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We lead multidisciplinary applied research and training to rethink the way health care is delivered in general practice and across the community.
Real world hospital costs following stress echocardiography in the UK: a costing study from the EVAREST/BSE-NSTEP multi-entre study
Background: Stress echocardiography is widely used to detect coronary artery disease, but little evidence on downstream hospital costs in real-world practice is available. We examined how stress echocardiography accuracy and downstream hospital costs vary across NHS hospitals and identified key factors that affect costs to help inform future clinical planning and guidelines. Methods: Data on 7636 patients recruited from 31 NHS hospitals within the UK between 2014 and 2020 as part of EVAREST/BSE-NSTEP clinical study, were used. Data included all diagnostic tests, procedures, and hospital admissions for 12 months after a stress echocardiogram and were costed using the NHS national unit costs. A decision tree was built to illustrate the clinical pathway and estimate average downstream hospital costs. Multi-level regression analysis was performed to identify variation in accuracy and costs at both patient, procedural, and hospital level. Linear regression and extrapolation were used to estimate annual hospital cost-savings associated with increasing predictive accuracy at hospital and national level. Results: Stress echocardiography accuracy varied with patient, hospital and operator characteristics. Hypertension, presence of wall motion abnormalities and higher number of hospital cardiology outpatient attendances annually reduced accuracy, adjusted odds ratio of 0.78 (95% CI 0.65 to 0.93), 0.27 (95% CI 0.15 to 0.48), 0.99 (95% CI 0.98 to 0.99) respectively, whereas a prior myocardial infarction, angiotensin receptor blocker medication, and greater operator experience increased accuracy, adjusted odds ratio of 1.77 (95% CI 1.34 to 2.33), 1.64 (95% CI 1.22 to 2.22), and 1.06 (95% CI 1.02 to 1.09) respectively. Average downstream costs were £646 per patient (SD 1796) with significant variation across hospitals. The average downstream costs between the 31 hospitals varied from £384–1730 per patient. False positive and false negative tests were associated with average downstream costs of £1446 (SD £601) and £4192 (SD 3332) respectively, driven by increased non-elective hospital admissions, adjusted odds ratio 2.48 (95% CI 1.08 to 5.66), 21.06 (95% CI 10.41 to 42.59) respectively. We estimated that an increase in accuracy by 1 percentage point could save the NHS in the UK £3.2 million annually. Conclusion: This study provides real-world evidence of downstream costs associated with stress echocardiography practice in the UK and estimates how improvements in accuracy could impact healthcare expenditure in the NHS. A real-world downstream costing approach could be adopted more widely in evaluation of imaging tests and interventions to reflect actual value for money and support realistic planning.
Integrated care in a Beveridge system: experiences from England and Denmark
Health systems internationally face demands to deliver care that is better coordinated and integrated. The health system financing and delivery model may go some, but not all the way in explaining health system fragmentation. In this paper, we consider the road to care integration in two countries with Beveridge style health systems, England and Denmark, that are both ranked as highly Integrated systems in Toth's health integration index. We use the SELFIE framework to compare the policies and reforms that have affected care integration over the past 30 years in the two countries. The countries both started their reform path by reforming to introduce choice and competition, but did so in different ways that set them on different pathways. Nevertheless, after two decades, the countries ended the period with largely similar structures that emphasised the creation of a cross-sectoral governance structure. In the relatively centralised England, by introducing decentralised Integrated Care Systems, and in the relatively decentralised Denmark with a centralising element in the form of new Health Clusters.
Predictors of positive patient-reported outcomes from 'Early Intervention in Psychosis': A national cross-sectional study
Background The components of care delivered by Early Intervention in Psychosis (EIP) services vary, but the impact on patient experience is unknown. Objective To investigate associations between components of care provided by EIP services in England and patient-reported outcomes. Methods 2374 patients from EIP services in England were surveyed during the National Clinical Audit of Psychosis. Participants were asked about the care they received, and completed the 'Patient Global Impressions' Scale (rating whether their mental health had improved), and 'Friends and Family Test' (rating whether they would recommend their service). Information about service structure was obtained from service providers. We analysed associations between outcomes and components of care using multilevel regression. Findings The majority of participants were likely to recommend the treatment they had received (89.8%), and felt that their mental health had improved (89.0%). Participants from services where care coordinators had larger case loads were less likely to recommend their care. Participants were more likely to recommend their care if they had been offered cognitive behavioural therapy for psychosis, family therapy or targeted interventions for carers. Participants were more likely to report that their mental health had improved if they had been offered cognitive behavioural therapy for psychosis or targeted interventions for carers. Conclusions Specific components of EIP care were associated with improved patient reported outcomes. Psychosocial interventions and carer support may be particularly important in optimising outcomes for patients. Clinical implications These findings emphasise the need for small case load sizes and comprehensive packages of treatment in EIP services.
Therapist-assisted online psychological therapies differing in trauma focus for post-traumatic stress disorder (STOP-PTSD): a UK-based, single-blind, randomised controlled trial
Background: Many patients are currently unable to access psychological treatments for post-traumatic stress disorder (PTSD), and it is unclear which types of therapist-assisted internet-based treatments work best. We aimed to investigate whether a novel internet-delivered cognitive therapy for PTSD (iCT-PTSD), which implements all procedures of a first-line, trauma-focused intervention recommended by the UK National Institute for Health and Care Excellence (NICE) for PTSD, is superior to internet-delivered stress management therapy for PTSD (iStress-PTSD), a comprehensive cognitive behavioural treatment programme focusing on a wide range of coping skills. Methods: We did a single-blind, randomised controlled trial in three locations in the UK. Participants (≥18 years) were recruited from UK National Health Service (NHS) Improving Access to Psychological Therapies (IAPT) services or by self-referral and met DSM-5 criteria for PTSD to single or multiple events. Participants were randomly allocated by a computer programme (3:3:1) to iCT-PTSD, iStress-PTSD, or a 3-month waiting list with usual NHS care, after which patients who still met PTSD criteria were randomly allocated (1:1) to iCT-PTSD or iStress-PTSD. Randomisation was stratified by location, duration of PTSD (<18 months or ≥18 months), and severity of PTSD symptoms (high vs low). iCT-PTSD and iStress-PTSD were delivered online with therapist support by messages and short weekly phone calls over the first 12 weeks (weekly treatment phase), and three phone calls over the next 3 months (booster phase). The primary outcome was the severity of PTSD symptoms at 13 weeks after random assignment, measured by self-report on the PTSD Checklist for DSM-5 (PCL-5), and analysed by intention-to-treat. Safety was assessed in all participants who started treatment. Process analyses investigated acceptability and compliance with treatment, and candidate moderators and mediators of outcome. The trial was prospectively registered with the ISRCTN registry, ISRCTN16806208. Findings: Of the 217 participants, 158 (73%) self-reported as female, 57 (26%) as male, and two (1%) as other; 170 (78%) were White British, 20 (9%) were other White, six (3%) were Asian, ten (5%) were Black, eight (4%) had a mixed ethnic background, and three (1%) had other ethnic backgrounds. Mean age was 36·36 years (SD 12·11; range 18–71 years). 52 (24%) participants met self-reported criteria for ICD-11 complex PTSD. Fewer than 10% of participants dropped out of each treatment group. iCT-PTSD was superior to iStress-PTSD in reducing PTSD symptoms, showing an adjusted difference on the PCL-5 of –4·92 (95% CI –8·92 to –0·92; p=0·016; standardised effect size d=0·38 [0·07 to 0·69]) for immediate allocations and –5·82 (–9·59 to –2·04; p=0·0027; d=0·44 [0·15 to 0·72]) for all treatment allocations. Both treatments were superior to the waiting list for PCL-5 at 13 weeks (d=1·67 [1·23 to 2·10] for iCT-PTSD and 1·29 [0·85 to 1·72] for iStress-PTSD). The advantages in outcome for iCT-PTSD were greater for participants with high dissociation or complex PTSD symptoms, and mediation analyses showed both treatments worked by changing negative meanings of the trauma, unhelpful coping, and flashback memories. No serious adverse events were reported. Interpretation: Trauma-focused iCT-PTSD is effective and acceptable to patients with PTSD, and superior to a non-trauma-focused cognitive behavioural stress management therapy, suggesting that iCT-PTSD is an effective way of delivering the contents of CT-PTSD, one of the NICE-recommended first-line treatments for PTSD, while reducing therapist time compared with face-to-face therapy. Funding: Wellcome Trust, UK National Institute for Health and Care Research Oxford Health Biomedical Research Centre.
Budget impact and transferability of cost-effectiveness of DPYD testing in metastatic breast cancer in three health systems
The cost-effectiveness and budget impact of introducing extended DPYD testing prior to fluoropyrimidine-based chemotherapy in metastatic breast cancer patients in the UK, The Netherlands and Hungary were examined. DPYD testing with ToxNav© was cost-effective in all three countries. In the UK and The Netherlands, the ToxNav strategy led to more quality-adjusted life years and fewer costs to the health systems compared with no genetic testing and standard dosing of capecitabine/5-fluorouracil. In Hungary, the ToxNav strategy produced more quality-adjusted life years at a higher cost compared with no testing and standard dose. The ToxNav strategy was found to offer budget savings in the UK and in The Netherlands, while in Hungary it resulted in additional budget costs.
Financial incentives to promote personalized medicine in Europe: an overview and guidance for implementation
The implementation of adequate financing and reimbursement of personalized medicine (PM) in Europe is still turbulent. The views and experience of stakeholders about barriers in financing and reimbursing PM and potential solutions were elicited and supplemented with literature findings to draft a set of recommendations. Key recommendations to overcome the barriers for adequately financing and reimbursing PM in different healthcare systems in Europe included the provision of legal foundations and establishment of large pan-European databases, use of financial-based agreements and regulation of transparency of prices and reimbursement, and creating a business-friendly environment and attractive market for innovation. The recommendations could be used by health authorities for designing a sequence of policy steps to ensure the timely access to beneficial PM.
Cost-effectiveness and budget impact analysis of screening strategies for maturity-onset diabetes of the young in three European countries
Background: Correct diagnosis of maturity-onset diabetes of the young (MODY), which is often misdiagnosed as Type 1 or 2 diabetes, is important for providing appropriate treatment. Materials & Methods: A diabetes model was adapted to Hungary, the Netherlands, and the UK to analyse the cost-effectiveness and budget impact of different screening strategies for MODY with 20 years time horizon. Results: Compared with no screening, screening with the MODY calculator then genetic testing is considered cost-effective with respect to each country's willingness to pay threshold. The addition of autoantibody testing dominated the no screening strategy. The budget impact of the strategies ranges between 0.001 and 0.025% of annual public healthcare spending. Conclusion: The analysed strategies are considered good value for money with potential cost savings in the long term.
Cost-effectiveness of genetic-based screening strategies for maturity-onset diabetes of the young
Maturity-onset diabetes of the young (MODY) is often misdiagnosed as Type I or II diabetes. This study was designed to assess the cost-effectiveness of MODY screening strategies in Hungary, which included a recent genetic test compared with no routine screening for MODY. A simulation model that combined a decision tree and an individual-level Markov model was constructed to assess the costs per quality-adjusted life year of screening strategies. Stratifying patients based on age and insulin treatment followed by a risk assessment questionnaire, a laboratory test and genetic testing was the most cost-effective strategy, saving EUR 12 and generating 0.0047 quality-adjusted life years gained per screened patient. This screening strategy could be considered for reimbursement, especially in countries with limited resources.
Lessons learned from the application of the HEcoPerMed guidance to three modeling case studies
Background: The HEcoPerMed consortium developed a methodological guidance for the harmonization and improvement of economic evaluations in personalized medicine. Materials & methods: In three therapeutic areas, health economic models were developed to scrutinize the recommendations of the guidance. Results: Altogether, 20 of the 23 recommendations of the guidance were addressed by the models. Seven recommendations were applied in all studies, six in two of the studies and seven in one of the studies. Recommendations with an essential role on the final conclusions of the analyses were identified in each study. Conclusion: The guidance was found to be best used as a tool to identify and prioritize issues, verify solutions and justify decisions during the economic analysis of personalized interventions.
Cost-effectiveness of extended DPYD testing before fluoropyrimidine chemotherapy in metastatic breast cancer in the UK
The aim of this study was to evaluate the cost-effectiveness of ToxNav©, a multivariant genetic test, to screen for DPYD followed by personalized chemotherapy dosing for metastatic breast cancer in the UK compared with no testing followed by standard dose, standard of care. In the main analysis, ToxNav was dominant over standard of care, producing 0.19 additional quality-adjusted life years and savings of £78,000 per patient over a lifetime. The mean additional quality-adjusted life years per person from 1000 simulations was 0.23 savings (95% CI: 0.22-0.24) at £99,000 (95% CI: £95-102,000). Varying input parameters independently by range of 20% was unlikely to change the results in the main analysis. The probabilistic sensitivity analysis showed ~97% probability of the ToxNav strategy to be dominant.
Survival and community care use by care home residents in England: does mental health matter?
The aim was to provide evidence of mortality and community care costs of people living in care homes and to investigate its association with mental health based on the Mental Health Clustering Tool (MHCT). In an observational study, 5,782 residents living in 104 care homes were followed from 2014 to 2016. Residents were categorised into four groups using the MCHT: three with mental health conditions, 'non-psychotic', 'psychotic' or 'organic'; and one without mental health conditions, 'non-clustered'. Generalised estimating equations were used to explore associations between mean community care costs over 6 months per patient and the clustering of residents into the four groups. Differences in survival rates of residents were plotted using Kaplan-Meier curves and tested with the log-rank test and Cox regression analysis. Community care costs were similar among residents with dementia (£431) and without mental health conditions (£407), while costs were higher among residents with non-psychotic (£762) and psychotic (£1,724) mental health conditions. After adjusting for patient and care home characteristics, residents with dementia were 30 per cent less likely to die compared with residents without mental health conditions. Similarly, residents with psychotic conditions and residents with non-psychotic conditions were 25 and 20 per cent less likely to die, respectively, than residents without mental health conditions. The MHCT seems to provide an informative stratification of care home residents with regards to survival and community care use.
The Use of Multicriteria Decision Analysis to Support Decision Making in Healthcare: An Updated Systematic Literature Review
Objectives: Multicriteria decision analysis (MCDA) is increasingly used for decision making in healthcare. However, its application in different decision-making contexts is still unclear. This study aimed to provide a comprehensive review of MCDA studies performed to inform decisions in healthcare and to summarize its application in different decision contexts. Methods: We updated a systematic review conducted in 2013 by searching Embase, MEDLINE, and Google Scholar for MCDA studies in healthcare, published in English between August 2013 and November 2020. We also expanded the search by reviewing grey literature found via Trip Medical Database and Google, published between January 1990 and November 2020. A comprehensive template was developed to extract information about the decision context, criteria, methods, stakeholders involved, and sensitivity analyses conducted. Results: From the 4295 identified studies, 473 studies were eligible for full-text review after assessing titles and abstracts. Of those, 228 studies met the inclusion criteria and underwent data extraction. The use of MCDA continues to grow in healthcare literature, with most of the studies (49%) informing priority-setting decisions. Safety, cost, and quality of care delivery are the most frequently used criteria, although there are considerable differences across decision contexts. Almost half of the MCDA studies used the linear additive model whereas scales and the analytical hierarchy process were the most used techniques for scoring and weighting, respectively. Not all studies report on each one of the MCDA steps, consider axiomatic properties, or justify the methods used. Conclusions: A guide on how to conduct and report MCDA that acknowledges the particularities of the different decision contexts and methods needs to be developed.
Cost-Effectiveness Analysis of Treating Patients With NTRK-Positive Cancer With the Histology-Independent Therapy Entrectinib
Objectives: This study tackles several challenges of evaluating histology-independent treatments using entrectinib as an example. Histology-independent treatments are provided based on genetic marker(s) of tumors, regardless of the tumor type. We evaluated the lifetime cost-effectiveness of testing all patients for NTRK fusions and treating the positive cases with entrectinib compared with no testing and standard of care (SoC) for all patients. Methods: The health economic model consisted of a decision tree reflecting the NTRK testing phase followed by a microsimulation model reflecting treatment with either entrectinib or SoC. Efficacy of entrectinib was based on data from basket trials, whereas historical data from NTRK-negative patients were corrected for the prognostic value of NTRK fusions to model SoC. Results: “Testing” (testing for NTRK fusions, with subsequent entrectinib treatment in NTRK-positive patients and SoC in NTRK-negative patients) had higher per-patient quality-adjusted life-years (QALYs) and costs than “No testing” (SoC for all patients), with a difference of 0.0043 and €732, respectively. This corresponded to an incremental cost-effectiveness ratio (ICER) of €169 957/QALY and, using a cost-effectiveness threshold of €80 000/QALY, an incremental net monetary benefit of −€388. When excluding the costs of genetic testing for NTRK fusions, the ICER was reduced to €36 290/QALY and the incremental net monetary benefit increased to €188. Conclusions: When treatment requires the identification of a genetic marker, the associated costs and effects need to be accounted for. Because of the low prevalence of NTRK fusions, the number needed-to-test to identify patients eligible for entrectinib is large. Excluding the testing phase reduces the ICER substantially.
Predictors of positive outcomes from ‘Early Intervention in Psychosis’: protocol for a national retrospective cohort study
Background: Psychotic disorders are severe and prevalent mental health conditions associated with long-term disability, reduced quality of life, and substantial economic costs. Early Intervention in Psychosis (EIP) services aim to provide timely and comprehensive treatment for psychotic disorders, and EIP service input is associated with improved outcomes. However, there is limited understanding of the specific components of EIP care that contribute to these improvements. There is significant nationwide variability in the commissioning and delivery of EIP, with individuals receiving different packages of components from different services. In this study, we seek to explore associations between EIP components and clinically significant outcomes, in order to understand the mechanisms underlying improved psychosis care. Methods: This national retrospective cohort study will utilize data from the 2019 National Clinical Audit of Psychosis (NCAP), examining the care received by 10,560 individuals treated by EIP services in England. Exposure data from the NCAP, capturing the components of care delivered by EIP services, will be linked with outcome data from routine NHS Digital datasets over a three-year follow-up period. This will be the first study to use this method to examine this population in England. The primary outcomes will be surrogate measures of relapse of psychosis (hospital admission and referral to community-based crisis intervention services). Secondary outcomes include duration of admissions, emergency hospital attendances, episodes of detention under the Mental Health Act, and all-cause mortality. We will use multilevel regression to examine associations between exposures and outcome events. We will handle missing data using appropriate imputation techniques. Discussion: This study aims to provide valuable insights into the long-term effects of variations in EIP service delivery. The study involves a large, diverse cohort including individuals treated by every EIP service in England. While there are limitations inherent in the observational nature of the study, any associations identified will be of great relevance to clinicians, researchers, and policymakers seeking to optimize EIP care. The results will enable more targeted treatment planning, resource allocation, and potential innovations in EIP care, ultimately leading to improved prognoses for people experiencing psychosis.
Can upfront DPYD extended variant testing reduce toxicity and associated hospital costs of fluoropyrimidine chemotherapy? A propensity score matched analysis of 2022 UK patients
Aim: To independently assess the impact of mandatory testing using an extended DPYD variant panel (ToxNav®) and consequent dose adjustment of Capecitabine/5-FU on recorded quantitative toxicity, symptoms of depression, and hospital costs. Methods: We used propensity score matching (PSM) to match 466 patients tested with ToxNav® with 1556 patients from a historical cohort, and performed regression analysis to estimate the impact of ToxNav®on toxicity, depression, and hospital costs. Results: ToxNav® appeared to reduce the likelihood of experiencing moderate (OR: 0.59; 95%CI: 0.45–0.77) and severe anaemia (OR: 0.55; 95%CI: 0.33–0.90), and experience of pain for more than 4 days a week (OR: 0.50; 95%CI: 0.30–0.83), while it increased the likelihood of mild neutropenia (OR: 1.73; 95%CI: 1.27–2.35). It also reduced the cost of chemotherapy by 12% (95%CI: 3–31) or £9765, the cost of non-elective hospitalisation by 23% (95%CI: 8–36) or £2331, and the cost of critical care by 21% (95%CI: 2–36) or £1219 per patient. For the DPYD variant associated with critical risk of toxicity (rs3918290), the improved non-elective hospital costs were > £20,000, whereas variants associated with hand-foot syndrome toxicity had no detectable cost improvement. Conclusion: Upfront testing of DPYD variants appears to reduce the toxicity burden of Capecitabine and 5-FU in cancer patients and can lead to substantial hospital cost savings, only if the dose management of the drugs in response to variants detected is standardised and regulated.
Moving Beyond Quality-Adjusted Life-Years in Elderly Care: How Can Multicriteria Decision Analysis Complement Cost-Effectiveness Analysis in Local-Level Decision Making
Objectives: This study aimed to investigate how multicriteria decision analysis (MCDA) could complement cost-effectiveness analysis (CEA) to support investment decisions in elderly care at local level. Methods: We used an integrated elderly care program in The Netherlands as a case study to demonstrate the application of both methods. In a 12-month quasi-experimental study (n = 384), data on the following outcome measures were collected: quality-adjusted life-years (CEA) and physical functioning, psychological well-being, social relationships and participation, enjoyment of life, resilience, person centeredness, continuity of care, and costs (MCDA). We performed regression analysis on inversed probability weighted data and controlled for potential confounders to obtain a double robust estimate of the outcomes. Probabilistic sensitivity analyses determined uncertainty for both methods. Results: The integrated elderly care program was not likely (ie, 36%) to be cost-effective according to the CEA (incremental cost-effectiveness ratios: €88 249 from a societal perspective) using the conventional Dutch willingness-to-pay threshold (ie, €50 000). The MCDA demonstrated that informal caregivers and professionals slightly preferred the intervention over usual care, driven by enjoyment of life and person centeredness. Patients did not prefer either the intervention or usual care, whereas payers and policy makers slightly preferred usual care, mainly due to higher costs of the intervention. Conclusions: MCDA could provide local-level decision makers with a broader measurement of effectiveness by including outcomes beyond health and longevity and the preferences of multiple stakeholders. This additional information could foster the acceptability and implementability of cost-effective innovations in elderly care.
The WISDOM self-management intervention: A cost-effectiveness analysis to support the transformation of type 2 diabetes care in England
Objectives: To assess the cost-effectiveness of the WISDOM self-management intervention for type 2 diabetes compared with care as usual. Design: We performed a difference-in-differences analysis to estimate differences in risk factors for diabetes complications between people in the WISDOM group (n = 25, 276) and a control group (n = 15, 272) using GP records. A decision analytic model was then used to extrapolate differences in risk factors into costs and outcomes in the long term. Setting: Participating GP practices in West Hampshire and Southampton, UK. Participants: All people diagnosed with type 2 diabetes between January 1990 and March 2020 (n = 40,548). Outcomes: Diabetes-related complications, quality-adjusted life years (QALYs) and costs to the English National Health Service at 5 years and lifetime. Interventions: The WISDOM intervention included risk stratification, self-management education programme to professionals and people with type 2 diabetes, and monitoring of key treatment targets. Results: WISDOM was associated with less atrial fibrillation [p = 0.001], albuminuria [p = 0.002] and blood pressure [p = 0.098]. Among all people in the intervention group, WISDOM led to 51 [95%CI: 25; 76] QALYs gained and saved £278,036 [95%CI: −631,900; 176,392] in the first 5 years after its implementation compared with care as usual. During those people' lifetime, WISDOM led to 253 [95%CI: 75; 404] QALYs gained and cost saving of £126,380 [95%CI: −1,466,008; 1,339,628]. The gains in QALYs were a result of reduced diabetes-related complications through improved management of the associated risk factors. Conclusions: The WISDOM risk-stratification and education intervention for type 2 diabetes appear to be cost-effective compared to usual care by reducing diabetes complications.