Background and ObjectivesMetastatic castration-sensitive prostate cancer (mCSPC) imposes a significant economic burden and necessitates more cost-effective treatment strategies. The variability among the components of published economic evaluation models leads to methodological inconsistencies, underscoring the need for an optimal framework to minimise unwarranted structural variation. This paper reviews existing economic evaluations, establishes a comprehensive framework and aims to support future economic evaluations and decision-making in mCSPC.MethodsA systematic literature review (SLR) was conducted to identify relevant economic evaluations in mCSPC. Health technology assessments (HTAs) by the National Institute for Health and Care Excellence, and Canada's Drug Agency were reviewed to gather insights on critiques and limitations. On the basis of these findings, a comprehensive cost-effectiveness modelling framework was established. Furthermore, two additional SLRs were conducted to identify cost and resource utilisation inputs, as well as health state utility scores derived from published studies and HTA assessments.ResultsMarkov models and partitioned survival models (PSMs) were commonly reported in literature and published HTA evaluations. Despite the strong precedence of PSMs, we propose an optimal framework for mCSPC utilising a semi-Markov structure. This approach offers increased flexibility, allowing transition rates from progressed states to depend on time since progression occurred. We also present key sources of cost and utility data identified in the SLR.DiscussionThis work aligns with methodologies recommended by the Innovative Medicine Initiative (IMI) PIONEER external group and published studies. The optimal framework, including healthcare resource utilisation and utility data, consolidates existing modelling precedents in mCSPC and will assist the cost-effectiveness assessment of treatments for this condition.

BackgroundPopulation-adjusted indirect comparison using parametric Simulated Treatment Comparison (STC) has had limited application to survival outcomes in unanchored settings. Matching-Adjusted Indirect Comparison (MAIC) is commonly used but does not account for violation of proportional hazards or enable extrapolations of survival. We developed and applied a novel methodology for STC in unanchored settings. We compared overall survival (OS) and progression-free survival (PFS) of lenvatinib plus pembrolizumab (LEN + PEM) against nivolumab plus ipilimumab (NIVO + IPI), pembrolizumab plus axitinib (PEM + AXI), avelumab plus axitinib (AVE + AXI), and nivolumab plus cabozontanib (NIVO + CABO) in patients with advanced renal cell carcinoma (RCC). Unanchored comparison was necessitated as the control groups differed in their use of PD-1/PD-L1 rescue therapy.MethodsWe fit covariate-adjusted survival models to individual patient data from phase 3 trial of LEN + PEM, including standard parametric distributions and Royston-Parmar spline models with up to 3 knots. We used these models to predict OS and PFS in the population of comparator treatments. The base case model was selected by minimum Akaike Information Criterion (AIC). Treatment effects were measured using difference in restricted mean survival time (RMST), over shortest follow-up of input trials, and hazard ratios at 6, 12, 18, and 24 months.ResultsThe survival model with the lowest AIC was 1-knot spline odds for OS and log-logistic for PFS. Difference in RMST OS was 6.90 months (95% CI: 1.95, 11.36), 5.31 (3.58, 7.28), 5.99 (1.82, 9.42), and 11.59 (8.41, 15.38) versus NIVO + IPI (over 64.8 months follow-up), AVE + AXI (46.7 months), PEM + AXI (64.8 months), NIVO + CABO (53.0 months), respectively. Difference in RMST PFS was 4.50 months (95% CI: 0.92, 8.26), 8.23 (5.60, 10.57), 5.38 (2.06, 9.09), and 4.58 (0.09, 9.44) versus NIVO + IPI (over 57.8 months), AVE + AXI (44.9 months), PEM + AXI (57.8 months), NIVO + CABO (23.8 months), respectively. Hazard ratios indicated strong evidence of greater OS and PFS on LEN + PEM at most timepoints.ConclusionsWe developed and applied a novel methodology for comparing survival outcomes in unanchored settings using STC. Pending investigation with a simulation study or further examples, this methodology could be used for clinical decision-making and, if long-term data are available, inform economic models designed to extrapolate outcomes for the evaluation of lifetime cost-effectiveness.Trial registrationNCT02811861 (registered: 23/06/2016).

The reliability of a decision model to guide decision making depends on its ability to accurately predict patient outcomes. We present results of an external validation of the MicroSimulation Core Obesity Model (MS-COM) that was developed to compare the cost effectiveness of obesity management interventions in adults. We updated a 2018 systematic literature review of economic models in overweight and obesity and conducted additional targeted searches to identify suitable sources and outcomes to validate against MS-COM in people with overweight or obesity with or without type 2 diabetes. We extracted baseline characteristics and cardiovascular and mortality outcomes, where these were closely matched with MS-COM, and incidence of type 2 diabetes. We performed external-dependent (sources used in MS-COM) and external-independent (sources not used in MS-COM) validation. The extent of concordance between predicted and observed outcomes was assessed using the coefficient of determination (R2), ordinary least-squares linear regression line (OLS LRL), mean absolute percentage error, root mean square percentage error and mean squared log of accuracy ratio. Ninety-nine potential independent validation sources were identified from 6381 screened records, of which nine studies reported cardiovascular and mortality outcomes that were closely matched with MS-COM, along with two studies that reported type 2 diabetes incidence (number of endpoints = 106). The dependent validation of cardiovascular and mortality outcomes (N = 18), based on the QRisk3 risk equation (normoglycaemia/prediabetes population) and UKPDS 82 (type 2 diabetes population), showed a good linear correlation with observed outcomes (R2 = 0.99 and 0.98, respectively). There was some slight overprediction of QRisk3 (OLS LRL slope = 1.11) and underprediction of UKPDS 82 (OLS LRL slope = 0.97). The independent validation of cardiovascular and mortality outcomes also showed a good linear correlation with observed outcomes, particularly in adults with normoglycaemia/prediabetes (R2 = 0.90; OLS LRL slope = 0.86); however, an independent validation of type 2 diabetes incidence showed a poorer fit with some degree of underprediction (R2 = 0.74; OLS LRL slope = 0.66). Mean error estimates were lower in the dependent validation, showing good concordance between predicted and observed values. External validation of MS-COM showed good concordance with dependent and independent sources, suggesting the model accurately predicts obesity-related complications in an overweight/obese population with normoglycaemia/prediabetes and type 2 diabetes.

Ritlecitinib and baricitinib are recently approved systemic treatments for severe alopecia areata (AA). Both demonstrated superiority over placebo in hair regrowth measured by the Severity of Alopecia Tool (SALT), but they have not been directly compared in randomized controlled trials (RCTs). We conducted a systematic review of RCTs evaluating treatments in AA and estimated the efficacy and safety of ritlecitinib and baricitinib at Week 24 using Bayesian network meta-analysis. To adjust and explore effect modifiers, population-adjusted indirect comparison was performed via multilevel network meta-regression (ML-NMR) using ritlecitinib individual patient data (IPD). Co-primary endpoints were SALT ≤20 and SALT ≤10 at Week 24. Unanchored population adjusted ITCs were also computed to evaluate SALT ≤10 and SALT ≤20 endpoints at Week 48/52. Four RCTs (ALLEGRO 2a [NCT02974868], ALLEGRO 2b/3 [NCT03732807], BRAVE-AA1 [NCT03570749] and BRAVE-AA2 [NCT03899259]) were included. No evidence of a difference between ritlecitinib 50 mg and baricitinib 4 mg on SALT ≤10 (odds ratio, OR: 0.96, 95% credible interval, CrI: 0.18-7.21) and SALT ≤20 (OR: 2.16, 95% CrI: 0.48-16.46) at Week 24 was found. ML-NMR using ALLEGRO IPD adjusted for sex, SALT score at baseline, duration of current episode and disease duration found evidence of effect modification, although relative efficacy between ritlecitinib 50 mg and baricitinib 4 mg remained unchanged. Unanchored population-adjusted ITC at Week 48/52 was consistent with previous results. We found similar efficacy between ritlecitinib 50 mg and baricitinib 4 mg. These ITCs was informed by only four RCTs, uncertainty was considerable, and there was evidence of effect modification, highlighting the need for further quality research in AA.

Aim: Indirect treatment comparisons (ITCs) are anchored on a placebo comparator, and the placebo response may vary according to drug administration route. Migraine preventive treatment studies were used to evaluate ITCs and determine whether mode of administration influences placebo response and the overall study findings. Materials & methods: Change from baseline in monthly migraine days produced by monoclonal antibody treatments (subcutaneous, intravenous) was compared using fixed-effects Bayesian network meta-analysis (NMA), network meta-regression (NMR), and unanchored simulated treatment comparison (STC). Results: NMA and NMR provide mixed, rarely differentiated results between treatments, whereas unanchored STC strongly favors eptinezumab over other preventive treatments. Conclusion: Further investigations are needed to determine which ITC best reflects the impact of mode of administration on placebo.

BACKGROUND:Approximately 60% of antibiotics issued in primary care are for acute respiratory tract infections (RTIs), which are largely self-limiting and do not require antibiotics. Point-of-care testing (POCT) devices that measure C-reactive protein (CRP)-a biomarker for infection-can be used to guide prescribing decisions.OBJECTIVE:We evaluated the cost-effectiveness and budget impact of a national CRP POCT program to guide antibiotic prescribing for acute RTIs in primary care in Ireland.METHODS:We compared CRP POCT with and without enhanced communication skills training of general practitioners against usual care. A probabilistic decision tree was used to investigate cost-effectiveness from the perspective of the healthcare system. The model considered outcomes for the Irish population over a 5-year time horizon. Inputs were synthesized from published studies. Cost-effectiveness was estimated using an incremental cost per prescription avoided.RESULTS:CRP POCT with and without communication training were more costly but more effective than usual care over 5 years. CRP POCT alone was dominated, while the combined intervention had a cost per prescription avoided of €111 (95% CI: €45-243) versus usual care. The budget impact was costly over 5 years, but potential budget savings were available depending on the implementation scenario. The findings were largely robust to sensitivity analyses.CONCLUSIONS:CRP POCT reduces antibiotic prescribing, but increases healthcare costs. The most cost-effective program of CRP POCT includes enhanced communication skills training. Further research on the impact of CRP POCT beyond 5 years is warranted, as well as the potential impact on antimicrobial resistance.

To systematically identify and appraise the international literature on the cost-effectiveness of metabolic surgery for the treatment of comorbid type 2 diabetes (T2D) and obesity. A systematic search was conducted in electronic databases and grey literature sources up to 20 January 2021. Economic evaluations in a T2D population or a subpopulation with T2D were eligible for inclusion. Screening, data extraction, critical appraisal of methodological quality (Consensus Health Economic Criteria list) and assessment of transferability (International Society for Pharmacoeconomics and Outcomes Research questionnaire) were undertaken in duplicate. The incremental cost-effectiveness ratio (ICER) was the main outcome. Costs were reported in 2020 Irish Euro. Cost-effectiveness was interpreted using willingness-to-pay (WTP) thresholds of €20,000 and €45,000/quality-adjusted life year (QALY). Due to heterogeneity arising from various sources, a narrative synthesis was undertaken. Thirty studies across seventeen jurisdictions met the inclusion criteria; 16 specifically in a T2D population and 14 in a subpopulation with T2D. Overall, metabolic surgery was found to be cost-effective or cost-saving. Where undertaken, the results were robust to sensitivity and scenario analyses. Of the 30 studies included, 15 were considered high quality. Identified limitations included limited long-term follow-up data and uncertainty regarding the utility associated with T2D remission. Published high-quality studies suggest metabolic surgery is a cost-effective or cost-saving intervention. As the prevalence of obesity and obesity-related diseases increases worldwide, significant investment and careful consideration of the resource requirements needed for metabolic surgery programmes will be necessary to ensure that service provision is adequate to meet demand.

Antimicrobial resistance (AMR) is a global public health concern that can lead to increased morbidity and mortality. Patients with antimicrobial-resistant infections typically require longer hospital admissions, which may impact other health services. We estimated the additional bed day costs associated with treating resistant relative to susceptible infections in Ireland. A simulation model was developed to estimate the cost due to excess length-of-stay of treating 16 common antibiotic-resistance bacterium combinations. Infections were classified as either bloodstream, respiratory, urinary tract, surgical site or 'other' infections. The incidence of resistant infections was based on European Antimicrobial Resistance Surveillance Network data, collected from all public acute hospitals in Ireland in 2019. Attributable length-of-stay data were sourced from the literature. The national average cost of an inpatient bed day was applied. Intensive care bed-day costs were considered in scenario analysis. The estimated additional cost of AMR due to excess length-of-stay was €12,020,068 (95% CI: €4,879,603-€23,267,352). Resistant 'other infections' accounted for 36.7% of costs, followed by resistant surgical site (25.0%), bloodstream (18.7%), respiratory (10.6%) and urinary tract (9.0%) infections. When intensive care costs were applied for cases potentially admitted to intensive care (based on a weighted probability of admission for infection type), the estimated additional cost was €15,515,044 (95% CI: €6,594,222-€28,723,702). The estimated economic burden of AMR on public acute hospitals in Ireland due to excess length-of-stay likely exceeded €12 million in 2019. The analysis was limited to hospital costs relating to excess length-of-stay for routinely collected antibiotic-resistance bacterium combinations, so is likely to be a considerable underestimate of total costs to the health system and to the individuals affected. Nonetheless, it provides a baseline against which progress can be measured. Expanded surveillance is needed to effectively identify and manage AMR, as well as to allow broader evaluations of AMR-associated costs.

Rapid antigen detection tests (RADTs) offer advantages over gold-standard reverse transcription polymerase chain reaction (RT-PCR) tests in that they are cheaper and provide faster results, thus enabling prompt isolation of positive SARS-CoV-2 cases and quarantine of close contacts. The aim of this study was to collate and synthesise empirical evidence on the effectiveness of rapid antigen testing for the screening (including serial testing) and surveillance of asymptomatic individuals to limit the transmission of SARS-CoV-2. A rapid review was undertaken in MEDLINE (EBSCO), EMBASE (OVID), Cochrane Library, Europe PMC and Google Scholar up until 19 July 2021, supplemented by a grey literature search. Of the identified 1222 records, 19 reports referring to 16 studies were included. Eight included studies examined the effectiveness of RADTs for population-level screening, four for pre-event screening and four for serial testing (schools, a prison, a university sports programme and in care homes). Overall, there is uncertainty regarding the effectiveness of rapid antigen testing for the screening of asymptomatic individuals to limit the transmission of SARS-CoV-2. This uncertainty is due to the inconsistent results, the relatively low number of studies identified, the predominantly observational and/or uncontrolled nature of the study designs used, and concerns regarding methodological quality. Given this uncertainty, more real-world research evidence in relevant settings, which is of good quality and timely, as well as economic evaluation, is required to inform public policy on the widespread use of RADTs in asymptomatic individuals.

Background Since March 2020, members of the Health Technology Assessment (HTA) team in HIQA have been identifying, reviewing and presenting COVID-19 public health guidance produced by international organisations. The aim of this work has been to inform the development of public health guidance and policy by the Health Protection Surveillance Centre (HPSC), Department of Health and Health Service Executive (HSE), using international evidence and best practice. Methods International resources are searched on a weekly basis to identify new or updated public health guidance on COVID-19. The three distinct steps in the process include, searching relevant international resources, reviewing identified relevant public health guidance for COVID-19, and presenting new or updated guidance in a COVID-19 Public Health Guidance Database, which was created by the team using Microsoft Excel. The international organisations reviewed include the World Health Organisation, European Centre for Disease Prevention and Control and Centers for Disease Control and Prevention, as well as a range of ministries of health and public health agencies from 10 countries. These were chosen, based on guidance being available in English, widespread use of the organisation's advice, and/or the working constraints of the HTA team. Results The COVID-19 Public Health Guidance Database is updated weekly and provided to the relevant individuals within HPSC, Department of Health, and HSE, who are responsible for developing public health and infection, prevention and control guidance related to COVID-19 in Ireland. Following this the database is published online and may be utilised by the public or other international organisations. Conclusions The COVID-19 Public Health Guidance Database is used to inform the ongoing response to the COVID-19 pandemic, specifically, to inform the development of public health and infection, prevention and control guidance to prevent the spread of COVID-19.

Background and Objectives Recognising the significant public health threat posed by hepatitis C, international targets have been established by the World Health Organization with the aim of eradicating the hepatitis C virus (HCV) by 2030. With the availability of safe and effective therapies, the greatest challenge to achieving elimination is the identification and treatment of those currently undiagnosed. This systematic review aimed to identify and appraise the international literature on the cost-effectiveness of birth cohort, universal, and age-based general population testing for identifying people with undiagnosed chronic HCV infection. Methods A comprehensive literature search was undertaken in Medline, Embase and grey literature sources to identify studies published between 1 January 2000 and 17 July 2020. Retrieved citations were independently reviewed by two reviewers according to pre-defined eligibility criteria. Data extraction and critical appraisal were completed in duplicate. Study quality, relevance and credibility were assessed using the Consensus for Health Economic Criteria and the ISPOR questionnaires. All costs were reported in 2019 Irish Euro following adjustment for inflation and purchasing power parity. Willingness-to-pay (WTP) thresholds of €20,000 and €45,000 were adopted as reference points for interpreting cost-effectiveness in the narrative synthesis. The systematic review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Results Overall, 4622 citations were retrieved in the literature search. Of these, 27 studies met the inclusion criteria. Six (22%) of the 27 studies were rated as low quality, 17 (63%) were moderate quality and four (15%) were high quality. Compared with no testing or risk-based testing: 14 of 16 (88%) cost-utility analyses found that birth cohort testing was cost effective, eight of nine (89%) analyses found that universal testing was cost effective, and eight of eight (100%) analyses found that age-based general population testing was cost effective. Cost effectiveness was influenced by disease prevalence and progression, testing and treatment uptake, treatment eligibility of those identified by testing, the cost of treatment and the proportion of those treated that achieve sustained virological response. Conclusion Overall, the international evidence supports the potential cost effectiveness of birth cohort, universal, and age-based general population testing, but is caveated by study generalisability, specifically the transferability of findings from one jurisdiction to another, and institutional variations in healthcare delivery systems and budgetary constraints. The cost effectiveness of each approach will vary according to population- and health system-specific characteristics such as epidemiological context, testing coverage, linkage to care and capacity to treat. Given issues regarding the transferability of economic evaluations (for example, model inputs and assumptions) and the significant resources required to implement these interventions, jurisdiction-specific economic evaluations and budget impact analyses will likely be required to inform investment and implementation decisions. Registration PROSPERO, CRD42019127159. Registered 29 April 2019.

Mass gatherings play an important role in society, but since the onset of the Covid-19 pandemic, they have generally been restricted in order to mitigate transmission of SARS-CoV-2. The aim of this study was to summarise the evidence regarding the effectiveness of public health measures at preventing the transmission of SARS-CoV-2 at mass gatherings, and hence inform guidance on the organisation of these events. A rapid review was undertaken in Cochrane, Embase (OVID), Medline (OVID), Google, Web of Science and Europe PMC from 1 January 2020 to 3 June 2021. Of the identified 1,624 citations, 14 articles referring to 11 unique studies were included. This rapid review found evidence from 11 studies (involving approximately 30,482 participants) that implementing a range of measures may reduce the risk of SARS-CoV-2 transmission at mass gatherings; however, it is unlikely that this risk can be eliminated entirely. All studies adopted a layered mitigation approach involving multiple measures, which may be more effective than relying on any single measure. The number and intensity of measures implemented varied across studies, with most implementing resource intense measures. Importantly, all included studies were only of 'fair' to 'poor' quality. In conclusion, there is currently limited evidence on the effectiveness of measures to prevent SARS-CoV-2 transmission at mass gatherings. As mass gatherings recommence, continued adoption of known mitigation measures is required to limit the risk of transmission, as well as ongoing research and surveillance to monitor the potential impact of these events on the wider population and healthcare system.

The hepatitis C virus (HCV) is a blood-borne virus which may not become symptomatic until decades following exposure. Focus has shifted towards identifying currently undiagnosed patients with chronic HCV since the introduction of direct-acting antiviral (DAA) treatment (in 2011) which is curative and acceptable to patients. We undertook a systematic review of the international cost-effectiveness evidence of birth cohort screening for HCV in an asymptomatic population to understand why cost-effectiveness may vary and what implications this has for countries considering its introduction. Economic evaluations comparing birth cohort screening with no screening or risk-based screening, where patients were treated with DAAs, were eligible for inclusion. Embase, Medline and grey literature sources were searched up to February 2019. Screening, data extraction, quality and transferability assessment were conducted in duplicate. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The proposed methodology was registered on PROSPERO (CRD42019127159). Costs are presented in 2018 Euro. Thirteen studies were included. Study quality and transferability were variable, ranging from low to high. The estimated incremental cost-effectiveness ratios (ICERs) ranged from €7,574 to €105,121 per QALY gained. One study found that birth cohort screening dominated no screening. The uncertainty surrounding the cost-effectiveness of screening was mainly influenced by the uptake rates of screening and treatment, liver fibrosis score at diagnosis and prevalence of chronic HCV infection. No study modelled a systematic population-based screening programme (associated with higher uptake). The ICERs estimated by international studies varied considerably due mainly to differences in input parameters (prevalence, treatment costs, treatment effectiveness and treatment criteria). Of the 13 studies included, eight would be considered cost-effective at a willingness-to-pay threshold of €45,000/QALY. Given the variation in results and potential cost of implementing birth cohort screening, jurisdiction-specific economic evaluations will generally be required to inform policy decision-making.

BACKGROUND:Depression is usually managed in primary care, but most antidepressant trials are of patients from secondary care mental health services, with eligibility criteria based on diagnosis and severity of depressive symptoms. Antidepressants are now used in a much wider group of people than in previous regulatory trials. We investigated the clinical effectiveness of sertraline in patients in primary care with depressive symptoms ranging from mild to severe and tested the role of severity and duration in treatment response. METHODS:The PANDA study was a pragmatic, multicentre, double-blind, placebo-controlled randomised trial of patients from 179 primary care surgeries in four UK cities (Bristol, Liverpool, London, and York). We included patients aged 18 to 74 years who had depressive symptoms of any severity or duration in the past 2 years, where there was clinical uncertainty about the benefit of an antidepressant. This strategy was designed to improve the generalisability of our sample to current use of antidepressants within primary care. Patients were randomly assigned (1:1) with a remote computer-generated code to sertraline or placebo, and were stratified by severity, duration, and site with random block length. Patients received one capsule (sertraline 50 mg or placebo orally) daily for one week then two capsules daily for up to 11 weeks, consistent with evidence on optimal dosages for efficacy and acceptability. The primary outcome was depressive symptoms 6 weeks after randomisation, measured by Patient Health Questionnaire, 9-item version (PHQ-9) scores. Secondary outcomes at 2, 6 and 12 weeks were depressive symptoms and remission (PHQ-9 and Beck Depression Inventory-II), generalised anxiety symptoms (Generalised Anxiety Disorder Assessment 7-item version), mental and physical health-related quality of life (12-item Short-Form Health Survey), and self-reported improvement. All analyses compared groups as randomised (intention-to-treat). The study is registered with EudraCT, 2013-003440-22 (protocol number 13/0413; version 6.1) and ISRCTN, ISRCTN84544741, and is closed to new participants. FINDINGS:Between Jan 1, 2015, and Aug 31, 2017, we recruited and randomly assigned 655 patients-326 (50%) to sertraline and 329 (50%) to placebo. Two patients in the sertraline group did not complete a substantial proportion of the baseline assessment and were excluded, leaving 653 patients in total. Due to attrition, primary outcome analyses were of 550 patients (266 in the sertraline group and 284 in the placebo group; 85% follow-up that did not differ by treatment allocation). We found no evidence that sertraline led to a clinically meaningful reduction in depressive symptoms at 6 weeks. The mean 6-week PHQ-9 score was 7·98 (SD 5·63) in the sertraline group and 8·76 (5·86) in the placebo group (adjusted proportional difference 0·95, 95% CI 0·85-1·07; p=0·41). However, for secondary outcomes, we found evidence that sertraline led to reduced anxiety symptoms, better mental (but not physical) health-related quality of life, and self-reported improvements in mental health. We observed weak evidence that depressive symptoms were reduced by sertraline at 12 weeks. We recorded seven adverse events-four for sertraline and three for placebo, and adverse events did not differ by treatment allocation. Three adverse events were classified as serious-two in the sertraline group and one in the placebo group. One serious adverse event in the sertraline group was classified as possibly related to study medication. INTERPRETATION:Sertraline is unlikely to reduce depressive symptoms within 6 weeks in primary care but we observed improvements in anxiety, quality of life, and self-rated mental health, which are likely to be clinically important. Our findings support the prescription of SSRI antidepressants in a wider group of participants than previously thought, including those with mild to moderate symptoms who do not meet diagnostic criteria for depression or generalised anxiety disorder. FUNDING:National Institute for Health Research.

OBJECTIVES:Direct-acting antivirals containing nonstructural protein 5A (NS5A) inhibitors administered over 8 to 12 weeks are effective in ∼95% of patients with hepatitis C virus. Nevertheless, patients resistant to NS5A inhibitors have lower cure rates over 8 weeks (<85%); for these patients, 12 weeks of treatment produces cure rates greater than 95%. We evaluated the lifetime cost-effectiveness of testing for NS5A resistance at baseline and optimizing treatment duration accordingly in genotype 1 noncirrhotic treatment-naïve patients from the perspective of the UK National Health Service. METHODS:A decision-analytic model compared (1) standard 12-week treatment (no testing), (2) shortened 8-week treatment (no testing), and (3) baseline testing with 12-/8-week treatment for those with/without NS5A polymorphisms. Patients who failed first-line therapy were retreated for 12 weeks. Model inputs were derived from published studies. Costs, quality-adjusted life-years, and the probability of cost-effectiveness were calculated. RESULTS:Baseline testing had an incremental net monetary benefit (INMB) of £11 838 versus standard 12 weeks of therapy (no testing) and low probability (31%) of being the most cost-effective, assuming £30 000 willingness to pay. Shortened 8 weeks of treatment (no testing) had an INMB of £12 294 and the highest probability (69%) of being most cost-effective. Scenario analyses showed baseline testing generally had the highest INMB and probability of being most cost-effective if first- and second-line drug prices were low (<£20k). CONCLUSIONS:Optimizing treatment duration based on NS5A polymorphisms for genotype 1 noncirrhotic treatment-naive patients in the United Kingdom is not cost-effective if the drug costs are high; the strategy is generally most cost-effective when drug prices are low (<£20k).

Services for cardiac conditions such as acute coronary syndrome (ACS) can be organised into specialist cardiac networks. Although these networks have been shown to improve the quality of care, it is unclear how they are organised in practice. The aim of this scoping review was to identify and describe these models of specialist cardiac networks thereby informing the work of the National Review of Specialist Cardiac Services in Ireland. A scoping review of models of specialist cardiac networks located in EU or high-income countries was undertaken, for the period 01/01/2008 to 13/03/2019. The focus of the scoping review was adult specialist cardiac networks that were hospital-/cardiologist-led, managed and hierarchical. A narrative synthesis was conducted. Eighty-two specialist cardiac networks (ACS-related [n=75]; non ACS-related [n=7]) were identified, located across 21 countries. A key feature of networks was the use of clinical audit to assess performance and inform quality improvement. In the 75 ACS-related networks, 'hub and spoke' models featured prominently; at least 55 (73%) ACS networks offered a 24/7 service; the maximum distance between a percutaneous coronary intervention (PCI) centre and a non-PCI centre within a network ranged from 11km to 430km, averaging 113km; and the population served per 24/7 PCI centre ranged from 120,000 to 2.5 million inhabitants, averaging 758,000 inhabitants. In general, increased efficiencies associated with the establishment of the ACS-related networks were reported, both in terms of improvements in time-to-treatment and the proportion of patients receiving primary PCI. There was limited evidence regarding the structure, organisation or efficiencies of networks for non-ACS cardiac conditions. Certain commonalities were found across specialist cardiac networks in particular the use of clinical audit; however, important organisational differences were observed. Efficiencies were noted as a result of the networked provision of care. These findings have implications for the configuration of adult cardiac services.