Inflammatory risk and cardiovascular events in patients without obstructive coronary artery disease: the ORFAN multicentre, longitudinal cohort study.

BACKGROUND: Coronary computed tomography angiography (CCTA) is the first line investigation for chest pain, and it is used to guide revascularisation. However, the widespread adoption of CCTA has revealed a large group of individuals without obstructive coronary artery disease (CAD), with unclear prognosis and management. Measurement of coronary inflammation from CCTA using the perivascular fat attenuation index (FAI) Score could enable cardiovascular risk prediction and guide the management of individuals without obstructive CAD. The Oxford Risk Factors And Non-invasive imaging (ORFAN) study aimed to evaluate the risk profile and event rates among patients undergoing CCTA as part of routine clinical care in the UK National Health Service (NHS); to test the hypothesis that coronary arterial inflammation drives cardiac mortality or major adverse cardiac events (MACE) in patients with or without CAD; and to externally validate the performance of the previously trained artificial intelligence (AI)-Risk prognostic algorithm and the related AI-Risk classification system in a UK population. METHODS: This multicentre, longitudinal cohort study included 40 091 consecutive patients undergoing clinically indicated CCTA in eight UK hospitals, who were followed up for MACE (ie, myocardial infarction, new onset heart failure, or cardiac death) for a median of 2·7 years (IQR 1·4-5·3). The prognostic value of FAI Score in the presence and absence of obstructive CAD was evaluated in 3393 consecutive patients from the two hospitals with the longest follow-up (7·7 years [6·4-9·1]). An AI-enhanced cardiac risk prediction algorithm, which integrates FAI Score, coronary plaque metrics, and clinical risk factors, was then evaluated in this population. FINDINGS: In the 2·7 year median follow-up period, patients without obstructive CAD (32 533 [81·1%] of 40 091) accounted for 2857 (66·3%) of the 4307 total MACE and 1118 (63·7%) of the 1754 total cardiac deaths in the whole of Cohort A. Increased FAI Score in all the three coronary arteries had an additive impact on the risk for cardiac mortality (hazard ratio [HR] 29·8 [95% CI 13·9-63·9], p<0·001) or MACE (12·6 [8·5-18·6], p<0·001) comparing three vessels with an FAI Score in the top versus bottom quartile for each artery. FAI Score in any coronary artery predicted cardiac mortality and MACE independently from cardiovascular risk factors and the presence or extent of CAD. The AI-Risk classification was positively associated with cardiac mortality (6·75 [5·17-8·82], p<0·001, for very high risk vs low or medium risk) and MACE (4·68 [3·93-5·57], p<0·001 for very high risk vs low or medium risk). Finally, the AI-Risk model was well calibrated against true events. INTERPRETATION: The FAI Score captures inflammatory risk beyond the current clinical risk stratification and CCTA interpretation, particularly among patients without obstructive CAD. The AI-Risk integrates this information in a prognostic algorithm, which could be used as an alternative to traditional risk factor-based risk calculators. FUNDING: British Heart Foundation, NHS-AI award, Innovate UK, National Institute for Health and Care Research, and the Oxford Biomedical Research Centre.

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.

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.

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.

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 Net Benefit of Personalized Medicine: A Systematic Literature Review and Regression Analysis.

OBJECTIVES: Amidst conflicting expectations about the benefits of personalized medicine (PM) and the potentially high implementation costs, we reviewed the available evidence on the cost-effectiveness of PM relative to non-PM. METHODS: We conducted a systematic literature review of economic evaluations of PM and extracted data, including incremental quality-adjusted life-years (ΔQALYs) and incremental costs (Δcosts). ΔQALYs and Δcosts were combined with estimates of national cost-effectiveness thresholds to calculate incremental net monetary benefit (ΔNMB). Regression analyses were performed with these variables as dependent variables and PM intervention characteristics as independent variables. Random intercepts were used to cluster studies according to country. RESULTS: Of 4774 studies reviewed, 128 were selected, providing cost-effectiveness data for 279 PM interventions. Most studies were set in the United States (48%) and the United Kingdom (16%) and adopted a healthcare perspective (82%). Cancer treatments (60%) and pharmaceutical interventions (72%) occurred frequently. Prognostic tests (19%) and tests to identify (non)responders (37%) were least and most common, respectively. Industry sponsorship occurred in 32%. Median ΔQALYs, Δcosts, and ΔNMB per individual were 0.03, Int$575, and Int$18, respectively. We found large heterogeneity in cost-effectiveness. Regression analysis showed that gene therapies were associated with higher ΔQALYs than other interventions. PM interventions for neoplasms brought higher ΔNMB than PM interventions for other conditions. Nonetheless, average ΔNMB in the 'neoplasm' group was found to be negative. CONCLUSIONS: PM brings improvements in health but often at a high cost, resulting in 0 to negative ΔNMB on average. Pricing policies may be needed to reduce the costs of interventions with negative ΔNMB.

Is comprehensive geriatric assessment hospital at home a cost-effective alternative to hospital admission for older people?

BACKGROUND: hospital level healthcare in the home guided by comprehensive geriatric assessment (CGA) might provide a less costly alternative to hospitalisation for older people. OBJECTIVE: to determine the cost-effectiveness of CGA admission avoidance hospital at home (HAH) compared with hospital admission. DESIGN/INTERVENTION: a cost-effectiveness study alongside a randomised trial of CGA in an admission avoidance HAH setting, compared with admission to hospital. PARTICIPANTS/SETTING: older people considered for a hospital admission in nine locations across the UK were randomised using a 2:1 randomisation schedule to admission avoidance HAH with CGA (N = 700), or admission to hospital with CGA when available (N = 355). MEASUREMENTS: quality adjusted life years, resource use and costs at baseline and 6 months; incremental cost-effectiveness ratios were calculated. The main analysis used complete cases. RESULTS: adjusting for baseline covariates, HAH was less costly than admission to hospital from a health and social care perspective (mean -£2,265, 95% CI: -4,279 to -252), and remained less costly with the addition of informal care costs (mean difference -£2,840, 95% CI: -5,495 to -185). There was no difference in quality adjusted survival. Using multiple imputation for missing data, the mean difference in health and social care costs widened to -£2,458 (95% CI: -4,977 to 61) and societal costs remained significantly lower (-£3,083, 95% CI: -5,880 to -287). There was little change to quality adjusted survival. CONCLUSIONS: CGA HAH is a cost-effective alternative to admission to hospital for selected older people.

Heterogeneity in preferences for outcomes of integrated care for persons with multiple chronic diseases: a latent class analysis of a discrete choice experiment.

PURPOSE: For an integrated care programme to be successful, preferences of the stakeholders involved should be aligned. The aim of this study is to investigate to which extent outcomes beyond health are valued and to study the heterogeneity of preferences of those involved in integrated care. METHODS: A discrete choice experiment (DCE) was conducted to elicit preferences for eight Triple Aim outcomes, i.e., physical functioning, psychological well-being, social relationships & participation, enjoyment of life, resilience, person-centeredness, continuity of care and total health and social care costs. Stakeholders were recruited among Dutch persons with multi-morbidity, informal caregivers, professionals, payers, and policymakers. A Bayesian mixed-logit model was used to analyse the data. Subsequently, a latent class analysis was performed to identify stakeholders with similar preferences. RESULTS: 739 stakeholders completed the DCE. Enjoyment of life was perceived as the most important outcome (relative importance: 0.221) across stakeholders, while total health and social care costs were perceived as least important (0.063). The latent class analysis identified four classes. The first class (19.9%) put most weight on experience with care outcomes. The second class (39%) favoured enjoyment of life. The third class (18%) focused relatively more on physical health. The fourth class (24%) had the least consistent preferences. CONCLUSION: This study has highlighted the heterogeneity in views of stakeholders in integrated care on what is important in health(care) for persons with multi-morbidity. To accurately value integrated care a variety of outcomes beyond health-e.g., enjoyment of life and experience with care-should be taken into account.

Appraisal of patient-level health economic models of severe mental illness: systematic review.

BACKGROUND: Healthcare decision makers require accurate long-term economic models to evaluate the cost-effectiveness of new mental health interventions. AIMS: To assess the suitability of current patient-level economic models to estimate long-term economic outcomes in severe mental illness. METHOD: We undertook pre-specified systematic searches in MEDLINE, Embase and PsycINFO to identify reviews and stand-alone publications of economic models of interventions for schizophrenia, bipolar disorder and major depressive disorder (PROSPERO: CRD42020158243). We screened paper titles and abstracts to identify unique patient-level economic models. We conducted a structured extraction of identified models, recording the presence of key predefined model features. Model quality and validation were appraised using the 2014 ISPOR and 2016 AdViSHE model checklists. RESULTS: We identified 15 unique patient-level models for psychosis and major depressive disorder from 1481 non-duplicate records. Models addressed schizophrenia (n = 6), bipolar disorder (n = 2) and major depressive disorder (n = 7). The predominant model type was discrete event simulation (n = 9). Model complexity and incorporation of patient heterogeneity varied considerably, and only five models extrapolated costs and outcomes over a lifetime horizon. Key model parameters were often based on low-quality evidence, and checklist quality assessment revealed weak model verification procedures. CONCLUSIONS: Existing patient-level economic models of interventions for severe mental illness have considerable limitations. New modelling efforts must be supplemented by the generation of good-quality, contemporary evidence suitable for model building. Combined effort across the research community is required to build and validate economic extrapolation models suitable for accurately assessing the long-term value of new interventions from short-term clinical trial data.

Economic Evaluation of New Models of Care: Does the Decision Change Between Cost-Utility Analysis and Multi-Criteria Decision Analysis?

OBJECTIVES: To experiment with new approaches of collaboration in healthcare delivery, local authorities implement new models of care. Regarding the local decision context of these models, multi-criteria decision analysis (MCDA) may be of added value to cost-utility analysis (CUA), because it covers a wider range of outcomes. This study compares the 2 methods using a side-by-side application. METHODS: A new Dutch model of care, Primary Care Plus (PC+), was used as a case study to compare the results of CUA and MCDA. Data of patients referred to PC+ or care-as-usual were retrieved by questionnaires and administrative databases with a 3-month follow-up. Propensity score matching together with generalized linear regression models was used to reduce confounding. Univariate and probabilistic sensitivity analyses were performed to explore uncertainty in the results. RESULTS: Although both methods indicated PC+ as the dominant alternative, complementary differences were observed. MCDA provided additional evidence that PC+ improved access to care (standardized performance score of 0.742 vs 0.670) and that improvement in health-related quality of life was driven by the psychological well-being component (standardized performance score of 0.710 vs 0.704). Furthermore, MCDA estimated the budget required for PC+ to be affordable in addition to preferable (€521.42 per patient). Additionally, MCDA was less sensitive to the utility measures used. CONCLUSIONS: MCDA may facilitate an auditable and transparent evaluation of new models of care by providing additional information on a wider range of outcomes and incorporating affordability. However, more effort is needed to increase the usability of MCDA among local decision makers.

Estimating EQ-5D utilities based on the Short-Form Long Term Conditions Questionnaire (LTCQ-8).

PURPOSE: The aim of this work was to develop a mapping algorithm for estimating EuroQoL 5 Dimension (EQ-5D) utilities from responses to the Long-Term Conditions Questionnaire (LTCQ), thus increasing LTCQ's potential as a comprehensive outcome measure for evaluating integrated care initiatives. METHODS: We combined data from three studies to give a total sample of 1334 responses. In each of the three datasets, we randomly selected 75% of the sample and combined the selected random samples to generate the estimation dataset, which consisted of 1001 patients. The unselected 25% observations from each dataset were combined to generate an internal validation dataset of 333 patients. We used direct mapping models by regressing responses to the LTCQ-8 directly onto EQ-5D-5L and EQ-5D-3L utilities as well as response (or indirect) mapping to predict the response level that patients selected for each of the five EQ-5D-5L domains. Several models were proposed and compared on mean squared error and mean absolute error. RESULTS: A two-part model with OLS was the best performing based on the mean squared error (0.038) and mean absolute error (0.147) when estimating the EQ-5D-5L utilities. A multinomial response mapping model using LTCQ-8 responses was used to predict EQ-5D-5L responses levels. CONCLUSIONS: This study provides a mapping algorithm for estimating EQ-5D utilities from LTCQ responses. The results from this study can help broaden the applicability of the LTCQ by producing utility values for use in economic analyses.

Exploring characteristics of COPD patients with clinical improvement after integrated disease management or usual care: post-hoc analysis of the RECODE study.

BACKGROUND: The cluster randomized controlled trial on (cost-)effectiveness of integrated chronic obstructive pulmonary disease (COPD) management in primary care (RECODE) showed that integrated disease management (IDM) in primary care had no effect on quality of life (QOL) in COPD patients compared with usual care (guideline-supported non-programmatic care). It is possible that only a subset of COPD patients in primary care benefit from IDM. We therefore examined which patients benefit from IDM, and whether patient characteristics predict clinical improvement over time. METHOD: Post-hoc analyses of the RECODE trial among 1086 COPD patients. Logistic regression analyses were performed with baseline characteristics as predictors to examine determinants of improvement in QOL, defined as a minimal decline in Clinical COPD Questionnaire (CCQ) of 0.4 points after 12 and 24 months of IDM. We also performed moderation analyses to examine whether predictors of clinical improvement differed between IDM and usual care. RESULTS: Regardless of treatment type, more severe dyspnea (MRC) was the most important predictor of clinically improved QOL at 12 and 24 months, suggesting that these patients have most room for improvement. Clinical improvement with IDM was associated with female gender (12-months) and being younger (24-months), and improvement with usual care was associated with having a depression (24-months). CONCLUSIONS: More severe dyspnea is a key predictor of improved QOL in COPD patients over time. More research is needed to replicate patient characteristics associated with clinical improvement with IDM, such that IDM programs can be offered to patients that benefit the most, and can potentially be adjusted to meet the needs of other patient groups as well. TRIAL REGISTRATION: Netherlands Trial Register, NTR2268. Registered 31 March 2010.

Introducing a single point of access (SPA) to child and adolescent mental health services in England: a mixed-methods observational study.

BACKGROUND: In many high-income countries, primary care practitioners are the main point of referral for specialist mental health services. In England, Child and Adolescent Mental Health Services (CAMHS) are increasingly adopting a Single Point of Access (SPA) to streamline referrals and introduce self and parent/carer-referrals. This involves a significant shift of responsibility from primary care towards CAMHS who adopt a more active role as gatekeeper for their service. This study evaluates the adoption of a SPA in CAMHS across a large region in England. METHODS: We conducted an observational mixed methods study in two CAMHS from January 2018 to March 2019 to evaluate the adoption of a SPA. We collected quantitative data from electronic patient records and qualitative data through ethnographic observation and in-depth interviews of staff and stakeholders with experience of using CAMHS. Additional data on volumes was shared directly from the SPAs and a further snapshot of 1 week's users was collected. RESULTS: A similar SPA model emerged across the two services. Staff were positive about what the model could achieve and access rates grew quickly following awareness-raising activities. Despite the initial focus being on a telephone line, online referrals became the more regularly used referral method. Increased access brought challenges in terms of resourcing, including identifying the right staff for the role of call handlers. A further challenge was to impose consistency on triage decisions, which required structured information collection during the assessment process. Similar to GP referrals, those self-referring via the SPA were mainly from the least deprived areas. CONCLUSIONS: The introduction of a SPA has the potential to improve young people's access to mental health services. By addressing some of the barriers to access, simplifying where to go to get help and making it easier to contact the service directly, a SPA can help more individuals and families access timely support. However, the introduction of a SPA does not in itself expand the capacity of CAMHS, and therefore expectations within services and across sectors need to be tempered accordingly. SPA services providing different referral approaches can further improve access for the harder to reach populations.

Impact of achieving primary care targets in type 2 diabetes on health outcomes and healthcare costs.

AIMS: In England and Wales, the National Diabetes Audit (NDA) assesses the quality of management of type 2 diabetes (T2D) in primary care using treatment targets for HbA1c ≤58 mmol/mol, total cholesterol <5 mmol/L and blood pressure ≤140/80 mm Hg. We quantified the impact of variation in achieving these targets on health outcomes and healthcare costs across general practitioners' (GP) practices. METHODS: Summary of characteristics of T2D patients from the 2015-2016 NDA were used to generate representative populations of T2D patients. The UKPDS Outcomes Model 2 was used to estimate long-term health outcomes and healthcare costs. The effects of achieving treatment targets on these outcomes were evaluated using regression models. RESULTS: Achieving more of the HbA1c, cholesterol and blood pressure targets led to a lower incidence of diabetes-related complications. Approximately 0.5 (95% CI, 0.4-0.6) quality-adjusted life years (QALYs) and 0.6 (95% CI, 0.4-0.7) years of life (LYs) were gained by T2D patients over a lifetime for each additional target met. The projected healthcare cost savings arising from fewer diabetes-related complications as the result of achieving one, two or three targets compared to none were £859 (95% CI, £553-£1165), £940 (95% CI, £485-£1395) and £1037 (95% CI, £414-£1660) over a patient's lifetime. A typical GP practice in the lowest performing decile (average, 371 T2D patients per practice, with 27% achieving all targets) is projected to gain 201 (95% CI, 123-279) QALYs and 231 (95% CI, 133-329) LYs, if all T2D patients achieved all three targets. CONCLUSIONS: Substantial gains in health outcomes and reductions in healthcare costs could be achieved with further improvements in attainment of HbA1c, cholesterol and blood pressure targets for T2D patients.

Strengthening the evidence-base of integrated care for people with multi-morbidity in Europe using Multi-Criteria Decision Analysis (MCDA).

BACKGROUND: Evaluation of integrated care programmes for individuals with multi-morbidity requires a broader evaluation framework and a broader definition of added value than is common in cost-utility analysis. This is possible through the use of Multi-Criteria Decision Analysis (MCDA). METHODS AND RESULTS: This paper presents the seven steps of an MCDA to evaluate 17 different integrated care programmes for individuals with multi-morbidity in 8 European countries participating in the 4-year, EU-funded SELFIE project. In step one, qualitative research was undertaken to better understand the decision-context of these programmes. The programmes faced decisions related to their sustainability in terms of reimbursement, continuation, extension, and/or wider implementation. In step two, a uniform set of decision criteria was defined in terms of outcomes measured across the 17 programmes: physical functioning, psychological well-being, social relationships and participation, enjoyment of life, resilience, person-centeredness, continuity of care, and total health and social care costs. These were supplemented by programme-type specific outcomes. Step three presents the quasi-experimental studies designed to measure the performance of the programmes on the decision criteria. Step four gives details of the methods (Discrete Choice Experiment, Swing Weighting) to determine the relative importance of the decision criteria among five stakeholder groups per country. An example in step five illustrates the value-based method of MCDA by which the performance of the programmes on each decision criterion is combined with the weight of the respective criterion to derive an overall value score. Step six describes how we deal with uncertainty and introduces the Conditional Multi-Attribute Acceptability Curve. Step seven addresses the interpretation of results in stakeholder workshops. DISCUSSION: By discussing our solutions to the challenges involved in creating a uniform MCDA approach for the evaluation of different programmes, this paper provides guidance to future evaluations and stimulates debate on how to evaluate integrated care for multi-morbidity.

Comprehensive geriatric assessment for older adults admitted to hospital.

BACKGROUND: Comprehensive geriatric assessment (CGA) is a multi-dimensional, multi-disciplinary diagnostic and therapeutic process conducted to determine the medical, mental, and functional problems of older people with frailty so that a co-ordinated and integrated plan for treatment and follow-up can be developed. This is an update of a previously published Cochrane review. OBJECTIVES: We sought to critically appraise and summarise current evidence on the effectiveness and resource use of CGA for older adults admitted to hospital, and to use these data to estimate its cost-effectiveness. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, three other databases, and two trials registers on 5 October 2016; we also checked reference lists and contacted study authors. SELECTION CRITERIA: We included randomised trials that compared inpatient CGA (delivered on geriatric wards or by mobile teams) versus usual care on a general medical ward or on a ward for older people, usually admitted to hospital for acute care or for inpatient rehabilitation after an acute admission. DATA COLLECTION AND ANALYSIS: We followed standard methodological procedures expected by Cochrane and Effective Practice and Organisation of Care (EPOC). We used the GRADE approach to assess the certainty of evidence for the most important outcomes. For this update, we requested individual patient data (IPD) from trialists, and we conducted a survey of trialists to obtain details of delivery of CGA. We calculated risk ratios (RRs), mean differences (MDs), or standardised mean differences (SMDs), and combined data using fixed-effect meta-analysis. We estimated cost-effectiveness by comparing inpatient CGA versus hospital admission without CGA in terms of cost per quality-adjusted life year (QALY) gained, cost per life year (LY) gained, and cost per life year living at home (LYLAH) gained. MAIN RESULTS: We included 29 trials recruiting 13,766 participants across nine, mostly high-income countries. CGA increases the likelihood that patients will be alive and in their own homes at 3 to 12 months' follow-up (risk ratio (RR) 1.06, 95% confidence interval (CI) 1.01 to 1.10; 16 trials, 6799 participants; high-certainty evidence), results in little or no difference in mortality at 3 to 12 months' follow-up (RR 1.00, 95% CI 0.93 to 1.07; 21 trials, 10,023 participants; high-certainty evidence), decreases the likelihood that patients will be admitted to a nursing home at 3 to 12 months follow-up (RR 0.80, 95% CI 0.72 to 0.89; 14 trials, 6285 participants; high-certainty evidence) and results in little or no difference in dependence (RR 0.97, 95% CI 0.89 to 1.04; 14 trials, 6551 participants; high-certainty evidence). CGA may make little or no difference to cognitive function (SMD ranged from -0.22 to 0.35 (5 trials, 3534 participants; low-certainty evidence)). Mean length of stay ranged from 1.63 days to 40.7 days in the intervention group, and ranged from 1.8 days to 42.8 days in the comparison group. Healthcare costs per participant in the CGA group were on average GBP 234 (95% CI GBP -144 to GBP 605) higher than in the usual care group (17 trials, 5303 participants; low-certainty evidence). CGA may lead to a slight increase in QALYs of 0.012 (95% CI -0.024 to 0.048) at GBP 19,802 per QALY gained (3 trials; low-certainty evidence), a slight increase in LYs of 0.037 (95% CI 0.001 to 0.073), at GBP 6305 per LY gained (4 trials; low-certainty evidence), and a slight increase in LYLAH of 0.019 (95% CI -0.019 to 0.155) at GBP 12,568 per LYLAH gained (2 trials; low-certainty evidence). The probability that CGA would be cost-effective at a GBP 20,000 ceiling ratio for QALY, LY, and LYLAH was 0.50, 0.89, and 0.47, respectively (17 trials, 5303 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Older patients are more likely to be alive and in their own homes at follow-up if they received CGA on admission to hospital. We are uncertain whether data show a difference in effect between wards and teams, as this analysis was underpowered. CGA may lead to a small increase in costs, and evidence for cost-effectiveness is of low-certainty due to imprecision and inconsistency among studies. Further research that reports cost estimates that are setting-specific across different sectors of care are required.

Cost-Effectiveness of Disease Management Programs for Cardiovascular Risk and COPD in The Netherlands.

BACKGROUND: Disease management programs (DMPs) for cardiovascular risk (CVR) and chronic obstructive pulmonary disease (COPD) are increasingly implemented in The Netherlands to improve care and patient's health behavior. OBJECTIVE: The aim of this study was to provide evidence about the (cost-) effectiveness of Dutch DMPs as implemented in daily practice. METHODS: We compared the physical activity, smoking status, quality-adjusted life-years, and yearly costs per patient between the most and the least comprehensive DMPs in four disease categories: primary CVR prevention, secondary CVR prevention, both types of CVR prevention, and COPD (N = 1034). Propensity score matching increased comparability between DMPs. A 2-year cost-utility analysis was performed from the health care and societal perspectives. Sensitivity analysis was performed to estimate the impact of DMP development and implementation costs on cost-effectiveness. RESULTS: Patients in the most comprehensive DMPs increased their physical activity more (except for primary CVR prevention) and had higher smoking cessation rates. The incremental QALYs ranged from -0.032 to 0.038 across all diseases. From a societal perspective, the most comprehensive DMPs decreased costs in primary CVR prevention (certainty 57%), secondary CVR prevention (certainty 88%), and both types of CVR prevention (certainty 98%). Moreover, the implementation of comprehensive DMPs led to QALY gains in secondary CVR prevention (certainty 92%) and COPD (certainty 69%). CONCLUSIONS: The most comprehensive DMPs for CVR and COPD have the potential to be cost saving, effective, or cost-effective compared with the least comprehensive DMPs. The challenge for Dutch stakeholders is to find the optimal mixture of interventions that is most suited for each target group.

Changes in costs and effects after the implementation of disease management programs in the Netherlands: variability and determinants.

OBJECTIVES: The aim of the study was to investigate the changes in costs and outcomes after the implementation of various disease management programs (DMPs), to identify their potential determinants, and to compare the costs and outcomes of different DMPs. METHODS: We investigated the 1-year changes in costs and effects of 1,322 patients in 16 DMPs for cardiovascular risk (CVR), chronic obstructive pulmonary disease (COPD), and diabetes mellitus (DMII) in the Netherlands. We also explored the within-DMP predictors of these changes. Finally, a cost-utility analysis was performed from the healthcare and societal perspective comparing the most and the least effective DMP within each disease category. RESULTS: This study showed wide variation in development and implementation costs between DMPs (range:€16;€1,709) and highlighted the importance of economies of scale. Changes in health care utilization costs were not statistically significant. DMPs were associated with improvements in integration of CVR care (0.10 PACIC units), physical activity (+0.34 week-days) and smoking cessation (8% less smokers) in all diseases. Since an increase in physical activity and in self-efficacy were predictive of an improvement in quality-of-life, DMPs that aim to improve these are more likely to be effective. When comparing the most with the least effective DMP in a disease category, the vast majority of bootstrap replications (range:73%;97) pointed to cost savings, except for COPD (21%). QALY gains were small (range:0.003;+0.013) and surrounded by great uncertainty. CONCLUSIONS: After one year we have found indications of improvements in level of integrated care for CVR patients and lifestyle indicators for all diseases, but in none of the diseases we have found indications of cost savings due to DMPs. However, it is likely that it takes more time before the improvements in care lead to reductions in complications and hospitalizations.

Identifying and explaining the variability in development and implementation costs of disease management programs in the Netherlands.

BACKGROUND: In the Netherlands, disease management programs (DMPs) are used to treat chronic diseases. Their aim is to improve care and to control the rising expenditures related to chronic diseases. A bundled payment was introduced to facilitate the implementation of DMPs. This payment is an all-inclusive price per patient per year for a pre-specified care package. However, it is unclear to which extent the costs of developing and implementing DMPs are included in this price. Consequently, the organizations providing DMPs bear financial risk because the development and implementation (D&I) costs may be substantial. The aim of this paper is to investigate the variability in and drivers of D&I costs among 22 DMPs and highlight characteristics that impact these. METHODS: The data was analyzed using a mixed methods approach. Descriptive statistical analysis explored the variability in D&I costs as measured by a self-developed costing instrument and investigated the drivers. In addition, qualitative research, including document analysis and interviews, was conducted to explain the possible underlying reasons of cost variability. RESULTS: The development costs varied from €5,891 to €274,783 and the implementation costs varied from €7,278 to €387,879 across DMPs. Personnel costs were the main component of development. Development costs were strongly correlated with the implementation costs (ρ = 0.55), development duration (ρ = 0.74), and number of FTEs dedicated DMP development. Organizations with large size and high level of care prior to the implementation of a DMP had relatively low development costs. These findings were in line with the cross-case qualitative comparison where programs with a longer history, more experienced project leadership, previously established ICT systems, and less complex patient populations had lower D&I costs. CONCLUSIONS: There is wide variation in D&I costs of DMPs, which is driven primarily by the duration of the development phase and the staff needed to develop and implement a DMP. These drivers are influenced by the attributes of the DMP, characteristics of the target population, project leadership, and ICT involved. There are indications of economies of scale and economies of scope, which may reduce D&I costs.