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Background: When clinically effective, cost-effective health interventions are not fully implemented in clinical practice, population health suffers. Economic factors are among the most commonly cited reasons for suboptimal implementation. Despite this, implementation and economic evaluation are not routinely performed in conjunction with one another. This review sought to identify and describe what methods are available for researchers to incorporate implementation within economic evaluation, how these methods differ, when they should be used, and where gaps remain., Methods: We conducted a scoping review using systematic methods. A pearl-growing approach was used to identify studies. References and citations were identified using Web of Science and Scopus. We included for review any study that contained terms relating to economic evaluation and a series of implementation-related terms in the title or abstract. The search was conducted and validated using two independent researchers., Results: Our review identified 42 unique studies that included a methodology for combining implementation and economic evaluation. The methods identified could be categorized into four broad themes: (i) policy cost-effectiveness approach (11 studies), (ii) value of information and value of implementation approach (16 studies), (iii) mixed methods approach (6 studies), and (iv) costing approach (9 studies). We identified a trend over time from methods that adopted the policy cost-effectiveness approach to methods that considered the trade-off between the value of information and value of implementation. More recently, mixed methods approaches to incorporate economic evaluation and implementation have been developed, alongside methods to define, measure and cost individual components of the implementation process for use in economic evaluation., Conclusion: Our review identified a range of methods currently available for researchers considering implementation alongside economic evaluation. There is no single method or tool that can incorporate all the relevant issues to fully incorporate implementation within an economic evaluation. Instead, there are a suite of tools available, each of which can be used to answer a specific question relating to implementation. Researchers, reimbursement agencies and national and local decision-makers need to consider how best to utilize these tools to improve implementation., (© 2024. The Author(s).)

Background: The use of robotic-assisted surgery (RAS) is growing rapidly. However, economic evaluation of this technology is challenging. This study aims to identify and discuss the different economic evaluation methods which have been used to evaluate RAS., Method: This scoping review systematically searched PubMed and Embase from 2015 to 2023. We included economic evaluation studies comparing RAS versus laparoscopic or open surgery. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist was used to aid data extraction and was extended to cover additional features relevant to RAS, including learning curve, organisational impact, incremental innovation and dynamic pricing., Results: A total of 50 economic evaluations of RAS were included. Cost-utility analysis (46%) was the most commonly applied economic evaluation method, followed by cost-consequence analysis (32%). The studies focused on the specialties of urology (42%), hepato-pancreato-biliary (20%), colorectal (14%) and gynaecology (6%). Distinctive features related to the assessment of RAS were under-addressed in economic evaluations. Only 40% of the included studies considered learning curve and organisational impact and less than 12% of the included studies reflected on incremental innovation and dynamic pricing., Conclusions: This review found that some studies have incorporated challenges specific to RAS in their evaluations. However, most studies still lack key aspects of importance. In particular, studies rarely considered the ability of RAS platforms to be shared across multiple specialities. Incorporating these distinctive features offers an opportunity for economic evaluation to provide decision-makers with a more realistic assessment of the cost-effectiveness of this technology and to ensure its optimal utilisation in clinical practice., (© 2024. The Author(s).)

Background: We investigated the usefulness of invasive coronary function testing to diagnose the cause of angina in patients with no obstructive coronary arteries., Methods: Outpatients referred for coronary computed tomography angiography in 3 hospitals in the United Kingdom were prospectively screened. After coronary computed tomography angiography, patients with unobstructed coronary arteries, and who consented, underwent invasive endotyping. The diagnostic assessments included coronary angiography, fractional flow reserve (patient excluded if ≤0.80), and, for those without obstructive coronary artery disease, coronary flow reserve (abnormal <2.0), index of microvascular resistance (abnormal ≥25), and intracoronary infusion of acetylcholine (0.182, 1.82, and 18.2 μg/mL; 2 mL/min for 2 minutes) to assess for microvascular and coronary spasm. Participants were randomly assigned to disclosure of the results of the coronary function tests to the invasive cardiologist (intervention group) or nondisclosure (control group, blinded). In the control group, a diagnosis of vasomotor angina was based on medical history, noninvasive tests, and coronary angiography. The primary outcome was the between-group difference in the reclassification rate of the initial diagnosis on the basis of coronary computed tomography angiography versus the final diagnosis after invasive endotyping. The Seattle Angina Questionnaire summary score and Treatment Satisfaction Questionnaire for Medication were secondary outcomes., Results: Of 322 eligible patients, 250 (77.6%) underwent invasive endotyping; 19 (7.6%) had obstructive coronary disease, 127 (55.0%) had microvascular angina, 27 (11.7%) had vasospastic angina, 17 (7.4%) had both, and 60 (26.0%) had no abnormality. A total of 231 patients (mean age, 55.7 years; 64.5% women) were randomly assigned and followed up (median duration, 19.9 [12.6-26.9] months). The clinician diagnosed vasomotor angina in 51 (44.3%) patients in the intervention group and in 55 (47.4%) patients in the control group. After randomization, patients in the intervention group were 4-fold (odds ratio, 4.05 [95% CI, 2.32-7.24]; P <0.001) more likely to be diagnosed with a coronary vasomotor disorder; the frequency of this diagnosis increased to 76.5%. The frequency of normal coronary function (ie, no vasomotor disorder) was not different between the groups before randomization (51.3% versus 50.9%) but was reduced in the intervention group after randomization (23.5% versus 50.9%, P <0.001). At 6 and 12 months, the Seattle Angina Questionnaire summary score in the intervention versus control groups was 59.2±24.2 (2.3±16.2 change from baseline) versus 60.4±23.9 (4.6±16.4 change) and 63.7±23.5 (4.7±14.7 change) versus 66.0±19.3 (7.9±17.1 change), respectively, and not different between groups (global P =0.36). Compared with the control group, global treatment satisfaction was higher in the intervention group at 12 months (69.9±22.8 versus 61.7±26.9, P =0.013)., Conclusions: For patients with angina and no obstructive coronary arteries, a diagnosis informed by invasive functional assessment had no effect on long-term angina burden, whereas treatment satisfaction improved., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03477890., Competing Interests: Disclosures Dr Berry is employed by the University of Glasgow, which holds consultancy and research agreements with companies that have interests in the management of angina. The companies include Abbott Vascular, AstraZeneca, Auxilius Pharma, Boehringer Ingelheim, Coroventis, HeartFlow, Novartis, Siemens Healthcare, Therox, and Valo Health. Dr McEntegart provides consultancy for Biosensors, Boston Scientific, Shockwave Medical and Teleflex, and has received honoraria from Biosensors, Boston Scientific and Medtronic. Dr Ford provides consultancy for Abbott Vascular. None of the other authors have any potential conflicts of interest.

Objectives: Patients undergoing long-term anticancer therapy typically require one of 3 venous access devices: Hickman-type device (HICK), peripherally inserted central catheter (PICC), or implantable chest wall port (PORT). Recent evidence has shown PORT is safer and improves patient satisfaction. However, PORT did not show improvement in quality-adjusted life-years and was more expensive. Decisions regarding cost-effectiveness in the United Kingdom are typically informed by a cost-per-quality-adjusted life-year metric. However, this approach is limited in its ability to capture the full range of relevant outcomes, especially in the context of medical devices. This study assessed the potential cost-effectiveness of HICK, PICC, and PORT in routine clinical practice., Methods: This is a cost-consequence analysis to determine the trade-offs between the following outcomes: complication, infection, noninfection, chemotherapy interruption, unplanned device removals, health utilities, device insertion cost, follow-up cost, and total cost, using data from the Cancer and Venous Access clinical trial. We conducted value of implementation analysis of a PORT service., Results: PORT was superior in terms of overall complication rate compared with both HICK (incidence rate ratio 0.422; 95% CI 0.286-0.622) and PICC (incidence rate ratio 0.295; 95% CI 0.189-0.458) and less likely to lead to an unplanned device removal. There was no difference in chemotherapy interruption or health utilities. Total cost with device in situ was lower on PORT than HICK (-£98.86; 95% CI -189.20 to -8.53) and comparable with PICC -£48.57 (95% CI -164.99 to 67.86). Value of implementation analysis found that PORT was likely to be considered cost-effective within the National Health Service., Conclusion: Decision makers should consider including PORT within the suite of venous access devices available within in the National Health Service., Competing Interests: Author Disclosures Links to the individual disclosure forms provided by the authors are available here., (Copyright © 2023. Published by Elsevier Inc.)

Background: Coronary microvascular dysfunction may cause myocardial ischemia with no obstructive coronary artery disease (INOCA). If functional testing is not performed INOCA may pass undetected. Stress perfusion cardiovascular MRI (CMR) quantifies myocardial blood flow (MBF) but the clinical utility of stress CMR in the management of patients with suspected angina with no obstructive coronary arteries (ANOCA) is uncertain., Objectives: First, to undertake a diagnostic study using stress CMR in patients with ANOCA following invasive coronary angiography and, second, in a nested, double-blind, randomized, controlled trial to assess the effect of disclosure on the final diagnosis and health status in the longer term., Design: All-comers referred for clinically indicated coronary angiography for the investigation of suspected coronary artery disease will be screened in 3 regional centers in the United Kingdom. Following invasive coronary angiography, patients with ANOCA who provide informed consent will undergo noninvasive endotyping using stress CMR within 3 months of the angiogram., Diagnostic Study: Stress perfusion CMR imaging to assess the prevalence of coronary microvascular dysfunction and clinically significant incidental findings in patients with ANOCA. The primary outcome is the between-group difference in the reclassification rate of the initial diagnosis based on invasive angiography versus the final diagnosis after CMR imaging., Randomized, Controlled Trial: Participants will be randomized to inclusion (intervention group) or exclusion (control group) of myocardial blood flow to inform the final diagnosis. The primary outcome of the clinical trial is the mean within-subject change in the Seattle Angina Questionnaire summary score (SAQSS) at 6 months. Secondary outcome assessments include the EUROQOL EQ-5D-5L questionnaire, the Brief Illness Perception Questionnaire (Brief-IPQ), the Treatment Satisfaction Questionnaire (TSQM-9), the Patient Health Questionnaire-4 (PHQ-4), the Duke Activity Status Index (DASI), the International Physical Activity Questionnaire- Short Form (IPAQ-SF), the Montreal Cognitive Assessment (MOCA) and the 8-item Productivity Cost Questionnaire (iPCQ). Health and economic outcomes will be assessed using electronic healthcare records., Value: To clarify if routine stress perfusion CMR imaging reclassifies the final diagnosis in patients with ANOCA and whether this strategy improves symptoms, health-related quality of life and health economic outcomes., Clinicaltrials: GOV: NCT04805814., Competing Interests: Conflict of interest CB is employed by the University of Glasgow, which holds consultancy and research agreements with companies that have commercial interests in the diagnosis and management of angina, including Abbott Vascular, AstraZeneca, Boehringer Ingelheim, GSK, Heartflow, Menarini Pharmaceuticals, Neovasc, Siemens Healthcare, Therox and Valo Health. The authors received no support from any of these organizations for the submitted work., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Health Technology Assessment (HTA) is a multidisciplinary tool to inform healthcare decision-making. HTA has been implemented in high-income countries (HIC) for several decades but has only recently seen a growing investment in low- and middle-income countries. A scoping review was undertaken to define and compare the role of HTA in least developed and lower middle-income countries (LLMIC). MEDLINE and EMBASE databases were searched from January 2015 to August 2021. A matrix comprising categories on HTA objectives, methods, geographies, and partnerships was used for data extraction and synthesis to present our findings. The review identified 50 relevant articles. The matrix was populated and sub-divided into further categories as appropriate. We highlight topical aspects of HTA, including initiatives to overcome well-documented challenges around data and capacity development, and identify gaps in the research for consideration. Those areas we found to be under-studied or under-utilized included disinvestment, early HTA/implementation, system-level interventions, and cross-sectoral partnerships. We consider broad practical implications for decision-makers and researchers aiming to achieve greater interconnectedness between HTA and health systems and generate recommendations that LLMIC can use for HTA implementation. Whilst HIC may have led the way, LLMIC are increasingly beginning to develop HTA processes to assist in their healthcare decision-making. This review provides a forward-looking model that LLMIC can point to as a reference for their own implementation. We hope this can be seen as timely and useful contributions to optimize the impact of HTA in an era of investment and expansion and to encourage debate and implementation.

It has been suggested that health economists need to improve their methods in order to meet the challenges of evaluating genomic/genetic tests. In this article, we set out twelve challenges identified from a rapid review of the literature and suggest solutions to the challenges identified. Two challenges were common to all economic evaluations: choice of perspective and time-horizon. Five challenges were relevant for all diagnostic technologies: complexity of analysis; range of costs; under-developed evidence base; behavioral aspects; and choice of outcome metrics. The final five challenges were pertinent for genomic tests and only these may require methodological development: heterogeneity of tests and platforms, increasing stratification, capturing personal utility; incidental findings; and spillover effects. Current methods of economic evaluation are generally able to cope with genomic/genetic tests, although a renewed focus on specific decision-makers' needs and a willingness to move away from cost-utility analysis may be required. Certain analysts may be constrained by reference cases developed primarily for the assessment of pharmaceuticals. The combined impact of multiple challenges may require analysts to be particularly careful in setting the scope of their analysis in order to ensure that feasibility is balanced with usefulness to the decision maker. A key issue is the under-developed evidence-base and it may be necessary to rethink translation processes to ensure sufficient, relevant evidence is available to support economic evaluation and adoption of genomic/genetic tests.

Given the advantages in transparency, reproducibility, adaptability and computational efficiency in R, there is a growing interest in converting existing spreadsheet-based models into an R script for model re-use and upskilling training among health economic modellers. The objective of this exercise was to convert the Scottish Cardiovascular Disease (CVD) Policy Model from Excel to R and discuss the lessons learnt throughout this process. The CVD model is a competing risk state transition cohort model. Four health economists, with varied experience of R, attempted to replicate an identical model structure in R based on the model in Excel and reproduce the intermediate and final results. Replications varied in their use of specialist health economics packages in addition to standard data management packages. Two versions of the CVD model were created in R along with a Shiny app. Version 1 was developed without health economics specialist packages and produced identical results to the Excel version. Version 2 used the heemod package and did not achieve the same results, possibly due to the non-standard elements of the model and limited time to adapt the functions. The R model requires less than half the computational time than the Excel model. Conversion of the spreadsheet models to script models is feasible for health economists. A step-by-step guide for the conversion process is provided and modellers' experience is discussed. Coding without specialist packages allows full flexibility, while specialist packages may add convenience if the model structure is suitable. Whichever approach is taken, transparency and replicability remain the key criteria in model programming. Model conversions must maintain standards in these areas regardless of the choice of software., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: The diagnosis of preterm labour is challenging. False-positive diagnoses are common and result in unnecessary, potentially harmful treatments (e.g. tocolytics, antenatal corticosteroids and magnesium sulphate) and costly hospital admissions. Measurement of fetal fibronectin in vaginal fluid is a biochemical test that can indicate impending preterm birth., Objectives: To develop an externally validated prognostic model using quantitative fetal fibronectin concentration, in combination with clinical risk factors, for the prediction of spontaneous preterm birth and to assess its cost-effectiveness., Design: The study comprised (1) a qualitative study to establish the decisional needs of pregnant women and their caregivers, (2) an individual participant data meta-analysis of existing studies to develop a prognostic model for spontaneous preterm birth within 7 days in women with symptoms of preterm labour based on quantitative fetal fibronectin and clinical risk factors, (3) external validation of the prognostic model in a prospective cohort study across 26 UK centres, (4) a model-based economic evaluation comparing the prognostic model with qualitative fetal fibronectin, and quantitative fetal fibronectin with cervical length measurement, in terms of cost per QALY gained and (5) a qualitative assessment of the acceptability of quantitative fetal fibronectin., Data Sources/setting: The model was developed using data from five European prospective cohort studies of quantitative fetal fibronectin. The UK prospective cohort study was carried out across 26 UK centres., Participants: Pregnant women at 22 +0 -34 +6 weeks' gestation with signs and symptoms of preterm labour., Health Technology Being Assessed: Quantitative fetal fibronectin., Main Outcome Measures: Spontaneous preterm birth within 7 days., Results: The individual participant data meta-analysis included 1783 women and 139 events of spontaneous preterm birth within 7 days (event rate 7.8%). The prognostic model that was developed included quantitative fetal fibronectin, smoking, ethnicity, nulliparity and multiple pregnancy. The model was externally validated in a cohort of 2837 women, with 83 events of spontaneous preterm birth within 7 days (event rate 2.93%), an area under the curve of 0.89 (95% confidence interval 0.84 to 0.93), a calibration slope of 1.22 and a Nagelkerke R 2 of 0.34. The economic analysis found that the prognostic model was cost-effective compared with using qualitative fetal fibronectin at a threshold for hospital admission and treatment of ≥ 2% risk of preterm birth within 7 days., Limitations: The outcome proportion (spontaneous preterm birth within 7 days of test) was 2.9% in the validation study. This is in line with other studies, but having slightly fewer than 100 events is a limitation in model validation., Conclusions: A prognostic model that included quantitative fetal fibronectin and clinical risk factors showed excellent performance in the prediction of spontaneous preterm birth within 7 days of test, was cost-effective and can be used to inform a decision support tool to help guide management decisions for women with threatened preterm labour., Future Work: The prognostic model will be embedded in electronic maternity records and a mobile telephone application, enabling ongoing data collection for further refinement and validation of the model., Study Registration: This study is registered as PROSPERO CRD42015027590 and Current Controlled Trials ISRCTN41598423., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 25, No. 52. See the NIHR Journals Library website for further project information.

Objectives: Health interventions in a clinical setting may be complex. This is particularly true of clinical interventions which require systems reorganization or behavioural change, and/or when implementation involves additional challenges not captured within a clinical trial setting. Medical Research Council guidance on complex interventions highlights the need to consider economic evaluation alongside implementation. However, the extent to which this guidance has been adhered to, and how, is unclear. The failure to incorporate implementation within the evaluation of an intervention may hinder the translation of research findings into routine practice. This will have consequences for patient care. This study examined the methods used to address implementation within health research conducted through funding from the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme., Methods: We conducted a rapid review using a systematic approach. We included all NIHR HTA monographs which contained the word "implementation" within the title or abstract published between 2014 and 2020. We assessed the studies according to existing recommendations for specifying and reporting implementation approaches in research. Additional themes which were not included in the recommendation, but were of particular relevance to our research question, were also identified and summarized in a narrative synthesis., Results: The extent to which implementation was formally incorporated, and defined, varied among studies. Methods for examining implementation ranged from single stakeholder engagement events to the more comprehensive process evaluation. There was no obvious pattern as to whether approaches to implementation had evolved over recent years. Approximately 50% (22/42) of studies included an economic evaluation. Of these, two studies included the use of qualitative data obtained within the study to quantitatively inform aspects relating to implementation and economic evaluation in their study., Discussion: A variety of approaches were identified for incorporating implementation within an HTA. However, they did not go far enough in terms of incorporating implementation into the actual design and evaluation. To ensure the implementation of clinically effective and cost-effective interventions, we propose that further guidance on how to incorporate implementation within complex interventions is required. Incorporating implementation into economic evaluation provides a step in this direction., (© 2021. The Author(s).)

Background: Hickman-type tunnelled catheters (Hickman), peripherally inserted central catheters (PICCs), and totally implanted ports (PORTs) are used to deliver systemic anticancer treatment (SACT) via a central vein. We aimed to compare complication rates and costs of the three devices to establish acceptability, clinical effectiveness, and cost-effectiveness of the devices for patients receiving SACT., Methods: We did an open-label, multicentre, randomised controlled trial (Cancer and Venous Access [CAVA]) of three central venous access devices: PICCs versus Hickman (non-inferiority; 10% margin); PORTs versus Hickman (superiority; 15% margin); and PORTs versus PICCs (superiority; 15% margin). Adults (aged ≥18 years) receiving SACT (≥12 weeks) for solid or haematological malignancy from 18 oncology units in the UK were included. Four randomisation options were available: Hickman versus PICCs versus PORTs (2:2:1), PICCs versus Hickman (1:1), PORTs versus Hickman (1:1), and PORTs versus PICCs (1:1). Randomisation was done using a minimisation algorithm stratifying by centre, body-mass index, type of cancer, device history, and treatment mode. The primary outcome was complication rate (composite of infection, venous thrombosis, pulmonary embolus, inability to aspirate blood, mechanical failure, and other) assessed until device removal, withdrawal from study, or 1-year follow-up. This study is registered with ISRCTN, ISRCTN44504648., Findings: Between Nov 8, 2013, and Feb 28, 2018, of 2714 individuals screened for eligibility, 1061 were enrolled and randomly assigned, contributing to the relevant comparison or comparisons (PICC vs Hickman n=424, 212 [50%] on PICC and 212 [50%] on Hickman; PORT vs Hickman n=556, 253 [46%] on PORT and 303 [54%] on Hickman; and PORT vs PICC n=346, 147 [42%] on PORT and 199 [58%] on PICC). Similar complication rates were observed for PICCs (110 [52%] of 212) and Hickman (103 [49%] of 212). Although the observed difference was less than 10%, non-inferiority of PICCs was not confirmed (odds ratio [OR] 1·15 [95% CI 0·78-1·71]) potentially due to inadequate power. PORTs were superior to Hickman with a complication rate of 29% (73 of 253) versus 43% (131 of 303; OR 0·54 [95% CI 0·37-0·77]). PORTs were superior to PICCs with a complication rate of 32% (47 of 147) versus 47% (93 of 199; OR 0·52 [0·33-0·83])., Interpretation: For most patients receiving SACT, PORTs are more effective and safer than both Hickman and PICCs. Our findings suggest that most patients receiving SACT for solid tumours should receive a PORT within the UK National Health Service., Funding: UK National Institute for Health Research Health Technology Assessment Programme., Competing Interests: Declaration of interests JGM is paid a personal fee to run PORT training courses for Smith Medical and received PORTs free of charge from four manufacturers. OW is deputy chair of NIHR HTA general funding board (2020 onwards) and was a committee member of NIHR HTA general funding board 2016–19. BLJ receives payment for lectures from Merck Sharp and Dohme and Pfizer; attendance at advisory board for Menarini; owns shares in Novartis and Gilead Sciences; and is a member of the Scottish Medicines Consortium. All other authors declare no competing interests, (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Venous access devices are used for patients receiving long-term chemotherapy. These include centrally inserted tunnelled catheters or Hickman-type devices (Hickman), peripherally inserted central catheters (PICCs) and centrally inserted totally implantable venous access devices (PORTs)., Objectives: To evaluate the clinical effectiveness, safety, cost-effectiveness and acceptability of these devices for the central delivery of chemotherapy., Design: An open, multicentre, randomised controlled trial to inform three comparisons: (1) peripherally inserted central catheters versus Hickman, (2) PORTs versus Hickman and (3) PORTs versus peripherally inserted central catheters. Pre-trial and post-trial qualitative research and economic evaluation were also conducted., Setting: This took place in 18 UK oncology centres., Participants: Adult patients (aged ≥ 18 years) receiving chemotherapy (≥ 12 weeks) for either a solid or a haematological malignancy were randomised via minimisation., Interventions: Hickman, peripherally inserted central catheters and PORTs., Primary Outcome: A composite of infection (laboratory confirmed, suspected catheter related and exit site infection), mechanical failure, venous thrombosis, pulmonary embolism, inability to aspirate blood and other complications in the intention-to-treat population., Results: Overall, 1061 participants were recruited to inform three comparisons. First, for the comparison of peripherally inserted central catheters ( n  = 212) with Hickman ( n  = 212), it could not be concluded that peripherally inserted central catheters were significantly non-inferior to Hickman in terms of complication rate (odds ratio 1.15, 95% confidence interval 0.78 to 1.71). The use of peripherally inserted central catheters compared with Hickman was associated with a substantially lower cost (-£1553) and a small decrement in quality-adjusted life-years gained (-0.009). Second, for the comparison of PORTs ( n  = 253) with Hickman ( n  = 303), PORTs were found to be statistically significantly superior to Hickman in terms of complication rate (odds ratio 0.54, 95% confidence interval 0.37 to 0.77). PORTs were found to dominate Hickman with lower costs (-£45) and greater quality-adjusted life-years gained (0.004). This was alongside a lower complications rate (difference of 14%); the incremental cost per complication averted was £1.36. Third, for the comparison of PORTs ( n  = 147) with peripherally inserted central catheters ( n  = 199), PORTs were found to be statistically significantly superior to peripherally inserted central catheters in terms of complication rate (odds ratio 0.52, 95% confidence interval 0.33 to 0.83). PORTs were associated with an incremental cost of £2706 when compared with peripherally inserted central catheters and a decrement in quality-adjusted life-years gained (-0.018) PORTs are dominated by peripherally inserted central catheters: alongside a lower complications rate (difference of 15%), the incremental cost per complication averted was £104. The qualitative work showed that attitudes towards all three devices were positive, with patients viewing their central venous access device as part of their treatment and recovery. PORTs were perceived to offer unique psychological benefits, including a greater sense of freedom and less intrusion in the context of personal relationships. The main limitation was the lack of adequate power (54%) in the non-inferiority comparison between peripherally inserted central catheters and Hickman., Conclusions: In the delivery of long-term chemotherapy, peripherally inserted central catheters should be considered a cost-effective option when compared with Hickman. There were significant clinical benefits when comparing PORTs with Hickman and with peripherally inserted central catheters. The health economic benefits were less clear from the perspective of incremental cost per quality-adjusted life-years gained. However, dependent on the willingness to pay, PORTs may be considered to be cost-effective from the perspective of complications averted., Future Work: The deliverability of a PORTs service merits further study to understand the barriers to and methods of improving the service., Trial Registration: This trial is registered as ISRCTN44504648., Funding: This project was funded by the National Institute for Health Research (NHIR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 25, No. 47. See the NIHR Journals Library website for further project information.

Background: Diabetes-related foot ulcers give rise to considerable morbidity, generate a high monetary cost for health and social care services and precede the majority of diabetes-related lower extremity amputations. There are many clinical prediction rules in existence to assess risk of foot ulceration but few have been subject to validation., Objectives: Our objectives were to produce an evidence-based clinical pathway for risk assessment and management of the foot in people with diabetes mellitus to estimate cost-effective monitoring intervals and to perform cost-effectiveness analyses and a value-of-information analysis., Design: We developed and validated a prognostic model using predictive modelling, calibration and discrimination techniques. An overview of systematic reviews already completed was followed by a review of randomised controlled trials of interventions to prevent foot ulceration in diabetes mellitus. A review of the health economic literature was followed by the construction of an economic model, an analysis of the transitional probability of moving from one foot risk state to another, an assessment of cost-effectiveness and a value-of-information analysis., Interventions: The effects of simple and complex interventions and different monitoring intervals for the clinical prediction rules were evaluated., Main Outcome Measure: The main outcome was the incidence of foot ulceration. We compared the new clinical prediction rules in conjunction with the most effective preventative interventions at different monitoring intervals with a 'treat-all' strategy., Data Sources: Data from an electronic health record for 26,154 people with diabetes mellitus in one Scottish health board were used to estimate the monitoring interval. The Prediction Of Diabetic foot UlcerationS (PODUS) data set was used to develop and validate the clinical prediction rule., Review Methods: We searched for eligible randomised controlled trials of interventions using search strategies created for Ovid ® (Wolters Kluwer, Alphen aan den Rijn, the Netherlands), MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. Randomised controlled trials in progress were identified via the International Standard Randomised Controlled Trial Number Registry and systematic reviews were identified via PROSPERO. Databases were searched from inception to February 2019., Results: The clinical prediction rule was found to accurately assess the risk of foot ulceration. Digital infrared thermometry, complex interventions and therapeutic footwear with offloading devices were found to be effective in preventing foot ulcers. The risk of developing a foot ulcer did not change over time for most people. We found that interventions to prevent foot ulceration may be cost-effective but there is uncertainty about this. Digital infrared thermometry and therapeutic footwear with offloading devices may be cost-effective when used to treat all people with diabetes mellitus regardless of their ulcer risk., Limitations: The threats to the validity of the results in some randomised controlled trials in the review and the large number of missing data in the electronic health record mean that there is uncertainty in our estimates., Conclusions: There is evidence that interventions to prevent foot ulceration are effective but it is not clear who would benefit most from receiving the interventions. The ulceration risk does not change over an 8-year period for most people with diabetes mellitus. A change in the monitoring interval from annually to every 2 years for those at low risk would be acceptable., Future Work Recommendations: Improving the completeness of electronic health records and sharing data would help improve our knowledge about the most clinically effective and cost-effective approaches to prevent foot ulceration in diabetes mellitus., Study Registration: This study is registered as PROSPERO CRD42016052324., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 24, No. 62. See the NIHR Journals Library website for further project information.

Background: Recent clinical trials have demonstrated the efficacy of mechanical thrombectomy in acute ischemic stroke., Aims: To determine the cost-effectiveness, value of future research, and value of implementation of mechanical thrombectomy., Methods: Using UK clinical and cost data from the Pragmatic Ischemic Stroke Thrombectomy Evaluation (PISTE) trial, we estimated the cost-effectiveness of mechanical thrombectomy over time horizons of 90-days and lifetime, based on a decision-analytic model, using all existing evidence. We performed a meta-analysis of seven clinical trials to estimate treatment effects. We used sensitivity analysis to address uncertainty. Value of implementation analysis was used to estimate the potential value of additional implementation activities to support routine delivery of mechanical thrombectomy., Results: Over the trial period (90 days), compared with best medical care alone, mechanical thrombectomy incurred an incremental cost of £5207 and 0.025 gain in QALY (incremental cost-effectiveness ratio (ICER) £205,279), which would not be considered cost-effective. However, mechanical thrombectomy was shown to be cost-effective over a lifetime horizon, with an ICER of £3466 per QALY gained. The expected value of perfect information per patient eligible for mechanical thrombectomy in the UK is estimated at £3178. The expected value of full implementation of mechanical thrombectomy is estimated at £1.3 billion over five years., Conclusion: Mechanical thrombectomy was cost-effective compared with best medical care alone over a patient's lifetime. On the assumption of 30% implementation being achieved throughout the UK healthcare system, we estimate that the population health benefits obtained from this treatment are greater than the cost of implementation., Trial Registration: NCT01745692.

Aims/hypothesis: Foot ulceration is a serious complication for people with diabetes that results in high levels of morbidity for individuals and significant costs for health and social care systems. Nineteen systematic reviews of preventative interventions have been published, but none provides a reliable numerical summary of treatment effects. The aim of this study was to systematically review the evidence from RCTs and, where possible, conduct meta-analyses to make the best possible use of the currently available data., Methods: We conducted a systematic review and meta-analysis of RCTs of preventative interventions for foot ulceration. OVID MEDLINE and EMBASE were searched to February 2019 and the Cochrane Central Register of Controlled Trials to October 2018. RCTs of interventions to prevent foot ulcers in people with diabetes who were free from foot ulceration at trial entry were included. Two independent reviewers read the full-text articles and extracted data. The quality of trial reporting was assessed using the Cochrane Risk of Bias tool. The primary outcome of foot ulceration was summarised using pooled relative risks in meta-analyses., Results: Twenty-two RCTs of eight interventions were eligible for analysis. One trial of digital silicone devices (RR 0.07 [95% CI 0.01, 0.55]) and meta-analyses of dermal infrared thermometry (RR 0.41 [95% CI 0.19, 0.86]), complex interventions (RR 0.59 [95% CI 0.38, 0.90], and custom-made footwear and offloading insoles (RR 0.53 [95% CI 0.33, 0.85]) showed beneficial effects for these interventions., Conclusions/interpretation: Four interventions were identified as being effective in preventing foot ulcers in people with diabetes, but uncertainty remains about what works and who is most likely to benefit.

A recent study showed that the Prostate Health Index may avoid unnecessary biopsies in men with prostate specific antigen 4-10ng/ml and normal digital rectal examination in the diagnosis of prostate cancer in Hong Kong. This study aimed to conduct an economic evaluation of the impact of adopting this commercially-available test in the Hong Kong public health service to determine whether further research is justified. A cost-consequence analysis was undertaken comparing the current diagnostic pathway with a proposed diagnostic pathway using the Prostate Health Index. Data for the model was taken from a prospective cohort study recruited at a single-institution and micro-costing studies. Using a cut off PHI score of 35 to avoid biopsy would cost HK$3,000 and save HK$7,988 per patient in biopsy costs and HK$511 from a reduction in biopsy-related adverse events. The net cost impact of the change was estimated to be HK$5,500 under base case assumptions. At the base case sensitivity and specificity for all grades of cancer (61.3% and 77.5% respectively) all grade cancer could be missed in 4.22% of the population and high grade cancer in 0.53%. The introduction of the prostate health index into the diagnostic pathway for prostate cancer in Hong Kong has the potential to reduce biopsies, biopsy costs and biopsy-related adverse events. Policy makers should consider the clinical and economic impact of this proposal., Competing Interests: Beckman Coulter Inc., the manufacturer of the Prostate Health Index provided instruments and reagents for the clinical trial reported elsewhere (see reference 2) which provides the context for this economic evaluation. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Objective:: To examine the feasibility of a trial to evaluate web-based physiotherapy compared to a standard home exercise programme in people with multiple sclerosis., Design:: Multi-centre, randomized controlled, feasibility study., Setting:: Three multiple sclerosis out-patient centres., Participants:: A total of 90 people with multiple sclerosis (Expanded Disability Status Scale 4-6.5)., Interventions:: Participants were randomized to a six-month individualized, home exercise programme delivered via web-based physiotherapy ( n = 45; intervention) or a sheet of exercises ( n = 45; active comparator)., Outcome Measures:: Outcome measures (0, three, six and nine months) included adherence, two-minute walk test, 25 foot walk, Berg Balance Scale, physical activity and healthcare resource use. Interviews were undertaken with 24 participants and 3 physiotherapists., Results:: Almost 25% of people approached agreed to take part. No intervention-related adverse events were recorded. Adherence was 40%-63% and 53%-71% in the intervention and comparator groups. There was no difference in the two-minute walk test between groups at baseline (Intervention-80.4(33.91)m, Comparator-70.6(31.20)m) and no change over time (at six-month Intervention-81.6(32.75)m, Comparator-74.8(36.16)m. There were no significant changes over time in other outcome measures except the EuroQol-5 Dimension at six months which decreased in the active comparator group. For a difference of 8(17.4)m in two-minute walk test between groups, 76 participants/group would be required (80% power, P > 0.05) for a future randomized controlled trial., Conclusion:: No changes were found in the majority of outcome measures over time. This study was acceptable and feasible by participants and physiotherapists. An adequately powered study needs 160 participants.

Introduction: Studies evaluating the cost-effectiveness of screening for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are generally heterogeneous in terms of risk groups, settings, screening intervention, outcomes and the economic modelling framework. It is therefore difficult to compare cost-effectiveness results between studies. This systematic review aims to summarise and critically assess existing economic models for HBV and HCV in order to identify the main methodological differences in modelling approaches., Methods: A structured search strategy was developed and a systematic review carried out. A critical assessment of the decision-analytic models was carried out according to the guidelines and framework developed for assessment of decision-analytic models in Health Technology Assessment of health care interventions., Results: The overall approach to analysing the cost-effectiveness of screening strategies was found to be broadly consistent for HBV and HCV. However, modelling parameters and related structure differed between models, producing different results. More recent publications performed better against a performance matrix, evaluating model components and methodology., Conclusion: When assessing screening strategies for HBV and HCV infection, the focus should be on more recent studies, which applied the latest treatment regimes, test methods and had better and more complete data on which to base their models. In addition to parameter selection and associated assumptions, careful consideration of dynamic versus static modelling is recommended. Future research may want to focus on these methodological issues. In addition, the ability to evaluate screening strategies for multiple infectious diseases, (HCV and HIV at the same time) might prove important for decision makers.