Optimising the analysis of vascular prevention trials: Re-Assessment of the TARDIS trial, the first prevention trial to adopt an ordinal primary outcome measure.

Background: Ordinalised vascular outcomes incorporating event severity are more informative than binary outcomes that just include event numbers. The TARDIS trial was the first vascular prevention study to use an ordinalised vascular outcome as its primary efficacy and safety measures and collected severity information for other vascular events. Methods: TARDIS was an international prospective randomised open-label blinded-endpoint trial assessing one month of intensive versus guideline antiplatelet therapy in patients with acute non-cardioembolic stroke or TIA. Vascular events and their severity were recorded up to final follow-up at 90 days post randomisation. For each outcome, statistical techniques compared ordinal/continuous (10 models) and dichotomous (5 models) analyses; results were then ranked with the smallest p-value being given the smallest rank. Outcomes were also assessed within the pre-defined subgroup of participants with mild stroke (NIHSS≤3), or TIA recruited within 24 h. Results: Ordinal versions of vascular event outcomes were created in 3096 participants for stroke, myocardial infarction, major cardiac events, bleeding events, serious adverse events and venous thromboembolism (VTE), with 32 outcomes being created overall (29 in the subgroup population due to the absence of VTE events). Overall, the tests run on ordinal outcomes tended to rank higher than tests performed on binary outcomes. 764 (24.7%) participants were recruited within 24 h of a mild stroke/TIA; again, tests run on ordinal outcomes ranked higher. Conclusions: In TARDIS, tests performed on ordinal vascular outcomes tended to attain a higher rank than those performed on binary outcomes. Trial registration: ISRCTN47823388.

Effectiveness and cost effectiveness of digital hearing aids in patients with tinnitus and hearing loss: a randomised feasibility trial (THE HUSH Trial).

BACKGROUND: Education and advice is provided for tinnitus management in all UK audiology clinics. Sound therapy, including provision of hearing aids may be offered, but this is often dependent on a clinician's decision rather than UK policy. This inconsistent management reflects a lack of evidence around the effectiveness of hearing aids for tinnitus. This open-label, two-arm multicentre randomised controlled feasibility trial gathered data around recruitment, acceptability and outcome assessments to determine the feasibility of conducting a large randomised controlled trial investigating the effectiveness of hearing aids for tinnitus management. METHODS: Adults referred to audiology for tinnitus, with an aidable hearing loss were recruited at five UK audiology clinics. They were randomised 1:1 to either education and advice (treatment as usual (TAU), n = 41) or TAU plus hearing aids (n = 42). Outcomes were collected by questionnaires 12 weeks after randomisation. After participation, interviews were conducted with a subset of both participants and clinicians from each trial centre. RESULTS: Eighty three participants from five sites were randomised. Non-aidable hearing loss was the main reason for ineligibility to participate in the trial reported by the sites. Seventy three percent of participants returned the 12-week questionnaires, with return rates by site ranging from 61 to 100%. Fifteen out of 33 participants (45%) reported using hearing aids for the clinician-recommended time, or longer, during the day. The Tinnitus Functional Index (TFI) was the outcome measure most responsive to change. The majority of participants also agreed it was relevant to their tinnitus and hearing loss. Qualitative data demonstrated that the trial was acceptable to participants. Feedback from clinicians revealed a potential lack of equipoise. It also highlighted the differences in referral and treatment pathways between departments and differences in audiometric criteria for fitting hearing aids. Health economic measures were well completed for those returned. No change in health-related quality of life was observed. Costs were higher in the intervention arm, but self-reports of healthcare service use indicated participant confusion in treatment pathways. CONCLUSIONS: This feasibility trial is the first step towards obtaining high quality evidence to determine potential clinical effectiveness and cost effectiveness of hearing aids for tinnitus versus usual care. A definitive trial was deemed to be feasible, with some modifications based on feasibility findings and using the TFI as the primary outcome. This trial was funded by the National Institute for Health Research, Research for Patient Benefit Programme (PB-PG-0816-20,014) and registered with ISRCTN (ISRCTN14218416).

STAndardised DIagnostic Assessment for children and young people with emotional difficulties (STADIA): protocol for a multicentre randomised controlled trial.

INTRODUCTION: Emotional disorders (such as anxiety and depression) are associated with considerable distress and impairment in day-to-day function for affected children and young people and for their families. Effective evidence-based interventions are available but require appropriate identification of difficulties to enable timely access to services. Standardised diagnostic assessment (SDA) tools may aid in the detection of emotional disorders, but there is limited evidence on the utility of SDA tools in routine care and equipoise among professionals about their clinical value. METHODS AND ANALYSIS: A multicentre, two-arm, parallel group randomised controlled trial, with embedded qualitative and health economic components. Participants will be randomised in a 1:1 ratio to either the Development and Well-Being Assessment SDA tool as an adjunct to usual clinical care, or usual care only. A total of 1210 participants (children and young people referred to outpatient, specialist Child and Adolescent Mental Health Services with emotional difficulties and their parent/carers) will be recruited from at least 6 sites in England. The primary outcome is a clinician-made diagnosis about the presence of an emotional disorder within 12 months of randomisation. Secondary outcomes include referral acceptance, diagnosis and treatment of emotional disorders, symptoms of emotional difficulties and comorbid disorders and associated functional impairment. ETHICS AND DISSEMINATION: The study received favourable opinion from the South Birmingham Research Ethics Committee (Ref. 19/WM/0133). Results of this trial will be reported to the funder and published in full in the Health Technology Assessment (HTA) Journal series and also submitted for publication in a peer reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN15748675; Pre-results.

Safety and cost-effectiveness of individualised screening for diabetic retinopathy: the ISDR open-label, equivalence RCT.

AIMS/HYPOTHESIS: Using variable diabetic retinopathy screening intervals, informed by personal risk levels, offers improved engagement of people with diabetes and reallocation of resources to high-risk groups, while addressing the increasing prevalence of diabetes. However, safety data on extending screening intervals are minimal. The aim of this study was to evaluate the safety and cost-effectiveness of individualised, variable-interval, risk-based population screening compared with usual care, with wide-ranging input from individuals with diabetes. METHODS: This was a two-arm, parallel-assignment, equivalence RCT (minimum 2 year follow-up) in individuals with diabetes aged 12 years or older registered with a single English screening programme. Participants were randomly allocated 1:1 at baseline to individualised screening at 6, 12 or 24 months for those at high, medium and low risk, respectively, as determined at each screening episode by a risk-calculation engine using local demographic, screening and clinical data, or to annual screening (control group). Screening staff and investigators were observer-masked to allocation and interval. Data were collected within the screening programme. The primary outcome was attendance (safety). A secondary safety outcome was the development of sight-threatening diabetic retinopathy. Cost-effectiveness was evaluated within a 2 year time horizon from National Health Service and societal perspectives. RESULTS: A total of 4534 participants were randomised. After withdrawals, there were 2097 participants in the individualised screening arm and 2224 in the control arm. Attendance rates at first follow-up were equivalent between the two arms (individualised screening 83.6%; control arm 84.7%; difference -1.0 [95% CI -3.2, 1.2]), while sight-threatening diabetic retinopathy detection rates were non-inferior in the individualised screening arm (individualised screening 1.4%, control arm 1.7%; difference -0.3 [95% CI -1.1, 0.5]). Sensitivity analyses confirmed these findings. No important adverse events were observed. Mean differences in complete case quality-adjusted life-years (EuroQol Five-Dimension Questionnaire, Health Utilities Index Mark 3) did not significantly differ from zero; multiple imputation supported the dominance of individualised screening. Incremental cost savings per person with individualised screening were £17.34 (95% CI 17.02, 17.67) from the National Health Service perspective and £23.11 (95% CI 22.73, 23.53) from the societal perspective, representing a 21% reduction in overall programme costs. Overall, 43.2% fewer screening appointments were required in the individualised arm. CONCLUSIONS/INTERPRETATION: Stakeholders involved in diabetes care can be reassured by this study, which is the largest ophthalmic RCT in diabetic retinopathy screening to date, that extended and individualised, variable-interval, risk-based screening is feasible and can be safely and cost-effectively introduced in established systematic programmes. Because of the 2 year time horizon of the trial and the long time frame of the disease, robust monitoring of attendance and retinopathy rates should be included in any future implementation. TRIAL REGISTRATION: ISRCTN 87561257 FUNDING: The study was funded by the UK National Institute for Health Research. Graphical abstract.

The ESCAPS study: a feasibility randomized controlled trial of early electrical stimulation to the wrist extensors and flexors to prevent post-stroke complications of pain and contractures in the paretic arm.

OBJECTIVE: To establish feasibility of initiating electrical stimulation treatment of wrist extensors and flexors in patients early after stroke to prevent muscle contractures and pain. DESIGN: Feasibility randomized controlled trial with economic evaluation. SETTING: A specialist stroke unit in Nottinghamshire. SUBJECTS: A total of 40 patients recruited within 72 hours post-stroke with arm hemiparesis. INTERVENTIONS: Participants were randomized to receive usual care or usual care and electrical stimulation to wrist flexors and extensors for 30 minutes, twice a day, five days a week for three months. Initial treatment was delivered by an occupational therapist or physiotherapist who trained participants to self-manage subsequent treatments. MEASURES: Measures of feasibility included recruitment and attrition rates, completion of treatment, and successful data collection. Outcome data on wrist range of motion, pain, arm function, independence, quality of life, and resource use were measured at 3-, 6-, and 12-months post-randomization. RESULTS: A total of 40 participants (of 215 potentially eligible) were recruited in 15 months (20 men; mean age: 72 (SD: 13.0)). Half the participants lacked mental capacity and were recruited by consultee consent. Attrition at three-month follow-up was 12.5% (death (n = 2), end-of-life care (n = 2), and unable to contact (n = 1)). Compliance varied (mean: 65 (SD: 53)) and ranged from 10 to 166 treatments per patient (target dosage was 120). Data for a valid economic analysis can be adequately collected. CONCLUSION: Early initiation of electrical stimulation was acceptable and feasible. Data collection methods used were feasible and acceptable to participants. A large definitive study is needed to determine if electrical stimulation is efficacious and cost effective.

Individualised screening for diabetic retinopathy: the ISDR study-rationale, design and methodology for a randomised controlled trial comparing annual and individualised risk-based variable-interval screening.

INTRODUCTION: Currently, all people with diabetes (PWD) aged 12 years and over in the UK are invited for screening for diabetic retinopathy (DR) annually. Resources are not increasing despite a 5% increase in the numbers of PWD nationwide each year. We describe the rationale, design and methodology for a randomised controlled trial (RCT) evaluating the safety, acceptability and cost-effectiveness of personalised variable-interval risk-based screening for DR. This is the first randomised trial of personalised screening for DR and the largest ophthalmic RCT in the UK. METHODS AND ANALYSIS: PWD attending seven screening clinics in the Liverpool Diabetic Eye Screening Programme were recruited into a single site RCT with a 1:1 allocation to individualised risk-based variable-interval or annual screening intervals. A risk calculation engine developed for the trial estimates the probability that an individual will develop referable disease (screen positive DR) within the next 6, 12 or 24 months using demographic, retinopathy and systemic risk factor data from primary care and screening programme records. Dynamic, secure, real-time data connections have been developed. The primary outcome is attendance for follow-up screening. We will test for equivalence in attendance rates between the two arms. Secondary outcomes are rates and severity of DR, visual outcomes, cost-effectiveness and health-related quality of life. The required sample size was 4460 PWD. Recruitment is complete, and the trial is in follow-up. ETHICS AND DISSEMINATION: Ethical approval was obtained from National Research Ethics Service Committee North West - Preston, reference 14/NW/0034. Results will be presented at international meetings and published in peer-reviewed journals. This pragmatic RCT will inform screening policy in the UK and elsewhere. TRIAL REGISTRATION NUMBER: ISRCTN87561257; Pre-results.

Clinical and economic outcomes of remotely delivered cognitive behaviour therapy versus treatment as usual for repeat unscheduled care users with severe health anxiety: a multicentre randomised controlled trial.

BACKGROUND: It is challenging to engage repeat users of unscheduled healthcare with severe health anxiety in psychological help and high service costs are incurred. We investigated whether clinical and economic outcomes were improved by offering remote cognitive behaviour therapy (RCBT) using videoconferencing or telephone compared to treatment as usual (TAU). METHODS: A single-blind, parallel group, multicentre randomised controlled trial was undertaken in primary and general hospital care. Participants were aged ≥18 years with ≥2 unscheduled healthcare contacts within 12 months and scored >18 on the Health Anxiety Inventory. Randomisation to RCBT or TAU was stratified by site, with allocation conveyed to a trial administrator, research assessors masked to outcome. Data were collected at baseline, 3, 6, 9 and 12 months. The primary outcome was change in HAI score from baseline to six months on an intention-to-treat basis. Secondary outcomes were generalised anxiety, depression, physical symptoms, function and overall health. Health economics analysis was conducted from a health service and societal perspective. RESULTS: Of the 524 patients who were referred and assessed for trial eligibility, 470 were eligible and 156 (33%) were recruited; 78 were randomised to TAU and 78 to RCBT. Compared to TAU, RCBT significantly reduced health anxiety at six months, maintained to 9 and 12 months (mean change difference HAI -2.81; 95% CI -5.11 to -0.50; P = 0.017). Generalised anxiety, depression and overall health was significantly improved at 12 months, but there was no significant change in physical symptoms or function. RCBT was strictly dominant with a net monetary benefit of £3,164 per participant at a willingness to pay threshold of £30,000. No treatment-related adverse events were reported in either group. CONCLUSIONS: RCBT may reduce health anxiety, general anxiety and depression and improve overall health, with considerable reductions in health and informal care costs in repeat users of unscheduled care with severe health anxiety who have previously been difficult to engage in psychological treatment. RCBT may be an easy-to-implement intervention to improve clinical outcome and save costs in one group of repeat users of unscheduled care. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov on 19 Nov 2014 with reference number NCT02298036.

Bathing adaptations in the homes of older adults (BATH-OUT): results of a feasibility randomised controlled trial (RCT).

BACKGROUND: Housing adaptations have been identified as an important environmental and prevention intervention for older adults, which may improve health and quality of life. The onset of disability in bathing can act as a warning for further disability in other activities and may therefore be a judicious time-point for intervention. The aim of this study was to determine the feasibility of conducting a Randomised Controlled Trial (RCT) of bathing adaptations, to evaluate whether they improve older adults' perceived health status and quality of life, prevent further functional deterioration, and reduce the use of other health and social care resources. This study was conducted in preparation for a powered RCT. METHOD: Eligibility criteria were aged > 65 and referred to local authority housing adaptations service for an accessible flush-floor shower. Participants were randomised to either usual adaptations (3-4 month wait) or immediate adaptations (no wait). Outcomes were assessed at 3, 6 and 9 months and included perceived physical and mental health status, health and social care related quality of life, independence in activities of daily living (ADL) and bathing, and falls. Data on costs and the use of health and social care resources were collected during follow-up in order to inform a definitive health economic evaluation. RESULTS: Sixty participants were recruited and randomised, 31 to immediate adaptations and 29 to waiting list control. Mean age was 77(SD8), 58% women and 58% living alone. Follow-ups were completed with 90, 85 and 72% at 3, 6 and 9 months respectively. Adaptations were delivered to 65% of participants within the requisite timescales as there were delays with some privately owned properties. There were improvements from baseline in both groups on all outcome measures following the completion of the adaptations. CONCLUSIONS: This is the first RCT of housing adaptations in the UK. We demonstrated the feasibility of using a waiting list control, subject to minor alterations to the timescales for privately owned properties. A powered trial would evaluate the impact on older adults' quality of life and investigate the impact of waiting times on functional outcomes and health and care resource use. TRIAL REGISTRATION: ISRCTN14876332 Registered 12 July 2016.

Triple versus guideline antiplatelet therapy to prevent recurrence after acute ischaemic stroke or transient ischaemic attack: the TARDIS RCT.

BACKGROUND: Two antiplatelet agents are better than one for preventing recurrent stroke after acute ischaemic stroke or transient ischaemic attack (TIA). Therefore, intensive treatment with three agents might be better still, providing it does not cause undue bleeding. OBJECTIVE: To compare the safety and efficacy of intensive therapy with guideline antiplatelet therapy for acute ischaemic stroke and TIA. DESIGN: International prospective randomised open-label blinded end-point parallel-group superiority clinical trial. SETTING: Acute hospitals at 106 sites in four countries. PARTICIPANTS: Patients > 50 years of age with acute non-cardioembolic ischaemic stroke or TIA within 48 hours of ictus (stroke). INTERVENTIONS: Participants were allocated at random by computer to 1 month of intensive (combined aspirin, clopidogrel and dipyridamole) or guideline (combined aspirin and dipyridamole, or clopidogrel alone) antiplatelet agents, and followed for 90 days. MAIN OUTCOME MEASURES: The primary outcome was the incidence and severity of any recurrent stroke (ischaemic, haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days by blinded telephone follow-up. Analysis using ordinal logistic regression was by intention to treat. Other outcomes included bleeding and its severity, death, myocardial infarction (MI), disability, mood, cognition and quality of life. RESULTS: The trial was stopped early on the recommendation of the Data Monitoring Committee after recruitment of 3096 participants (intensive, n = 1556; guideline, n = 1540) from 106 hospitals in four countries between April 2009 and March 2016. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy in 3070 (99.2%) participants with data [93 vs. 105 stroke/TIA events; adjusted common odds ratio 0.90, 95% confidence interval (CI) 0.67 to 1.20; p = 0.47]. Major (encompassing fatal) bleeding was increased with intensive as compared with guideline therapy [39 vs. 17 participants; adjusted hazard ratio (aHR) 2.23, 95% CI 1.25 to 3.96; p = 0.006]. There were no differences between the treatment groups in all-cause mortality, or the composite of death, stroke, MI and major bleeding (aHR 1.02, 95% CI 0.77 to 1.35; p = 0.88). LIMITATIONS: Patients and investigators were not blinded to treatment. The comparator group comprised two guideline strategies because of changes in national guidelines during the trial. The trial was stopped early, thereby reducing its statistical power. CONCLUSIONS: The use of three antiplatelet agents is associated with increased bleeding without any significant reduction in recurrence of stroke or TIA. FUTURE WORK: The safety and efficacy of dual antiplatelet therapy (combined aspirin and clopidogrel) versus aspirin remains to be defined. Further research is required on identifying individual patient response to antiplatelets, and the relationship between response and the subsequent risks of vascular recurrent events and bleeding complications. TRIAL REGISTRATION: Current Controlled Trials ISRCTN47823388. 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. 48. See the NIHR Journal Library website for further project information. The Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) vanguard phase was funded by the British Heart Foundation (grant PG/08/083/25779, from 1 April 2009 to 30 September 2012) and indirect funding was provided by the Stroke Association through its funding of the Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, Nottingham, UK. There was no commercial support for the trial and antiplatelet drugs were sourced locally at each site. The trial was sponsored by the University of Nottingham.

The impact of a computerised test of attention and activity (QbTest) on diagnostic decision-making in children and young people with suspected attention deficit hyperactivity disorder: single-blind randomised controlled trial.

BACKGROUND: Diagnosis of attention deficit hyperactivity disorder (ADHD) relies on subjective methods which can lead to diagnostic uncertainty and delay. This trial evaluated the impact of providing a computerised test of attention and activity (QbTest) report on the speed and accuracy of diagnostic decision-making in children with suspected ADHD. METHODS: Randomised, parallel, single-blind controlled trial in mental health and community paediatric clinics in England. Participants were 6-17 years-old and referred for ADHD diagnostic assessment; all underwent assessment-as-usual, plus QbTest. Participants and their clinician were randomised to either receive the QbTest report immediately (QbOpen group) or the report was withheld (QbBlind group). The primary outcome was number of consultations until a diagnostic decision confirming/excluding ADHD within 6-months from baseline. Health economic cost-effectiveness and cost utility analysis was conducted. Assessing QbTest Utility in ADHD: A Randomised Controlled Trial was registered at ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT02209116). RESULTS: One hundred and thirty-two participants were randomised to QbOpen group (123 analysed) and 135 to QbBlind group (127 analysed). Clinicians with access to the QbTest report (QbOpen) were more likely to reach a diagnostic decision about ADHD (hazard ratio 1.44, 95% CI 1.04-2.01). At 6-months, 76% of those with a QbTest report had received a diagnostic decision, compared with 50% without. QbTest reduced appointment length by 15% (time ratio 0.85, 95% CI 0.77-0.93), increased clinicians' confidence in their diagnostic decisions (odds ratio 1.77, 95% CI 1.09-2.89) and doubled the likelihood of excluding ADHD. There was no difference in diagnostic accuracy. Health economic analysis showed a position of strict dominance; however, cost savings were small suggesting that the impact of providing the QbTest report within this trial can best be viewed as 'cost neutral'. CONCLUSIONS: QbTest may increase the efficiency of ADHD assessment pathway allowing greater patient throughput with clinicians reaching diagnostic decisions faster without compromising diagnostic accuracy.

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial.

BACKGROUND: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. METHODS: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. FINDINGS: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67-1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05-3·16, p<0·0001). INTERPRETATION: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice. FUNDING: National Institutes of Health Research Health Technology Assessment Programme, British Heart Foundation.

Bathing adaptations in the homes of older adults (BATH-OUT): protocol for a feasibility randomised controlled trial (RCT).

INTRODUCTION: The Care Act 2014 has placed a responsibility on local authorities in England to provide services that prevent deterioration and minimise the use of other health and social care services. Housing adaptations have been identified as 1 of the 10 most promising prevention services for older adults, with bathing adaptations being the most requested. However, many local authorities have lengthy waiting times which may increase costs, reduce effectiveness and reduce the preventive effect. There is no robust evidence of the effect of these adaptations on: health, well-being and functional ability. METHODS AND ANALYSIS: This is a feasibility randomised controlled trial (RCT) with nested qualitative interview study. The RCT will recruit between 40 and 60 people who have been referred for an accessible showering facility, and their carers, from 1 local authority in England. They will be randomised to either usual adaptations (∼3-month wait) or immediate adaptations (no wait). The primary outcome is the feasibility of conducting a powered study. The outcomes assessed will be: health and social care-related quality of life, independence in activities of daily living and bathing, falls and use of health and social care services. Outcomes will be assessed at 3 and 6 months. Preliminary health economic feasibility will be established. ETHICS AND DISSEMINATION: Favourable ethical opinion was provided by the Social Care Research Ethics Committee (reference number 16/IEC08/0017). The results of this study will lay the foundations for a further powered study. This would investigate the effect of bathing adaptations on quality of life and whether increased waiting times are associated with poorer outcomes and increased costs. The results have further potential to inform trials of other housing or social care interventions using the novel waiting list control method. Dissemination will include peer-reviewed publications and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: ISRCTN14876332; Pre-results.

Protocol investigating the clinical outcomes and cost-effectiveness of cognitive-behavioural therapy delivered remotely for unscheduled care users with health anxiety: randomised controlled trial.

BACKGROUND: Health anxiety and medically unexplained symptoms cost the National Health Service (NHS) an estimated £3 billion per year in unnecessary costs with little evidence of patient benefit. Effective treatment is rarely taken up due to issues such as stigma or previous negative experiences with mental health services. An approach to overcome this might be to offer remotely delivered psychological therapy, which can be just as effective as face-to-face therapy and may be more accessible and suitable. AIMS: To investigate the clinical outcomes and cost-effectiveness of remotely delivered cognitive-behavioural therapy (CBT) to people with high health anxiety repeatedly accessing unscheduled care (trial registration: NCT02298036). METHOD: A multicentre randomised controlled trial (RCT) will be undertaken in primary and secondary care providers of unscheduled care across the East Midlands. One hundred and forty-four eligible participants will be equally randomised to receive either remote CBT (6-12 sessions) or treatment as usual (TAU). Two doctoral research studies will investigate the barriers and facilitators to delivering the intervention and the factors contributing to the optimisation of therapeutic outcome. RESULTS: This trial will be the first to test the clinical outcomes and cost-effectiveness of remotely delivered CBT for the treatment of high health anxiety. CONCLUSIONS: The findings will enable an understanding as to how this intervention might fit into a wider care pathway to enhance patient experience of care. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-commercial, No Derivatives (CC BY-NC-ND) licence.

Efficacy and cost-effectiveness of a specialist depression service versus usual specialist mental health care to manage persistent depression: a randomised controlled trial.

BACKGROUND: Persistent moderate or severe unipolar depression is common and expensive to treat. Clinical guidelines recommend combined pharmacotherapy and psychotherapy. Such treatments can take up to 1 year to show an effect, but no trials of suitable duration have been done. We investigated the efficacy and cost-effectiveness of outpatient-based, specialist depression services (SDS) versus treatment as usual (TAU) on depression symptoms and function. METHODS: We did a multicentre, single-blind, patient-level, parallel, randomised controlled trial (RCT), as part of the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) study, in three mental health outpatient settings in England. Eligible participants were in secondary care, were older than 18 years, had unipolar depression (with a current major depressive episode, a 17-item Hamilton Depression Rating Scale [HDRS17] score of ≥16, and a Global Assessment of Function [GAF] score of ≤60), and had not responded to 6 months or more of treatment for depression. Randomisation was stratified by site with allocation conveyed to a trial administrator, with research assessors masked to outcome. Patients were randomised (1:1) using a computer-generated pseudo-random code with random permuted blocks of varying sizes of two, four, or six to either SDS (collaborative care approach between psychiatrists and cognitive behavioural therapists for 12 months, followed by graduated transfer of care up to 15 months) or to the TAU group. Intention-to-treat primary outcome measures were changes in HDRS17 and GAF scores between baseline and 6, 12, and 18 months' follow-up. We will separately publish follow-up outcomes for months 24 and 36. Clinical efficacy and cost-effectiveness were examined from health and social care persp ectives at 18 months, as recommended by the National Institute for Health and Care Excellence. This trial is registered at ClinicalTrials.gov (NCT01047124) and the ISRCTN registry (ISRCTN10963342); the trial has ended. FINDINGS: 307 patients were assessed for eligibility between Dec 21, 2009, and Oct 31, 2012. 94 patients were assigned to TAU and 93 patients to SDS, and were included in intention-to-treat analyses. The changes from baseline to 6 months in HDRS17 and GAF scores did not significantly differ between treatment groups (mean change difference in HDRS17 score -1·01 [95% CI -3·30 to 1·28], p=0·385; and in GAF score 1·33 [-2·92 to 5·57], p=0·538). Primary outcome data were available for 134 (72%) patients at 12 months. We noted no differences at 12 months' follow-up between SDS and TAU for mean HDRS17 score (14·8 [SD 7·9] in the SDS group vs 17·2 [7·3] in the TAU group, p=0·056) or GAF score (60·4 [11·7] vs 55·8 [12·7], p=0·064), and the changes from baseline to 12 months in HDRS17 and GAF scores did not significantly differ between treatment groups (mean change difference in HDRS17 score -2·45 [95% CI -5·04 to 0·14], p=0·064; and in GAF score 4·12 [-0·11 to 8·35], p=0·056). The mean change in HDRS17 score from baseline to 18 months was significantly improved in the SDS group compared with the TAU group (13·6 [SD 8·8] in the SDS group vs 16·1 [6·6] in the TAU group; mean change difference -2·96 [95% CI -5·33 to -0·59], p=0·015), but the GAF scores showed no significant differences between the groups (61·2 [SD 13·0] vs 57·7 [11·9]; mean change difference 3·82 [-9·3 to 8·57], p=0·113). We reported no deaths, but one (1%) patient was admitted to hospital for myocardial infarction, and three episodes of self-harm were reported in three (2%) patients (two receiving TAU, one receiving SDS care). The incremental cost-effectiveness ratio of SDS versus TAU was £43 603 per quality-adjusted life-year. INTERPRETATION: Compared with usual specialist mental health secondary care, SDS might improve depression symptoms for patients with persistent moderate to severe depression, but functional outcomes and economic benefits are equivocal. FUNDING: National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care, UK Medical Research Council, Nottinghamshire Healthcare NHS Foundation Trust, Derbyshire Healthcare NHS Foundation Trust, Cambridgeshire and Peterborough NHS Foundation Trust, University of Nottingham.

Cognitive behaviour therapy for long-term frequent attenders in primary care: a feasibility case series and treatment development study.

BACKGROUND: Most frequent attendance in primary care is temporary. Long-term frequent attendance may be suitable for psychological intervention to address health management and service use. AIM: To explore the feasibility and acceptability of cognitive behaviour therapy (CBT) for long-term frequent attendance in primary care and obtain preliminary evidence regarding clinical and cost effectiveness. DESIGN AND SETTING: A CBT case series was carried out in five GP practices in the East Midlands. METHOD: Frequent attenders (FAs) were identified from case notes and invited by their practice for assessment, then offered CBT. Feasibility and acceptability were assessed by CBT session attendance and thematic analysis of semi-structured questionnaires. Clinical and cost effectiveness was assessed by primary care use and clinically important change on a range of health and quality of life instruments. RESULTS: Of 462 FAs invited to interview, 87 (19%) consented to assessment. Thirty-two (7%) undertook CBT over a median of 3 months. Twenty-four (75%) attended at least six sessions. Eighteen FAs (86%, n = 21) reported overall satisfaction with treatment. Patients reported valuing listening without judgement alongside support to develop coping strategies. Thirteen (54%, n = 24), achieved clinically important improvement on the SF-36 Mental-Component Scale at 6-month follow-up and improved quality of life, but no improvement on other outcomes. Primary care use reduced from a median of eight contacts in 3 months at baseline (n = 32) to three contacts in 3 months at 1 year (n = 18). CONCLUSION: CBT appears feasible and acceptable to a subset of long-term FAs in primary care who halved their primary care use. With improved recruitment strategies, this approach could contribute to decreasing GP workload and merits larger-scale evaluation.

ESCAPS study protocol: a feasibility randomised controlled trial of 'Early electrical stimulation to the wrist extensors and wrist flexors to prevent the post-stroke complications of pain and contractures in the paretic arm'.

INTRODUCTION: Approximately 70% of patients with stroke experience impaired arm function, which is persistent and disabling for an estimated 40%. Loss of function reduces independence in daily activities and impacts on quality of life. Muscles in those who do not recover functional movement in the stroke affected arm are at risk of atrophy and contractures, which can be established as early as 6 weeks following stroke. Pain is also common. This study aims to evaluate the feasibility of a randomised controlled trial to test the efficacy and cost-effectiveness of delivering early intensive electrical stimulation (ES) to prevent post-stroke complications in the paretic upper limb. METHODS AND ANALYSIS: This is a feasibility randomised controlled trial (n=40) with embedded qualitative studies (patient/carer interviews and therapist focus groups) and feasibility economic evaluation. Patients will be recruited from the Stroke Unit at the Nottingham University Hospitals National Health Service (NHS) Trust within 72 h after stroke. Participants will be randomised to receive usual care or usual care and early ES to the wrist flexors and extensors for 30 min twice a day, 5 days a week for 3 months. The initial treatment(s) will be delivered by an occupational therapist or physiotherapist who will then train the patient and/or their nominated carer to self-manage subsequent treatments. ETHICS AND DISSEMINATION: This study has been granted ethical approval by the National Research Ethics Service, East Midlands Nottingham1 Research Ethics Committee (ref: 15/EM/0006). To our knowledge, this is the first study of its kind of the early application (within 72 h post-stroke) of ES to both the wrist extensors and wrist flexors of stroke survivors with upper limb impairment. The results will inform the design of a definitive randomised controlled trial. Dissemination will include 2 peer-reviewed journal publications and presentations at national conferences. TRIAL REGISTRATION NUMBER: ISRCTN1648908; Pre-results. Clinicaltrials.gov ID: NCT02324634.

Health state utility values for diabetic retinopathy: protocol for a systematic review and meta-analysis.

BACKGROUND: People with diabetic retinopathy tend to have lower levels of health-related quality of life than individuals with no retinopathy. Strategies for screening and treatment have been shown to be cost-effective. In order to reduce the bias in cost-effectiveness estimates, systematic reviews of health state utility values (HSUVs) are crucial for health technology assessment and the development of decision analytic models. A review and synthesis of HSUVs for the different stages of disease progression in diabetic retinopathy has not previously been conducted. METHODS/DESIGN: We will conduct a systematic review of the available literature that reports HSUVs for people with diabetic retinopathy, in correspondence with current stage of disease progression and/or visual acuity. We will search Medline, EMBASE, Web of Science, Cost-Effectiveness Analysis Registry, Centre for Reviews and Dissemination Database, and EconLit to identify relevant English-language articles. Data will subsequently be synthesized using linear mixed effects modeling meta-regression. Additionally, reported disease severity classifications will be mapped to a four-level grading scale for diabetic retinopathy. DISCUSSION: The systematic review and meta-analysis will provide important evidence for future model-based economic evaluations of technologies for diabetic retinopathy. The meta-regression will enable the estimation of utility values at different disease stages for patients with particular characteristics and will also highlight where the design of the study and HSUV instrument have influenced the reported utility values. We believe this protocol to be the first of its kind to be published. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014012891.

Spending by primary care practices - does it show what we expect?

BACKGROUND: Over recent years, a number of policies and financial incentives in primary care have been proposed to tackle issues such as deprivation and health outcomes. This article investigates the association between healthcare spending, deprivation and outcomes. It argues that individual practice data are analysed before blanket application and acceptance that one size fits all in a local area. METHODS: Financial data were analysed alongside key outcome data, including quality and outcomes framework (QOF) indicators for a large urban primary care trust (PCT) in the UK. The PCT had a large population and number of practices, including single-handed practices and an average list size in excess of 5000. The PCT will remain anonymous. RESULTS: There was no relationship between primary care investment and the practices' deprivation score. There was a strong statistically significant negative correlation between QOF payments and deprivation, (correlation = -0.46, p < 0.001). There were only weak links between primary care investment and health outcomes. There was no relationship between high emergency spending and health outcome. CONCLUSIONS: The data presented suggest that one size does not necessarily fit all - in terms of providing the appropriate incentives in primary care, nor do national incentives and policies always have the desired effect.

Cost implications of treatment non-completion in a forensic personality disorder service.

BACKGROUND: A high proportion of individuals admitted to specialist secure hospital services for treatment of personality disorder do not complete treatment. Non-completion has been associated with poorer treatment outcomes and increased rates of recidivism and hospital readmission, when compared with individuals who do complete treatment or who do not receive treatment at all. AIMS: In this study, we sought to determine the economic consequences of non-completion of treatment, using case study data from a secure hospital sample. Both health and criminal justice service perspectives were taken into account. METHODS: Data were collected from a medium secure hospital personality disorder unit. A probabilistic decision-analytic model was constructed, using a Markov cohort simulation with 10,000 iterations. The expected cost differential between those who do and those who do not complete treatment was estimated, as was the probability of a cost differential over a 10-year post-admission time horizon. RESULTS: On average, in the first 10 years following admission, those who do not complete treatment go on to incur £52,000 more in costs to the National Health Service and criminal justice system than those who complete treatment. The model estimates that the probability that non-completers incur greater costs than completers is 78%. CONCLUSION: It is possible that an improvement in treatment completion rates in secure hospital personality disorder units would lead to some cost savings. This might be achievable through better selection into treatment or improved strategies for engagement and retention. Our study highlights a financial cost to society of individuals discharged from secure hospital care when incompletely treated. We suggest that it could, therefore, be useful for secure hospitals to introduce routine monitoring of treatment completion.

Persistent frequent attenders in primary care: costs, reasons for attendance, organisation of care and potential for cognitive behavioural therapeutic intervention.

BACKGROUND: The top 3% of frequent attendance in primary care is associated with 15% of all appointments in primary care, a fivefold increase in hospital expenditure, and more mental disorder and functional somatic symptoms compared to normal attendance. Although often temporary if these rates of attendance last more than two years, they may become persistent (persistent frequent or regular attendance). However, there is no long-term study of the economic impact or clinical characteristics of regular attendance in primary care. Cognitive behaviour formulation and treatment (CBT) for regular attendance as a motivated behaviour may offer an understanding of the development, maintenance and treatment of regular attendance in the context of their health problems, cognitive processes and social context. METHODS/DESIGN: A case control design will compare the clinical characteristics, patterns of health care use and economic costs over the last 10 years of 100 regular attenders (≥30 appointments with general practitioner [GP] over 2 years) with 100 normal attenders (6-22 appointments with GP over 2 years), from purposefully selected primary care practices with differing organisation of care and patient demographics. Qualitative interviews with regular attending patients and practice staff will explore patient barriers, drivers and experiences of consultation, and organisation of care by practices with its challenges. Cognitive behaviour formulation analysed thematically will explore the development, maintenance and therapeutic opportunities for management in regular attenders. The feasibility, acceptability and utility of CBT for regular attendance will be examined. DISCUSSION: The health care costs, clinical needs, patient motivation for consultation and organisation of care for persistent frequent or regular attendance in primary care will be explored to develop training and policies for service providers. CBT for regular attendance will be piloted with a view to developing this approach as part of a multifaceted intervention.