Overview and Use of Tools for Selecting Modelling Techniques in Health Economic Studies.

The availability and use of tools to guide the choice of modelling technique are not well understood. Our study aims to review existing tools and explore the use of those tools in health economic models. Two reviews and one case study were conducted. Review 1 aimed to identify tools based on expert opinion and citation searching and explore the value of the tools for health economic models. Review 2, based on citation searching, aimed to describe how those tools have been used in health economic models. Both reviews were conducted using Web of Science and Scopus. Two independent reviewers selected studies for inclusion. A case study, focused on economic evaluations of antipsychotic medication in schizophrenia, was conducted to compare the modelling techniques used by existing models with modelling techniques recommended by identified tools. Seven tools were identified, of which the revised Brennan's toolkit, was assessed to be the most appropriate for health economic models. The seven tools were cited 126 times in publications reporting health economic models. Only 17 of these (13.5%) reported that they used the tool(s) to guide the choice of modelling technique. Application of these tools suggested discrete event simulation is most appropriate for modelling antipsychotic medication in schizophrenia, but discrete event simulation was only used by 17% of existing models. There is considerable inconsistency between the modelling techniques used by existing models and modelling techniques recommended by tools. It is recommended that for future modelling studies the choice of modelling technique should be justified, this can be achieved by the application of model selection tools, such as the revised Brennan's toolkit. Future research is required to explore the barriers to using model selection tools in health economic models and to update existing tools and make them easier to use.

Systematic review of the methods of health economic models assessing antipsychotic medication for schizophrenia.

BACKGROUND: Numerous economic models have assessed the cost-effectiveness of antipsychotic medications in schizophrenia. It is important to understand what key impacts of antipsychotic medications were considered in the existing models and limitations of existing models in order to inform the development of future models. OBJECTIVES: This systematic review aims to identify which clinical benefits, clinical harms, costs and cost savings of antipsychotic medication have been considered by existing models, to assess quality of existing models and to suggest good practice recommendations for future economic models of antipsychotic medications. METHODS: An electronic search was performed on multiple databases (MEDLINE, EMBASE, PsycInfo, Cochrane database of systematic reviews, The NHS Economic Evaluation Database and Health Technology Assessment database) to identify economic models of schizophrenia published between 2005-2020. Two independent reviewers selected studies for inclusion. Study quality was assessed using the National Institute for Health and Care Excellence (NICE) checklist and the Cooper hierarchy. Key impacts of antipsychotic medications considered by exiting models were descriptively summarised. RESULTS: Sixty models were included. Existing models varied greatly in key impacts of antipsychotic medication included in the model, especially in clinical outcomes used for assessing reduction in psychotic symptoms and types of adverse events considered in the model. Quality of existing models was generally low due to failure to capture the health and cost impact of adverse events of antipsychotic medications and input data not obtained from best available source. Good practices for modelling antipsychotic medications are suggested. DISCUSSIONS: This review highlights inconsistency in key impacts considered by different models, and limitations of the existing models. Recommendations on future research are provided.

A Systematic Review of Economic Models Across the Entire Schizophrenia Pathway.

BACKGROUND: Schizophrenia is associated with a high economic burden. Economic models can help to inform resource allocation decisions to maximise benefits to patients. OBJECTIVES: This systematic review aims to assess the availability, quality and consistency of conclusions of health economic models evaluating the cost effectiveness of interventions for schizophrenia. METHODS: An electronic search was performed on multiple databases (MEDLINE, EMBASE, PsycINFO, Cochrane database of systematic reviews, NHS Economic Evaluation Database and Health Technology Assessment database) to identify economic models of interventions for schizophrenia published between 2005 and 2020. Two independent reviewers selected studies for inclusion. Study quality was assessed using the National Institute for Health and Care Excellence (NICE) checklist and the Cooper hierarchy. Model characteristics and conclusions were descriptively summarised. RESULTS: Seventy-three models met inclusion criteria. Seventy-eight percent of existing models assessed antipsychotics; however, due to inconsistent conclusions reported by different studies, no antipsychotic can be considered clearly cost effective compared with the others. A very limited number of models suggest that the following non-pharmacological interventions might be cost effective: psychosocial interventions, stratified tests, employment intervention and intensive intervention to improve liaison between primary and secondary care. The quality of included models is generally low due to use of a short time horizon, omission of adverse events of interventions, poor data quality and potential conflicts of interest. CONCLUSIONS: This review highlights a lack of models for non-pharmacological interventions, and limitations of the existing models, including low quality and inconsistency in conclusions. Recommendations on future modelling approaches for schizophrenia are provided.

Coping with Unusual ExperienceS for 12-18 year olds (CUES+): a transdiagnostic randomised controlled trial of the effectiveness of cognitive therapy in reducing distress associated with unusual experiences in adolescent mental health services: study protocol for a randomised controlled trial.

BACKGROUND: Childhood 'unusual experiences' (such as hearing voices that others cannot, or suspicions of being followed) are common, but can become more distressing during adolescence, especially for young people in contact with Child and Adolescent Mental Health Services (CAMHS). Unusual experiences that are distressing or have adverse life impact (UEDs) are associated with a range of current and future emotional, behavioural and mental health difficulties. Recommendations for psychological intervention are based on evidence from adult studies, with some support from small, pilot, child-specific evaluations. Research is needed to ensure that the recommendations suit children as well as adults. The CUES+ study (Coping with Unusual ExperienceS for 12-18 year olds) aims to find out whether cognitive behaviour therapy for UEDs (CBT-UED) is a helpful and cost-effective addition to usual community care for 12-18 year olds presenting to United Kingdom National Health Service Child and Adolescent Mental Health Services in four London boroughs. METHODS: The CUES+ study is a randomised controlled trial comparing CBT-UED plus routine care to routine care alone. CBT-UED comprises up to 16 sessions, including up to 12 individual and up to four family support meetings, each lasting around 45-60 min, delivered weekly. The primary outcome is emotional distress. Secondary outcomes are change in UEDs, risk events (self-harm, attendance at emergency services, other adverse events) and health economic outcomes. Participants will be randomised in a 1:1 ratio after baseline assessment. Randomisation will be stratified by borough and by severity of mental health presentation: 'severe' (an identified psychotic or bipolar disorder) or any 'other' condition. Outcomes will be assessed by a trained assessor blind to treatment condition at 0, 16 and 24 weeks. Recruitment began in February, 2015 and is ongoing until the end of March, 2017. DISCUSSION: The CUES+ study will contribute to the currently limited child-specific evidence base for psychological interventions for UEDs occurring in the context of psychosis or any other mental health presentation. TRIAL REGISTRATION: International Standard Randomised Controlled Trials, ID: ISRCTN21802136 . Prospectively registered on 12 January 2015. Protocol V3 31 August 2015 with screening amended.

A Single, One-Off Measure of Depression and Anxiety Predicts Future Symptoms, Higher Healthcare Costs, and Lower Quality of Life in Coronary Heart Disease Patients: Analysis from a Multi-Wave, Primary Care Cohort Study.

OBJECTIVE: To determine whether a one-off, baseline measure of depression and anxiety in a primary care, coronary heart disease (CHD) population predicts ongoing symptoms, costs, and quality of life across a 3-year follow-up. DESIGN: Longitudinal cohort study. SETTING: 16 General Practice surgeries across South-East London. PARTICIPANTS: 803 adults (70% male, mean age 71 years) contributing up to 7 follow-up points. MAIN OUTCOME MEASURES: Ongoing reporting of symptoms, health care costs, and quality of life. RESULTS: At baseline, 27% of the sample screened positive for symptoms of depression and anxiety, as measured by the Hospital Anxiety and Depression Scale (HADS). The probability of scoring above the cut-off throughout the follow-up was 71.5% (p<0.001) for those screening positive at baseline, and for those screening negative, the probability of scoring below the cut-off throughout the follow-up was 97.6% (p<0.001). Total health care costs were 39% higher during follow-up for those screening positive (p<0.05). Quality of life as measured by the SF-12 was lower on the mental component during follow-up for those screening positive (-0.75, CI -1.53 to 0.03, p = 0.059), and significantly lower on the physical component (-4.99, CI -6.23 to -.376, p<0.001). CONCLUSIONS: A one-off measure for depression and anxiety symptoms in CHD predicts future symptoms, costs, and quality of life over the subsequent three-years. These findings suggest symptoms of depression and anxiety in CHD persist throughout long periods and are detrimental to a patient's quality of life, whilst incurring higher health care costs for primary and secondary care services. Screening for these symptoms at the primary care level is important to identify and manage patients at risk of the negative effects of this comorbidity. Implementation of screening, and possible collaborative care strategies and interventions that help mitigate this risk should be the ongoing focus of researchers and policy-makers.

Economic burden of multimorbidity among older adults: impact on healthcare and societal costs.

BACKGROUND: Multimorbidity is not uncommon and the associated impact it places on healthcare utilisation and societal costs is of increased concern. The aim of the current study was to estimate the economic burden of multimorbidity among older adults in Singapore by investigating its association with the healthcare and societal resource use and cost. METHODS: The Well-being of the Singapore Elderly (WiSE) study was a single phase, cross sectional survey among a nationally representative sample of Singapore residents (N = 2565) aged 60 years and above. Multimorbidity was defined in this study as having two or more chronic conditions, from a list of 10 conditions. Care was classified into healthcare which included direct medical care, intermediate and long-term care, indirect care, and social care, provided by paid caregivers and family members or friends. Costs were calculated from the societal perspective, including healthcare and social care costs, by multiplying each service unit with the relevant unit cost. Generalized linear models were used to investigate the relationship between total annual costs and various socio-demographic factors. RESULTS: The prevalence of multimorbidity was 51.5 %. Multimorbid respondents utilised more healthcare and social care resources than those with one or no chronic conditions. The total societal cost of multimorbidity equated to SGD$15,148 per person, annually, while for those with one or no chronic conditions the total annual societal costs per person were SGD$5,610 and SGD$2,806, respectively. Each additional chronic condition was associated with increased healthcare (SGD$2,265) and social care costs (SGD$3,177). Older age (i.e. 75-84 years old, and especially over 85 years), Indian ethnicity and being retired were significantly associated with higher total costs from the societal perspective, while older age (75 years and above) and 'Other' ethnicity were significantly associated with higher total healthcare costs. CONCLUSION: Multimorbidity was associated with substantially higher healthcare utilisation and social care costs among older adults in Singapore. With the prevalence of multimorbidity increasing, especially as the population ages, we need healthcare systems that are evolving to address the emerging challenges associated with multimorbidity and the respective healthcare and societal costs.

The Societal Cost of Dementia in Singapore: Results from the WiSE Study.

BACKGROUND: There is currently limited evidence on the economic burden that dementia exerts on multi-ethnic Asian populations. OBJECTIVE: The present study aimed to estimate the economic cost of dementia in Singapore. METHODS: We used data from the Well-being of the Singapore Elderly study, a nationally representative survey of the older Singapore Resident population aged 60 years and above. Generalized linear modeling was used to estimate factors associated with costs. RESULTS: The total cost of dementia in 2013 was estimated at S$532 million (95% CI, S$361 million to S$701 million) while the annual cost per person was estimated at S$10,245 per year (95% CI, S$6,954 to S$12,495). Apart from dementia, higher total societal cost were also significantly associated with older age, Indian ethnicity, and those who were diagnosed with heart problems, stroke, diabetes or depression, whereas being divorced/separated, lower education, and those who were diagnosed with hypertension were significantly associated with lower total societal cost. CONCLUSION: The study provides a rich body of information on healthcare utilization and cost of dementia, which is essential for future planning of services for the elderly population.

The UPBEAT nurse-delivered personalized care intervention for people with coronary heart disease who report current chest pain and depression: a randomised controlled pilot study.

BACKGROUND: Depression is common in people with coronary heart disease (CHD) and associated with worse outcome. This study explored the acceptability and feasibility of procedures for a trial and for an intervention, including its potential costs, to inform a definitive randomized controlled trial (RCT) of a nurse-led personalised care intervention for primary care CHD patients with current chest pain and probable depression. METHODS: Multi-centre, outcome assessor-blinded, randomized parallel group study. CHD patients reporting chest pain and scoring 8 or more on the HADS were randomized to personalized care (PC) or treatment as usual (TAU) for 6 months and followed for 1 year. Primary outcome was acceptability and feasibility of procedures; secondary outcomes included mood, chest pain, functional status, well being and psychological process variables. RESULT: 1001 people from 17 General Practice CHD registers in South London consented to be contacted; out of 126 who were potentially eligible, 81 (35% female, mean age = 65 SD11 years) were randomized. PC participants (n = 41) identified wide ranging problems to work on with nurse-case managers. Good acceptability and feasibility was indicated by low attrition (9%), high engagement and minimal nurse time used (mean/SD = 78/19 mins assessment, 125/91 mins telephone follow up). Both groups improved on all outcomes. The largest between group difference was in the proportion no longer reporting chest pain (PC 37% vs TAU 18%; mixed effects model OR 2.21 95% CI 0.69, 7.03). Some evidence was seen that self efficacy (mean scale increase of 2.5 vs 0.9) and illness perceptions (mean scale increase of 7.8 vs 2.5) had improved in PC vs TAU participants at 1 year. PC appeared to be more cost effective up to a QALY threshold of approximately £3,000. CONCLUSIONS: Trial and intervention procedures appeared to be feasible and acceptable. PC allowed patients to work on unaddressed problems and appears cheaper than TAU. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN21615909.

The cost effectiveness of long-acting/extended-release antipsychotics for the treatment of schizophrenia: a systematic review of economic evaluations.

BACKGROUND: Antipsychotic medication is the mainstay of treatment in schizophrenia. Long-acting medication has potential advantages over daily medication in improving compliance and thus reducing hospitalization and relapse rates. The high acquisition and administration costs of such formulations raise the need for pharmacoeconomic evaluation. OBJECTIVE: The aim of this article is to provide a comprehensive review of the available evidence on the cost effectiveness of long-acting/extended-release antipsychotic medication and critically appraise the strength of evidence reported in the studies from a methodological viewpoint. METHODS: Relevant studies were identified by searching five electronic databases: PsycINFO, MEDLINE, EMBASE, the NHS Economic Evaluation Database and the Health Technology Assessment database (HTA). Search terms included, but were not limited to, 'long-acting injection', 'economic evaluation', 'cost-effectiveness' and 'cost-utility'. No limits were applied for publication dates and language. Full economic evaluations on long-acting/extended-release antipsychotics were eligible for inclusion. Observational studies and clinical trials were also checked for cost-effectiveness information. Conference abstracts and poster presentations on the cost effectiveness of long-acting antipsychotics were excluded. Thirty-two percent of identified studies met the selection criteria. Pertinent abstracts were reviewed independently by two reviewers. Relevant studies underwent data extraction by one reviewer and were checked by a second, with any discrepancies being clarified during consensus meetings. Eligible studies were assessed for methodological quality using the quality checklist for economic studies recommended by the NICE guideline on interventions in the treatment and management of schizophrenia. RESULTS: After applying the selection criteria, the final sample consisted of 28 studies. The majority of studies demonstrated that risperidone long-acting injection, relative to oral or other long-acting injectable drugs, was associated with cost savings and additional clinical benefits and was the dominant strategy in terms of cost effectiveness. However, olanzapine in either oral or long-acting injectable formulation dominated risperidone long-acting injection in a Slovenian and a US study. Furthermore, in two UK studies, the use of long-acting risperidone increased the hospitalization days and overall healthcare costs, relative to other atypical or typical long-acting antipsychotics. Finally, paliperidone extended-release was the most cost-effective treatment compared with atypical oral or typical long-acting formulations. From a methodological viewpoint, most studies employed decision analytic models, presented results using average cost-effectiveness ratios and conducted comprehensive sensitivity analyses to test the robustness of the results. LIMITATIONS: Variations in study methodologies restrict consistent and direct comparisons across countries. The exclusion of a large body of potentially relevant conference abstracts as well as some papers being unobtainable may have increased the likelihood of misrepresenting the overall cost effectiveness of long-acting antipsychotics. Finally, the review process was restricted to qualitative assessment rather than a quantitative synthesis of results, which could provide more robust conclusions. CONCLUSIONS: Atypical long-acting (especially risperidone)/extended-release antipsychotic medication is likely to be a cost-effective, first-line strategy for managing schizophrenia, compared with long-acting haloperidol and other oral or depot formulations, irrespective of country-specific differences. However, inconsistencies in study methodologies and in the reporting of study findings suggest caution needs to be applied in interpreting these findings.