Physiotherapy for primary frozen shoulder in secondary care: Developing and implementing stand-alone and post-operative protocols for UK FROST and inferences for wider practice

Abstract Objectives The United Kingdom Frozen Shoulder Trial (UK FROST) compares stand alone physiotherapy and two operative procedures, both with post-operative rehabilitation, for primary frozen shoulder in secondary care. We developed physiotherapy protocols for UK FROST, incorporating best evidence but recognizing uncertainty and allowing flexibility. Methods We screened a UK Department of Health systematic review and UK evidence based guidelines 1, 2 for recommendations, and previous surveys of UK physiotherapists 3, 4 for strong consensus. We conducted a two-stage, questionnaire-based, modified Delphi survey of shoulder specialist physiotherapists in the UK National Health Service. This required positive, negative or neutral ratings of possible interventions in four clinical contexts (stand-alone physiotherapy for, respectively, predominantly painful and predominantly stiff frozen shoulder; and post-operative physiotherapy for, respectively, predominantly painful and predominantly stiff frozen shoulder). We proposed respectively mandating or recommending interventions with 100% and 90% positive consensus, and respectively disallowing or discouraging interventions with 90% and 80% negative consensus. Other interventions would be optional. Results The systematic review and guideline recommended including steroid injection and manual mobilizations in non-operative care, and we mandated these for standalone physiotherapy. Consensus in the pre-existing surveys strongly favoured advice, education and home exercises, which we mandated across contexts. The Delphi survey led to recommendation of some supervised exercise modalities, plus the disallowing or discouragement—in various contexts—of immobilization and some ‘higher-tech’ electrotherapies and alternative therapies. Conclusions We developed physiotherapy protocols despite incomplete empirical evidence. Their clear structure enabled implementation in data-sheets designed to facilitate recording, monitoring of fidelity and reporting of interventions. Other trials involving physiotherapy may benefit from this approach

Tissue inflammation signatures point towards resolution in adhesive capsulitis

Proresolving receptors, macrophage and fibroblast activation point towards a resolving inflammatory milieu in adhesive capsulitis

Expert clinical consensus in the delivery of hydrodilatation for the management of patients with a primary frozen shoulder

Aims To achieve expert clinical consensus in the delivery of hydrodilatation for the treatment of primary frozen shoulder to inform clinical practice and the design of an intervention for evaluation. Methods We conducted a two-stage, electronic questionnaire-based, modified Delphi survey of shoulder experts in the UK NHS. Round one required positive, negative, or neutral ratings about hydrodilatation. In round two, each participant was reminded of their round one responses and the modal (or ‘group’) response from all participants. This allowed participants to modify their responses in round two. We proposed respectively mandating or encouraging elements of hydrodilatation with 100% and 90% positive consensus, and respectively disallowing or discouraging with 90% and 80% negative consensus. Other elements would be optional. Results Between 4 August 2020 and4 August 2021, shoulder experts from 47 hospitals in the UK completed the study. There were 106 participants (consultant upper limb orthopaedic surgeons, n = 50; consultant radiologists, n = 52; consultant physiotherapist, n = 1; extended scope physiotherapists, n = 3) who completed round one, of whom 97 (92%) completed round two. No elements of hydrodilatation were “mandated” (100% positive rating). Elements that were “encouraged” (≥ 80% positive rating) were the use of image guidance, local anaesthetic, normal saline, and steroids to deliver the injection. Injecting according to patient tolerance, physiotherapy, and home exercises were also “encouraged”. No elements were “discouraged” (≥ 80% negative rating) although using hypertonic saline was rated as being “disallowed” (≥ 90% negative rating). Conclusion In the absence of rigorous evidence, our Delphi study allowed us to achieve expert consensus about positive, negative, and neutral ratings of hydrodilatation in the management of frozen shoulder in a hospital setting. This should inform clinical practice and the design of an intervention for evaluation

Cost-effective clinical trial design : application of a Bayesian sequential model to the ProFHER pragmatic trial

Background/Aims: There is growing interest in the use of adaptive designs to improve the efficiency of clinical trials. We apply a Bayesian decision-theoretic model of a sequential experiment using cost and outcome data from the ProFHER pragmatic trial. We assess the model's potential for delivering value-based research. Methods: Using parameter values estimated from the ProFHER pragmatic trial, including the costs of carrying out the trial, we establish when the trial could have stopped, had the model's value-based stopping rule been used. We use a bootstrap analysis and simulation study to assess a range of operating characteristics, which we compare with a fixed sample size design which does not allow for early stopping. Results: We estimate that application of the model could have stopped the ProFHER trial early, reducing the sample size by about 14%, saving about 5% of the research budget and resulting in a technology recommendation which was the same as that of the trial. The bootstrap analysis suggests that the expected sample size would have been 38% lower, saving around 13% of the research budget, with a probability of 0.92 of making the same technology recommendation decision. It also shows a large degree of variability in the trial's sample size. Conclusions: Benefits to trial cost stewardship may be achieved by monitoring trial data as they accumulate and using a stopping rule which balances the benefit of obtaining more information through continued recruitment with the cost of obtaining that information. We present recommendations for further research investigating the application of value-based sequential designs

Embedding qualitative research in randomised controlled trials to improve recruitment: findings from two recruitment optimisation studies of orthopaedic surgical trials

Background: Recruitment of patients is one of the main challenges when designing and conducting randomised controlled trials (RCTs). Trials of rare injuries, or those that include surgical interventions pose added challenges due to the small number of potentially eligible patients and issues with patient preferences and surgeon equipoise. We explore key issues to consider when recruiting to orthopaedic surgical trials from the perspective of staff and patients with the aim of informing the development ofstrategies to improve recruitment in future research. Design: Two qualitative process evaluations of a United Kingdom-wide orthopaedic surgical RCT (ACTIVE) and mixed methods randomised feasibility study (PRESTO). Qualitative semi-structured interviews were conducted and data was analysed thematically. Setting: NHS secondary care organisations throughout the United Kingdom. Interviewswere undertaken via telephone. Participants: 37 health professionals including UK based spinal and orthopaedic surgeons and individuals involved in recruitment to the ACTIVE and PRESTO studies (e.g. research nurses, surgeons, physiotherapists). 22 patients including patients who agreed to participate in the ACTIVE and PRESTO studies (n=15) and patients that declined participation in the ACTIVE study (n=7) were interviewed. Results: We used a mixed methods systematic review of recruiting patients to randomised controlled trials as a framework for reporting and analysing our findings. Our findings mapped onto those identified in the systematic review and highlighted the importance of equipoise, randomisation, communication, patient’s circumstances, altruism and trust in clinical and research teams. Our findings also emphasised the importance of considering how eligibility criteria are operationalised and the impact of complex patient pathways when recruiting to surgical trials. In particular, the influence of health professionals, who are not involved in trial recruitment, on patients’ treatment preferences by suggesting they would receive a certain treatment ahead of recruitment consultations should not be underestimated. Conclusions: A wealth of evidence exploring factors affecting recruitment to randomised controlled trials exists. A methodological shift is now required to ensure that this evidence is used by all those involved in recruitment and to ensure that existing knowledge is translated into methods for optimising recruitment to future trials. Trial registries: ACTIVE: (ISRCTN98152560) PRESTO: (ISRCTN12094890

Mapping the Oxford Shoulder Score onto the EQ‑5D utility index

Abstract Purpose In order to enable cost-utility analysis of shoulder pain conditions and treatments, this study aimed to develop and evaluate mapping algorithms to estimate the EQ-5D health index from the Oxford Shoulder Score (OSS) when health outcomes are only assessed with the OSS. Methods 5437 paired OSS and EQ-5D questionnaire responses from four national multicentre randomised controlled trials investigating diferent shoulder pathologies and treatments were split into training and testing samples. Separate EQ-5D-3L and EQ-5D-5L analyses were undertaken. Transfer to utility (TTU) regression (univariate linear, polynomial, spline, multivariable linear, two-part logistic-linear, tobit and adjusted limited dependent variable mixture models) and response mapping (ordered logistic regression and seemingly unrelated regression (SUR)) models were developed on the training sample. These were internally validated, and their performance evaluated on the testing sample. Model performance was evaluated over 100-fold repeated training–testing sample splits. Results For the EQ-5D-3L analysis, the multivariable linear and splines models had the lowest mean square error (MSE) of 0.0415. The SUR model had the lowest mean absolute error (MAE) of 0.136. Model performance was greatest in the midrange and best health states, and lowest in poor health states. For the EQ-5D-5L analyses, the multivariable linear and splines models had the lowest MSE (0.0241–0.0278) while the SUR models had the lowest MAE (0.105–0.113). Conclusion The developed models now allow accurate estimation of the EQ-5D health index when only the OSS responses are available as a measure of patient-reported health outcome

Cost-effectiveness of surgical treatments compared with early structured physiotherapy in secondary care for adults with primary frozen shoulder: economic evaluation of UK FROST trial

Background A pragmatic multicentre randomised controlled trial (UK FROST) was conducted in the UK National Health Service (NHS) comparing the cost-effectiveness of commonly used treatments for adults with primary frozen shoulder in secondary care. Methods A cost utility analysis from the NHS perspective was performed. Differences between manipulation under anaesthesia (MUA), arthroscopic capsular release (ACR) and early structured physiotherapy plus steroid injection (ESP) in costs (2018 GBP) and quality adjusted life years (QALYs) at one year were used to estimate the cost effectiveness of the treatments using regression methods. Results ACR was £1,734 more costly than ESP [(95% confidence intervals (CI) £1,529 to £1,938)] and £1,457 more costly than MUA (95% CI £1,283 to £1,632). MUA was £276 (95% CI £66 to £487) more expensive than ESP. Overall, ACR had worse QALYs compared with MUA (-0·0293; 95% CI -0·0616 to 0·0030) and MUA had better QALYs compared with ESP (0·0396; 95% CI -·0008 to 0·0800). At a £20,000 per QALY willingness-to-pay threshold, MUA had the highest probability of being cost-effective (0·8632) then ESP (0·1366) and ACR (0·0002). The results were robust to sensitivity analyses. Conclusions While ESP was less costly, MUA was the most cost-effective option. ACR was not cost-effective

Remote or on-site visits were feasible for the initial setup meetings with hospitals in a multicenter surgical trial : an embedded randomized trial

Objectives To investigate the effects, costs and feasibility of providing on-site compared with remote meetings to set-up hospital sites in a multi-centre, surgical randomised controlled trial. Study Design and Setting Hospitals were randomised to receive the initial trial set-up meetings on-site (i.e. face-toface) or remotely (i.e. via teleconference). Data were collected on site set-up, recruitment, follow-up and costs for the two methods. The hospital staff experience of trial set-up was also surveyed. Results Thirty-nine sites were randomised and 33 sites set-up to recruit (19 on-site and 14 remote). For sites randomised to an on-site meeting compared with remote meeting respectively, the time from first contact to first recruit was a median of 246 days [interquartile range (IQR) 196 to 346] vs 212 days [IQR 154 to 266], mean recruitment was 10 participants [median 10, IQR 2 to 17] vs 11 participants [median 6, IQR 5 to 23] and participant follow-up at 12 months was 81% vs 82%. Sites allocated to an initial on-site visit cost on average 289.83 more to set-up. Conclusion Remote or on-site visits are feasible for the initial set-up meetings with hospitals in a multicentre surgical trial. This embedded trial should be replicated to improve generalisability and increase statistical power using meta-analysis. ISRCTN78899574. Keywords: Study Within a Trial; Randomised Controlled Trial; Recruitment; Response rate; Costs; Feasibility A running title: Remote and on-site visits were feasible for the initial set-up meetings with hospitals in a multi-centre surgical tria

Evaluating an intervention to improve the safety and experience of transitions from hospital to home for older people (Your Care Needs You) : a protocol for a cluster randomised controlled trial and process evaluation

Background Older patients often experience safety issues when transitioning from hospital to home. The ‘Your Care Needs You’ (YCNY) intervention aims to support older people to‘know more’ and‘do more’ whilst in hospital so that they are better prepared for managing at home. Methods A multi-centre cluster randomised controlled trial (cRCT) will evaluate the efectiveness and cost-efectiveness of the YCNY intervention. Forty acute hospital wards (clusters) in England from varying medical specialities will be randomised to deliver YCNY or care-as-usual on a 1:1 basis. The primary outcome will be unplanned hospital readmission rates within 30 days of discharge. This will be extracted from routinely collected data of at least 5440 patients (aged 75 years and older) discharged to their own homes during the 4- to 5-month YCNY intervention period. A nested cohort of up to 1000 patients will be recruited to the study to collect secondary outcomes via follow-up questionnaires at 5-, 30-and 90-day post-discharge. These will include measures of patient experience of transitions, patient-reported safety events, quality of life and healthcare resource use. Unplanned hospital readmission rates at 60 and 90 days of discharge will be collected from routine data. A process evaluation (primarily interviews and observations with patients, carers and staff) will be conducted to understand the implementation of the intervention and the contextual factors that shape this, as well as the inter- vention’s underlying mechanisms of action. Fidelity of intervention delivery will also be assessed across all intervention wards

Staff training to improve participant recruitment into surgical randomised controlled trials : a feasibility Study Within A Trial (SWAT) across four host randomised controlled trials simultaneously

Objective To test the feasibility of undertaking a simultaneous Study Within A Trial (SWAT) to train staff who recruit participants into surgical randomised controlled trials (RCTs), by assessing key uncertainties around recruitment, randomisation, intervention delivery and data collection. Study design and setting Twelve surgical RCTs were eligible. Interested sites (clusters) were randomised 1:1, with recruiting staff (surgeons and nurses) offered training or no training. The primary outcome was the feasibility of recruiting sites across multiple surgical trials simultaneously. Secondary outcomes included numbers/types of staff enrolled, attendance at training, training acceptability, confidence in recruiting and participant recruitment rates six months later. Results Four RCTs (33%) comprising 91 sites participated. Of these, 29 sites agreed to participate (32%) and were randomised to intervention (15 sites, 29 staff) or control (14 sites, 29 staff). Research nurses attended and found the training to be acceptable; no surgeons attended. In the intervention group, there was evidence of increased confidence when pre and post training scores were compared (mean difference in change 1.42; 95% CI 0.56, 2.27; p = 0.002) – there was no effect on recruitment rate. Conclusion It was feasible to randomise sites across four surgical RCTs in a simultaneous SWAT design. However, as small numbers of trials and sites participated, and no surgeons attended training, strategies to improve these aspects are needed for future evaluations. Trial registration ISRCTN registry: DISC (ISRCTN18254597), registered on 4th April 2017; PROFHER 2 (ISRCTN76296703), registered on 5th April 2018; IntAct (ISRCTN13334746), registered on 10th April 2017; and START:REACTS (ISRCTN17825590), registered on 5th March 2018. The training SWAT has been submitted to the MRC SWAT repository (SWAT111) Keywords: Randomised controlled trial (RCT), Study Within A Trial (SWAT), recruitment, staff training, professional education, feasibility study, surgical trial