Is the Comparator in Your Diagnostic Cost-Effectiveness Model "Standard of Care"? Recommendations from Literature Reviews and Expert Interviews on How to Identify and Operationalize It.

OBJECTIVES: This research aimed to develop best-practice recommendations for identifying the "standard of care" (SoC) and integrate it when it is the comparator in diagnostic economic models (SoC comparator). METHODS: A multi-methods approach comprising 2 pragmatic literature reviews and 9 expert interviews was used. Experts rated their agreement with draft recommendations based on the authors' analysis of the reviews. These were refined iteratively to produce final recommendations. RESULTS: Fourteen best-practice recommendations are provided. Care pathway mapping (using quantitative, qualitative, or mixed-methods approaches) should be used for identifying the SoC comparator. Guidelines analysis can be integrated with expert opinion to identify pathway variability and discrepancies from clinical practice. For integrating the SoC comparator into the model, recommendations around structure, input sourcing, data aggregation and reporting, input uncertainty, and model variability are presented. For example, modelers should consider that the reference standard is not synonymous with the SoC, and the SoC may not be the only comparator. The comparator limitations should be discussed with clinical experts, but elicitation of its diagnostic accuracy is not recommended. Probabilistic sensitivity analysis is recommended when evaluating the overall input uncertainty, and deterministic sensitivity analysis is useful when there is high model uncertainty or SoC variability. Consensus could not be reached for some topics (eg, the role of real-world data, model averaging, and alternative model structures), but the reported discussions provide points for consideration. CONCLUSIONS: To our knowledge, this is the first guidance to support modelers when identifying and operationalizing the SoC comparator in diagnostic cost-effectiveness models.

Transarterial therapies in patients with hepatocellular carcinoma eligible for transarterial embolization: a US cost-effectiveness analysis.

OBJECTIVES: To assess the cost-effectiveness of transarterial radioembolization (TARE) versus conventional transarterial chemoembolization (cTACE) and drug-eluting beads chemoembolization (DEE-TACE) for patients with unresectable early- to intermediate-stage hepatocellular carcinoma (HCC). DESIGN: A cohort-based Markov model with a five-year time horizon was developed to evaluate the cost-effectiveness of the three embolization treatments. Upon entering the model, patients with HCC received either TARE or one of the two other embolization treatments. Patients remained in a "watch and wait" state for tumor downstaging that allowed them to move to health states such as liver transplant, resection, systemic therapies, or cure. Clinical input parameters were retrieved from the published literature, and where values could not be sourced, assumptions were made and validated by clinical experts. Health benefits were quantified using quality-adjusted life years (QALYs). Cost input parameters were obtained from various sources, including the Medicare Cost Report, IBM® Micromedex RED BOOK, and published literature. RESULTS: At five years, TARE was found to be cost-saving (saving $15,779 per person compared to cTACE) and produced 0.33 more QALYs per person than cTACE. TARE cost $13,696 more but produced 0.33 more QALYs than DEE-TACE, with an incremental cost-effectiveness ratio of $41,474 per QALY gained at five years. After accounting for parameter uncertainty, the likelihood of TARE being cost-effective was at least 90% against all comparators at a cost-effectiveness threshold of $100,000 per QALY gained. CONCLUSIONS: TARE produces more QALYs than cTACE and DEE-TACE, with a high probability of being cost-effective against both comparators.

The Barcelona Clinic Liver Cancer guideline recommends the use of transarterial radioembolization (TARE), conventional (cTACE), or drug-eluting bead transarterial chemoembolization (DEE-TACE) for treating hepatocellular carcinoma (HCC). This study evaluated the cost-effectiveness of TARE versus two alternative embolization treatments (cTACE and DEE-TACE) in treating patients with unresectable early- to intermediate-stage HCC.A cohort-based Markov model was developed to analyze the costs and benefits of these treatments from a US healthcare perspective within a 5-year time horizon. A 20-year time horizon was assessed as a scenario. In the model, patients were assigned to receive TARE, cTACE, or DEE-TACE and remained in the "watch and wait" stage for tumor downstaging. Data used in the model was taken from previous studies and in consultation with clinical experts. The benefits of the treatments were measured by considering the impact on the patient's quality of life. The costs associated with the treatments were obtained from various sources, including reports, publicly available databases, and published literature.The findings show that TARE is not only cost-saving compared to cTACE but also results in a higher number of quality-adjusted life years (QALYs) per person. While TARE was more expensive than DEE-TACE, it produced more QALYs, further indicating more favorable patient outcomes and overall treatment effectiveness. These findings could potentially impact resource allocation and decision-making for the treatment of HCC.

Cost-Effectiveness Analysis of Antimicrobial Prescribing in the Treatment of Clostridioides Difficile Infection in England.

BACKGROUND: An economic model was developed with guidance from the National Institute for Health and Care Excellence (NICE) 'Managing Common Infections' (MCI) Committee to evaluate the cost effectiveness of different antibiotic treatment sequences for treating Clostridioides difficile infection (CDI) in England. METHODS: The model consisted of a 90-day decision tree followed by a lifetime cohort Markov model. Efficacy data were taken from a network meta-analysis and published literature, while cost, utility and mortality data were taken from published literature. A treatment sequence was defined as a first-line intervention or a different second-line intervention, and used constant third- and fourth-line interventions. The possible first- and second-line interventions were vancomycin, metronidazole, teicoplanin and fidaxomicin (standard and extended regimens). Total costs and quality-adjusted life-years (QALYs) were calculated and were used to run a fully incremental cost-effectiveness analysis. Threshold analysis was conducted around pricing. RESULTS: Sequences including teicoplanin, fidaxomicin (extended regimen) and second-line metronidazole were excluded based on recommendations from the committee. The final pairwise comparison was between first-line vancomycin and second-line fidaxomicin (VAN-FID), and the reverse (FID-VAN). The incremental cost-effectiveness ratio for FID-VAN compared with VAN-FID was £156,000 per QALY gained, and FID-VAN had a 0.2% likelihood of being cost effective at a £20,000 threshold. CONCLUSION: First-line vancomycin and second-line fidaxomicin was the most cost-effective treatment sequence at the NICE threshold for treating CDI in England. The main limitation of this study was that the initial cure and recurrence rates of each intervention were applied constantly across each line of treatment and each round of recurrence.

Economic evaluation of Optilume, a drug-coated balloon for recurrent anterior male urethral stricture.

Objectives: We aim to conduct an economic evaluation of the Optilume urethral drug-coated balloon (DCB) compared with endoscopic management for the treatment of recurrent anterior male urethral stricture in England. Patients and Methods: A cohort Markov model was developed to estimate the costs and savings to the NHS over a 5-year time horizon of adopting Optilume for the treatment of anterior urethral male stricture versus current endoscopic standard of care. A scenario analysis was conducted which compared Optilume to urethroplasty. Probabilistic and deterministic sensitivity analyses were performed to estimate the impact of uncertainties in model parameters. Results: When compared with current endoscopic standard of care Optilume resulted in an estimated cost saving of £2502 per patient if introduced in the NHS for the treatment of recurrent anterior male urethral stricture. In the scenario analysis, the use of Optilume compared with urethroplasty resulted in an estimated cost saving of £243. Results were robust to changes in individual input parameters as demonstrated in the deterministic sensitivity analyses, with the monthly probability of symptom recurrence associated with endoscopic management the only exception. Probabilistic sensitivity analysis results demonstrated that Optilume was cost saving in 93.4% of model iterations, when running 1000 iterations. Conclusion: Our analysis suggests that the Optilume urethral DCB treatment can be a cost-saving alternative management option for the treatment of recurrent anterior male urethral stricture within the NHS in England.

A cost-effectiveness evaluation of latent tuberculosis infection screening of a migrant population in Malaysia.

To estimate the costs and benefits of screening for latent tuberculosis infection (LTBI) in a migrant population in Malaysia. An economic model was developed from a Malaysian healthcare perspective to compare QuantiFERON-TB Gold Plus (QuantiFERON) with the tuberculin skin test (TST). A decision tree was used to capture outcomes relating to LTBI screening followed by a Markov model that simulated the lifetime costs and benefits of the patient cohort. The Markov model did not capture the impact of secondary infections. The model included an R shiny interactive interface to allow adaptation to other scenarios and settings. QuantiFERON is both more effective and less costly than TST (dominant). Compared with QuantiFERON, the lifetime risk of developing active TB increases by approximately 40% for TST due to missed LTBI cases during screening (i.e. a higher number of false negative cases for TST). For a migrant population in Malaysia, QuantiFERON is cost-effective when compared with TST. Further research should consider targeted LTBI screening for migrants in Malaysia based on common risk factors.

Developing a Modeling Framework for Quantifying the Health and Cost Implications of Antibiotic Resistance for Surgical Procedures.

Background. Antimicrobial resistance (AMR) is a global public health threat. The wider implications of AMR, such as the impact of antibiotic resistance (ABR) on surgical procedures, are yet to be quantified. The objective of this study was to produce a conceptual modeling framework to provide a basis for estimating the current and potential future consequences of ABR for surgical procedures in England. Design. A framework was developed using literature-based evidence and structured expert elicitation. This was applied to populations undergoing emergency repair of the neck of the femur and elective colorectal resection surgery. Results. The framework captures the implications of increasing ABR by allowing for higher rates of surgical site infection (SSI) as the effectiveness of antibiotic prophylaxis wanes and worsened outcomes following SSIs to reflect reduced antibiotic treatment effectiveness. The expert elicitation highlights the uncertainty in quantifying the impact of ABR, reflected in the results. A hypothetical SSI rate increase of 14% in a person undergoing emergency repair of the femur could increase costs by 39% (-2% to 108% credible interval [CI]) and decrease quality-adjusted life-years by 11% (0.4% to 62% CI) over 15 y. Conclusions. The modeling framework is a starting point for addressing the implication of ABR on the outcomes and costs of surgeries. Due to clinical uncertainty highlighted in the expert elicitation process, the numerical outputs of the case studies should not be focused on but rather the framework itself, illustration of the evidence gaps, the benefit of expert elicitation in quantifying parameters with limited data, and the potential magnitude of the impact of ABR on surgical procedures. Implications. The framework can be used to support research surrounding the health and cost burden of ABR in England. Highlights: The modeling framework is a starting point for assessing the health and cost impacts of antibiotic resistance on surgeries in England.Formulating a framework and synthesizing evidence to parameterize data gaps provides targets for future research.Once data gaps are addressed, this modeling framework can be used to feed into overall estimates of the health and cost burden of antibiotic resistance and evaluate control policies.

Self-controlled responses to COVID-19: Self-control and uncertainty predict responses to the COVID-19 pandemic.

Two online studies (Total N = 331) tested the hypothesis that individual differences in self-control and responses to uncertainty would predict adherence to Centers for Disease Control and Prevention (CDC, 2020a) guidelines, reported stockpiling, and intentions to engage in hedonic behavior in response to the COVID-19 pandemic. Trait self-control (b = 0.27, p = .015), desire for self-control (Study 1: b = 0.28, p = .001; Study 2: b = 0.27, p = .005), and cognitive uncertainty (b = 0.73, p < .001) predicted more CDC adherence. State self-control (Study 1: b = -0.15, p = .012; Study 2: b = -0.26, p < .001) predicted less stockpiling, whereas emotional uncertainty (b = 0.56, p < .001) and cognitive uncertainty (b = 0.61, p < .001) predicted more stockpiling. State self-control (b = -0.18, p = .003) predicted less hedonic behavior, whereas desire for self-control (b = 0.42, p < .001) and emotional uncertainty (b = 0.26, p = .018) predicted more hedonic behavior. Study 2 (pre-registered) also found that emotional uncertainty predicted more stockpiling and hedonic behavior for participants low in state self-control (stockpiling: b = -0.31, p < .001; hedonic behavior: b = 0.28, p = .025), but not for participants high in state self-control (stockpiling: b = 0.03, p = .795; hedonic behavior: b = -0.24, p = .066). These findings provide evidence that some forms of self-control and uncertainty influenced compliance with behavioral recommendations during the COVID-19 pandemic. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-021-02066-y.

A systematic review of cost-utility analyses of screening methods in latent tuberculosis infection in high-risk populations.

BACKGROUND: The World Health Organisation (WHO) recommends that testing and treatment for latent tuberculosis infection (LTBI) should be undertaken in high-risk groups using either interferon gamma release assays (IGRAs) or a tuberculin skin test (TST). As IGRAs are more expensive than TST, an assessment of the cost-effectiveness of IGRAs can guide decision makers on the most appropriate choice of test for different high-risk populations. This current review aimed to provide the most up to date evidence on the cost-effectiveness evidence on LTBI testing in high-risk groups-specifically evidence reporting the costs per QALY of different testing strategies. METHODS: A comprehensive search of databases including MEDLINE, EMBASE and NHS-EED was undertaken from 2011 up to March 2021. Studies were screened and extracted by two independent reviewers. The study quality was assessed using the Bias in Economic Evaluation Checklist (ECOBIAS). A narrative synthesis of the included studies was undertaken. RESULTS: Thirty-two studies reported in thirty-three documents were included in this review. Quality of included studies was generally high, although there was a weakness across all studies referencing sources correctly and/or justifying choices of parameter values chosen or assumptions where parameter values were not available. Inclusions of IGRAs in testing strategies was consistently found across studies to be cost-effective but this result was sensitive to underlying LTBI prevalence rates. CONCLUSION: While some concerns remain about uncertainty in parameter values used across included studies, the evidence base since 2010 has grown with modelling approaches addressing the weakness pointed out in previous reviews but still reaching the same conclusion that IGRAs are likely to be cost-effective in high-income countries for high-risk populations. Evidence is also required on the cost-effectiveness of different strategies in low to middle income countries and countries with high TB burden.

Evaluation of the Cost-Utility of the York Faecal Calprotectin Care Pathway.

Background: Lower gastrointestinal symptoms are common in the general population and it can be difficult to discriminate between inflammatory bowel disease (IBS) and irritable bowel syndrome (IBD) due to overlap of symptoms. The York Fecal Calprotectin Care Pathway (YFCCP) was introduced in 2016 as an alternative to the NICE fecal calprotectin pathway (DG11). This analysis uses the prospective data from the first 1005 patients in the YFCCP. Previous analysis demonstrated the YFCCP may be cost-saving when compared with the DG11 pathway. This analysis examined the short-term health-related quality of life (HRQoL) impact for patients in the YFCCP for IBD and IBS.Methods: A decision tree model was used to estimate the proportion of people presenting with lower gastrointestinal symptoms that were correctly or falsely diagnosed with IBS and IBD. Time to diagnosis data was estimated and HRQoL data was estimated from published sources. Costs and QALYs were calculated for the YFCCP and each comparator.Results: The YFCCP was cost-effective at a £20,000 threshold when compared with the current NICE recommended pathways and was cost-saving with a QALY gain (dominant)in four of the five comparators. Conclusions: The YFCCP demonstrated a QALY benefit when compared with all alternative pathways.

Indoor Air Quality at Home-An Economic Analysis.

Background: People with respiratory conditions are susceptible to health problems caused by exposure to indoor air pollutants. An economic framework was developed to inform a guideline developed by National Institute for Health and Care Excellence (NICE) to estimate the required level of efficacy necessary for an intervention to be cost-saving in dwellings across England. Methods: An economic modelling framework was built to estimate the incremental costs pre- and post-implementation of interventions designed to reduce exposure to indoor air pollution within dwellings of varying building-related risk factors and profiles. The intervention cost was varied simultaneously with the relative reduction in symptomatic cases of each health condition to estimate the point at which an intervention may become cost-saving. Four health conditions were considered. Results: People living in dwellings with either an extreme risk profile or usable floor area <90m2 have the greatest capacity to benefit and save National Health Service (NHS) costs from interventions at any given level of effectiveness and upfront cost. Conclusions: At any effectiveness level, the threshold for the upfront intervention cost to remain cost-saving is equivalent across the different home characteristics. The flexible model can be used to guide decision-making under a range of scenarios.

The cost-effectiveness of TheraSphere in patients with hepatocellular carcinoma who are eligible for transarterial embolization.

INTRODUCTION: The aim of the study is to estimate the cost-effectiveness of TheraSphere against other embolic treatments in a population with early to intermediate stage hepatocellular carcinoma (HCC) who are unresectable at presentation and are eligible for transarterial embolization (TAE), conventional transarterial chemoembolization (cTACE) or drug-eluting bead TACE (DEB-TACE). MATERIALS AND METHODS: A Markov model was constructed using a UK National Health Service (NHS) perspective, a 20-year time horizon, and four-week cycles. The eight health states included 'watch and wait', 'transplantation' (pre-, post and post (No HCC)), 'resection', 'no HCC other', 'pharmacological management' and 'death'. Clinical data were sourced from literature and expert opinion. Resource use and costs were reflective of the NHS, and benefits were quantified using Quality-Adjusted Life Years (QALYs), with utility weights sourced from literature. Comparators were TAE, cTACE and DEB-TACE. The primary output was the Incremental Cost-Effectiveness Ratio (ICER) expressed as cost per QALY gained. An ICER of under £20,000/QALY gained for an intervention is cost-effective and represents efficient use of healthcare resources. Extensive deterministic and probabilistic sensitivity analyses were undertaken. RESULTS: TheraSphere patients were predicted to gain 0.7 additional QALYs compared to all other treatments. The base case ICERs for TheraSphere were £17,300, £17,279 and £23,020 per QALY gained compared to TAE, cTACE and DEB-TACE, respectively. In the TheraSphere cohort, 87% more patients were predicted to achieve downstaging compared to all other treatment options. CONCLUSIONS: This study indicates that treatment with TheraSphere is a potentially cost-effective option for patients with early to intermediate stage HCC.

Economic Evaluation of Senshio® (Ospemifene) for the Treatment of Vulvovaginal Atrophy in Scotland.

BACKGROUND: Local oestrogens, the current treatment for vulvar and vaginal atrophy (VVA), are not suitable for all women. Standard of care (SoC) consists of over-the-counter lubricants and moisturisers. Senshio® (ospemifene) provides a treatment option for postmenopausal women who are not candidates for local vaginal oestrogen therapy who would otherwise have an unmet clinical need. OBJECTIVES: The aim of this study was to estimate the cost-effectiveness of ospemifene, a selective oestrogen receptor modulator, for the treatment of moderate to severe symptomatic VVA in postmenopausal women who are not candidates for local vaginal oestrogen therapy. METHODS: The Scottish Medicines Consortium (SMC) recently evaluated the clinical and cost-effectiveness evidence of ospemifene plus SoC compared with SoC alone. A cost-effectiveness study, from a National Health Service (NHS) Scotland perspective over a lifetime time horizon, was submitted to the SMC. The cohort-based Markov model used robust clinical evidence from two large pivotal phase III randomised controlled studies and included four health states classified by dyspareunia symptom severity: none, mild, moderate and severe. The movement of women between health states was dependent on the effectiveness of treatment in reducing dyspareunia. Extensive sensitivity analyses were undertaken to assess the level of confidence associated with the base-case results. RESULTS: Treatment with ospemifene was associated with an additional cost of £847 per patient and an increase in quality-adjusted life-years (QALY) of 0.06 per patient. Ospemifene had an incremental cost-effectiveness ratio of £14,138 per QALY. In the probabilistic sensitivity analysis, there was a probability of 89% that ospemifene was cost-effective at a threshold of £20,000 per QALY gained. Ospemifene remained cost-effective under all scenario analyses. The SMC reviewed the clinical and economic evidence and judged that the evidence demonstrated a robust case to support prescribing ospemifene in NHS Scotland. CONCLUSION: Ospemifene is a cost-effective intervention that has recently been accepted by the SMC for the treatment of postmenopausal women with moderate to severe VVA who are not candidates for local oestrogen.

Interpersonal consequences of legal handgun carrying on college campuses.

Objective: This study assessed whether college students felt less safe or were less likely to work with another student when they thought the person they would work with was carrying a handgun than when they did not. Participants: Seventy participants were recruited from a public US university where campus carry was legal. Methods: Participants were led to believe a confederate was carrying a handgun or not. Participants' perceived safety and willingness to work with others was assessed. Results: No difference was found in participants' perceived safety. Participants who believed another student was carrying a concealed handgun reported they would be less likely to perform certain tasks with the handgun carrier than they would with the non-carrier. Conclusions: People do not feel less safe around a handgun-carrying confederate and that allowing concealed handguns on campus might affect handgun carriers' interpersonal interactions with others in suboptimal ways.

Evaluation of the clinical and cost-effectiveness of the York Faecal Calprotectin Care Pathway.

OBJECTIVE: To evaluate the sensitivity and specificity of the York Faecal Calprotectin Care Pathway (YFCCP) and undertake a health economics analysis. The YFCCP has been introduced in support of the National Institute for Health and Care Excellence (NICE) guidance DG11. It is designed to improve the sensitivity and specificity of faecal calprotectin (FC) in discriminating the irritable bowel syndrome from inflammatory bowel disease in primary care. DESIGN: To prospectively evaluate the clinical outcomes at 6 months of the first 1005 patients entering the YFCCP. To develop a cost-consequence model using two comparators: one based on clinical assessment and the C reactive protein/erythrocyte sedimentation rate without using FC, and the second using single testing of the standard FC cut-off. SETTING: North Yorkshire primary care practices. PATIENTS: Primary care patients fulfilling NICE DG11. INTERVENTIONS: The YFCCP. MAIN OUTCOME MEASURES: Clinical outcome measures from secondary care records. RESULTS: The sensitivity and specificity of the YFCCP are 0.94 (0.85 to 0.98) and 0.92 (0.90 to 0.94), giving a negative and positive predictive value of 0.99 (0.98 to 1.0) and 0.51 (0.43 to 0.59), respectively. CONCLUSIONS: The YFCCP overcomes the challenges experienced with FC use in primary care, its efficacy matching initial NICE projections. It is readily incorporated into clinical practice. It should represent the framework on which to increase NICE DG11 implementation nationally.

Economic Value of Improved Accuracy for Self-Monitoring of Blood Glucose Devices for Type 1 and Type 2 Diabetes in England.

OBJECTIVE: The objective was to model clinical and economic outcomes of self-monitoring blood glucose (SMBG) devices with varying error ranges and strip prices for type 1 and insulin-treated type 2 diabetes patients in England. METHODS: We programmed a simulation model that included separate risk and complication estimates by type of diabetes and evidence from in silico modeling validated by the Food and Drug Administration. Changes in SMBG error were associated with changes in hemoglobin A1c (HbA1c) and separately, changes in hypoglycemia. Markov cohort simulation estimated clinical and economic outcomes. A SMBG device with 8.4% error and strip price of £0.30 (exceeding accuracy requirements by International Organization for Standardization [ISO] 15197:2013/EN ISO 15197:2015) was compared to a device with 15% error (accuracy meeting ISO 15197:2013/EN ISO 15197:2015) and price of £0.20. Outcomes were lifetime costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). RESULTS: With SMBG errors associated with changes in HbA1c only, the ICER was £3064 per QALY in type 1 diabetes and £264 668 per QALY in insulin-treated type 2 diabetes for an SMBG device with 8.4% versus 15% error. With SMBG errors associated with hypoglycemic events only, the device exceeding accuracy requirements was cost-saving and more effective in insulin-treated type 1 and type 2 diabetes. CONCLUSIONS: Investment in devices with higher strip prices but improved accuracy (less error) appears to be an efficient strategy for insulin-treated diabetes patients at high risk of severe hypoglycemia.