Digital variance angiography in patients undergoing lower limb arterial recanalization: cost-effectiveness analysis within the English healthcare setting.

Aim: Digital variance angiography (DVA) is a recently developed image processing method capable of improving image quality compared with the traditionally used digital subtraction angiography (DSA), among patients undergoing lower limb x-ray angiography. This study aims to explore the potential cost-effectiveness of DVA from an English National Health Service perspective. Materials & methods: A two-part economic model, consisting of a decision tree and a Markov model, was developed to consider the costs and health outcomes associated with the use of DVA as part of current practice imaging, compared with x-ray angiography using standard DSA. The model explored the impact of DVA on the development of acute kidney injury (AKI), chronic kidney disease and radiation-induced cancer over a lifetime horizon. Both deterministic and probabilistic analyses were performed to assess the cost per quality-adjusted life-year (QALY). Results: Base-case results indicate that DVA results in cost savings of £309 per patient, with QALYs also improving (+0.025) over a lifetime. As shown in sensitivity analysis, a key driver of model results is the relative risk (RR) reduction of contrast-associated acute kidney injury associated with use of DVA. The intervention also decreases the risk of carcinoma over a lifetime. Scenario analyses show that cost savings range from £310 to £553, with QALY gains ranging from 0.048 to 0.109 per patient. Conclusion: The use of DVA could result in a decrease in costs and an increase in QALYs over a lifetime, compared with existing imaging practice. The potential for this technology to offer an economically viable alternative to existing image processing methods, through a reduction in contrast media volume and radiation exposure, has been demonstrated.

Cost-Utility Analysis of the Caresyntax Platform to Identify Patients at Risk of Surgical Site Infection Undergoing Colorectal Surgery.

BACKGROUND: Surgical site infections (SSIs) account for up to 18% of all healthcare-associated infections (HAIs). The Caresyntax data-driven surgery platform incorporates the most common risk factors for SSI, to identify high-risk surgical patients before they leave the operating theatre and treat them prophylactically with negative pressure wound therapy (NPWT). An economic analysis was performed to assess the costs and health outcomes associated with introduction of the technology in the English healthcare setting. METHODS: A hybrid decision tree/Markov model was developed to reflect the treatment pathways that patients undergoing colorectal surgery would typically follow, both over the short term (30-day hospital setting) and long term (lifetime). The analysis considered implementation of Caresyntax's platform-based SSI predictive algorithm in the hospital setting, compared with standard of care, from an English National Health Service (NHS) perspective. The base-case analysis presents results in terms of cost per quality-adjusted life-year (QALY) gained, as well as operational impact. RESULTS: The base-case analysis indicates that the intervention leads to a cost saving of £55.52m across the total NHS colorectal surgery patient population in 1 year. In addition, the intervention has a 98.36% probability of being cost effective over a lifetime horizon. The intervention results in the avoidance of 19,744 SSI events, as well 191,911 excess hospital bed days saved. CONCLUSION: Caresyntax's platform-based SSI predictive algorithm has the potential to result in cost savings and improved patient quality of life. Additionally, operational gains for the healthcare provider, including reduced infection rates and hospital bed days saved, have been shown through the economic modeling.

Early Cost-Effectiveness and Price Threshold Analyses of Resmetirom: An Investigational Treatment for Management of Nonalcoholic Steatohepatitis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is characterized by inflammation and hepatocellular damage caused by accumulation of fat in the liver. Resmetirom (MGL-3196) is an orally administered, small-molecule, liver-targeted, selective thyroid hormone receptor-ß agonist. This early analysis explored the potential cost effectiveness of resmetirom for the treatment of NASH from a US commercial payer perspective. METHODS: An early economic model was developed to reflect the clinical pathways typically followed by patients with NASH and liver fibrosis. Use of resmetirom, compared with placebo, was assessed. The Markov model structure was informed by a previous modeling study and a randomized, double-blind, placebo-controlled, phase II trial of resmetirom. Costs and outcomes were assessed over a lifetime time horizon with results presented in terms of cost per quality-adjusted life-year (QALY) gained. RESULTS: Resmetirom treatment resulted in increased costs of US$66,764 per patient, while increasing QALYs by 1.24. The incremental cost-effectiveness ratio was US$53,929 per QALY gained, indicating resmetirom treatment would potentially be cost effective at a willingness-to-pay (WTP) threshold of US$100,000. Results indicated that resmetirom would reduce the lifetime number of cases of decompensated cirrhosis (- 87), hepatocellular carcinoma (- 59), and liver transplants (- 30) per 1,000 patients compared with placebo. Resmetirom treatment remained cost effective at a US$100,000 WTP threshold up to a daily price point of US$72.00. CONCLUSION: Resmetirom is a potentially cost-effective treatment option for patients with NASH and liver fibrosis based on an analysis performed from a US commercial payer perspective. Future economic analyses of the technology should, however, focus on overcoming the limitations of existing modeling methodology.

Systematic review of the cost-effectiveness of screening for lung cancer with low dose computed tomography.

OBJECTIVES: Lung cancer (LC) remains a burden for patients and healthcare systems, with most cases only diagnosed once disease is late stage. Screening for LC with low-dose computed tomography (LDCT) has shown a stage shift and led to a lung cancer-specific mortality reduction. Economic evaluations have been conducted which explore the benefits and costs of screening, however, previous systematic reviews concluded results were heterogeneous. LC screening has evolved and there have been further cost-effectiveness analyses conducted. The aim of this study was to provide an up-to-date systematic review of the cost-effectiveness of LC screening with LDCT. METHODS AND MATERIALS: Databases were searched for full papers published in English 01/1994-02/2022. Inclusion criteria was full economic evaluation of LC screening using LDCT compared to either no screening or chest X-ray. RESULTS: Forty-five evaluations were identified, three conducted alongside trials and 42 modelling studies. Thirty-nine evaluations (86.7%) found LC screening with LDCT to be cost-effective. Several findings were broadly consistent across studies: cost-effectiveness was optimal in those age 55-75 years and smoking history of at least 20 pack-years. Biennial screening was often more cost-effective than annual screening and would likely result in less additional findings and radiation exposure. A smoking cessation intervention alongside screening improved cost-effectiveness, but which intervention was optimal was unclear. Risk predictions models using more parameters to target participants for screening did not have more benefits than those using age and smoking alone, and cost-effectiveness was equivalent. Cost-effectiveness was sensitive to cost and specificity of LDCT, and disutility associated with screening. CONCLUSION: Overall, LC screening with LDCT is cost-effective in a high-risk population. Questions remain regarding risk prediction models, smoking cessation interventions and appropriateness of utility values in the screened population. Once these uncertainties are addressed, further economic evaluation may be required to inform policymakers prior to implementation.

Cost-Effectiveness Analysis of a Medial Meniscus Replacement Prosthesis for the Treatment of Patients with Medial Compartment Pain in the United Kingdom.

BACKGROUND: The most common intra-articular knee injury is a meniscal tear, which commonly occurs secondary to trauma following twisting or hyperflexion. Treatment options for meniscal tears can either be surgical or non-surgical, and range from rest, exercise, bracing and physical therapy to surgical intervention, including meniscal repair and partial meniscectomy. In patients with persistent pain following loss of meniscus tissue, treatment can include partial replacement or meniscal allograft transplantation. The NUsurface® prosthesis has been developed as a treatment option for patients experiencing persistent knee pain post medial meniscus (MM) surgery. OBJECTIVE: The aim of this study was to assess the cost effectiveness of MM replacement using NUsurface for the treatment of patients with medial compartment pain following previous partial medial meniscectomy, from a UK health service perspective. METHODS: An economic decision-analytic model was developed to assess the cost per quality-adjusted life-year (QALY) gained associated with the introduction of MM replacement using NUsurface compared with non-surgical standard of care, over a lifetime time horizon. The model structure was primarily informed by a previous clinical trial (VENUS) and was developed based on the clinical pathways typically followed by patients with this condition, with treatment pathways and probabilities of clinical progression adjusted depending on whether patients were receiving the intervention or undergoing current practice. A hypothetical cohort of adult patients (mean age of 50 years) was modelled, with clinical data sourced from the VENUS study as well as relevant UK literature. Both deterministic and probabilistic sensitivity analyses were carried out to explore uncertainty in the model results. RESULTS: The base-case probabilistic results indicate that MM replacement using NUsurface is likely to be cost effective across a range of willingness-to-pay (WTP) thresholds (95% probability of being cost effective at the National Institute for Health and Care Excellence (NICE)-recommended £20,000 WTP threshold). Although per-patient costs increase, QALYs are also gained, with the incremental cost per QALY (probabilistic value = £5011) being below £20,000. Deterministic sensitivity analyses indicate that the parameters that have the greatest impact on results are the failure rate in the control group (current practice), utility scores, and the cost of undergoing MM replacement using NUsurface. CONCLUSIONS: Based on the analysis presented, MM replacement with the NUsurface prosthetic implant is likely to be a cost-effective use of UK health care service resources compared with current standard care.

Economic Analysis of the CADScor System for Ruling Out Coronary Artery Disease in England.

BACKGROUND: Coronary artery disease (CAD) is the most common type of heart and circulatory disease and is the leading cause of death worldwide. The current diagnostic pathway can lead to patient complications and is also extremely costly. A new medical device, the CADScor System (Acarix AB), was developed for the acoustic detection of CAD before patients undergo invasive diagnostic procedures. OBJECTIVES: Our objective was to assess the cost utility of the CADScor System for the diagnosis of CAD at an early stage in the diagnostic testing pathway in England. METHODS: A two-part economic model, consisting of a decision tree and Markov model, was developed to consider the cost utility (cost per quality-adjusted life-year [QALY] gained) of introducing the CADScor System for the diagnosis of CAD. The decision tree component explored the short-term costs and diagnostic outcomes associated with introduction of the test compared with the existing testing pathway. A Markov model was developed to explore the longer-term health and economic implications of the condition and original diagnosis, with costs and health effects estimated over different time horizons. Parameter uncertainty was explored in deterministic and probabilistic sensitivity analyses. RESULTS: Base-case results indicated that the CADScor System would result in cost savings (- £131 per patient) and a marginal increase in QALYs (0.00001) over a 1-year time horizon. Probabilistic results indicated that the intervention had a > 99% probability of being cost effective at a willingness-to-pay threshold of £20,000 per QALY gained and 100% probability of being cost saving. Results from the deterministic sensitivity analyses indicated that variations in parameters related to the accuracy and cost of the CADScor System, and the prevalence of CAD, had the greatest impact on the overall results. The overall cost saving was estimated to be over £12.3 million per 100,000 eligible patient population. CONCLUSIONS: The CADScor System is a potentially cost-saving test for the diagnosis of CAD. When initiated before the use of non-invasive cardiac imaging tests such as computed tomography coronary angiography, the test reduced costs to the healthcare service over various time horizons.

The COVID-19 pandemic in Ireland: An overview of the health service and economic policy response.

OBJECTIVES: To outline the situation in Ireland with regard to the COVID-19 pandemic. METHODS: Analyse the evolution of the COVID-19 pandemic in Ireland. Review the key public health and health system responses. RESULTS: Over 1700 people have died with COVID-19 by July 19th while almost 3000 people had been admitted to hospital with COVID-19. A high proportion of the deaths occurred in nursing homes and other residential centres who did not receive sufficient attention during the early phase of the pandemic. CONCLUSIONS: Ireland's response to the COVID-19 crisis has been comprehensive and timely. Transparency, a commitment to a relatively open data policy, the use of traditional and social media to inform the population, and the frequency of updates from the Department of Health and the Health Services Executive are all commendable and have led to a high level of compliance among the general public with the various non-medical measures introduced by the government.

Economic evaluation of surgical treatments for women with stress urinary incontinence: a cost-utility and value of information analysis.

OBJECTIVES: Stress urinary incontinence (SUI) and stress-predominant mixed urinary incontinence (MUI) are common conditions that can have a negative impact on the quality of life of patients and serious cost implications for healthcare providers. The objective of this study was to assess the cost-effectiveness of nine different surgical interventions for treatment of SUI and stress-predominant MUI from a National Health Service and personal social services perspective in the UK. METHODS: A Markov microsimulation model was developed to compare the costs and effectiveness of nine surgical interventions. The model was informed by undertaking a systematic review of clinical effectiveness and network meta-analysis. The main clinical parameters in the model were the cure and incidence rates of complications after different interventions. The outcomes from the model were expressed in terms of cost per quality-adjusted life-years (QALYs) gained. In addition, expected value of perfect information (EVPI) analyses were conducted to quantify the main uncertainties facing decision-makers. RESULTS: The base-case results suggest that retropubic mid-urethral sling (retro-MUS) is the most cost-effective surgical intervention over a 10-year and lifetime time horizon. The probabilistic results show that retro-MUS and traditional sling are the interventions with the highest probability of being cost-effective across all willingness-to-pay thresholds over a lifetime time horizon. The value of information analysis results suggest that the largest value appears to be in removing uncertainty around the incidence rates of complications, the relative treatment effectiveness and health utility values. CONCLUSIONS: Although retro-MUS appears, at this stage, to be a cost-effective intervention, research is needed on possible long-term complications of all surgical treatments to provide reassurance of safety, or earlier warning of unanticipated adverse effects. The value of information analysis supports the need, as a first step, for further research to improve our knowledge of the actual incidence of complications.

Surgical treatments for women with stress urinary incontinence: a systematic review of economic evidence.

BACKGROUND: Surgical interventions for the treatment of stress urinary incontinence (SUI) in women are commonly employed following the failure of minimally invasive therapies. Due to the limited information available on the relative cost-effectiveness of available surgeries for treating SUI, a de novo economic analysis was conducted to assess costs and effects of all relevant surgeries. To inform the economic analysis, the objective of this review was to identify and assess the quality of existing economic evaluation studies on different surgical interventions for the treatment of SUI in women. METHODS: The following databases were searched during the review process: Medical Literature Analysis and Retrieval System Online (MEDLINE), MEDLINE In-Process, Excerpta Medica Database (Embase), National Health Service Economic Evaluation Database (NHS EED), and Health Management Information Consortium and Cost-Effectiveness Analysis Registry (CEA registry). The key criteria for inclusion were that the study population included women with SUI and that the surgical interventions considered were utilised as either a primary or a follow-up surgery. The review included only full economic evaluations. Studies were quality assessed using the Drummond checklist for economic evaluations. No quantitative synthesis of the results by meta-analysis was conducted due to the high methodological heterogeneity. RESULTS: Twenty-six economic evaluations were included, of which 13 were model-based analyses. Surgical treatments assessed most frequently were mid-urethral slings and open and laparoscopic colposuspension. There were some differences in the methodological approaches taken, including differences in type of economic analysis, perspective, time horizon, types of resource use, and costs and outcomes that were included in the analysis. The majority of studies conducted a cost-utility analysis from a health system perspective and applied a time horizon of between 1 and 5 years. The cost-effectiveness results suggest that single-incision mini-sling and mid-urethral slings are among the most cost-effective options. CONCLUSIONS: The review has shown that methods used for the economic evaluation of surgical treatments for SUI vary widely in terms of study design, analysis type, compared alternatives, time horizon, costing methodologies and effect outcomes. Future economic evaluation studies on surgical treatments for SUI may be improved by the application of available guidelines. SYSTEMATIC REVIEW REGISTRATION: Registered in PROSPERO in 2016, CRD42016049339.

Optimising clinical effectiveness and quality along the atrial fibrillation anticoagulation pathway: an economic analysis.

BACKGROUND: Atrial fibrillation (AF) represents the most common sustained cardiac arrhythmia. A service evaluation was carried out at an anticoagulation clinic in Newcastle upon-Tyne to explore the efficacy of introducing self-testing of anticoagulation status for AF patients on warfarin. The analysis presented aims to assess the potential cost savings and clinical outcomes associated with introducing self-testing at a clinic in the Northeast of England, and to determine the cost-effectiveness of a redesigned treatment pathway including genetic testing and self-testing components. METHODS: Questionnaires were administered to individuals participating in the service evaluation to understand the patient costs associated with clinical monitoring (139 patients), and quality-of-life before and after the introduction of self-testing (varying numbers). Additionally, data on time in therapeutic range (TTR) were captured at multiple time points to identify any change in outcome. Finally, an economic model was developed to assess the cost-effectiveness of introducing a redesigned treatment pathway, including genetic testing and self-testing, for AF patients. RESULTS: The average cost per patient of attending the anticoagulation clinic was £16.24 per visit (including carer costs). Costs were higher amongst patients tested at the hospital clinic than those tested at the community clinic. Improvements in quality-of-life across all psychological topics, and improved TTR, were seen following the introduction of self-testing. Results of the cost-effectiveness analysis showed that the redesigned treatment pathway was less costly and more effective than current practice. CONCLUSIONS: Allowing AF patients on warfarin to self-test, rather than attend clinic to have their anticoagulation status assessed, has the potential to reduce patient costs. Additionally, self-testing may result in improved quality-of-life and TTR. Introducing genetic testing to guide patient treatment based on sensitivity to warfarin, and applying this in combination with self-testing, may also result in improved patient outcomes and reduced costs to the health service in the long-term.

Early Economic Evaluation of Diagnostic Technologies: Experiences of the NIHR Diagnostic Evidence Co-operatives.

Diagnostic tests are expensive and time-consuming to develop. Early economic evaluation using decision modeling can reduce commercial risk by providing early evidence on cost-effectiveness. The National Institute for Health Research Diagnostic Evidence Co-operatives (DECs) was established to catalyze evidence generation for diagnostic tests by collaborating with commercial developers; DEC researchers have consequently made extensive use of early modeling. The aim of this article is to summarize the experiences of the DECs using early modeling for diagnostics. We draw on 8 case studies to illustrate the methods, highlight methodological strengths and weaknesses particular to diagnostics, and provide advice. The case studies covered diagnosis, screening, and treatment stratification. Treatment effectiveness was a crucial determinant of cost-effectiveness in all cases, but robust evidence to inform this parameter was sparse. This risked limiting the usability of the results, although characterization of this uncertainty in turn highlighted the value of further evidence generation. Researchers evaluating early models must be aware of the importance of treatment effect evidence when reviewing the cost-effectiveness of diagnostics. Researchers planning to develop an early model of a test should also 1) consult widely with clinicians to ensure the model reflects real-world patient care; 2) develop comprehensive models that can be updated as the technology develops, rather than taking a "quick and dirty" approach that may risk producing misleading results; and 3) use flexible methods of reviewing evidence and evaluating model results, to fit the needs of multiple decision makers. Decision models can provide vital information for developers at an early stage, although limited evidence mean researchers should proceed with caution.

A PCR-based diagnostic testing strategy to identify carbapenemase-producing Enterobacteriaceae carriers upon admission to UK hospitals: early economic modelling to assess costs and consequences.

BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE), bacteria which are resistant to the carbapenem class of antibiotics, present an urgent public health risk. The objective of this study was to assess the potential costs and consequences of implementing a testing strategy involving a polymerase chain reaction (PCR)-based diagnostic test for CPE amongst high risk patients upon admission to UK hospitals, to replace the current culture-based testing strategy. METHODS: A decision-analytic model was developed to estimate the expected medical care costs associated with a PCR testing strategy for CPE compared with the current culture testing strategy, and to consider the consequences, in terms of the diagnostic accuracy and associated cost implications, of each approach. The modelled population were patients admitted to hospital at high risk of colonisation with CPE, with model pathways for current practice based on those described in the Public Health England (PHE) toolkit for CPE testing. Costs were estimated from a UK National Health Service (NHS) perspective, with outcomes presented in terms of percentage of samples identified as true positive, false positive, true negative and false negative following each method of testing. RESULTS: Results indicated that the PCR testing strategy led to an estimated cost saving of £462 per patient for a 5-day hospital stay. For all sensitivity analyses conducted, PCR testing resulted in an expected cost saving. Potential cost savings approached £850 per patient for the sensitivity analysis assuming a 15-day hospital stay, indicating that PCR testing results in greater cost savings as length of stay increases. Fewer false positive, and more true negative, cases were identified with the PCR testing strategy in all analyses conducted. CONCLUSIONS: This economic analysis gives an insight into the potential cost savings that could be made by the UK NHS through the introduction of a PCR-based diagnostic testing strategy to replace current recommended culture-based methods for the detection of CPE. Savings are due primarily to a faster time to result with PCR, meaning that CPE-free patients are not isolated unnecessarily. Therefore, a PCR-based diagnostic may aid appropriate use of isolation resource.

Efficiency and Health Economic Evaluations of BD OneFlow™ Flow Cytometry Reagents for Diagnosing Chronic Lymphoid Leukemia.

REASON FOR THE STUDY: To standardize the use of flow cytometry for classifying hematological malignancies and make the results reliable and reproducible across laboratories, the EuroFlow™ Consortium published a comprehensive specification of antibody-fluorochrome conjugates, standard protocols, and algorithms for analysis. The BD OneFlow™ system builds on, and further standardizes, the EuroFlow protocols. We aimed to assess the effects on safety, efficiency, and costs for laboratories of adopting the BD OneFlow reagent tubes (LST and B-CLPD T1) for diagnosing chronic lymphocytic leukemia. METHODS: We compared in-house laboratory processes and results with those using the LST and B-CLPD T1 reagent tubes with, and without, blood film morphology. Outcome measures included concordance in classification results, and efficiency within the laboratory, that is, resource usage, staff time, unwanted events, and cost-consequences. RESULTS: There was 100% concordance between the classifications made with in-house flow cytometry and those with the BD OneFlow reagent tubes. Using BD OneFlow tubes required 13 hours less staff time per month (i.e. for 100 samples) than the in-house process. Sensitivity analyses explored the effects of uncertainties in the price of the BD OneFlow tubes and the prevalence of CLL and identified the thresholds at which laboratories might expect cost-savings from adopting the BD OneFlow system. Laboratory and clinical staff considered the BD OneFlow system to be safe and effective. CONCLUSIONS: Laboratories adopting the BD OneFlow system for classifying patients with suspected CLL can expect safe, efficient processes that can be cost saving if the discount on the list price, and prevalence of CLL (which will both vary between sites and countries), is within the thresholds suggested by the health economics sensitivity analysis. © 2019 International Clinical Cytometry Society.

Surgical treatments for women with stress urinary incontinence: the ESTER systematic review and economic evaluation.

BACKGROUND: Urinary incontinence in women is a distressing condition that restricts quality of life and results in a large economic burden to both the NHS and women themselves. OBJECTIVE: To evaluate the clinical effectiveness, safety and cost-effectiveness of surgical treatment for stress urinary incontinence (SUI) in women and explore women's preferences. DESIGN: An evidence synthesis, a discrete choice experiment (DCE) and an economic decision model, with a value-of-information (VOI) analysis. Nine surgical interventions were compared. Previous Cochrane reviews for each were identified and updated to include additional studies. Systematic review methods were applied. The outcomes of interest were 'cure' and 'improvement'. Both a pairwise and a network meta-analysis (NMA) were conducted for all available surgical comparisons. A DCE was undertaken to assess the preferences of women for treatment outcomes. An economic model assessed the cost-effectiveness of alternative surgeries and a VOI analysis was undertaken. RESULTS: Data from 175 studies were included in the effectiveness review. The majority of included studies were rated as being at high or unclear risk of bias across all risk-of-bias domains. The NMA, which included 120 studies that reported data on 'cure' or 'improvement', showed that retropubic mid-urethral sling (MUS), transobturator MUS, traditional sling and open colposuspension were more effective than other surgical procedures for both primary outcomes. The results for other interventions were variable. In general, rate of tape and mesh exposure was higher after transobturator MUS than after retropubic MUS or single-incision sling, whereas the rate of tape or mesh erosion/extrusion was similar between transobturator MUS and retropubic MUS. The results of the DCE, in which 789 women completed an anonymous online questionnaire, indicate that women tend to prefer surgical treatments associated with no pain or mild chronic pain and shorter length of hospital stay as well as those treatments that have a smaller risk for urinary symptoms to reoccur after surgery. The cost-effectiveness results suggest that, over a lifetime, retropubic MUS is, on average, the least costly and most effective surgery. However, the high level of uncertainty makes robust estimates difficult to ascertain. The VOI analysis highlighted that further research around the incidence rates of complications would be of most value. LIMITATIONS: Overall, the quality of the clinical evidence was low, with limited data available for the assessment of complications. Furthermore, there is a lack of robust evidence and significant uncertainty around some parameters in the economic modelling. CONCLUSIONS: To our knowledge, this is the most comprehensive assessment of published evidence for the treatment of SUI. There is some evidence that retropubic MUS, transobturator MUS and traditional sling are effective in the short to medium term and that retropubic MUS is cost-effective in the medium to long term. The VOI analysis highlights the value of further research to reduce the uncertainty around the incidence rates of complications. There is a need to obtain robust clinical data in future work, particularly around long-term complication rates. STUDY REGISTRATION: This study is registered as PROSPERO CRD42016049339. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Urinary incontinence, defined as involuntary leakage of urine, is a common condition that varies in type and severity and can have a huge impact on the quality of life of women. The aim of this project was to summarise the evidence on the clinical effectiveness, safety and cost-effectiveness of nine surgical operations for stress urinary incontinence in women and assess the need for further research. Women's preferences for surgery were also explored. Currently there is no agreement among decision-makers, doctors and patients about which of the available surgical operations is best. Based on previous Cochrane reviews, the effects and safety of each operation were systematically reviewed and analysed. Their cost-effectiveness and the value of conducting further research were also evaluated. To better understand the preference of women, an online survey containing a discrete choice experiment was conducted. Finally, patient representatives were consulted to help us to understand the consequences of the findings from a patient's perspective. The evidence on surgical operations was predominantly short to medium term (up to 12 months). This analysis found that the quality of the evidence varied, with the majority of trials being subject to high or unclear risk of bias, making the conclusions that can be drawn less robust. The findings of the clinical evidence review suggest that retropubic sling procedures, transobturator sling procedures and traditional sling procedures are more effective than other surgical procedures for both 'cure' and 'improvement' of stress urinary incontinence. The results of the economic analyses support these findings, suggesting that retropubic mid-urethral sling is the most cost-effective surgical operation. However, data on complications were lacking, limiting any strong conclusions. The results suggest that there is value in undertaking further research to reduce the uncertainty around the medium- to long-term complications of all surgical treatments and this was reflected in patients' views.

Systematic Review of Economic Models Used to Compare Techniques for Detecting Peripheral Arterial Disease.

BACKGROUND AND OBJECTIVE: Peripheral arterial disease (PAD) is a common condition, in which atherosclerotic narrowing in the arteries restricts blood supply to the leg muscles. In order to support future model-based economic evaluations comparing methods of diagnosis in this area, a systematic review of economic modelling studies was conducted. METHODS: A systematic literature review was performed in June 2017 to identify model-based economic evaluations of diagnostic tests to detect PAD, with six individual databases searched. The review was conducted in accordance with the methods outlined in the Centre for Reviews and Dissemination's guidance for undertaking reviews in healthcare, and appropriate inclusion criteria were applied. Relevant data were extracted, and studies were quality assessed. RESULTS: Seven studies were included in the final review, all of which were published between 1995 and 2014. There was wide variation in the types of diagnostic test compared. The majority of the studies (six of seven) referenced the sources used to develop their model, and all studies stated and justified the structural assumptions. Reporting of the data within the included studies could have been improved. Only one identified study focused on the cost-effectiveness of a test typically used in primary care. CONCLUSIONS: This review brings together all applied modelling methods for tests used in the diagnosis of PAD, which could be used to support future model-based economic evaluations in this field. The limited modelling work available on tests typically used for the detection of PAD in primary care, in particular, highlights the importance of future work in this area.

Gastrostomy versus nasogastric tube feeding for chemoradiation patients with head and neck cancer: the TUBE pilot RCT.

BACKGROUND: Approximately 9000 new cases of head and neck squamous cell cancers (HNSCCs) are treated by the NHS each year. Chemoradiation therapy (CRT) is a commonly used treatment for advanced HNSCC. Approximately 90% of patients undergoing CRT require nutritional support via gastrostomy or nasogastric tube feeding. Long-term dysphagia following CRT is a primary concern for patients. The effect of enteral feeding routes on swallowing function is not well understood, and the two feeding methods have, to date (at the time of writing), not been compared. The aim of this pilot randomised controlled trial (RCT) was to compare these two options. METHODS: This was a mixed-methods multicentre study to establish the feasibility of a RCT comparing oral feeding plus pre-treatment gastrostomy with oral feeding plus as-required nasogastric tube feeding in patients with HNSCC. Patients were recruited from four tertiary centres treating cancer and randomised to the two arms of the study (using a 1 : 1 ratio). The eligibility criteria were patients with advanced-staged HNSCC who were suitable for primary CRT with curative intent and who presented with no swallowing problems. MAIN OUTCOME MEASURES: The primary outcome was the willingness to be randomised. A qualitative process evaluation was conducted alongside an economic modelling exercise. The criteria for progression to a Phase III trial were based on a hypothesised recruitment rate of at least 50%, collection of outcome measures in at least 80% of those recruited and an economic value-of-information analysis for cost-effectiveness. RESULTS: Of the 75 patients approached about the trial, only 17 consented to be randomised [0.23, 95% confidence interval (CI) 0.13 to 0.32]. Among those who were randomised, the compliance rate was high (0.94, 95% CI 0.83 to 1.05). Retention rates were high at completion of treatment (0.94, 95% CI 0.83 to 1.05), at the 3-month follow-up (0.88, 95% CI 0.73 to 1.04) and at the 6-month follow-up (0.88, 95% CI 0.73 to 1.04). No serious adverse events were recorded in relation to the trial. The qualitative substudy identified several factors that had an impact on recruitment, many of which are amenable to change. These included organisational factors, changing cancer treatments and patient and clinician preferences. A key reason for the differential recruitment between sites was the degree to which the multidisciplinary team gave a consistent demonstration of equipoise at all patient interactions at which supplementary feeding was discussed. An exploratory economic model generated from published evidence and expert opinion suggests that, over the 6-month model time horizon, pre-treatment gastrostomy tube feeding is not a cost-effective option, although this should be interpreted with caution and we recommend that this should not form the basis for policy. The economic value-of-information analysis indicates that additional research to eliminate uncertainty around model parameters is highly likely to be cost-effective. STUDY LIMITATIONS: The recruitment issues identified for this cohort may not be applicable to other populations undergoing CRT. There remains substantial uncertainty in the economic evaluation. CONCLUSIONS: The trial did not meet one of the three criteria for progression, as the recruitment rate was lower than hypothesised. Once patients were recruited to the trial, compliance and retention in the trial were both high. The implementation of organisational and operational measures can increase the numbers recruited. The economic analysis suggests that further research in this area is likely to be cost-effective. FUTURE WORK: The implementation of organisational and operational measures can increase recruitment. The appropriate research question and design of a future study needs to be identified. More work is needed to understand the experiences of nasogastric tube feeding in patients undergoing CRT. TRIAL REGISTRATION: Current Controlled Trials ISRCTN48569216. 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. 22, No. 16. See the NIHR Journals Library website for further project information.

Evaluation of a complex healthcare intervention to increase smoking cessation in pregnant women: interrupted time series analysis with economic evaluation.

OBJECTIVES: To evaluate the effectiveness of a complex intervention to improve referral and treatment of pregnant smokers in routine practice, and to assess the incremental costs to the National Health Service (NHS) per additional woman quitting smoking. DESIGN: Interrupted time series analysis of routine data before and after introducing the intervention, within-study economic evaluation. SETTING: Eight acute NHS hospital trusts and 12 local authority areas in North East England. PARTICIPANTS: 37 726 records of singleton delivery including 10 594 to mothers classified as smoking during pregnancy. INTERVENTIONS: A package of measures implemented in trusts and smoking cessation services, aimed at increasing the proportion of pregnant smokers quitting during pregnancy, comprising skills training for healthcare and smoking cessation staff; universal carbon monoxide monitoring with routine opt-out referral for smoking cessation support; provision of carbon monoxide monitors and supporting materials; and an explicit referral pathway and follow-up protocol. MAIN OUTCOME MEASURES: Referrals to smoking cessation services; probability of quitting smoking during pregnancy; additional costs to health services; incremental cost per additional woman quitting. RESULTS: After introduction of the intervention, the referral rate increased more than twofold (incidence rate ratio=2.47, 95% CI 2.16 to 2.81) and the probability of quitting by delivery increased (adjusted OR=1.81, 95% CI 1.54 to 2.12). The additional cost per delivery was £31 and the incremental cost per additional quit was £952; 31 pregnant women needed to be treated for each additional quitter. CONCLUSIONS: The implementation of a system-wide complex healthcare intervention was associated with significant increase in rates of quitting by delivery.

Interventions for hyperhidrosis in secondary care: a systematic review and value-of-information analysis.

BACKGROUND: Hyperhidrosis is uncontrollable excessive sweating that occurs at rest, regardless of temperature. The symptoms of hyperhidrosis can significantly affect quality of life. The management of hyperhidrosis is uncertain and variable. OBJECTIVE: To establish the expected value of undertaking additional research to determine the most effective interventions for the management of refractory primary hyperhidrosis in secondary care. METHODS: A systematic review and economic model, including a value-of-information (VOI) analysis. Treatments to be prescribed by dermatologists and minor surgical treatments for hyperhidrosis of the hands, feet and axillae were reviewed; as endoscopic thoracic sympathectomy (ETS) is incontestably an end-of-line treatment, it was not reviewed further. Fifteen databases (e.g. CENTRAL, PubMed and PsycINFO), conference proceedings and trial registers were searched from inception to July 2016. Systematic review methods were followed. Pairwise meta-analyses were conducted for comparisons between botulinum toxin (BTX) injections and placebo for axillary hyperhidrosis, but otherwise, owing to evidence limitations, data were synthesised narratively. A decision-analytic model assessed the cost-effectiveness and VOI of five treatments (iontophoresis, medication, BTX, curettage, ETS) in 64 different sequences for axillary hyperhidrosis only. RESULTS AND CONCLUSIONS: Fifty studies were included in the effectiveness review: 32 randomised controlled trials (RCTs), 17 non-RCTs and one large prospective case series. Most studies were small, rated as having a high risk of bias and poorly reported. The interventions assessed in the review were iontophoresis, BTX, anticholinergic medications, curettage and newer energy-based technologies that damage the sweat gland (e.g. laser, microwave). There is moderate-quality evidence of a large statistically significant effect of BTX on axillary hyperhidrosis symptoms, compared with placebo. There was weak but consistent evidence for iontophoresis for palmar hyperhidrosis. Evidence for other interventions was of low or very low quality. For axillary hyperhidrosis cost-effectiveness results indicated that iontophoresis, BTX, medication, curettage and ETS was the most cost-effective sequence (probability 0.8), with an incremental cost-effectiveness ratio of £9304 per quality-adjusted life-year. Uncertainty associated with study bias was not reflected in the economic results. Patients and clinicians attending an end-of-project workshop were satisfied with the sequence of treatments for axillary hyperhidrosis identified as being cost-effective. All patient advisors considered that the Hyperhidrosis Quality of Life Index was superior to other tools commonly used in hyperhidrosis research for assessing quality of life. LIMITATIONS: The evidence for the clinical effectiveness and safety of second-line treatments for primary hyperhidrosis is limited. This meant that there was insufficient evidence to draw conclusions for most interventions assessed and the cost-effectiveness analysis was restricted to hyperhidrosis of the axilla. FUTURE WORK: Based on anecdotal evidence and inference from evidence for the axillae, participants agreed that a trial of BTX (with anaesthesia) compared with iontophoresis for palmar hyperhidrosis would be most useful. The VOI analysis indicates that further research into the effectiveness of existing medications might be worthwhile, but it is unclear that such trials are of clinical importance. Research that established a robust estimate of the annual incidence of axillary hyperhidrosis in the UK population would reduce the uncertainty in future VOI analyses. STUDY REGISTRATION: This study is registered as PROSPERO CRD42015027803. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Treatments for hyperemesis gravidarum and nausea and vomiting in pregnancy: a systematic review and economic assessment.

BACKGROUND: Nausea and vomiting in pregnancy (NVP) affects up to 85% of all women during pregnancy, but for the majority self-management suffices. For the remainder, symptoms are more severe and the most severe form of NVP - hyperemesis gravidarum (HG) - affects 0.3-1.0% of pregnant women. There is no widely accepted point at which NVP becomes HG. OBJECTIVES: This study aimed to determine the relative clinical effectiveness and cost-effectiveness of treatments for NVP and HG. DATA SOURCES: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, PsycINFO, Commonwealth Agricultural Bureaux (CAB) Abstracts, Latin American and Caribbean Health Sciences Literature, Allied and Complementary Medicine Database, British Nursing Index, Science Citation Index, Social Sciences Citation Index, Scopus, Conference Proceedings Index, NHS Economic Evaluation Database, Health Economic Evaluations Database, China National Knowledge Infrastructure, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects were searched from inception to September 2014. References from studies and literature reviews identified were also examined. Obstetric Medicine was hand-searched, as were websites of relevant organisations. Costs came from NHS sources. REVIEW METHODS: A systematic review of randomised and non-randomised controlled trials (RCTs) for effectiveness, and population-based case series for adverse events and fetal outcomes. Treatments: vitamins B6 and B12, ginger, acupressure/acupuncture, hypnotherapy, antiemetics, dopamine antagonists, 5-hydroxytryptamine receptor antagonists, intravenous (i.v.) fluids, corticosteroids, enteral and parenteral feeding or other novel treatment. Two reviewers extracted data and quality assessed studies. Results were narratively synthesised; planned meta-analysis was not possible due to heterogeneity and incomplete reporting. A simple economic evaluation considered the implied values of treatments. RESULTS: Seventy-three studies (75 reports) met the inclusion criteria. For RCTs, 33 and 11 studies had a low and high risk of bias respectively. For the remainder (n = 20) it was unclear. The non-randomised studies (n = 9) were low quality. There were 33 separate comparators. The most common were acupressure versus placebo (n = 12); steroid versus usual treatment (n = 7); ginger versus placebo (n = 6); ginger versus vitamin B6 (n = 6); and vitamin B6 versus placebo (n = 4). There was evidence that ginger, antihistamines, metoclopramide (mild disease) and vitamin B6 (mild to severe disease) are better than placebo. Diclectin® [Duchesnay Inc.; doxylamine succinate (10 mg) plus pyridoxine hydrochloride (10 mg) slow release tablet] is more effective than placebo and ondansetron is more effective at reducing nausea than pyridoxine plus doxylamine. Diclectin before symptoms of NVP begin for women at high risk of severe NVP recurrence reduces risk of moderate/severe NVP compared with taking Diclectin once symptoms begin. Promethazine is as, and ondansetron is more, effective than metoclopramide for severe NVP/HG. I.v. fluids help correct dehydration and improve symptoms. Dextrose saline may be more effective at reducing nausea than normal saline. Transdermal clonidine patches may be effective for severe HG. Enteral feeding is effective but extreme method treatment for very severe symptoms. Day case management for moderate/severe symptoms is feasible, acceptable and as effective as inpatient care. For all other interventions and comparisons, evidence is unclear. The economic analysis was limited by lack of effectiveness data, but comparison of costs between treatments highlights the implications of different choices. LIMITATIONS: The main limitations were the quantity and quality of the data available. CONCLUSION: There was evidence of some improvement in symptoms for some treatments, but these data may not be transferable across disease severities. Methodologically sound and larger trials of the main therapies considered within the UK NHS are needed. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013006642. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

The prognostic utility of tests of platelet function for the detection of 'aspirin resistance' in patients with established cardiovascular or cerebrovascular disease: a systematic review and economic evaluation.

BACKGROUND: The use of aspirin is well established for secondary prevention of cardiovascular disease. However, a proportion of patients suffer repeat cardiovascular events despite being prescribed aspirin treatment. It is uncertain whether or not this is due to an inherent inability of aspirin to sufficiently modify platelet activity. This report aims to investigate whether or not insufficient platelet function inhibition by aspirin ('aspirin resistance'), as defined using platelet function tests (PFTs), is linked to the occurrence of adverse clinical outcomes, and further, whether or not patients at risk of future adverse clinical events can be identified through PFTs. OBJECTIVES: To review systematically the clinical effectiveness and cost-effectiveness evidence regarding the association between PFT designation of 'aspirin resistance' and the risk of adverse clinical outcome(s) in patients prescribed aspirin therapy. To undertake exploratory model-based cost-effectiveness analysis on the use of PFTs. DATA SOURCES: Bibliographic databases (e.g. MEDLINE from inception and EMBASE from 1980), conference proceedings and ongoing trial registries up to April 2012. METHODS: Standard systematic review methods were used for identifying clinical and cost studies. A risk-of-bias assessment tool was adapted from checklists for prognostic and diagnostic studies. (Un)adjusted odds and hazard ratios for the association between 'aspirin resistance', for different PFTs, and clinical outcomes are presented; however, heterogeneity between studies precluded pooling of results. A speculative economic model of a PFT and change of therapy strategy was developed. RESULTS: One hundred and eight relevant studies using a variety of PFTs, 58 in patients on aspirin monotherapy, were analysed in detail. Results indicated that some PFTs may have some prognostic utility, i.e. a trend for more clinical events to be associated with groups classified as 'aspirin resistant'. Methodological and clinical heterogeneity prevented a quantitative summary of prognostic effect. Study-level effect sizes were generally small and absolute outcome risk was not substantially different between 'aspirin resistant' and 'aspirin sensitive' designations. No studies on the cost-effectiveness of PFTs for 'aspirin resistance' were identified. Based on assumptions of PFTs being able to accurately identify patients at high risk of clinical events and such patients benefiting from treatment modification, the economic model found that a test-treat strategy was likely to be cost-effective. However, neither assumption is currently evidence based. LIMITATIONS: Poor or incomplete reporting of studies suggests a potentially large volume of inaccessible data. Analyses were confined to studies on patients prescribed aspirin as sole antiplatelet therapy at the time of PFT. Clinical and methodological heterogeneity across studies precluded meta-analysis. Given the lack of robust data the economic modelling was speculative. CONCLUSIONS: Although evidence indicates that some PFTs may have some prognostic value, methodological and clinical heterogeneity between studies and different approaches to analyses create confusion and inconsistency in prognostic results, and prevented a quantitative summary of their prognostic effect. Protocol-driven and adequately powered primary studies are needed, using standardised methods of measurements to evaluate the prognostic ability of each test in the same population(s), and ideally presenting individual patient data. For any PFT to inform individual risk prediction, it will likely need to be considered in combination with other prognostic factors, within a prognostic model. STUDY REGISTRATION: This study is registered as PROSPERO 2012:CRD42012002151. FUNDING: The National Institute for Health Research Health Technology Assessment programme.