Advances in Addressing Patient Heterogeneity in Economic Evaluation: A Review of the Methods Literature.

Cost-effectiveness analyses commonly use population or sample averages, which can mask key differences across subgroups and may lead to suboptimal resource allocation. Despite there being several new methods developed over the last decade, there is no recent summary of what methods are available to researchers. This review sought to identify advances in methods for addressing patient heterogeneity in economic evaluations and to provide an overview of these methods. A literature search was conducted using the Econlit, Embase and MEDLINE databases to identify studies published after 2011 (date of a previous review on this topic). Eligible studies needed to have an explicit methodological focus, related to how patient heterogeneity can be accounted for within a full economic evaluation. Sixteen studies were included in the review. Methodologies were varied and included regression techniques, model design and value of information analysis. Recent publications have applied methodologies more commonly used in other fields, such as machine learning and causal forests. Commonly noted challenges associated with considering patient heterogeneity included data availability (e.g., sample size), statistical issues (e.g., risk of false positives) and practical factors (e.g., computation time). A range of methods are available to address patient heterogeneity in economic evaluation, with relevant methods differing according to research question, scope of the economic evaluation and data availability. Researchers need to be aware of the challenges associated with addressing patient heterogeneity (e.g., data availability) to ensure findings are meaningful and robust. Future research is needed to assess whether and how methods are being applied in practice.

Development and evaluation of a de-escalation training intervention in adult acute and forensic units: the EDITION systematic review and feasibility trial.

Background: Containment (e.g. physical restraint and seclusion) is used frequently in mental health inpatient settings. Containment is associated with serious psychological and physical harms. De-escalation (psychosocial techniques to manage distress without containment) is recommended to manage aggression and other unsafe behaviours, for example self-harm. All National Health Service staff are trained in de-escalation but there is little to no evidence supporting training's effectiveness. Objectives: Objectives were to: (1) qualitatively investigate de-escalation and identify barriers and facilitators to use across the range of adult acute and forensic mental health inpatient settings; (2) co-produce with relevant stakeholders an intervention to enhance de-escalation across these settings; (3) evaluate the intervention's preliminary effect on rates of conflict (e.g. violence, self-harm) and containment (e.g. seclusion and physical restraint) and understand barriers and facilitators to intervention effects. Design: Intervention development informed by Experience-based Co-design and uncontrolled pre and post feasibility evaluation. Systematic reviews and qualitative interviews investigated contextual variation in use and effects of de-escalation. Synthesis of this evidence informed co-design of an intervention to enhance de-escalation. An uncontrolled feasibility trial of the intervention followed. Clinical outcome data were collected over 24 weeks including an 8-week pre-intervention phase, an 8-week embedding and an 8-week post-intervention phase. Setting: Ten inpatient wards (including acute, psychiatric intensive care, low, medium and high secure forensic) in two United Kingdom mental health trusts. Participants: In-patients, clinical staff, managers, carers/relatives and training staff in the target settings. Interventions: Enhancing de-escalation techniques in adult acute and forensic units: Development and evaluation of an evidence-based training intervention (EDITION) interventions included de-escalation training, two novel models of reflective practice, post-incident debriefing and feedback on clinical practice, collaborative prescribing and ward rounds, practice changes around admission, shift handovers and the social and physical environment, and sensory modulation and support planning to reduce patient distress. Main outcome measures: Outcomes measured related to feasibility (recruitment and retention, completion of outcome measures), training outcomes and clinical and safety outcomes. Conflict and containment rates were measured via the Patient-Staff Conflict Checklist. Clinical outcomes were measured using the Attitudes to Containment Measures Questionnaire, Attitudes to Personality Disorder Questionnaire, Violence Prevention Climate Scale, Capabilities, Opportunities, and Motivation Scale, Coercion Experience Scale and Perceived Expressed Emotion in Staff Scale. Results: Completion rates of the proposed primary outcome were very good at 68% overall (excluding remote data collection), which increased to 76% (excluding remote data collection) in the post-intervention period. Secondary outcomes had high completion rates for both staff and patient respondents. Regression analyses indicated that reductions in conflict and containment were both predicted by study phase (pre, embedding, post intervention). There were no adverse events or serious adverse events related to the intervention. Conclusions: Intervention and data-collection procedures were feasible, and there was a signal of an effect on the proposed primary outcome. Limitations: Uncontrolled design and self-selecting sample. Future work: Definitive trial determining intervention effects. Trial registration: This trial is registered as ISRCTN12826685 (closed to recruitment). Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/101/02) and is published in full in Health Technology Assessment; Vol. 28, No. 3. See the NIHR Funding and Awards website for further award information. Context: Conflict (a term used to describe a range of potentially unsafe events including violence, self-harm, rule-breaking, medication refusal, illicit drug and alcohol use and absconding) in mental health settings causes serious physical and psychological harm. Containment interventions which are intended to minimise harm from violence (and other conflict behaviours) such as restraint, seclusion and rapid tranquilisation can result in serious injuries to patients and, occasionally, death. Involvement in physical restraint is the most common cause of serious physical injury to National Health Service mental health staff in the United Kingdom. Violence to staff results in substantial costs to the health service in sickness and litigation payments. Containment interventions are also expensive (e.g. physical restraint costs mental health services £6.1 million and enhanced observations £88 million per annum). Despite these harms, recent findings indicate containment interventions such as seclusion and physical restraint continue to be used frequently in mental health settings. Clinical trials have demonstrated that interventions can reduce containment without increasing violence and other conflict behaviours (e.g. verbal aggression, self-harm). Substantial cost-savings result from reducing containment use. De-escalation, as an intervention to manage aggression and potential violence without restrictive practices, is a core intervention. 'De-escalation' is a collective term for a range of psychosocial techniques designed to reduce distress and anger without the need to use 'containment' interventions (measures to prevent harm through restricting a person's ability to act independently, such as physical restraint and seclusion). Evidence indicates that de-escalation involves ensuring conditions for safe intervention and effective communication are established, clarifying and attempting to resolve the patient's concern, conveyance of respect and empathy and regulating unhelpful emotions such as anxiety and anger. Despite featuring prominently in clinical guidelines and training policy domestically and internationally and being a component of mandatory National Health Service training, there is no evidence-based model on which to base training. A systematic review of de-escalation training effectiveness and acceptability conducted in 2015 concluded: (1) no model of training has demonstrated effectiveness in a sufficiently rigorous evaluation, (2) the theoretical underpinning of evaluated models was often unclear and (3) there has been inadequate investigation of the characteristics of training likely to enhance acceptability and uptake. Despite all National Health Service staff being trained in de-escalation there have been no high-quality trials evaluating the effectiveness and cost-effectiveness of training. Feasibility studies are needed to establish whether it is possible to conduct a definitive trial that can determine the clinical, safety and cost-effectiveness of this intervention.

Mental health hospitals are stressful places for patients and staff. Patients are often detained against their will, in places that are noisy, unfamiliar and frightening. Violence and self-injury happen quite frequently. Sometimes staff physically restrain patients or isolate patients in locked rooms (called seclusion). While these measures might sometimes be necessary to maintain safety, they are psychologically and physically harmful. To help reduce the use of these unsafe measures, staff are trained in communication skills designed to reduce anger and distress without using physical force. Professionals call these skills 'de-escalation'. Although training in de-escalation is mandatory, there is no good evidence to say whether it works or not, or what specific techniques staff should be trained in. The Enhancing de-escalation techniques in adult acute and forensic units: Development and evaluation of an evidence-based training intervention (EDITION) project aimed to develop and evaluate a de-escalation training programme informed by research evidence. We interviewed over one hundred people who either worked in or received treatment in a mental health hospital. These people were clear that the training should target key sources of interpersonal and environmental stress that prevent de-escalation from working. We also reviewed all the scientific studies on de-escalation and training, aiming to identify the elements of training that are most likely to increase use of de-escalation. Then, in partnership with current mental health service users and clinical staff, we developed the training programme. Training was delivered to more than 270 staff working in 10 different wards in mental health hospitals. We measured rates of violence, self-injury and use of physical restraint and seclusion 8 weeks before staff received training and 16 weeks after they received training (24 weeks of data collection in total). Analysis of these data showed that these unsafe events were occurring significantly less frequently after training than they were before training, which raised the possibility that the training was helping to reduce harm.

A randomised controlled trial of clinical and cost-effectiveness of the PASS Plus intervention for young children with autism spectrum disorder in New Delhi, India: study protocol for the COMPASS trial.

BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental disability affecting at least 5 million children in South Asia. Majority of these children are without access to evidence-based care. The UK Pre-school Autism Communication Therapy (PACT) is the only intervention to have shown sustained impact on autism symptoms. It was systematically adapted for non-specialist community delivery in South Asia, as the 'Parent-mediated Autism Social Communication Intervention for non-Specialists (PASS)' and extended 'PASS Plus' interventions. RCTs of both showed feasibility, acceptability and positive effect on parent and child dyadic outcomes. METHODS: The Communication-centred Parent-mediated treatment for Autism Spectrum Disorder in South Asia (COMPASS) trial is now a scale-up two-centre, two-arm single (rater) blinded random allocation parallel group study of the PASS Plus intervention in addition to treatment as usual (TAU) compared to TAU alone, plus health economic evaluation embedded in the India health system. Two hundred forty children (approximately 120 intervention/120 TAU) with ASD aged 2-9 years will be recruited from two tertiary care government hospitals in New Delhi, India. Accredited Social Health Activists will be one of the intervention delivery agents. Families will undertake up to 12 communication sessions over 8 months and will be offered the Plus modules which address coexisting problems. The trial's primary endpoint is at 9 months from randomisation, with follow-up at 15 months. The primary outcome is autism symptom severity; secondary outcomes include parent-child communication, child adaptation, quality of life and parental wellbeing. Primary analysis will follow intention-to-treat principles using linear mixed model regressions with group allocation and repeated measures as random effects. The cost-effectiveness analysis will use a societal perspective over the 15-month period of intervention and follow-up. DISCUSSION: If clinically and cost-effective, this programme will fill an important gap of scalable interventions delivered by non-specialist health workers within the current care pathways for autistic children and their families in low-resource contexts. The programme has been implemented through the COVID-19 pandemic when restrictions were in place; intervention delivery and evaluation processes have been adapted to address these conditions. TRIAL REGISTRATION: ISRCTN; ISRCTN21454676 ; Registered 22 June 2018.

The effectiveness of a primary care-based collaborative care model to improve quality of life in people with severe mental illness: PARTNERS2 cluster randomised controlled trial.

BACKGROUND: Individuals living with severe mental illness can have significant emotional, physical and social challenges. Collaborative care combines clinical and organisational components. AIMS: We tested whether a primary care-based collaborative care model (PARTNERS) would improve quality of life for people with diagnoses of schizophrenia, bipolar disorder or other psychoses, compared with usual care. METHOD: We conducted a general practice-based, cluster randomised controlled superiority trial. Practices were recruited from four English regions and allocated (1:1) to intervention or control. Individuals receiving limited input in secondary care or who were under primary care only were eligible. The 12-month PARTNERS intervention incorporated person-centred coaching support and liaison work. The primary outcome was quality of life as measured by the Manchester Short Assessment of Quality of Life (MANSA). RESULTS: We allocated 39 general practices, with 198 participants, to the PARTNERS intervention (20 practices, 116 participants) or control (19 practices, 82 participants). Primary outcome data were available for 99 (85.3%) intervention and 71 (86.6%) control participants. Mean change in overall MANSA score did not differ between the groups (intervention: 0.25, s.d. 0.73; control: 0.21, s.d. 0.86; estimated fully adjusted between-group difference 0.03, 95% CI -0.25 to 0.31; P = 0.819). Acute mental health episodes (safety outcome) included three crises in the intervention group and four in the control group. CONCLUSIONS: There was no evidence of a difference in quality of life, as measured with the MANSA, between those receiving the PARTNERS intervention and usual care. Shifting care to primary care was not associated with increased adverse outcomes.

Metacognitive therapy home-based self-help for anxiety and depression in cardiovascular disease patients in the UK: A single-blind randomised controlled trial.

BACKGROUND: Anxiety and depression in cardiac rehabilitation (CR) are associated with greater morbidity, mortality, and increased healthcare costs. Current psychological interventions within CR have small effects based on low-quality studies of clinic-based interventions with limited access to home-based psychological support. We tested the effectiveness of adding self-help metacognitive therapy (Home-MCT) to CR in reducing anxiety and depression in a randomised controlled trial (RCT). METHODS AND FINDINGS: We ran a single-blind, multi-centre, two-arm RCT. A total of 240 CR patients were recruited from 5 NHS-Trusts across North West England between April 20, 2017 and April 6, 2020. Patients were randomly allocated to Home-MCT+CR (n = 118, 49.2%) or usual CR alone (n = 122, 50.8%). Randomisation was 1:1 via randomised blocks within hospital site, balancing arms on sex and baseline Hospital Anxiety and Depression Scale (HADS) scores. The primary outcome was the HADS total score at posttreatment (4-month follow-up). Follow-up data collection occurred between August 7, 2017 and July 20, 2020. Analysis was by intention to treat. The 4-month outcome favoured the MCT intervention group demonstrating significantly lower end of treatment scores (HADS total: adjusted mean difference = -2.64 [-4.49 to -0.78], p = 0.005, standardised mean difference (SMD) = 0.38). Sensitivity analysis using multiple imputation (MI) of missing values supported these findings. Most secondary outcomes also favoured Home-MCT+CR, especially in reduction of post-traumatic stress symptoms (SMD = 0.51). There were 23 participants (19%) lost to follow-up in Home-MCT+CR and 4 participants (3%) lost to follow-up in CR alone. No serious adverse events were reported. The main limitation is the absence of longer term (e.g., 12-month) follow-up data. CONCLUSION: Self-help home-based MCT was effective in reducing total anxiety/depression in patients undergoing CR. Improvement occurred across most psychological measures. Home-MCT was a promising addition to cardiac rehabilitation and may offer improved access to effective psychological treatment in cardiovascular disease (CVD) patients. TRIAL REGISTRATION: NCT03999359.

Development of a cost of illness inventory questionnaire for children with autism spectrum disorder in South Asia.

BACKGROUND: The economic burden of autism is substantial and includes a range of costs, including healthcare, education, productivity losses, informal care and respite care, among others. In India, approximately, 2 million children aged 2-9 years have autism. Given the likely substantial burden of illness and the need to identify effective and cost-effective interventions, this research aimed to produce a comprehensive cost of illness inventory (COII) suitable for children with autism in South Asia (India) to support future research. METHODS: A structured and iterative design process was followed to create the COII, including literature reviews, interviews with caregivers, pilot testing and translation. Across the development of the COII, thirty-two families were involved in the design and piloting of the tool. The COII was forward translated (from English to Hindi) and back translated. Each stage of the process of development of the COII resulted in the further refinement of the tool. RESULTS: Domains covered in the final COII include education, childcare, relocation, healthcare contacts (outpatient, inpatient, medical emergencies, investigations and medication), religious retreats and rituals, specialist equipment, workshops and training, special diet, support and care, certification, occupational adjustments and government rebates/schemes. Administration and completion of the COII determined it to be feasible to complete in 35 minutes by qualified and trained researchers. The final COII is hosted by REDCap Cloud and is a bilingual instrument (Hindi and English). CONCLUSIONS: The COII was developed using experiences gathered from an iterative process in a metropolitan area within the context of one low- and middle-income country (LMIC) setting, India. Compared to COII tools used for children with autism in high-income country settings, additional domains were required, such as complimentary medication (e.g. religious retreats and homeopathy). The COII will allow future research to quantify the cost of illness of autism in India from a broad perspective and will support relevant economic evaluations. Understanding the process of developing the questionnaire will help researchers working in LMICs needing to adapt the current COII or developing similar questionnaires.

REACH-ASD: a UK randomised controlled trial of a new post-diagnostic psycho-education and acceptance and commitment therapy programme against treatment-as-usual for improving the mental health and adjustment of caregivers of children recently diagnosed with autism spectrum disorder.

BACKGROUND: Autism is a neurodevelopmental disability affecting over 1% of UK children. The period following a child's autism diagnosis can present real challenges in adaptation for families. Twenty to 50% of caregivers show clinically significant levels of mental health need within the post-diagnostic period and on an ongoing basis. Best practice guidelines recommend timely post-diagnostic family support. Current provision is patchy, largely unevidenced, and a source of dissatisfaction for both families and professionals. There is a pressing need for an evidenced programme of post-diagnostic support focusing on caregiver mental health and adjustment, alongside autism psycho-education. This trial tests the clinical and cost-effectiveness of a new brief manualised psychosocial intervention designed to address this gap. METHODS: This is a multi-centre two-parallel-group single (researcher)-blinded randomised controlled trial of the Empower-Autism programme plus treatment-as-usual versus usual local post-diagnostic offer plus treatment-as-usual. Caregivers of children aged 2-15 years with a recent autism diagnosis will be recruited from North West England NHS or local authority centres. Randomisation is individually by child, with one "index" caregiver per child, stratified by centre, using 2:1 randomisation ratio to assist recruitment and timely intervention. Empower-Autism is a group-based, manualised, post-diagnostic programme that combines autism psycho-education and psychotherapeutic components based on Acceptance and Commitment Therapy to support caregiver mental health, stress management and adjustment to their child's diagnosis. The comparator is any usual local group-based post-diagnostic psycho-education offer. Receipt of services will be specified through health economic data. PRIMARY OUTCOME: caregiver mental health (General Health Questionnaire-30) at 52-week follow-up. SECONDARY OUTCOMES: key caregiver measures (wellbeing, self-efficacy, adjustment, autism knowledge) at 12-, 26- and 52-week follow-up and family and child outcomes (wellbeing and functioning) at 52-week endpoint. SAMPLE: N=380 (approximately 253 intervention/127 treatment-as-usual). Primary analysis will follow intention-to-treat principles using linear mixed models with random intercepts for group membership and repeated measures. Cost-effectiveness acceptability analyses will be over 52 weeks, with decision modelling to extrapolate to longer time periods. DISCUSSION: If effective, this new approach will fill a key gap in the provision of evidence-based care pathways for autistic children and their families. TRIAL REGISTRATION: ISRCTN 45412843 . Prospectively registered on 11 September 2019.

A review of economic evaluations of health care for people at risk of psychosis and for first-episode psychosis.

BACKGROUND: Preventing psychotic disorders and effective treatment in first-episode psychosis are key priorities for the National Institute for Health and Care Excellence. This review assessed the evidence base for the cost-effectiveness of health and social care interventions for people at risk of psychosis and for first-episode psychosis. METHODS: Electronic searches were conducted using the PsycINFO, MEDLINE and Embase databases to identify relevant published full economic evaluations published before August 2020. Full-text English-language studies reporting a full economic evaluation of a health or social care intervention aiming to reduce or prevent symptoms in people at risk of psychosis or experiencing first-episode psychosis were included. Screening, data extraction, and critical appraisal were performed using pre-specified criteria and forms based on the NHS Economic Evaluation Database (EED) handbook and Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist for economic evaluations. The protocol was registered on the PROSPERO database (CRD42018108226). Results were summarised qualitatively. RESULTS: Searching identified 1,628 citations (1,326 following the removal of duplications). After two stages of screening 14 studies met the inclusion criteria and were included in the review. Interventions were varied and included multidisciplinary care, antipsychotic medication, psychological therapy, and assertive outreach. Evidence was limited in the at-risk group with only four identified studies, though all interventions were found to be cost-effective with a high probability (> 80%). A more substantial evidence base was identified for first-episode psychosis (11 studies), with a focus on early intervention (7/11 studies) which again had positive conclusions though with greater uncertainty. CONCLUSIONS: Study findings generally concluded interventions were cost-effective. The evidence for the population who are at-risk of psychosis was limited, and though there were more studies for the population with first-episode psychosis, limitations of the evidence base (including generalisability and heterogeneity across the methods used) affect the certainty of conclusions.

Acknowledging Patient Heterogeneity in Economic Evaluations in Schizophrenia: A Systematic Review.

OBJECTIVES: Schizophrenia is a severe mental illness with heterogeneous etiology, range of symptoms, and course of illness. Cost-effectiveness analysis often applies averages from populations, which disregards patient heterogeneity even though there are a range of methods available to acknowledge patient heterogeneity. This review evaluates existing economic evaluations of interventions in schizophrenia to understand how patient heterogeneity is currently reflected in economic evaluation. METHODS: Electronic searches of MEDLINE, Embase, and PsycINFO via Ovid and the Health Technology Assessment database were run to identify full economic evaluations of interventions aiming to reduce the symptoms associated with schizophrenia. Two levels of screening were used, and explicit inclusion criteria were applied. Prespecified data extraction and critical appraisal were performed. RESULTS: Seventy-six relevant studies were identified. More than half (41 of 76) of the articles acknowledged patient heterogeneity in some way through discussion or methods. There was a range of patient characteristics considered, including demographics and socioeconomic factors (eg, age, educational level, ethnicity), clinical characteristics (eg, symptom severity, comorbidities), and preferences (eg, preferences related to outcomes or symptoms). Subgroup analyses were rarely reported (8 of 76). CONCLUSIONS: Patient heterogeneity was frequently mentioned in studies but was rarely thoroughly investigated in the identified economic evaluations. When investigated, included patient characteristics and methods were found to be heterogeneous. Understanding and acknowledging patient heterogeneity may alter the conclusions of cost-effectiveness evaluations; subsequently, we would encourage further research in this area.

Factors Limiting Subgroup Analysis in Cost-Effectiveness Analysis and a Call for Transparency.

The use of population averages in cost-effectiveness analysis may hide important differences across subgroups, potentially resulting in suboptimal resource allocation, reduced population health and/or increased health inequalities. We discuss the factors that limit subgroup analysis in cost-effectiveness analysis and propose more thorough and transparent reporting. There are many issues that may limit whether subgroup analysis can be robustly included in cost-effectiveness analysis, including challenges with prespecifying and justifying subgroup analysis, identifying subgroups that can be implemented (identified and targeted) in practice, resource and data requirements, and statistical and ethical concerns. These affect every stage of the design, development and reporting of cost-effectiveness analyses. It may not always be possible to include and report relevant subgroups in cost effectiveness, e.g. due to data limitations. Reasons for not conducting subgroup analysis may be heterogeneous, and the consequences of not acknowledging patient heterogeneity can be substantial. We recommend that when potentially relevant subgroups have not been included in a cost-effectiveness analysis, authors report this and discuss their rationale and the limitations of this. Greater transparency of subgroup reporting should provide a starting point to overcoming these challenges in future research.

Evaluation of a primary care-based collaborative care model (PARTNERS2) for people with diagnoses of schizophrenia, bipolar, or other psychoses: study protocol for a cluster randomised controlled trial.

BACKGROUND: Current NHS policy encourages an integrated approach to provision of mental and physical care for individuals with long term mental health problems. The 'PARTNERS2' complex intervention is designed to support individuals with psychosis in a primary care setting. AIM: The trial will evaluate the clinical and cost-effectiveness of the PARTNERS2 intervention. DESIGN & SETTING: This is a cluster randomised controlled superiority trial comparing collaborative care (PARTNERS2) with usual care, with an internal pilot to assess feasibility. The setting will be primary care within four trial recruitment areas: Birmingham & Solihull, Cornwall, Plymouth, and Somerset. GP practices are randomised 1:1 to either (a) the PARTNERS2 intervention plus modified standard care ('intervention'); or (b) standard care only ('control'). METHOD: PARTNERS2 is a flexible, general practice-based, person-centred, coaching-based intervention aimed at addressing mental health, physical health, and social care needs. Two hundred eligible individuals from 39 GP practices are taking part. They were recruited through identification from secondary and primary care databases. The primary hypothesis is quality of life (QOL). Secondary outcomes include: mental wellbeing, time use, recovery, and process of physical care. A process evaluation will assess fidelity of intervention delivery, test hypothesised mechanisms of action, and look for unintended consequences. An economic evaluation will estimate its cost-effectiveness. Intervention delivery and follow-up have been modified during the COVID-19 pandemic. CONCLUSION: The overarching aim is to establish the clinical and cost-effectiveness of the model for adults with a diagnosis of schizophrenia, bipolar, or other types of psychoses.

Psychological intervention, antipsychotic medication or a combined treatment for adolescents with a first episode of psychosis: the MAPS feasibility three-arm RCT.

BACKGROUND: When psychosis emerges in young people there is a risk of poorer outcomes, and access to evidence-based treatments is paramount. The current evidence base is limited. Antipsychotic medications show only a small benefit over placebo, but young people experience more side effects than adults. There is sparse evidence for psychological intervention. Research is needed to determine the clinical effectiveness and cost-effectiveness of psychological intervention versus antipsychotic medication versus a combined treatment for adolescents with psychosis. OBJECTIVES: The objective of Managing Adolescent first-episode Psychosis: a feasibility Study (MAPS) was to determine the feasibility of conducting a definitive trial to answer the question of clinical effectiveness and cost-effectiveness of these three treatment options. DESIGN: This was a prospective, randomised, open-blinded, evaluation feasibility trial with a single blind. Participants were allocated 1 : 1 : 1 to receive antipsychotic medication, psychological intervention or a combination of both. A thematic qualitative study explored the acceptability and feasibility of the trial. SETTING: Early intervention in psychosis services and child and adolescent mental health services in Manchester, Oxford, Lancashire, Sussex, Birmingham, Norfolk and Suffolk, and Northumberland, Tyne and Wear. PARTICIPANTS: People aged 14-18 years experiencing a first episode of psychosis either with an International Classification of Diseases, Tenth Revision, schizophrenia spectrum diagnosis or meeting the entry criteria for early intervention in psychosis who had not received antipsychotic medication or psychological intervention within the last 3 months. INTERVENTIONS: Psychological intervention involved up to 26 hours of cognitive-behavioural therapy and six family intervention sessions over 6 months, with up to four booster sessions. Antipsychotic medication was prescribed by the participant's psychiatrist in line with usual practice. Combined treatment was a combination of psychological intervention and antipsychotic medication. MAIN OUTCOME MEASURES: The primary outcome was feasibility (recruitment, treatment adherence and retention). We used a three-stage progression criterion to determine feasibility. Secondary outcomes were psychosis symptoms, recovery, anxiety and depression, social and educational/occupational functioning, drug and alcohol use, health economics, adverse/metabolic side effects and adverse/serious adverse events. RESULTS: We recruited 61 out of 90 (67.8%; amber zone) potential participants (psychological intervention, n = 18; antipsychotic medication, n = 22; combined treatment, n = 21). Retention to follow-up was 51 out of 61 participants (83.6%; green zone). In the psychological intervention arm and the combined treatment arm, 32 out of 39 (82.1%) participants received six or more sessions of cognitive-behavioural therapy (green zone). In the combined treatment arm and the antipsychotic medication arm, 28 out of 43 (65.1%) participants received antipsychotic medication for 6 consecutive weeks (amber zone). There were no serious adverse events related to the trial and one related adverse event. Overall, the number of completed secondary outcome measures, including health economics, was small. LIMITATIONS: Medication adherence was determined by clinician report, which can be biased. The response to secondary outcomes was low, including health economics. The small sample size obtained means that the study lacked statistical power and there will be considerable uncertainty regarding estimates of treatment effects. CONCLUSIONS: It is feasible to conduct a trial comparing psychological intervention with antipsychotic medication and a combination treatment in young people with psychosis with some adaptations to the design, including adaptations to collection of health economic data to determine cost-effectiveness. FUTURE WORK: An adequately powered definitive trial is required to provide robust evidence. TRIAL REGISTRATION: Current Controlled Trials ISRCTN80567433. 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. 4. See the NIHR Journals Library website for further project information.

Psychosis is a mental health problem that can involve hearing, seeing or believing things that others do not. Although many young people who experience psychosis recover well from their first episode of psychosis, others can have more serious, longer-lasting problems. There has not been a large amount of research into the treatment of psychosis in young people; therefore, it is important to test different treatments against each other in clinical trials. 'Feasibility' trials, such as the one we carried out [Managing Adolescent first-episode Psychosis: a feasibility Study (MAPS)], test whether or not it is possible to run larger trials. MAPS was a small trial that was run in seven locations in the UK. People who were aged 14­18 years and experiencing psychosis were able to take part. Each participant was randomly assigned to receive psychological treatment (cognitive­behavioural therapy and optional family therapy), antipsychotic medication or a combination of both. All of the participants met with a trial research assistant three times for assessments about well-being and symptoms. Some clinicians, participants and family members were interviewed about their opinions of the trial and treatments. The trial also had patient and public involvement; service user researchers were involved in design, interview data collection, analysis and report writing. Sixty-one young people took part in MAPS, which was around 68% of our target number. In total, 84% completed the assessments with research assistants. The results showed that, overall, all treatments were acceptable to young people and their family members. However, a higher percentage of young people actually received the 'minimum dose' of psychological treatment than the 'minimum dose' of antipsychotic medication (82% vs. 65%). Results showed that it was possible to run a larger trial such as this. However, some changes would be required to run a larger trial, such as location (focusing on urban areas with well established early intervention in psychosis teams), increasing involvement of psychiatrists and increasing the age limit for participation to 25 years.

Eye movement desensitization and reprocessing therapy for psychosis (EMDRp): Protocol of a feasibility randomized controlled trial with early intervention service users.

AIM: Traumatic events are involved in the development and maintenance of psychotic symptoms. There are few trials exploring trauma-focused treatments as interventions for psychotic symptoms, especially in individuals with early psychosis. This trial will evaluate the feasibility and acceptability of conducting a definitive trial of Eye Movement Desensitization and Reprocessing for psychosis (EMDRp) in people with early psychosis. METHODS: Sixty participants with first episode psychosis and a history of a traumatic/adverse life event(s)will be recruited from early intervention services in the North West of England and randomized to receive16 sessions of EMDRp + Treatment as Usual (TAU) or TAU alone. Participants will be assessed at baseline, 6 and 12 months post-randomization using several measures of psychotic symptoms, trauma symptoms, anxiety, depression, functioning, service-user defined recovery, health economics indicators and quality of life. Two nested qualitative studies to assess participant feedback of therapy and views of professional stakeholders on the implementation of EMDRp into services will also be conducted. The feasibility of a future definitive efficacy and cost-effectiveness evaluation of EMDRp will be tested against several outcomes, including ability to recruit and randomize participants, trial retention at 6- and 12-month follow-up assessments, treatment engagement and treatment fidelity. CONCLUSIONS: If it is feasible to deliver a multi-site trial of this intervention, it will be possible to evaluate whether EMDRp represents a beneficial treatment to augment existing evidence-based care of individuals with early psychosis supported by early intervention services.

Protocol for the economic evaluation of metacognitive therapy for cardiac rehabilitation participants with symptoms of anxiety and/or depression.

INTRODUCTION: Cardiac rehabilitation (CR) is offered to reduce the risk of further cardiac events and to improve patients' health and quality of life following a cardiac event. Psychological care is a common component of CR as symptoms of depression and/or anxiety are more prevalent in this population, however evidence for the cost-effectiveness of current interventions is limited. Metacognitive therapy (MCT), is a recent treatment development that is effective in treating anxiety and depression in mental health settings and is being evaluated in CR patients. This protocol describes the planned approach to the economic evaluation of MCT for CR patients. METHODS AND ANALYSIS: The economic evaluation work will consist of a within-trial analysis and an economic model. The PATHWAY Group MCT study has been prospectively designed to collect comprehensive self-reported resource use and health outcome data, including the EQ-5D, within a randomised controlled trial study design (UK Clinical Trials Gateway). A within-trial economic evaluation and economic model will compare the cost-effectiveness of MCT plus usual care (UC) to UC, from a health and social care perspective in the UK. The within-trial analysis will use intention-to-treat and estimate total costs and quality-adjusted life-years (QALYs) for the trial follow-up. Single imputation will be used to impute missing baseline variables. Multiple imputation will be used to impute values missing at follow-up. Items of resource use will be multiplied by published national healthcare costs. Regression analysis will be used to estimate net costs and net QALYs and these estimates will be bootstrapped to generate 10 000 net pairs of costs and QALYs to inform the probability of cost-effectiveness. A decision analytical economic model will be developed to synthesise trial data with the published literature over a longer time frame. Sensitivity analysis will explore uncertainty. Guidance of the methods for economic models will be followed and dissemination will adhere to reporting guidelines. ETHICS AND DISSEMINATION: The economic evaluation includes a within-trial analysis. The trial which included the collection of this data was reviewed and approved by Ethics. Ethics approval was obtained by the Preston Research Ethics Committee (project ID 156862). The modelling analysis is not applicable for Ethics as it will use data from the trial (secondary analysis) and the published literature. Results of the main trial and economic evaluation will be published in the peer-reviewed National Institute for Health Research (NIHR) journals library (Programme Grants for Applied Research), submitted to a peer-reviewed journal and presented at appropriate conferences. TRIAL REGISTRATION NUMBER: ISRCTN74643496; Pre-results.

Health State Values of Deaf British Sign Language (BSL) Users in the UK: An Application of the BSL Version of the EQ-5D-5L.

BACKGROUND: Deaf people experience health inequalities compared to hearing populations. The EQ-5D, a widely used, standardised, generic measure of health status, which is available in over 100 languages, was recently translated into British Sign Language (BSL) and initial validation conducted. Using data from this previous study of the EQ-5D-5L BSL we aimed to assess (1) whether responses to the EQ-5D differed between a sample of Deaf BSL users and the general population (2) whether socio-demographic characteristics and clinical measures were associated with EQ-5D index scores in Deaf BSL users and (3) the impact of psychological distress and depression on health status in Deaf BSL users. METHODS: Published population tariffs were applied to the EQ-5D-5L BSL, using the crosswalk methodology, to estimate health state values. Descriptive statistics (mean, SD, 95% CIs) compared Deaf BSL signer participants' (n = 92) responses to data from the general population. Descriptive statistics and linear regression analyses were used to identify associations between Deaf participants' EQ-5D index scores, socio-demographic characteristics, physical health and depression. Descriptive statistics compared the BSL index scores for people with psychological distress/depression to those from two cross-sectional, population-based surveys. RESULTS: Using the EQ-5D, Deaf participants had lower mean health-state values (0.78; 95% CI 0.72-0.83; n = 89) than people participating in the 2017 Health Survey for England (0.84; 95% CI 0.83-0.84; n = 7169). Unlike larger studies, such as the Health Survey for England sample, there was insufficient evidence to assess whether Deaf participants' EQ-5D health state values were associated with their demographic characteristics. Nevertheless, analysis of the BSL study data indicated long-standing physical illness was associated with lower health-state values (ordinary least squares coefficient = - 0.354; 95% CI - 0.484, - 0.224; p < 0.01; n = 82). Forty-three percent of our Deaf participants had depression. Participants with depression had reduced health status (0.67; 95% CI 0.58-0.77; n = 36) compared to those with no psychological distress or depression (0.87; 95% CI 0.61-0.67; n = 36). CONCLUSIONS: The study highlights reduced health in the Deaf signing population, compared to the general population. Public health initiatives focused on BSL users, aiming to increase physical and mental health, are needed to address this gap.

Cost-Effectiveness Evaluations of Psychological Therapies for Schizophrenia and Bipolar Disorder: A Systematic Review.

OBJECTIVES: This review aims to assess the cost-effectiveness of psychological interventions for schizophrenia/bipolar disorder (BD), to determine the robustness of current evidence and identify gaps in the available evidence. METHODS: Electronic searches (PsycINFO, MEDLINE, Embase) identified economic evaluations relating incremental cost to outcomes in the form of an incremental cost-effectiveness ratio published in English since 2000. Searches were concluded in November 2018. Inclusion criteria were: adults with schizophrenia/BD; any psychological/psychosocial intervention (e.g., psychological therapy and integrated/collaborative care); probability of cost-effectiveness at explicitly defined thresholds reported. Comparators could be routine practice, no intervention, or alternative psychological therapies. Screening, data extraction, and critical appraisal were performed using pre-specified criteria and forms. Results were summarized qualitatively. The protocol was registered on the PROSPERO database (CRD42017056579). RESULTS: Of 3,864 studies identified, 12 met the criteria for data extraction. All were integrated clinical and economic randomized controlled trials. The most common intervention was cognitive behavioral therapy (CBT, 6/12 studies). The most common measure of health benefit was the quality-adjusted life-year (6/12). Follow-up ranged from 6 months to 5 years. Interventions were found to be cost-effective in most studies (9/12): the probability of cost-effectiveness ranged from 35-99.5 percent. All studies had limitations and demonstrated uncertainty (particularly related to incremental costs). CONCLUSIONS: Most studies concluded psychological interventions for schizophrenia/BD are cost-effective, including CBT, although there was notable uncertainty. Heterogeneity across studies makes it difficult to reach strong conclusions. There is a particular need for more evidence in the population with BD and for longer-term evidence across both populations.

Cognitive-behavioural therapy for clozapine-resistant schizophrenia: the FOCUS RCT.

BACKGROUND: Clozapine (clozaril, Mylan Products Ltd) is a first-choice treatment for people with schizophrenia who have a poor response to standard antipsychotic medication. However, a significant number of patients who trial clozapine have an inadequate response and experience persistent symptoms, called clozapine-resistant schizophrenia (CRS). There is little evidence regarding the clinical effectiveness of pharmacological or psychological interventions for this population. OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of cognitive-behavioural therapy (CBT) for people with CRS and to identify factors predicting outcome. DESIGN: The Focusing on Clozapine Unresponsive Symptoms (FOCUS) trial was a parallel-group, randomised, outcome-blinded evaluation trial. Randomisation was undertaken using permuted blocks of random size via a web-based platform. Data were analysed on an intention-to-treat (ITT) basis, using random-effects regression adjusted for site, age, sex and baseline symptoms. Cost-effectiveness analyses were carried out to determine whether or not CBT was associated with a greater number of quality-adjusted life-years (QALYs) and higher costs than treatment as usual (TAU). SETTING: Secondary care mental health services in five cities in the UK. PARTICIPANTS: People with CRS aged ≥ 16 years, with an International Classification of Diseases, Tenth Revision (ICD-10) schizophrenia spectrum diagnoses and who are experiencing psychotic symptoms. INTERVENTIONS: Individual CBT included up to 30 hours of therapy delivered over 9 months. The comparator was TAU, which included care co-ordination from secondary care mental health services. MAIN OUTCOME MEASURES: The primary outcome was the Positive and Negative Syndrome Scale (PANSS) total score at 21 months and the primary secondary outcome was PANSS total score at the end of treatment (9 months post randomisation). The health benefit measure for the economic evaluation was the QALY, estimated from the EuroQol-5 Dimensions, five-level version (EQ-5D-5L), health status measure. Service use was measured to estimate costs. RESULTS: Participants were allocated to CBT (n = 242) or TAU (n = 245). There was no significant difference between groups on the prespecified primary outcome [PANSS total score at 21 months was 0.89 points lower in the CBT arm than in the TAU arm, 95% confidence interval (CI) -3.32 to 1.55 points; p = 0.475], although PANSS total score at the end of treatment (9 months) was significantly lower in the CBT arm (-2.40 points, 95% CI -4.79 to -0.02 points; p = 0.049). CBT was associated with a net cost of £5378 (95% CI -£13,010 to £23,766) and a net QALY gain of 0.052 (95% CI 0.003 to 0.103 QALYs) compared with TAU. The cost-effectiveness acceptability analysis indicated a low likelihood that CBT was cost-effective, in the primary and sensitivity analyses (probability < 50%). In the CBT arm, 107 participants reported at least one adverse event (AE), whereas 104 participants in the TAU arm reported at least one AE (odds ratio 1.09, 95% CI 0.81 to 1.46; p = 0.58). CONCLUSIONS: Cognitive-behavioural therapy for CRS was not superior to TAU on the primary outcome of total PANSS symptoms at 21 months, but was superior on total PANSS symptoms at 9 months (end of treatment). CBT was not found to be cost-effective in comparison with TAU. There was no suggestion that the addition of CBT to TAU caused adverse effects. Future work could investigate whether or not specific therapeutic techniques of CBT have value for some CRS individuals, how to identify those who may benefit and how to ensure that effects on symptoms can be sustained. TRIAL REGISTRATION: Current Controlled Trials ISRCTN99672552. 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. 23, No. 7. See the NIHR Journals Library website for further project information.

Feasibility and acceptability of suicide prevention therapy on acute psychiatric wards: randomised controlled trial.

BACKGROUND: Suicidal behaviour is common in acute psychiatric wards resulting in distress, and burden for patients, carers and society. Although psychological therapies for suicidal behaviour are effective in out-patient settings, there is little research on their effectiveness for in-patients who are suicidal.AimsOur primary objective was to determine whether cognitive-behavioural suicide prevention therapy (CBSP) was feasible and acceptable, compared with treatment as usual (TAU) for in-patients who are suicidal. Secondary aims were to assess the impact of CBSP on suicidal thinking, behaviours, functioning, quality of life, service use, cost-effectiveness and psychological factors associated with suicide. METHOD: A single-blind pilot randomised controlled trial comparing TAU to TAU plus CBSP in in-patients in acute psychiatric wards who are suicidal (the Inpatient Suicide Intervention and Therapy Evaluation (INSITE) trial, trial registration: ISRCTN17890126). The intervention consisted of TAU plus up to 20 CBSP sessions, over 6 months continuing in the community following discharge. Participants were assessed at baseline and at 6 weeks and 6 months post-baseline. RESULTS: A total of 51 individuals were randomised (27 to TAU, 24 to TAU plus CBSP) of whom 37 were followed up at 6 months (19 in TAU, 18 in TAU plus CBSP). Engagement, attendance, safety and user feedback indicated that the addition of CBSP to TAU for in-patients who are acutely suicidal was feasible and acceptable while on in-patient wards and following discharge. Economic analysis suggests the intervention could be cost-effective.DiscussionPsychological therapy can be delivered safely to patients who are suicidal although modifications are required for this setting. Findings indicate a larger, definitive trial should be conducted.Declaration of interestThe trial was hosted by Greater Manchester Mental health NHS Trust (formerly, Manchester Mental Health and Social Care NHS Trust). The authors are affiliated to the University of Manchester, Greater Manchester Mental Health Foundation Trust, Lancashire Care NHS Foundation trust and the Manchester Academic Health Sciences Centre. Y.A. is a trustee for a North-West England branch of the charity Mind.

Risk assessment scales to predict risk of hospital treated repeat self-harm: A cost-effectiveness modelling analysis.

BACKGROUND: Risk scales are used widely for assessing individuals presenting to Emergency Departments (EDs) following self-harm. There is growing evidence that risk scales have limited clinical utility in identifying episodes at highest risk of repeat self-harm. However, their cost-effectiveness in terms of treatment allocation and subsequent repeat self-harm is unknown. We aimed to examine the cost-effectiveness of five risk scales (SAD PERSONS Scale, Modified SAD PERSONS Scale, ReACT Self-Harm Rule, Manchester Self-Harm Rule, Barratt Impulsivity Scale) and single item clinician and patient ratings of risk. METHOD: Quality-Adjusted Life Years were estimated for each episode. The five risk scales and the patient rating were compared to the clinician rating. Incremental cost-effectiveness ratios (ICERs) were estimated for each scale, using a range of ICER thresholds. Sensitivity analysis explored different model assumptions. RESULTS: The formal scales were less cost-effective than the clinician and patient ratings across a range of ICER thresholds (£0-£30,000). The five scales were also less cost-effective than the clinician rating in most alternative scenario analyses. However, the clinician rating would be likely to result in unnecessary treatment costs for over half of patients identified as high risk. LIMITATIONS: Our primary model depended on the assumption that high-intensity care reduced patients' risk of further self-harm. CONCLUSION: The use of formal assessment tools for managing self-harm presentations to EDs did not appear to be cost-effective. While the judgement of a mental health clinician was found to be slightly more cost-effective, it still resulted in incorrect allocation of costs and missed treatment opportunities.

Carer preferences for home support services in later stage dementia.

OBJECTIVES: To examine the relative importance of different home support attributes from the perspective of carers of people with later-stage dementia. METHOD: Preferences from 100 carers, recruited through carers' organisations, were assessed with a Discrete Choice Experiment (DCE) survey, administered online and by paper questionnaire. Attributes were informed by an evidence synthesis and lay consultations. A conditional logit model was used to estimate preference weights for the attributes within a home support 'package'. RESULTS: The most preferred attributes were 'respite care, available regularly to fit your needs' (coefficient 1.29, p = < 0.001) and 'home care provided regularly for as long as needed' (coefficient 0.93, p = < 0.001). Cost had a significant effect with lower cost packages preferred. Findings were similar regardless of the method of administration, with respite care considered to be the most important attribute for all carers. Carers reported that completing the DCE had been a positive experience; however, feedback was mixed overall. CONCLUSIONS: These carer preferences concur with emerging evidence on home support interventions for dementia. Respite care, home care and training on managing difficulties provided at home are important components. Carers' preferences revealed the daily challenges of caring for individuals with later stage dementia and the need for tailored and specialised home support.