Hanne Bruhn

Clinical effectiveness and cost-effectiveness of open and arthroscopic rotator cuff repair [the UK Rotator Cuff Surgery (UKUFF) randomised trial]

BACKGROUND Uncertainty exists regarding the best management of patients with degenerative tears of the rotator cuff. OBJECTIVE To evaluate the clinical effectiveness and cost-effectiveness of arthroscopic and open rotator cuff repair in patients aged ≥ 50 years with degenerative rotator cuff tendon tears. DESIGN Two parallel-group randomised controlled trial. SETTING Nineteen teaching and district general hospitals in the UK. PARTICIPANTS Patients (n = 273) aged ≥ 50 years with degenerative rotator cuff tendon tears. INTERVENTIONS Arthroscopic surgery and open rotator cuff repair, with surgeons using their usual and preferred method of arthroscopic or open repair. Follow-up was by telephone questionnaire at 2 and 8 weeks after surgery and by postal questionnaire at 8, 12 and 24 months after randomisation. MAIN OUTCOME MEASURES The Oxford Shoulder Score (OSS) at 24 months was the primary outcome measure. Magnetic resonance imaging evaluation of the shoulder was made at 12 months after surgery to assess the integrity of the repair. RESULTS The mean OSS improved from 26.3 [standard deviation (SD) 8.2] at baseline to 41.7 (SD 7.9) at 24 months for arthroscopic surgery and from 25.0 (SD 8.0) at baseline to 41.5 (SD 7.9) at 24 months for open surgery. When effect sizes are shown for the intervention, a negative sign indicates that an open procedure is favoured. For the intention-to-treat analysis, there was no statistical difference between the groups, the difference in OSS score at 24 months was -0.76 [95% confidence interval (CI) -2.75 to 1.22; p = 0.452] and the CI excluded the predetermined clinically important difference in the OSS of 3 points. There was also no statistical difference when the groups were compared per protocol (difference in OSS score -0.46, 95% CI -5.30 to 4.39; p = 0.854). The questionnaire response rate was > 86%. At 8 months, 77% of participants reported that shoulder problems were much or slightly better, and at 24 months this increased to 85%. There were no significant differences in mean cost between the arthroscopic group and the open repair group for any of the component resource-use categories, nor for the total follow-up costs at 24 months. The overall treatment cost at 2 years was £2567 (SD £176) for arthroscopic surgery and £2699 (SD £149) for open surgery, according to intention-to-treat analysis. For the per-protocol analysis there was a significant difference in total initial procedure-related costs between the arthroscopic group and the open repair group, with arthroscopic repair being more costly by £371 (95% CI £135 to £607). Total quality-adjusted life-years accrued at 24 months averaged 1.34 (SD 0.05) in the arthroscopic repair group and 1.35 (SD 0.05) in the open repair group, a non-significant difference of 0.01 (95% CI -0.11 to 0.10). The rate of re-tear was not significantly different across the randomised groups (46.4% and 38.6% for arthroscopic and open surgery, respectively). The participants with tears that were impossible to repair had the lowest OSSs, the participants with re-tears had slightly higher OSSs and the participants with healed repairs had the most improved OSSs. These findings were the same when analysed per protocol. CONCLUSION In patients aged > 50 years with a degenerative rotator cuff tear there is no difference in clinical effectiveness or cost-effectiveness between open repair and arthroscopic repair at 2 years for the primary outcome (OSS) and all other prespecified secondary outcomes. Future work should explore new methods to improve tendon healing and reduce the high rate of re-tears observed in this trial. TRIAL REGISTRATION Current Controlled Trials ISRCTN97804283. FUNDING This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 80. See the NIHR Journals Library website for further project information.

Pharmacist-led management of chronic pain in primary care: results from a randomised controlled exploratory trial.

Objectives To compare the effectiveness of pharmacist medication review, with or without pharmacist prescribing, with standard care, for patients with chronic pain. Design An exploratory randomised controlled trial. Setting Six general practices with prescribing pharmacists in Grampian (3) and East Anglia (3). Participants Patients on repeat prescribed pain medication (4815) were screened by general practitioners (GPs), and mailed invitations (1397). 196 were randomised and 180 (92%) completed. Exclusion criteria included: severe mental illness, terminally ill, cancer related pain, history of addiction. Randomisation and intervention Patients were randomised using a remote telephone service to: (1) pharmacist medication review with face-to-face pharmacist prescribing; (2) pharmacist medication review with feedback to GP and no planned patient contact or (3) treatment as usual (TAU). Blinding was not possible. Outcome measures Outcomes were the SF-12v2, the Chronic Pain Grade (CPG), the Health Utilities Index 3 and the Hospital Anxiety and Depression Scale (HADS). Outcomes were collected at 0, 3 and 6 months. Results In the prescribing arm (n=70) two patients were excluded/nine withdrew. In the review arm (n=63) one was excluded/three withdrew. In the TAU arm (n=63) four withdrew. Compared with baseline, patients had an improved CPG in the prescribing arm, 47.7% (21/44; p=0.003) and in the review arm, 38.6% (17/44; p=0.001), but not the TAU group, 31.3% (15/48; ns). The SF-12 Physical Component Score showed no effect in the prescribing or review arms but improvement in TAU (p=0.02). The SF-12 Mental Component Score showed no effect for the prescribing or review arms and deterioration in the TAU arm (p=0.002). HADS scores improved within the prescribing arm for depression (p=0.022) and anxiety (p=0.007), between groups (p=0.022 and p=0.045, respectively). Conclusions This is the first randomised controlled trial of pharmacist prescribing in the UK, and suggests that there may be a benefit for patients with chronic pain. A larger trial is required. Trial registration: www.isrctn.org/ISRCTN06131530. Medical Research Council funding.

Comparison of stapled haemorrhoidopexy with traditional excisional surgery for haemorrhoidal disease (eTHoS) : a pragmatic, multicentre, randomised controlled trial

Summary Background Two commonly performed surgical interventions are available for severe (grade II–IV) haemorrhoids; traditional excisional surgery and stapled haemorrhoidopexy. Uncertainty exists as to which is most effective. The eTHoS trial was designed to establish the clinical effectiveness and cost-effectiveness of stapled haemorrhoidopexy compared with traditional excisional surgery. Methods The eTHoS trial was a large, open-label, multicentre, parallel-group, pragmatic randomised controlled trial done in adult participants (aged 18 years or older) referred to hospital for surgical treatment for grade II–IV haemorrhoids. Participants were randomly assigned (1:1) to receive either traditional excisional surgery or stapled haemorrhoidopexy. Randomisation was minimised according to baseline EuroQol 5 dimensions 3 level score (EQ-5D-3L), haemorrhoid grade, sex, and centre with an automated system to stapled haemorrhoidopexy or traditional excisional surgery. The primary outcome was area under the quality of life curve (AUC) measured with the EQ-5D-3L descriptive system over 24 months, assessed according to the randomised groups. The primary outcome measure was analysed using linear regression with adjustment for the minimisation variables. This trial is registered with the ISRCTN registry, number ISRCTN80061723. Findings Between Jan 13, 2011, and Aug 1, 2014, 777 patients were randomised (389 to receive stapled haemorrhoidopexy and 388 to receive traditional excisional surgery). Stapled haemorrhoidopexy was less painful than traditional excisional surgery in the short term and surgical complication rates were similar between groups. The EQ-5D-3L AUC score was higher in the traditional excisional surgery group than the stapled haemorrhoidopexy group over 24 months; mean difference −0·073 (95% CI −0·140 to −0·006; p=0·0342). EQ-5D-3L was higher for stapled haemorrhoidopexy in the first 6 weeks after surgery, the traditional excisional surgery group had significantly better quality of life scores than the stapled haemorrhoidopexy group. 24 (7%) of 338 participants who received stapled haemorrhoidopexy and 33 (9%) of 352 participants who received traditional excisional surgery had serious adverse events. Interpretation As part of a tailored management plan for haemorrhoids, traditional excisional surgery should be considered over stapled haemorrhoidopexy as the surgical treatment of choice. Funding National Institute for Health Research Health Technology Assessment programme.

Protocol for the United Kingdom Rotator Cuff Study (UKUFF): a randomised controlled trial of open and arthroscopic rotator cuff repair

This protocol describes a pragmatic multicentre randomised controlled trial (RCT) to assess the clinical and cost effectiveness of arthroscopic and open surgery in the management of rotator cuff tears. This trial began in 2007 and was modified in 2010, with the removal of a non-operative arm due to high rates of early crossover to surgery. Cite this article: Bone Joint Res 2014;3:155–60.

Effectiveness of open and arthroscopic rotator cuff repair (UKUFF): a randomised controlled trial

AIMS The appropriate management for patients with a degenerative tear of the rotator cuff remains controversial, but operative treatment, particularly arthroscopic surgery, is increasingly being used. Our aim in this paper was to compare the effectiveness of arthroscopic with open repair of the rotator cuff. PATIENTS AND METHODS A total of 273 patients were recruited to a randomised comparison trial (136 to arthroscopic surgery and 137 to open surgery) from 19 teaching and general hospitals in the United Kingdom. The surgeons used their usual preferred method of repair. The Oxford Shoulder Score (OSS), two years post-operatively, was the primary outcome measure. Imaging of the shoulder was performed at one year after surgery. The trial is registered with Current Controlled Trials, ISRCTN97804283. RESULTS The mean OSS improved from 26.3 (standard deviation (sd) 8.2) at baseline, to 41.7 (sd 7.9) two years post-operatively for arthroscopic surgery and from 25.0 (sd 8.0) to 41.5 (sd 7.9) for open surgery. Intention-to-treat (ITT) analysis showed no statistical difference between the groups at two years (difference in OSS score -0.76; 95% confidence interval (CI) -2.75 to 1.22; p = 0.452). The confidence interval excluded the pre-determined clinically important difference in the OSS of three points. The rate of re-tear was not significantly different between the two groups (46.4% for arthroscopic and 38.6% for open surgery; 95% CI -6.9 to 25.8; p = 0.256). Healed repairs had the most improved OSS. These findings were the same when analysed per-protocol. CONCLUSION There is no evidence of difference in effectiveness between open and arthroscopic repair of rotator cuff tears. The rate of re-tear is high in both groups, for all sizes of tear and ages and this adversely affects the outcome. Cite this article: Bone Joint J 2017;99-B:107-15.

Pharmacist-led management of chronic pain in primary care : costs and benefits in a pilot randomised controlled trial

Objectives To explore differences in mean costs (from a UK National Health Service perspective) and effects of pharmacist-led management of chronic pain in primary care evaluated in a pilot randomised controlled trial (RCT), and to estimate optimal sample size for a definitive RCT. Design Regression analysis of costs and effects, using intention-to-treat and expected value of sample information analysis (EVSI). Setting Six general practices: Grampian (3); East Anglia (3). Participants 125 patients with complete resource use and short form-six-dimension questionnaire (SF-6D) data at baseline, 3 months and 6 months. Interventions Patients were randomised to either pharmacist medication review with face-to-face pharmacist prescribing or pharmacist medication review with feedback to general practitioner or treatment as usual (TAU). Main outcome measures Differences in mean total costs and effects measured as quality-adjusted life years (QALYs) at 6 months and EVSI for sample size calculation. Results Unadjusted total mean costs per patient were £452 for prescribing (SD: £466), £570 for review (SD: £527) and £668 for TAU (SD: £1333). After controlling for baseline costs, the adjusted mean cost differences per patient relative to TAU were £77 for prescribing (95% CI −82 to 237) and £54 for review (95% CI −103 to 212). Unadjusted mean QALYs were 0.3213 for prescribing (SD: 0.0659), 0.3161 for review (SD: 0.0684) and 0.3079 for TAU (SD: 0.0606). Relative to TAU, the adjusted mean differences were 0.0069 for prescribing (95% CI −0.0091 to 0.0229) and 0.0097 for review (95% CI −0.0054 to 0.0248). The EVSI suggested the optimal future trial size was between 460 and 690, and between 540 and 780 patients per arm using a threshold of £30 000 and £20 000 per QALY gained, respectively. Conclusions Compared with TAU, pharmacist-led interventions for chronic pain appear more costly and provide similar QALYs. However, these estimates are imprecise due to the small size of the pilot trial. The EVSI indicates that a larger trial is necessary to obtain more precise estimates of differences in mean effects and costs between treatment groups. Trial registration number ISRCTN06131530.

The iMpact on practice, oUtcomes and costs of New roles for health pROfeSsionals: a study protocol for MUNROS.

Introduction The size and composition of the European Union healthcare workforce are key drivers of expenditure and performance; it now includes new health professions and enhanced roles for established professions. This project will systematically analyse how this has contributed to health service redesign, integration and performance in 9 European countries (Scotland, England, Netherlands, Germany, Italy, Czech Republic, Poland, Norway, and Turkeyi). This paper describes the protocol for collection of survey data in 3 distinct care pathways, and sets it in the context of the wider programme. Methods Questionnaires will be distributed to healthcare professionals (n=14 580), managers (n=3564) and patients (n=19 440) in 3 care pathways (breast cancer; type 2 diabetes; and coronary heart disease) within 12 hospitals and associated primary care settings in each country. Questionnaire topics will include demography, the different professionals working on the care pathway, the tasks they do and the time taken, their decision-making abilities when considering skill mix, specialisation and integration of care. Patient satisfaction, healthcare utilisation and preferences will be explored. In later work, register data and data from patient records will be used to record clinical outcomes. Data will also be collected on workforce and procedure costs. Descriptive analysis will identify the different models of care and multivariate analysis will establish the most clinically and cost-effective models. Ethics and dissemination This protocol was approved by ethical committees in each country. Findings will be disseminated through national/international clinical, health services research and health workforce conferences, and publications in national/international peer-reviewed journals.

A pragmatic multicentre randomised controlled trial comparing stapled haemorrhoidopexy with traditional excisional surgery for haemorrhoidal disease: the eTHoS study

BACKGROUND Haemorrhoids are a benign anorectal condition and are highly prevalent in the UK population. Treatments involve clinic-based procedures and surgery. The surgical procedures available include stapled haemorrhoidopexy (SH) and traditional haemorrhoidectomy (TH), and over 25,000 operations are performed for haemorrhoids annually in the UK. The disease is therefore important both to patients and to health service commissioners. Debate remains as to which of these surgical procedures is the most clinically effective and cost-effective. OBJECTIVE The aim of this study was to compare the clinical effectiveness and cost-effectiveness of SH with that of TH. DESIGN A large, open two-arm parallel-group pragmatic multicentre randomised controlled trial involving 32 UK hospitals and a within-trial cost-benefit analysis. A discrete choice experiment was conducted to estimate benefits (willingness to pay). PARTICIPANTS Patients with grades II-IV haemorrhoids who had not previously undergone SH or TH were included in the study. INTERVENTIONS Participants were randomised to receive either SH or TH. Randomisation was minimised at 1 : 1, in accordance with baseline EuroQol-5 Dimensions, three-level version (EQ-5D-3L) score, haemorrhoid grade, sex and centre, via an automated system. MAIN OUTCOME MEASURES The primary outcome was area under the quality-of-life curve measured using the EQ-5D-3L descriptive system over 24 months, and the primary economic outcome was the incremental cost-effectiveness ratio. Secondary outcomes included disease-specific quality of life, recurrence, complications, further interventions and costs. RESULTS Between January 2011 and August 2014, 777 patients were randomised (389 to receive SH and 388 to receive TH). There were 774 participants included in the analysis as a result of one post-randomisation exclusion in the SH arm and two in the TH arm. SH was less painful than TH in the short term. Surgical complications were similar in both arms. EQ-5D-3L score was higher for the SH arm in the first 6 weeks after surgery, but over 24 months the TH group had significantly better EQ-5D-3L scores (-0.073, 95% confidence interval -0.140 to -0.006; p = 0.0342). Symptoms and further interventions were significantly fewer in the TH arm at 24 months. Continence was better in the TH arm and tenesmus occurred less frequently. The number of serious adverse events reported was 24 out of 337 (7.1%) for participants who received SH and 33 out of 352 (9.4%) for those who received TH. There were two deaths in the SH arm, both unrelated to the eTHoS (either Traditional Haemorrhoidectomy or Stapled haemorrhoidopexy for haemorrhoidal disease) study. Patient preference did not seem to influence the treatment difference. SH was dominated by TH as it cost more and was less effective. The net benefit for the TH arm was higher than that for the SH arm. LIMITATIONS Neither the participants nor the assessors were masked to treatment assignment and final recruitment was slightly short of the total target of 800. There were also substantial missing follow-up data. CONCLUSIONS While patients who received SH had less short-term pain, after 6 weeks, recurrence rates, symptoms, re-interventions and quality-of-life measures all favoured TH. In addition, TH is cheaper. As part of a tailored management plan for haemorrhoids, TH should be considered over SH as the surgical treatment of choice for haemorrhoids refractory to clinic-based interventions. FUTURE WORK Perform an updated meta-analysis incorporating recently conducted European trials [eTHoS, HubBLe (haemorrhoidal artery ligation versus rubber band ligation for the management of symptomatic second-degree and third-degree haemorrhoids) and LingaLongo (Cost-effectiveness of New Surgical Treatments for Haemorrhoidal Disease)]. TRIAL REGISTRATION Current Controlled Trials ISRCTN80061723. 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. 21, No. 70. See the NIHR Journals Library website for further project information.

Strategies to improve response rates to patient reported outcome measures in a surgical RCT

Difficulties achieving high response rates to patient reported outcome measures (PROMs) within clinical trials are well recognised. The NIHR HTA funded eTHoS trial, which compares Stapled Haemorrhoidopexy with Traditional Haemorrhoidectomy for the treatment of grade II-IV haemorrhoids, is no exception. Early response rates to postal PROMs on quality of life (distributed at 12 and 24 months post-randomisation) showed that their return was only 67% (112/166). Over the period of the study various methods have been employed to improve response rates including monetary incentives. The current literature base suggests that that this may improve such responses. High value incentives may have a greater overall effect than lower value incentives, however evidence from RCTs is limited. We examined whether introducing monetary incentives affected response rates in a subset of the eTHoS cohort. Two monetary incentive studies were conducted. In the first, participants (n=326) were randomly allocated to one of 4 groups: 1) no incentive; 2) £5 gift voucher enclosed with 12 and 24 month questionnaires; 3) £5 gift voucher at 12 months only; 4) £5 gift voucher at 24 months only. In the second (ongoing), participants are sent a £30 gift voucher on receipt of completed questionnaires (12 and 24 months). We will present the results from both studies. In addition, other methods adopted by the trial team, such as a shortened reminder questionnaire, enabling participants to complete questionnaires online, and administering a study newsletter one week before the 12 and 24 month questionnaires were sent will be discussed.

Do trial managers know when sites will fail to recruit? Preliminary results from the estimating site performance (ESP) study

A substantial investment of public money is made each year to fund large multicentre clinical trials. Around half will not recruit to target and require extensions, revised sample size targets or will be closed leaving the clinical question unanswered. For multicentre trials, a great amount of time, effort and cost is spent setting up clinical sites. One potential reason why a trial may fail to deliver is that some sites fail to fulfil their predicted recruitment potential. The ESP study explores whether there is a good (and simple) way of making informed decisions about which sites are worth investing scarce trial team resources. ESP hypotheses that trial managers, who work closely with recruitment sites, will be able to predict whether a site will be a ‘good’ recruitment site before recruitment starts. If confirmed, such knowledge would enable resources to be targeted where they can have most benefit. In ESP, trial managers actively involved in setting-up sites during 2014/15 from one CTUs portfolio studies were asked to predict the recruitment success of each site they opened to recruitment. Predictions comprise a ‘Yes/No’ to whether the site would recruit to target, and why. Predictions are sealed in envelopes, collected, stored for 6 months and will be compared to actual recruitment in a meeting with the trial managers that made the predictions. We will present preliminary results based on over 20 predictions, which will indicate whether trial managers identify features of sites that accurately predict site recruitment performance.