Cost-effectiveness of craniotomy versus decompressive craniectomy for UK patients with traumatic acute subdural haematoma.

OBJECTIVE: To estimate the cost-effectiveness of craniotomy, compared with decompressive craniectomy (DC) in UK patients undergoing evacuation of acute subdural haematoma (ASDH). DESIGN: Economic evaluation undertaken using health resource use and outcome data from the 12-month multicentre, pragmatic, parallel-group, randomised, Randomised Evaluation of Surgery with Craniectomy for Patients Undergoing Evacuation-ASDH trial. SETTING: UK secondary care. PARTICIPANTS: 248 UK patients undergoing surgery for traumatic ASDH were randomised to craniotomy (N=126) or DC (N=122). INTERVENTIONS: Surgical evacuation via craniotomy (bone flap replaced) or DC (bone flap left out with a view to replace later: cranioplasty surgery). MAIN OUTCOME MEASURES: In the base-case analysis, costs were estimated from a National Health Service and Personal Social Services perspective. Outcomes were assessed via the quality-adjusted life-years (QALY) derived from the EuroQoL 5-Dimension 5-Level questionnaire (cost-utility analysis) and the Extended Glasgow Outcome Scale (GOSE) (cost-effectiveness analysis). Multiple imputation and regression analyses were conducted to estimate the mean incremental cost and effect of craniotomy compared with DC. The most cost-effective option was selected, irrespective of the level of statistical significance as is argued by economists. RESULTS: In the cost-utility analysis, the mean incremental cost of craniotomy compared with DC was estimated to be -£5520 (95% CI -£18 060 to £7020) with a mean QALY gain of 0.093 (95% CI 0.029 to 0.156). In the cost-effectiveness analysis, the mean incremental cost was estimated to be -£4536 (95% CI -£17 374 to £8301) with an OR of 1.682 (95% CI 0.995 to 2.842) for a favourable outcome on the GOSE. CONCLUSIONS: In a UK population with traumatic ASDH, craniotomy was estimated to be cost-effective compared with DC: craniotomy was estimated to have a lower mean cost, higher mean QALY gain and higher probability of a more favourable outcome on the GOSE (though not all estimated differences between the two approaches were statistically significant). ETHICS: Ethical approval for the trial was obtained from the North West-Haydock Research Ethics Committee in the UK on 17 July 2014 (14/NW/1076). TRIAL REGISTRATION NUMBER: ISRCTN87370545.

A smoking cessation smartphone app that delivers real-time 'context aware' behavioural support: the Quit Sense feasibility RCT.

Background: During a quit attempt, cues from a smoker's environment are a major cause of brief smoking lapses, which increase the risk of relapse. Quit Sense is a theory-guided Just-In-Time Adaptive Intervention smartphone app, providing smokers with the means to learn about their environmental smoking cues and provides 'in the moment' support to help them manage these during a quit attempt. Objective: To undertake a feasibility randomised controlled trial to estimate key parameters to inform a definitive randomised controlled trial of Quit Sense. Design: A parallel, two-arm randomised controlled trial with a qualitative process evaluation and a 'Study Within A Trial' evaluating incentives on attrition. The research team were blind to allocation except for the study statistician, database developers and lead researcher. Participants were not blind to allocation. Setting: Online with recruitment, enrolment, randomisation and data collection (excluding manual telephone follow-up) automated through the study website. Participants: Smokers (323 screened, 297 eligible, 209 enrolled) recruited via online adverts on Google search, Facebook and Instagram. Interventions: Participants were allocated to 'usual care' arm (n = 105; text message referral to the National Health Service SmokeFree website) or 'usual care' plus Quit Sense (n = 104), via a text message invitation to install the Quit Sense app. Main outcome measures: Follow-up at 6 weeks and 6 months post enrolment was undertaken by automated text messages with an online questionnaire link and, for non-responders, by telephone. Definitive trial progression criteria were met if a priori thresholds were included in or lower than the 95% confidence interval of the estimate. Measures included health economic and outcome data completion rates (progression criterion #1 threshold: ≥ 70%), including biochemical validation rates (progression criterion #2 threshold: ≥ 70%), recruitment costs, app installation (progression criterion #3 threshold: ≥ 70%) and engagement rates (progression criterion #4 threshold: ≥ 60%), biochemically verified 6-month abstinence and hypothesised mechanisms of action and participant views of the app (qualitative). Results: Self-reported smoking outcome completion rates were 77% (95% confidence interval 71% to 82%) and health economic data (resource use and quality of life) 70% (95% CI 64% to 77%) at 6 months. Return rate of viable saliva samples for abstinence verification was 39% (95% CI 24% to 54%). The per-participant recruitment cost was £19.20, which included advert (£5.82) and running costs (£13.38). In the Quit Sense arm, 75% (95% CI 67% to 83%; 78/104) installed the app and, of these, 100% set a quit date within the app and 51% engaged with it for more than 1 week. The rate of 6-month biochemically verified sustained abstinence, which we anticipated would be used as a primary outcome in a future study, was 11.5% (12/104) in the Quit Sense arm and 2.9% (3/105) in the usual care arm (estimated effect size: adjusted odds ratio = 4.57, 95% CIs 1.23 to 16.94). There was no evidence of between-arm differences in hypothesised mechanisms of action. Three out of four progression criteria were met. The Study Within A Trial analysis found a £20 versus £10 incentive did not significantly increase follow-up rates though reduced the need for manual follow-up and increased response speed. The process evaluation identified several potential pathways to abstinence for Quit Sense, factors which led to disengagement with the app, and app improvement suggestions. Limitations: Biochemical validation rates were lower than anticipated and imbalanced between arms. COVID-19-related restrictions likely limited opportunities for Quit Sense to provide location tailored support. Conclusions: The trial design and procedures demonstrated feasibility and evidence was generated supporting the efficacy potential of Quit Sense. Future work: Progression to a definitive trial is warranted providing improved biochemical validation rates. Trial registration: This trial is registered as ISRCTN12326962. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: 17/92/31) and is published in full in Public Health Research; Vol. 12, No. 4. See the NIHR Funding and Awards website for further award information.

Smokers often fail to quit because of urges to smoke triggered by their surroundings (e.g. being around smokers). We developed a smartphone app ('Quit Sense') which learns about an individual's surroundings and locations where they smoke. During a quit attempt, Quit Sense uses in-built sensors to identify when smokers are in those locations and sends 'in the moment' advice to help prevent them from smoking. We ran a feasibility study to help plan for a future large study to see if Quit Sense helps smokers to quit. This feasibility study was designed to tell us how many participants complete study measures; recruitment costs; how many participants install and use Quit Sense; and estimate whether Quit Sense may help smokers to stop and how it might do this. We recruited 209 smokers using online adverts on Google search, Facebook and Instagram, costing £19 per participant. Participants then had an equal chance of receiving a web link to the National Health Service SmokeFree website ('usual care group') or receive that same web link plus a link to the Quit Sense app ('Quit Sense group'). Three-quarters of the Quit Sense group installed the app on their phone and half of these used the app for more than 1 week. We followed up 77% of participants at 6 months to collect study data, though only 39% of quitters returned a saliva sample for abstinence verification. At 6 months, more people in the Quit Sense group had stopped smoking (12%) than the usual care group (3%). It was not clear how the app helped smokers to quit based on study measures, though interviews found that the process of training the app helped people quit through learning about what triggered their smoking behaviour. The findings support undertaking a large study to tell us whether Quit Sense really does help smokers to quit.

A randomised, double blind, placebo-controlled trial of a two-week course of dexamethasone for adult patients with a symptomatic Chronic Subdural Haematoma (Dex-CSDH trial).

Background: Chronic subdural haematoma is a collection of 'old blood' and its breakdown products in the subdural space and predominantly affects older people. Surgical evacuation remains the mainstay in the management of symptomatic cases. Objective: The Dex-CSDH (DEXamethasone in Chronic SubDural Haematoma) randomised trial investigated the clinical effectiveness and cost-effectiveness of dexamethasone in patients with a symptomatic chronic subdural haematoma. Design: This was a parallel, superiority, multicentre, pragmatic, randomised controlled trial. Assigned treatment was administered in a double-blind fashion. Outcome assessors were also blinded to treatment allocation. Setting: Neurosurgical units in the UK. Participants: Eligible participants included adults (aged ≥ 18 years) admitted to a neurosurgical unit with a symptomatic chronic subdural haematoma confirmed on cranial imaging. Interventions: Participants were randomly assigned in a 1 : 1 allocation to a 2-week tapering course of dexamethasone or placebo alongside standard care. Main outcome measures: The primary outcome was the Modified Rankin Scale score at 6 months dichotomised to a favourable (score of 0-3) or an unfavourable (score of 4-6) outcome. Secondary outcomes included the Modified Rankin Scale score at discharge and 3 months; number of chronic subdural haematoma-related surgical interventions undertaken during the index and subsequent admissions; Barthel Index and EuroQol 5-Dimension 5-Level utility index score reported at discharge, 3 months and 6 months; Glasgow Coma Scale score reported at discharge and 6 months; mortality at 30 days and 6 months; length of stay; discharge destination; and adverse events. An economic evaluation was also undertaken, during which the net monetary benefit was estimated at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year. Results: A total of 748 patients were included after randomisation: 375 were assigned to dexamethasone and 373 were assigned to placebo. The mean age of the patients was 74 years and 94% underwent evacuation of their chronic subdural haematoma during the trial period. A total of 680 patients (91%) had 6-month primary outcome data available for analysis: 339 in the placebo arm and 341 in the dexamethasone arm. On a modified intention-to-treat analysis of the full study population, there was an absolute reduction in the proportion of favourable outcomes of 6.4% (95% confidence interval 11.4% to 1.4%; p = 0.01) in the dexamethasone arm compared with the control arm at 6 months. At 3 months, the between-group difference was also in favour of placebo (-8.2%, 95% confidence interval -13.3% to -3.1%). Serious adverse events occurred in 60 out of 375 (16.0%) in the dexamethasone arm and 24 out of 373 (6.4%) in the placebo arm. The net monetary benefit of dexamethasone compared with placebo was estimated to be -£97.19. Conclusions: This trial reports a higher rate of unfavourable outcomes at 6 months, and a higher rate of serious adverse events, in the dexamethasone arm than in the placebo arm. Dexamethasone was also not estimated to be cost-effective. Therefore, dexamethasone cannot be recommended for the treatment of chronic subdural haematoma in this population group. Future work and limitations: A total of 94% of individuals underwent surgery, meaning that this trial does not fully define the role of dexamethasone in conservatively managed haematomas, which is a potential area for future study. Trial registration: This trial is registered as ISRCTN80782810. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/15/02) and is published in full in Health Technology Assessment; Vol. 28, No. 12. See the NIHR Funding and Awards website for further award information.

Chronic subdural haematoma is one of the most common conditions managed in adult neurosurgery and mainly affects older people. It is an 'old' collection of blood and blood breakdown products found on the surface of the brain. Surgery to drain the liquid collection is effective, with most patients improving. Given that inflammation is involved in the disease process, a commonly used steroid, dexamethasone, has been used alongside surgery or instead of surgery since the 1970s. However, there is no consensus or high-quality studies confirming the effectiveness of dexamethasone for the treatment of chronic subdural haematoma. This study was designed to determine the effectiveness of adding dexamethasone to the normal treatment for patients with a symptomatic chronic subdural haematoma. The benefit of adding dexamethasone was measured using a disability score called the Modified Rankin Scale, which can be divided into favourable and unfavourable outcomes. This was assessed at 6 months after entry into the study. In total, 748 adults with a symptomatic chronic subdural haematoma treated in neurosurgical units in the UK participated. Each participant had an equal chance of receiving either dexamethasone or a placebo because they were assigned randomly. Neither the patients nor the investigators knew who received dexamethasone and who received placebo. Most patients in both groups had an operation to drain the haematoma and experienced significant functional improvement at 6 months compared with their initial admission to hospital. However, patients who received dexamethasone had a lower chance than patients who received placebo of favourable recovery at 6 months. Specifically, 84% of patients who received dexamethasone had recovered well at 6 months, compared with 90% of patients who received placebo. There were more complications in the group that received dexamethasone. This trial demonstrates that adding dexamethasone to standard treatment reduced the chance of a favourable outcome compared with standard treatment alone. Therefore, this study does not support the use of dexamethasone in treating patients with a symptomatic chronic subdural haematoma.

Cost-effectiveness of providing university students with a mindfulness-based intervention to reduce psychological distress: economic evaluation of a pragmatic randomised controlled trial.

OBJECTIVE: Increasing numbers of young people attending university has raised concerns about the capacity of student mental health services to support them. We conducted a randomised controlled trial (RCT) to explore whether provision of an 8 week mindfulness course adapted for university students (Mindfulness Skills for Students-MSS), compared with university mental health support as usual (SAU), reduced psychological distress during the examination period. Here, we conduct an economic evaluation of MSS+SAU compared with SAU. DESIGN AND SETTING: Economic evaluation conducted alongside a pragmatic, parallel, single-blinded RCT comparing provision of MSS+SAU to SAU. PARTICIPANTS: 616 university students randomised. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary economic evaluation assessed the cost per quality-adjusted life year (QALY) gained from the perspective of the university counselling service. Costs relate to staff time required to deliver counselling service offerings. QALYs were derived from the Clinical Outcomes in Routine Evaluation Dimension 6 Dimension (CORE-6D) preference based tool, which uses responses to six items of the Clinical Outcomes in Routine Evaluation Outcome Measure (CORE-OM; primary clinical outcome measure). Primary follow-up duration was 5 and 7 months for the two recruitment cohorts. RESULTS: It was estimated to cost £1584 (2022 prices) to deliver an MSS course to 30 students, £52.82 per student. Both costs (adjusted mean difference: £48, 95% CI £40-£56) and QALYs (adjusted mean difference: 0.014, 95% CI 0.008 to 0.021) were significantly higher in the MSS arm compared with SAU. The incremental cost-effectiveness ratio (ICER) was £3355, with a very high (99.99%) probability of being cost-effective at a willingness-to-pay threshold of £20 000 per QALY. CONCLUSIONS: MSS leads to significantly improved outcomes at a moderate additional cost. The ICER of £3355 per QALY suggests that MSS is cost-effective when compared with the UK's National Institute for Health and Care Excellence thresholds of £20 000 per QALY. TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trials Registry, ACTRN12615001160527.

Decompressive Craniectomy versus Craniotomy for Acute Subdural Hematoma.

BACKGROUND: Traumatic acute subdural hematomas frequently warrant surgical evacuation by means of a craniotomy (bone flap replaced) or decompressive craniectomy (bone flap not replaced). Craniectomy may prevent intracranial hypertension, but whether it is associated with better outcomes is unclear. METHODS: We conducted a trial in which patients undergoing surgery for traumatic acute subdural hematoma were randomly assigned to undergo craniotomy or decompressive craniectomy. An inclusion criterion was a bone flap with an anteroposterior diameter of 11 cm or more. The primary outcome was the rating on the Extended Glasgow Outcome Scale (GOSE) (an 8-point scale, ranging from death to "upper good recovery" [no injury-related problems]) at 12 months. Secondary outcomes included the GOSE rating at 6 months and quality of life as assessed by the EuroQol Group 5-Dimension 5-Level questionnaire (EQ-5D-5L). RESULTS: A total of 228 patients were assigned to the craniotomy group and 222 to the decompressive craniectomy group. The median diameter of the bone flap was 13 cm (interquartile range, 12 to 14) in both groups. The common odds ratio for the differences across GOSE ratings at 12 months was 0.85 (95% confidence interval, 0.60 to 1.18; P = 0.32). Results were similar at 6 months. At 12 months, death had occurred in 30.2% of the patients in the craniotomy group and in 32.2% of those in the craniectomy group; a vegetative state occurred in 2.3% and 2.8%, respectively, and a lower or upper good recovery occurred in 25.6% and 19.9%. EQ-5D-5L scores were similar in the two groups at 12 months. Additional cranial surgery within 2 weeks after randomization was performed in 14.6% of the craniotomy group and in 6.9% of the craniectomy group. Wound complications occurred in 3.9% of the craniotomy group and in 12.2% of the craniectomy group. CONCLUSIONS: Among patients with traumatic acute subdural hematoma who underwent craniotomy or decompressive craniectomy, disability and quality-of-life outcomes were similar with the two approaches. Additional surgery was performed in a higher proportion of the craniotomy group, but more wound complications occurred in the craniectomy group. (Funded by the National Institute for Health and Care Research; RESCUE-ASDH ISRCTN Registry number, ISRCTN87370545.).

An Automated, Online Feasibility Randomized Controlled Trial of a Just-In-Time Adaptive Intervention for Smoking Cessation (Quit Sense).

INTRODUCTION: Learned smoking cues from a smoker's environment are a major cause of lapse and relapse. Quit Sense, a theory-guided Just-In-Time Adaptive Intervention smartphone app, aims to help smokers learn about their situational smoking cues and provide in-the-moment support to help manage these when quitting. METHODS: A two-arm feasibility randomized controlled trial (N = 209) to estimate parameters to inform a definitive evaluation. Smoker's willing to make a quit attempt were recruited using online paid-for adverts and randomized to "usual care" (text message referral to NHS SmokeFree website) or "usual care" plus a text message invitation to install Quit Sense. Procedures, excluding manual follow-up for nonresponders, were automated. Follow-up at 6 weeks and 6 months included feasibility, intervention engagement, smoking-related, and economic outcomes. Abstinence was verified using cotinine assessment from posted saliva samples. RESULTS: Self-reported smoking outcome completion rates at 6 months were 77% (95% CI 71%, 82%), viable saliva sample return rate was 39% (95% CI 24%, 54%), and health economic data 70% (95% CI 64%, 77%). Among Quit Sense participants, 75% (95% CI 67%, 83%) installed the app and set a quit date and, of those, 51% engaged for more than one week. The 6-month biochemically verified sustained abstinence rate (anticipated primary outcome for definitive trial), was 11.5% (12/104) among Quit Sense participants and 2.9% (3/105) for usual care (adjusted odds ratio = 4.57, 95% CIs 1.23, 16.94). No evidence of between-group differences in hypothesized mechanisms of action was found. CONCLUSIONS: Evaluation feasibility was demonstrated alongside evidence supporting the effectiveness potential of Quit Sense. IMPLICATIONS: Running a primarily automated trial to initially evaluate Quit Sense was feasible, resulting in modest recruitment costs and researcher time, and high trial engagement. When invited, as part of trial participation, to install a smoking cessation app, most participants are likely to do so, and, for those using Quit Sense, an estimated one-half will engage with it for more than 1 week. Evidence that Quit Sense may increase verified abstinence at 6-month follow-up, relative to usual care, was generated, although low saliva return rates to verify smoking status contributed to considerable imprecision in the effect size estimate.

Evaluation of effectiveness and safety of pharmacist independent prescribers in care homes: cluster randomised controlled trial.

OBJECTIVE: To estimate the effectiveness, cost effectiveness (to be reported elsewhere), and safety of pharmacy independent prescribers in care homes. DESIGN: Cluster randomised controlled trial, with clusters based on triads of a pharmacist independent prescriber, a general practice, and one to three associated care homes. SETTING: Care homes across England, Scotland, and Northern Ireland, their associated general practices, and pharmacy independent prescribers, formed into triads. PARTICIPANTS: 49 triads and 882 residents were randomised. Participants were care home residents, aged ≥65 years, taking at least one prescribed drug, recruited to 20 residents/triad. INTERVENTION: Each pharmacy independent prescriber provided pharmaceutical care to approximately 20 residents across one to three care homes, with weekly visits over six months. Pharmacy independent prescribers developed a pharmaceutical care plan for each resident, did medicines reviews/reconciliation, trained staff, and supported with medicines related procedures, deprescribing, and authorisation of prescriptions. Participants in the control group received usual care. MAIN OUTCOMES MEASURES: The primary outcome was fall rate/person at six months analysed by intention to treat, adjusted for prognostic variables. Secondary outcomes included quality of life (EQ-5D by proxy), Barthel score, Drug Burden Index, hospital admissions, and mortality. Assuming a 21% reduction in falls, 880 residents were needed, allowing for 20% attrition. RESULTS: The average age of participants at study entry was 85 years; 70% were female. 697 falls (1.55 per resident) were recorded in the intervention group and 538 falls (1.26 per resident) in the control group at six months. The fall rate risk ratio for the intervention group compared with the control group was not significant (0.91, 95% confidence interval 0.66 to 1.26) after adjustment for all model covariates. Secondary outcomes were not significantly different between groups, with exception of the Drug Burden Index, which significantly favoured the intervention. A third (185/566; 32.7%) of pharmacy independent prescriber interventions involved medicines associated with falls. No adverse events or safety concerns were identified. CONCLUSIONS: Change in the primary outcome of falls was not significant. Limiting follow-up to six months combined with a small proportion of interventions predicted to affect falls may explain this. A significant reduction in the Drug Burden Index was realised and would be predicted to yield future clinical benefits for patients. This large trial of an intensive weekly pharmacist intervention with care home residents was also found to be safe and well received. TRIAL REGISTRATION: ISRCTN 17847169.

A randomised feasibility study of serial magnetic resonance imaging to reduce treatment times in Charcot neuroarthropathy in people with diabetes (CADOM).

AIM: This study aims to explore the feasibility of using serial MRI without contrast in the monitoring of Charcot neuroarthropathy to reduce duration of immobilisation of the foot, in order to decide whether a large-scale trial is warranted. METHODS: A multicentre, randomised, prospective, two arm, open, feasibility study (CADOM) of people with diabetes with a suspected or confirmed diagnosis of Charcot neuroarthropathy. Participants were randomised (1:1) to 'standard care plus', including repeated foot temperature measurements and X-rays, or the intervention arm, with additional three-monthly MRI, until remission of Charcot neuroarthropathy or a maximum 12 months (active phase). Participants were then followed-up for a further 6 months, post remission to monitor for relapse of the Charcot neuroarthropathy (follow-up phase). Feasibility outcomes were recruitment, retention, data completeness, adherence to study procedures and safety of the intervention MRI. We also collected clinical efficacy outcomes, this included time in cast/off-loading device which will be the primary outcome of a future definitive trial. Finally, we collected patient reported outcomes, and data on health and social care usage. RESULTS: One-hundred and five people were assessed for eligibility at five sites. 64/105 potential participants meet the eligibility criteria to participate in the study. Forty-three participants were randomised: 20 to standard care plus and 23 to MRI intervention. The main reason for ineligibility was a previous episode of Charcot neuroarthropathy. Thirteen participants were withdrawn post-randomisation due to an alternative diagnosis being made. Of the remaining 30 participants, 19 achieved remission, 6 had not gone into remission at the end of the 12 month active phase so exited the study. Five participants were lost to follow-up. Of the MRIs that were not disrupted by COVID-19 pandemic 26/31 (84%) were completed. For the visits that were conducted face-to-face, completion rates of patient-reported outcome measures were between 71 and 100%. There were no safety incidents associated with the intervention MRI. As this was a feasibility study it was not designed to test the effectiveness of serial MRI in diagnosing remission. The time in cast/off-loading device was 235 (±108.3) days for the standard care plus arm compared to 292 (±177.4) days for the intervention arm. There was no statistical difference in the time in cast/off-loading device between the two arms of the study: Hazard Ratio (HR) 0.405 (95% CI 0.140-1.172), p = 0.096. DISCUSSION: The findings support a definitive randomised controlled trial to evaluate the effectiveness of MRI in diagnosing remission in Charcot neuroarthropathy. The rates of recruitment, retention, data, and MRI completeness show that a definitive study is feasible. STUDY REGISTRATION: ISRCTN, 74101606 . Registered on 6 November 2017.

Clinical and cost-effectiveness of social recovery therapy for the prevention and treatment of long-term social disability among young people with emerging severe mental illness (PRODIGY): randomised controlled trial.

BACKGROUND: Young people with social disability and severe and complex mental health problems have poor outcomes, frequently struggling with treatment access and engagement. Outcomes may be improved by enhancing care and providing targeted psychological or psychosocial intervention. AIMS: We aimed to test the hypothesis that adding social recovery therapy (SRT) to enhanced standard care (ESC) would improve social recovery compared with ESC alone. METHOD: A pragmatic, assessor-masked, randomised controlled trial (PRODIGY: ISRCTN47998710) was conducted in three UK centres. Participants (n = 270) were aged 16-25 years, with persistent social disability, defined as under 30 hours of structured activity per week, social impairment for at least 6 months and severe and complex mental health problems. Participants were randomised to ESC alone or SRT plus ESC. SRT was an individual psychosocial therapy delivered over 9 months. The primary outcome was time spent in structured activity 15 months post-randomisation. RESULTS: We randomised 132 participants to SRT plus ESC and 138 to ESC alone. Mean weekly hours in structured activity at 15 months increased by 11.1 h for SRT plus ESC (mean 22.4, s.d. = 21.4) and 16.6 h for ESC alone (mean 27.7, s.d. = 26.5). There was no significant difference between arms; treatment effect was -4.44 (95% CI -10.19 to 1.31, P = 0.13). Missingness was consistently greater in the ESC alone arm. CONCLUSIONS: We found no evidence for the superiority of SRT as an adjunct to ESC. Participants in both arms made large, clinically significant improvements on all outcomes. When providing comprehensive evidence-based standard care, there are no additional gains by providing specialised SRT. Optimising standard care to ensure targeted delivery of existing interventions may further improve outcomes.

Social recovery therapy for young people with emerging severe mental illness: the Prodigy RCT.

BACKGROUND: Young people with social disability and non-psychotic severe and complex mental health problems are an important group. Without intervention, their social problems can persist and have large economic and personal costs. Thus, more effective evidence-based interventions are needed. Social recovery therapy is an individual therapy incorporating cognitive-behavioural techniques to increase structured activity as guided by the participant's goals. OBJECTIVE: This trial aimed to test whether or not social recovery therapy provided as an adjunct to enhanced standard care over 9 months is superior to enhanced standard care alone. Enhanced standard care aimed to provide an optimal combination of existing evidence-based interventions. DESIGN: A pragmatic, single-blind, superiority randomised controlled trial was conducted in three UK centres: Sussex, Manchester and East Anglia. Participants were aged 16-25 years with persistent social disability, defined as < 30 hours per week of structured activity with social impairment for at least 6 months. Additionally, participants had severe and complex mental health problems, defined as at-risk mental states for psychosis or non-psychotic severe and complex mental health problems indicated by a Global Assessment of Functioning score ≤ 50 persisting for ≥ 6 months. Two hundred and seventy participants were randomised 1 : 1 to either enhanced standard care plus social recovery therapy or enhanced standard care alone. The primary outcome was weekly hours spent in structured activity at 15 months post randomisation. Secondary outcomes included subthreshold psychotic, negative and mood symptoms. Outcomes were collected at 9 and 15 months post randomisation, with maintenance assessed at 24 months. RESULTS: The addition of social recovery therapy did not significantly increase weekly hours in structured activity at 15 months (primary outcome treatment effect -4.44, 95% confidence interval -10.19 to 1.31). We found no evidence of significant differences between conditions in secondary outcomes at 15 months: Social Anxiety Interaction Scale treatment effect -0.45, 95% confidence interval -4.84 to 3.95; Beck Depression Inventory-II treatment effect -0.32, 95% confidence interval -4.06 to 3.42; Comprehensive Assessment of At-Risk Mental States symptom severity 0.29, 95% confidence interval -4.35 to 4.94; or distress treatment effect 4.09, 95% confidence interval -3.52 to 11.70. Greater Comprehensive Assessment of At-Risk Mental States for psychosis scores reflect greater symptom severity. We found no evidence of significant differences at 9 or 24 months. Social recovery therapy was not estimated to be cost-effective. The key limitation was that missingness of data was consistently greater in the enhanced standard care-alone arm (9% primary outcome and 15% secondary outcome missingness of data) than in the social recovery therapy plus enhanced standard care arm (4% primary outcome and 9% secondary outcome missingness of data) at 15 months. CONCLUSIONS: We found no evidence for the clinical superiority or cost-effectiveness of social recovery therapy as an adjunct to enhanced standard care. Both arms made large improvements in primary and secondary outcomes. Enhanced standard care included a comprehensive combination of evidence-based pharmacological, psychotherapeutic and psychosocial interventions. Some results favoured enhanced standard care but the majority were not statistically significant. Future work should identify factors associated with the optimal delivery of the combinations of interventions that underpin better outcomes in this often-neglected clinical group. TRIAL REGISTRATION: Current Controlled Trials ISRCTN47998710. 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. 25, No. 70. See the NIHR Journals Library website for further project information.

Young people with social disability and non-psychotic severe and complex mental health problems are an important group. Their problems are often long-standing and they often have difficulty doing 'structured activity', such as work, sports and leisure activities (e.g. going shopping or to the cinema). They often avoid such activities because of anxiety or low mood. Other barriers may include financial and practical issues, and stigma from activity providers. Non-participation in structured activity increases the risk that mental health problems will continue and prevent these young people from reaching meaningful goals. We tested whether or not social recovery therapy might help. This is a talking and activity therapy, in which young people (participants) work individually with a social recovery therapy therapist. Social recovery therapy aims to help participants identify what activities they would like to do, practise spending more time doing them, and work through barriers to maintaining increased activity. By improving structured activity, young people feel more hopeful and better able to manage their symptoms. However, social recovery therapy has never been evaluated properly using the best research methods. The best way to evaluate treatments like this is a randomised controlled trial in which participants are allocated by chance, like tossing a coin, to have the new therapy or not to have the therapy. Both groups are followed up for a period to see if the new therapy works. We tested social recovery therapy in this way. We also tested whether or not it was cost-effective. We recruited 270 16- to 25-year-old participants in Sussex, East Anglia and Manchester. Participants had non-psychotic severe and complex mental health problems (not psychosis) and were doing < 30 hours of structured activity per week at the start of the study. All participants had enhanced standard care. This involved standard NHS treatment plus a full assessment and feedback from the study team, and a best practice guide to local support services that encouraged the best provision of standard evidence-based interventions. Half of the participants were randomly allocated to have social recovery therapy in addition to enhanced standard care over 9 months. All participants were invited to assessments 9, 15 and 24 months later. Therapists recorded the tasks and activities undertaken with participants. We asked both participants and therapists what they thought of the trial and the social recovery therapy. We found no evidence that adding social recovery therapy improved outcomes. Participants in both arms made large and clinically worthwhile improvements in structured activity and mental health outcomes. If anything, there was some evidence that people allocated to enhanced standard care improved more than those allocated to social recovery therapy plus enhanced standard care. The differences were small, however, and could have occurred by chance.

Effects of the Norfolk diabetes prevention lifestyle intervention (NDPS) on glycaemic control in screen-detected type 2 diabetes: a randomised controlled trial.

BACKGROUND: The purpose of this trial was to test if the Norfolk Diabetes Prevention Study (NDPS) lifestyle intervention, recently shown to reduce the incidence of type 2 diabetes in high-risk groups, also improved glycaemic control in people with newly diagnosed screen-detected type 2 diabetes. METHODS: We screened 12,778 participants at high risk of type 2 diabetes using a fasting plasma glucose and glycosylated haemoglobin (HbA1c). People with screen-detected type 2 diabetes were randomised in a parallel, three-arm, controlled trial with up to 46 months of follow-up, with a control arm (CON), a group-based lifestyle intervention of 6 core and up to 15 maintenance sessions (INT), or the same intervention with additional support from volunteers with type 2 diabetes trained to co-deliver the lifestyle intervention (INT-DPM). The pre-specified primary end point was mean HbA1c compared between groups at 12 months. RESULTS: We randomised 432 participants (CON 149; INT 142; INT-DPM 141) with a mean (SD) age of 63.5 (10.0) years, body mass index (BMI) of 32.4 (6.4) kg/m2, and HbA1c of 52.5 (10.2) mmol/mol. The primary outcome of mean HbA1c at 12 months (CON 48.5 (9.1) mmol/mol, INT 46.5 (8.1) mmol/mol, and INT-DPM 45.6 (6.0) mmol/mol) was significantly lower in the INT-DPM arm compared to CON (adjusted difference -2.57 mmol/mol; 95% CI -4.5, -0.6; p = 0.007) but not significantly different between the INT-DPM and INT arms (-0.55 mmol/mol; 95% CI -2.46, 1.35; p = 0.57), or INT vs CON arms (-2.14 mmol/mol; 95% CI -4.33, 0.05; p = 0.07). Subgroup analyses showed the intervention had greater effect in participants < 65 years old (difference in mean HbA1c compared to CON -4.76 mmol/mol; 95% CI -7.75, -1.78 mmol/mol) than in older participants (-0.46 mmol/mol; 95% CI -2.67, 1.75; interaction p = 0.02). This effect was most significant in the INT-DPM arm (-6.01 mmol/mol; 95% CI -9.56, -2.46 age < 65 years old and -0.22 mmol/mol; 95% CI -2.7, 2.25; aged > 65 years old; p = 0.007). The use of oral hypoglycaemic medication was associated with a significantly lower mean HbA1c but only within the INT-DPM arm compared to CON (-7.0 mmol/mol; 95% CI -11.5, -2.5; p = 0.003). CONCLUSION: The NDPS lifestyle intervention significantly improved glycaemic control after 12 months in people with screen-detected type 2 diabetes when supported by trained peer mentors with type 2 diabetes, particularly those receiving oral hypoglycaemics and those under 65 years old. The effect size was modest, however, and not sustained at 24 months. TRIAL REGISTRATION: ISRCTN34805606 . Retrospectively registered 14.4.16.

An International Comparison of EQ-5D-5L and EQ-5D-3L for Use in Cost-Effectiveness Analysis.

OBJECTIVES: To estimate the impact of using EQ5D-5L (5L) compared with EQ5D-3L (3L) in cost-effectiveness analyses in 6 countries with 3L and 5L values: Germany, Japan, Korea, The Netherlands, China, and Spain. METHODS: Eight cost-effectiveness analyses based on clinical studies with 3L provided 11 pairwise comparisons. We estimated cost-effectiveness by applying the appropriate country values for 3L to observed responses. We re-estimated cost-effectiveness for each country by predicting the 5L tariff score for each respondent, for each country, using a previously published mapping method. We compared results in terms of impact on estimated incremental quality-adjusted life-year (QALY) gain and cost-effectiveness ratios. RESULTS: For most countries the impact of moving from 3L to 5L is to lower the incremental QALY gain in the majority of comparisons. The only exception to this was Japan, where 4 out of 11 cases (37%) saw lower QALYs gained when using 5L. The mean and median reductions in health gain, in those case studies where 5L does lead to lower health gain, are largest in The Netherlands (84% mean reduction, 41% median reduction), Germany (68% and 27%), and Spain (30% and 31%). For most countries, those studies where 5L leads to lower health gain see larger reductions than the gains in studies showing the opposite tendency. CONCLUSIONS: Overall, 3L and 5L are not interchangeable in these countries. Differences between results are large, but the direction of change can be unpredictable. These findings should prompt further investigation into the reasons for differences.

Randomised controlled trial of a just-in-time adaptive intervention (JITAI) smoking cessation smartphone app: the Quit Sense feasibility trial protocol.

INTRODUCTION: A lapse (any smoking) early in a smoking cessation attempt is strongly associated with reduced success. A substantial proportion of lapses are due to urges to smoke triggered by situational cues. Currently, no available interventions proactively respond to such cues in real time. Quit Sense is a theory-guided just-in-time adaptive intervention smartphone app that uses a learning tool and smartphone sensing to provide in-the-moment tailored support to help smokers manage cue-induced urges to smoke. The primary aim of this randomised controlled trial (RCT) is to assess the feasibility of delivering a definitive online efficacy trial of Quit Sense. METHODS AND ANALYSES: A two-arm parallel-group RCT allocating smokers willing to make a quit attempt, recruited via online adverts, to usual care (referral to the NHS SmokeFree website) or usual care plus Quit Sense. Randomisation will be stratified by smoking rate (<16 vs ≥16 cigarettes/day) and socioeconomic status (low vs high). Recruitment, enrolment, baseline data collection, allocation and intervention delivery will be automated through the study website. Outcomes will be collected at 6 weeks and 6 months follow-up via the study website or telephone, and during app usage. The study aims to recruit 200 smokers to estimate key feasibility outcomes, the preliminary impact of Quit Sense and potential cost-effectiveness, in addition to gaining insights on user views of the app through qualitative interviews. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Wales NHS Research Ethics Committee 7 (19/WA/0361). The findings will be disseminated to the public, the funders, relevant practice and policy representatives and other researchers. TRIAL REGISTRATION NUMBER: ISRCTN12326962.

Lifestyle Intervention With or Without Lay Volunteers to Prevent Type 2 Diabetes in People With Impaired Fasting Glucose and/or Nondiabetic Hyperglycemia: A Randomized Clinical Trial.

Importance: Nearly half of the older adult population has diabetes or a high-risk intermediate glycemic category, but we still lack trial evidence for effective type 2 diabetes prevention interventions in most of the current high-risk glycemic categories. Objective: To determine whether a group-based lifestyle intervention (with or without trained volunteers with type 2 diabetes) reduced the risk of progression to type 2 diabetes in populations with a high-risk glycemic category. Design, Setting, and Participants: The Norfolk Diabetes Prevention Study was a parallel, 3-arm, group-based, randomized clinical trial conducted with up to 46 months of follow-up from August 2011 to January 2019 at 135 primary care practices and 8 intervention sites in the East of England. We identified 141 973 people at increased risk of type 2 diabetes, screened 12 778 (9.0%), and randomized those with a high-risk glycemic category, which was either an elevated fasting plasma glucose level alone (≥110 and <126 mg/dL [to convert to millimoles per liter, multiply by 0.0555]) or an elevated glycated hemoglobin level (≥6.0% to <6.5%; nondiabetic hyperglycemia) with an elevated fasting plasma glucose level (≥100 to <110 mg/dL). Interventions: A control arm receiving usual care (CON), a theory-based lifestyle intervention arm of 6 core and up to 15 maintenance sessions (INT), or the same intervention with support from diabetes prevention mentors, trained volunteers with type 2 diabetes (INT-DPM). Main Outcomes and Measures: Type 2 diabetes incidence between arms. Results: In this study, 1028 participants were randomized (INT, 424 [41.2%] [166 women (39.2%)]; INT-DPM, 426 [41.4%] [147 women (34.5%)]; CON, 178 [17.3%] [70 women (%39.3)]) between January 1, 2011, and February 24, 2017. The mean (SD) age was 65.3 (10.0) years, mean (SD) body mass index 31.2 (5) (calculated as weight in kilograms divided by height in meters squared), and mean (SD) follow-up 24.7 (13.4) months. A total of 156 participants progressed to type 2 diabetes, which comprised 39 of 171 receiving CON (22.8%), 55 of 403 receiving INT (13.7%), and 62 of 414 receiving INT-DPM (15.0%). There was no significant difference between the intervention arms in the primary outcome (odds ratio [OR], 1.14; 95% CI, 0.77-1.7; P = .51), but each intervention arm had significantly lower odds of type 2 diabetes (INT: OR, 0.54; 95% CI, 0.34-0.85; P = .01; INT-DPM: OR, 0.61; 95% CI, 0.39-0.96; P = .033; combined: OR, 0.57; 95% CI, 0.38-0.87; P = .01). The effect size was similar in all glycemic, age, and social deprivation groups, and intervention costs per participant were low at $153 (£122). Conclusions and Relevance: The Norfolk Diabetes Prevention lifestyle intervention reduced the risk of type 2 diabetes in current high-risk glycemic categories. Enhancing the intervention with DPM did not further reduce diabetes risk. These translatable results are relevant for current diabetes prevention efforts. Trial Registration: ISRCTN Registry Identifier: ISRCTN34805606.

Trial of Dexamethasone for Chronic Subdural Hematoma.

BACKGROUND: Chronic subdural hematoma is a common neurologic disorder that is especially prevalent among older people. The effect of dexamethasone on outcomes in patients with chronic subdural hematoma has not been well studied. METHODS: We conducted a multicenter, randomized trial in the United Kingdom that enrolled adult patients with symptomatic chronic subdural hematoma. The patients were assigned in a 1:1 ratio to receive a 2-week tapering course of oral dexamethasone, starting at 8 mg twice daily, or placebo. The decision to surgically evacuate the hematoma was made by the treating clinician. The primary outcome was a score of 0 to 3, representing a favorable outcome, on the modified Rankin scale at 6 months after randomization; scores range from 0 (no symptoms) to 6 (death). RESULTS: From August 2015 through November 2019, a total of 748 patients were included in the trial after randomization - 375 were assigned to the dexamethasone group and 373 to the placebo group. The mean age of the patients was 74 years, and 94% underwent surgery to evacuate their hematomas during the index admission; 60% in both groups had a score of 1 to 3 on the modified Rankin scale at admission. In a modified intention-to-treat analysis that excluded the patients who withdrew consent for participation in the trial or who were lost to follow-up, leaving a total of 680 patients, a favorable outcome was reported in 286 of 341 patients (83.9%) in the dexamethasone group and in 306 of 339 patients (90.3%) in the placebo group (difference, -6.4 percentage points [95% confidence interval, -11.4 to -1.4] in favor of the placebo group; P = 0.01). Among the patients with available data, repeat surgery for recurrence of the hematoma was performed in 6 of 349 patients (1.7%) in the dexamethasone group and in 25 of 350 patients (7.1%) in the placebo group. More adverse events occurred in the dexamethasone group than in the placebo group. CONCLUSIONS: Among adults with symptomatic chronic subdural hematoma, most of whom had undergone surgery to remove their hematomas during the index admission, treatment with dexamethasone resulted in fewer favorable outcomes and more adverse events than placebo at 6 months, but fewer repeat operations were performed in the dexamethasone group. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Dex-CSDH ISRCTN number, ISRCTN80782810.).

Protocol for the process evaluation of a cluster randomised controlled trial to determine the effectiveness and cost-effectiveness of independent pharmacist prescribing in care home: the CHIPPS study.

BACKGROUND: Prescribing, monitoring and administration of medicines in care homes could be improved. A cluster randomised controlled trial (RCT) is ongoing to evaluate the effectiveness of an independent prescribing pharmacist assuming responsibility for medicines management in care homes compared to usual care. AIMS AND OBJECTIVES: To conduct a mixed-methods process evaluation of the RCT, in line with Medical Research Council (MRC) process evaluation guidance, to inform interpretation of main trial findings and if the service is found to be effective and efficient, to inform subsequent implementation. OBJECTIVES: 1. To describe the intervention as delivered in terms of quality, quantity, adaptations and variations across triads and time. 2. To explore the effects of individual intervention components on the primary outcomes. 3. To investigate the mechanisms of impact. 4. To describe the perceived effectiveness of relevant intervention components [including pharmacist independent prescriber (PIP) training and care home staff training] from participant [general practitioner (GP), care home, PIP and resident/relative] perspectives. 5. To describe the characteristics of GP, care home, PIP and resident participants to assess reach. 6. To estimate the extent to which intervention delivery is normalised among the intervention healthcare professionals and related practice staff. METHODS: A mix of quantitative (surveys, record reviews) and qualitative (interviews) approaches will be used to collect data on the extent of the delivery of detailed tasks required to implement the new service, to collect data to confirm the mechanism of impact as hypothesised in the logic model, to collect explanatory process and final outcome data, and data on contextual factors which could have facilitated or hindered effective and efficient delivery of the service. DISCUSSION: Recruitment is ongoing and the trial should complete in early 2020. The systematic and comprehensive approach that is being adopted will ensure data is captured on all aspects of the study, and allow a full understanding of the implementation of the service and the RCT findings. With so many interrelated factors involved it is important that a process evaluation is undertaken to enable us to identify which elements of the service were deemed to be effective, explain any differences seen, and identify enablers, barriers and future adaptions. TRIAL REGISTRATION: ISRCTN17847169. Date registered: 15 December 2017.

MEDREV (pharmacy-health psychology intervention in people living with dementia with behaviour that challenges): the feasibility of measuring clinical outcomes and costs of the intervention.

BACKGROUND: People living with dementia in care homes frequently exhibit "behaviour that challenges". Anti-psychotics are used to treat such behaviour, but are associated with significant morbidity. This study researched the feasibility of conducting a trial of a full clinical medication review for care home residents with behaviour that challenges, combined with staff training. This paper focusses on the feasibility of measuring clinical outcomes and intervention costs. METHODS: People living with moderate to severe dementia, receiving psychotropics for behaviour that challenges, in care homes were recruited for a medication review by a specialist pharmacist. Care home and primary care staff received training on the management of challenging behaviour. Data were collected at 8 weeks, and 3 and 6 months. Measures were Neuropsychiatric Inventory-Nursing Home version (NPI-NH), cognition (sMMSE), quality of life (EQ-5D-5 L/DEMQoL) and costs (Client Services Receipt Inventory). Response rates, for clinical, quality of life and health economic measures, including the levels of resource-use associated with the medication review and other non-intervention costs were calculated. RESULTS: Twenty-nine of 34 participants recruited received a medication review. It was feasible to measure the effects of the complex intervention on the management of behaviour that challenges with the NPI-NH. There was valid NPI-NH data at each time point (response rate = 100%). The sMMSE response rate was 18.2%. Levels of resource-use associated with the medication review were estimated for all 29 participants who received a medication review. Good response levels were achieved for other non-intervention costs (100% completion rate), and the EQ-5D-5 L and DEMQoL (≥88% at each of the time points where data was collected). CONCLUSIONS: It is feasible to measure the clinical and cost effectiveness of a complex intervention for behaviour that challenges using the NPI-NH and quality of life measures. TRIAL REGISTRATION: ISRCTN58330068. Retrospectively registered, 15 October 2017.

Protocol for a cluster randomised controlled trial to determine the effectiveness and cost-effectiveness of independent pharmacist prescribing in care homes: the CHIPPS study.

BACKGROUND: Prescribing, monitoring and administration of medicines in care homes could be improved. Research has identified the need for one person to assume overall responsibility for the management of medicines within each care home. and shown that a pharmacist independent prescriber service is feasible in this context. AIMS AND OBJECTIVES: To conduct a cluster randomised controlled trial to determine the effectiveness and cost-effectiveness of a pharmacist-independent prescribing service in care homes compared to usual general practitioner (GP)-led care. OBJECTIVES: To perform a definitive randomised controlled trial (RCT) with an internal pilot to determine the intervention's effectiveness and cost-effectiveness and enable modelling beyond the end of the trial. METHODS: This protocol is for a cluster RCT with a 3-month internal pilot to confirm that recruitment is achievable, and there are no safety concerns. The unit of randomisation is a triad comprising a pharmacist-independent prescriber (PIP) based in a GP practice with sufficient registered patients resident in one or more care homes to allow recruitment of an average of 20 participants. In the intervention group, the PIP will, in collaboration with the GP: assume responsibility for prescribing and managing residents' medicines including medication review and pharmaceutical care planning; support systematic ordering and administration in the care home, GP practice and supplying pharmacy; train care home and GP practice staff; communicate with GP practice, care home, supplying community pharmacy and study team. The intervention will last 6 months. The primary outcome will be resident falls at 6 months. Secondary outcomes include resident health-related quality of life, falls at 3 months, medication burden, medication appropriateness, mortality and hospitalisations. A full health economic analysis will be undertaken. The target sample size is 880 residents (440) in each arm) from 44 triads. This number is sufficient to detect a decrease in fall rate from 1.5 per individual to 1.178 (relative reduction of 21%) with 80% power and an ICC of 0.05 or less. DISCUSSION: Recruitment is on-going and the trial should complete in early 2020. The trial results will have implications for the future management of residents in care homes and the ongoing implementation of independent pharmacist prescribing. TRIAL REGISTRATION: ISRCTN, ID: 17847169. Registered on 15 December 2017.

The construct validity and responsiveness of the EQ-5D-5L, AQL-5D and a bespoke TTO in acute asthmatics.

PURPOSE: Measuring quality of life in acute asthmatics is challenging, especially when asthma attacks can occur sporadically. Several questionnaires can be used to measure quality of life in this patient group; however, psychometric testing is limited on questionnaires that can be used to estimate Quality Adjusted Life years. The objective of this study is to assess the construct validity (convergent and discriminative validity) and responsiveness of the EuroQol-5-Dimensions 5-Level (EQ-5D-5L), Asthma Quality of Life Utility Index-5 Dimensions (AQL-5D) and Time Trade-Off (TTO) in acute asthma patients. METHODS: Data from a prospective cohort study were used to test the validity and responsiveness of the EQ-5D-5L, AQL-5D and TTO in asthma patients who were recruited from UK accident & emergency departments or hospital wards. The spearman's rank correlation coefficient, the Kruskal-Wallis test statistic and the standardized response mean were used to test for convergent validity, discriminative validity and responsiveness, respectively. RESULTS: One hundred and twenty-one participants were included in the available case analysis. The EQ-5D-5L and AQL-5D showed moderate to strong correlations for convergent validity at baseline, week 4 and week 8. The AQL-5D and TTO showed moderate correlations at week 4 and week 8. No statistical significance was observed for discriminative validity at baseline. Both the EQ-5D-5L and the AQL-5D also showed that they were sensitive to change for the recovery responses. CONCLUSIONS: The EQ-5D-5L and AQL-5D showed stronger construct validity and responsiveness compared to the TTO. Therefore, both the EQ-5D-5L and AQL-5D should be considered for use in future economic evaluations.

Dex-CSDH randomised, placebo-controlled trial of dexamethasone for chronic subdural haematoma: report of the internal pilot phase.

The Dex-CSDH trial is a randomised, double-blind, placebo-controlled trial of dexamethasone for patients with a symptomatic chronic subdural haematoma. The trial commenced with an internal pilot, whose primary objective was to assess the feasibility of multi-centre recruitment. Primary outcome data collection and safety were also assessed, whilst maintaining blinding. We aimed to recruit 100 patients from United Kingdom Neurosurgical Units within 12 months. Trial participants were randomised to a 2-week course of dexamethasone or placebo in addition to receiving standard care (which could include surgery). The primary outcome measure of the trial is the modified Rankin Scale at 6 months. This pilot recruited ahead of target; 100 patients were recruited within nine months of commencement. 47% of screened patients consented to recruitment. The primary outcome measure was collected in 98% of patients. No safety concerns were raised by the independent data monitoring and ethics committee and only five patients were withdrawn from drug treatment. Pilot trial data can inform on the design and resource provision for substantive trials. This internal pilot was successful in determining recruitment feasibility. Excellent follow-up rates were achieved and exploratory outcome measures were added to increase the scientific value of the trial.