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.

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.

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.

Hospital admissions and place of death of residents of care homes receiving specialist healthcare services: Protocol for a systematic review.

AIM: To synthesize the evidence relating to the ability of specialist care home support services to prevent the hospital admission of older care home residents, including hospital admission at the end-of-life. DESIGN: Systematic review and narrative synthesis. METHODS: Ten electronic databases will be searched from 2010 - 31 December 2018 using predetermined search terms. All studies of specialist healthcare services to meet care home residents' physical healthcare needs which provide outcome data on hospital admission or place of death compared with usual care will be included. Two reviewers will independently assess studies' eligibility and methodological quality using the Effective Public Health Practice Project Quality Assessment Tool. Data will be extracted by one reviewer and checked by a second according to predetermined categories. Data will be synthesized in evidence tables and narrative. Funder: National Institute for Health Research School for Social Care Research, November 2016. DISCUSSION: Care of older people in care home settings is a key aspect of nursing nationally and internationally. This review will increase understanding of the extent to which different models of specialist healthcare support for care homes are associated with key resident outcomes. IMPACT: Standard healthcare support for care home residents is often inadequate, resulting in avoidable hospital admissions and lack of resident choice as to place of death. Although a range of specialist healthcare services are emerging, little is known about their relative effectiveness. This paper marshalls evidence of relevance to commissioners investing in healthcare provision to care homes to meet NHS targets.

Cost-effectiveness of cardiac rehabilitation: a systematic review.

Patients may be offered cardiac rehabilitation (CR), a supervised programme often including exercises, education and psychological care, following a cardiac event, with the aim of reducing morbidity and mortality. Cost-constrained healthcare systems require information about the best use of budget and resources to maximise patient benefit. We aimed to systematically review and critically appraise economic studies of CR and its components. In January 2016, validated electronic searches of the National Health Service Economic Evaluation Database (NHS EED), Health Technology Assessment, PsycINFO, MEDLINE and Embase databases were run to identify full economic evaluations published since 2001. Two levels of screening were used and explicit inclusion criteria were applied. Prespecified data extraction and critical appraisal were performed using the NHS EED handbook and Drummond checklist. The majority of studies concluded that CR was cost-effective versus no CR (incremental cost-effectiveness ratios (ICERs) ranged from $1065 to $71 755 per quality-adjusted life-year (QALY)). Evidence for specific interventions within CR was varied; psychological intervention ranged from dominant (cost saving and more effective) to $226 128 per QALY, telehealth ranged from dominant to $588 734 per QALY and while exercise was cost-effective across all relevant studies, results were subject to uncertainty. Key drivers of cost-effectiveness were risk of subsequent events and hospitalisation, hospitalisation and intervention costs, and utilities. This systematic review of studies evaluates the cost-effectiveness of CR in the modern era, providing a fresh evidence base for policy-makers. Evidence suggests that CR is cost-effective, especially with exercise as a component. However, research is needed to determine the most cost-effective design of CR.

An external pilot study to test the feasibility of a randomised controlled trial comparing eye muscle surgery against active monitoring for childhood intermittent exotropia [X(T)].

INTRODUCTION: The evidence base for the treatment of strabismus (squint) is poor. Our main aim is to improve this evidence base for the treatment of a common type of childhood squint {intermittent exotropia, [X(T)]}. We conducted an external pilot study in order to inform the design and conduct of a future full randomised controlled trial (RCT). METHODS: Children of between 6 months and 16 years with a recent diagnosis of X(T) were eligible for recruitment. Participants were recruited from secondary care at the ophthalmology departments at four UK NHS foundation trusts. Participants were randomised to either active monitoring or surgery. This report describes the findings of the Pilot Rehearsal Trial and Qualitative Study, and assesses the success against the objectives proposed. RECRUITMENT AND RETENTION: The experience gained during the Pilot Rehearsal Trial demonstrates the ability to recruit and retain sites that are willing to randomise children to both trial arms, and for parents to agree to randomisation of their children to such a study. One child declined the group allocation. A total of 231 children were screened (expected 240), of whom 138 (60%) were eligible (expected 228: 95%) and 49 (35% of eligible) children were recruited (expected 144: 63% of eligible). Strategies that improved recruitment over the course of the trial are discussed, together with the reasons why fewer children were eligible for recruitment than initially anticipated. Attrition was low. Outcome data were obtained for 47 of 49 randomised children. TRIAL PROCESSES AND DATA COLLECTION: The Trial Management processes proved effective. There were high levels of completion on all of the data collection forms. However, the feedback from the treatment orthoptists revealed that some modifications should be made to the length and frequency of the health service assessment and travel assessment questionnaires, thus reducing the burden on participants in the main trial. Modifications to the wording of the questions also need to be made. MONITORING OF BIAS: Children who recruited to the trial were older and had more severe strabismus than those children eligible but declining participation. Strategies to account for this in a full trial are proposed. REASONS FOR PARTICIPATION OR DECLINING STUDY: These were identified using qualitative interviews. The principal reasons for declining entry into the study were strong preferences for and against surgical treatment. HARMS: There were no serious unexpected adverse events. Two children had overcorrection of their X(T) with reduction in binocular vision following surgery, which is in line with previous studies. No children in the active monitoring arm developed a constant strabismus although two showed some reduction in control. CONCLUSIONS: The SamExo study has demonstrated that it is possible to recruit and retain participants to a randomised trial of surgery compared with active monitoring for X(T). For longer-term full RCTs, in order to maximise the generalisability of future studies, consideration needs to be given to planning more time and clinic appointments to assess eligibility and to allow consideration of participation; the greater use of research nurses for recruitment; and accommodating the strong preferences of some parents both for and against surgical intervention. TRIAL REGISTRATION: Current Controlled Trials ISRCTN44114892. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 39. See the NIHR Journals Library website for further project information.

From plans to actions in patient and public involvement: qualitative study of documented plans and the accounts of researchers and patients sampled from a cohort of clinical trials.

UNLABELLED: : Patient and public involvement (PPI) in research is increasingly required, although evidence to inform its implementation is limited. OBJECTIVE: Inform the evidence base by describing how plans for PPI were implemented within clinical trials and identifying the challenges and lessons learnt by research teams. METHODS: We compared PPI plans extracted from clinical trial grant applications (funded by the National Institute for Health Research Health Technology Assessment Programme between 2006 and 2010) with researchers' and PPI contributors' interview accounts of PPI implementation. Analysis of PPI plans and transcribed qualitative interviews drew on the Framework technique. RESULTS: Of 28 trials, 25 documented plans for PPI in funding applications and half described implementing PPI before applying for funding. Plans varied from minimal to extensive, although almost all anticipated multiple modes of PPI. Interview accounts indicated that PPI plans had been fully implemented in 20/25 trials and even expanded in some. Nevertheless, some researchers described PPI within their trials as tokenistic. Researchers and contributors noted that late or minimal PPI engagement diminished its value. Both groups perceived uncertainty about roles in relation to PPI, and noted contributors' lack of confidence and difficulties attending meetings. PPI contributors experienced problems in interacting with researchers and understanding technical language. Researchers reported difficulties finding 'the right' PPI contributors, and advised caution when involving investigators' current patients. CONCLUSIONS: Engaging PPI contributors early and ensuring ongoing clarity about their activities, roles and goals, is crucial to PPI's success. Funders, reviewers and regulators should recognise the value of preapplication PPI and allocate further resources to it. They should also consider whether PPI plans in grant applications match a trial's distinct needs. Monitoring and reporting PPI before, during and after trials will help the research community to optimise PPI, although the need for ongoing flexibility in implementing PPI should also be recognised.