South Tees Hospitals NHS Foundation Trust, TS4 3BW, Middlesbrough, UK 3 The Physiotherapy Practice, 17A Beach Road, South Shields, Tyne and Wear, NE33 2QA, UK 4 Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, Windmill Road, University of Oxford, Oxford, OX3 7LD, UK 5 Department of Orthopaedics, Blackpool Victoria Hospital, Blackpool, FY3 8NR, UK, and School of Medicine, University of Central Lancashire, Preston, PR1 2HE, UK 6 School of Health & Social Care, Teesside University, Middlesbrough, Tees Valley, TS1 3BX, UK 7 University Hospitals of Leicester NHS Trust, Infirmary Square, Leicester, LE1 5WW, UK 8 Glasgow Royal Infirmary, 84 Castle Street, Glasgow, G4 0SF, UK 1 9 Centre for Health Economics, ARRC Building, University of York, York, Y010 5DD, UK 10 Postgraduate Medical Institute, Edge Hill University, Ormskirk, Lancashire, L39 4QP, UK 11 Physiotherapy Research Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK, OX37HE, UK Corresponding author Prof Amar Rangan Email: [email protected] Telephone number: 01642 854144 Conflicts of interest Dr Kottam reports other grants from NIHR HTA during the conduct of this study. South Tees Hospitals NHS Foundation Trust receives educational grant to the department from DePuy Synthes (J&J limited). Institution also receives payment from DePuy Synthes (J&J limited) for Dr Kottam as a study Co-ordinator for the GLOBAL ICON Stemless Shoulder System Post Market Clinical Follow Up Study: CT 1401. These are outside and unrelated to the submitted work. Professor Catherine Hewitt is a member of the NIHR HTA Commissioning Board. Dr Catriona McDaid receives funding from the British Orthopaedic Association and is a member of the National Institute for Health Research Health Technology Assessment (HTA) and Efficacy and Mechanism Evaluation Editorial Board. Professor Sarah Lamb reports grants from the NIHR Health Technology Assessment Programme during the conduct of the study and was a member of the following Boards:- HTA Additional Capacity Funding Board 2012-2015 HTA Clinical Trials Board 2010-2015 HTA End of Life Care and Add on Studies 2015-2015 HTA Funding Boards Policy Group (formerly CSG) 2010-2015 HTA MNCH Methods Group 2013-2015 HTA Post-board funding teleconference (PG members to attend) 2010-2015 HTA Primary Care Themed Call board 2013-2014 HTA Prioritisation Group 2010-2015 2 NIHR CTU Standing Advisory Committee 2012–2016 Professor Rangan reports other grants from NIHR HTA, ORUK and H2020 during the conduct of this study. South Tees Hospitals NHS Foundation Trust receives educational grant to the department from DePuy Synthes (J&J limited). Institution also receives payment from DePuy Synthes (J&J limited) for Professor Rangan as the co-ordinating Investigator for the GLOBAL ICON Stemless Shoulder System Post Market Clinical Follow Up Study: CT 1401. These are outside and unrelated to the submitted work. 3 Abstract (499 words) Background: Frozen shoulder causes pain and stiffness. It affects around 10% of people in their 50s and is slightly more common in women. Costly and invasive surgical interventions are used, without high-quality evidence. Objectives: To compare the clinical and cost-effectiveness of three treatments in secondary care for adults with a frozen shoulder. To qualitatively explore their acceptability to patients and healthcare professionals. Design: Multi-centre, pragmatic, three-arm, parallel, open randomised controlled trial (RCT) with unequal allocation (2:2:1). An economic evaluation and nested qualitative study. Setting: Orthopaedic departments of 35 hospitals across the United Kingdom recruited from April 2015 with final follow-up in December 2018. Participants: Adults (≥ 18 years) with unilateral frozen shoulder, characterised by restriction of passive external rotation in the affected shoulder to less than 50% of the opposite shoulder and plain radiographs excluding other pathology. Interventions: Early Structured Physiotherapy (ESP) with a steroid injection. Manipulation under anaesthesia (MUA) with a steroid injection. Arthroscopic capsular release (ACR) followed by manipulation. Both surgical interventions were followed with post-procedural physiotherapy. Main outcome measures: The primary outcome and end-point was the Oxford Shoulder Score (OSS) at 12 months post-randomisation. A difference of five points between ESP and MUA or ACR, or four points between MUA and ACR, was judged clinically important. Results: The mean age of 503 participants was 54 years, 319 were female (63%) and 150 were diabetic (30%). The primary analyses included 473 participants (94%). At the primary end point of 12 months, participants randomised to ACR had on average statistically significantly higher (better) OSS than MUA (2.01 points, 95% confidence interval (CI) 0.10 to 3.91, p=0.04) and ESP (3.06 points, 95% CI 0.71 to 5.41, p=0.01). MUA did not have 4 statistically significant better OSS than ESP (1.05 points, 95% CI -1.28 to 3.39, p=0.38). No differences were deemed of clinical importance. Serious adverse events (SAE’s) were rare but occurred in participants randomised to surgery (n=8 for ACR and n=2 for MUA). There was, however, one SAE in a participant who had non-trial physiotherapy. The base-case economic analysis showed that MUA was more expensive than ESP with slightly better utilities. The ICER for MUA was £6,984 per additional QALY and probably 86% cost- effective at the £20,000/QALY threshold. ACR was more costly than ESP and MUA, with no statistically significant benefit in utilities. Participants in the qualitative study wanted early medical help and a quicker pathway to resolve their shoulder problem. Limitations: Implementing physiotherapy to the trial standard in clinical practice might prove challenging but could avoid theatre use and post-procedural physiotherapy. There are potential confounding effects of waiting times. Conclusions: None of the three interventions were clearly superior. ESP with a steroid injection is an accessible and low-cost option. MUA is the most cost-effective option. ACR carries higher risks and costs. Future work: Evaluation in an RCT is recommended to address the increasing popularity of hydrodilatation despite the paucity of high-quality evidence. Trial registration: ISRCTN48804508 Funding details: National Institute for Health Research Health Technology Assessment programme (project number 11/26/01). 5 Contents Table of tables ....................................................................................................................................... 11 Table of figures ..................................................................................................................................... 13 List of Supplementary Material ............................................................................................................ 14 List of abbreviations .............................................................................................................................. 15 Plain English Summary .......................................................................................................................... 16 Scientific Summary ...............................................................................................................................