Low energy contact X-ray brachytherapy for treatment of rectal cancer: a health technology appraisal by Health Technology Wales.

AIM: Health Technology Wales sought to evaluate the clinical and cost-effectiveness of contact X-ray brachytherapy (CXB) for early-stage rectal cancer. METHODS: Relevant studies were identified through systematic searches of MEDLINE, Embase, Cochrane Library and Scopus. A cost-utility model was developed to estimate the cost-effectiveness of CXB in National Health Service Wales, using results of the Organ Preservation in Early Rectal Adenocarcinoma (OPERA) trial. Patient perspectives were obtained through the Papillon Patient Support group and All-Wales Cancer Network. RESULTS: The OPERA randomized controlled trial showed that CXB improved complete response and organ preservation rates compared with external-beam boost for people with T2-3b, N0-1, M0 rectal cancer who are fit for surgery. Managing more of this population non-operatively after CXB was estimated to provide 0.2 quality-adjusted life years at an additional cost of £887 per person. CXB was cost effective compared with external-beam boost at a cost of £4463 per quality-adjusted life year gained. This conclusion did not change in scenario analysis and CXB was cost effective in 91% of probabilistic sensitivity analyses. Patients valued receiving clear information on all available options to support their individual treatment choices. The detrimental impact of a stoma on quality of life led some patients to reject the idea that surgery was their only option. CONCLUSION: This evidence review and cost-utility analysis indicates that CXB is likely to be clinically and cost effective, as part of a watch and wait strategy for adults fit for surgery. Wider access to CXB is supported by patient testimonies.

Exploring Structural Uncertainty and Impact of Health State Utility Values on Lifetime Outcomes in Diabetes Economic Simulation Models: Findings from the Ninth Mount Hood Diabetes Quality-of-Life Challenge.

BACKGROUND: Structural uncertainty can affect model-based economic simulation estimates and study conclusions. Unfortunately, unlike parameter uncertainty, relatively little is known about its magnitude of impact on life-years (LYs) and quality-adjusted life-years (QALYs) in modeling of diabetes. We leveraged the Mount Hood Diabetes Challenge Network, a biennial conference attended by international diabetes modeling groups, to assess structural uncertainty in simulating QALYs in type 2 diabetes simulation models. METHODS: Eleven type 2 diabetes simulation modeling groups participated in the 9th Mount Hood Diabetes Challenge. Modeling groups simulated 5 diabetes-related intervention profiles using predefined baseline characteristics and a standard utility value set for diabetes-related complications. LYs and QALYs were reported. Simulations were repeated using lower and upper limits of the 95% confidence intervals of utility inputs. Changes in LYs and QALYs from tested interventions were compared across models. Additional analyses were conducted postchallenge to investigate drivers of cross-model differences. RESULTS: Substantial cross-model variability in incremental LYs and QALYs was observed, particularly for HbA1c and body mass index (BMI) intervention profiles. For a 0.5%-point permanent HbA1c reduction, LY gains ranged from 0.050 to 0.750. For a 1-unit permanent BMI reduction, incremental QALYs varied from a small decrease in QALYs (-0.024) to an increase of 0.203. Changes in utility values of health states had a much smaller impact (to the hundredth of a decimal place) on incremental QALYs. Microsimulation models were found to generate a mean of 3.41 more LYs than cohort simulation models (P = 0.049). CONCLUSIONS: Variations in utility values contribute to a lesser extent than uncertainty captured as structural uncertainty. These findings reinforce the importance of assessing structural uncertainty thoroughly because the choice of model (or models) can influence study results, which can serve as evidence for resource allocation decisions.HighlightsThe findings indicate substantial cross-model variability in QALY predictions for a standardized set of simulation scenarios and is considerably larger than within model variability to alternative health state utility values (e.g., lower and upper limits of the 95% confidence intervals of utility inputs).There is a need to understand and assess structural uncertainty, as the choice of model to inform resource allocation decisions can matter more than the choice of health state utility values.

Assessing the cost-effectiveness of sodium-glucose cotransporter-2 inhibitors in type 2 diabetes mellitus: A comprehensive economic evaluation using clinical trial and real-world evidence.

AIMS: The economic burden of diabetes is driven by the management of vascular complications. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated reductions in cardiovascular and renal complications, including hospitalization for heart failure (HHF) and renal disease progression, in randomized clinical trials. The objective of this study was to evaluate the cost-effectiveness of the SGLT2i class versus standard of care in type 2 diabetes mellitus (T2DM), using evidence from both clinical trial and real-world studies. METHODS: An established T2DM model was adapted to use contemporary outcomes evidence from real-world studies and randomized controlled trial evaluations of SGLT2i, and extrapolated over a lifetime for HHF, myocardial infarction, stroke, end-stage renal disease and all-cause mortality. The economic analysis considered adults with T2DM, with and without established cardiovascular disease, and was conducted over a lifetime from the perspective of the health care payer in the United Kingdom, United States and China, discounted at country-specific rates. RESULTS: SGLT2i were consistently associated with increased treatment costs, reduced complication costs and gains in quality-adjusted life years driven by differences in projected life expectancy, cardiovascular and microvascular morbidity and weight loss. SGLT2i were estimated to be cost-saving or cost-effective at relevant thresholds for the overall population in the United Kingdom, United States and China, with cost-effectiveness being the greatest in higher risk subgroups. CONCLUSIONS: The findings highlight the need to take into account cost savings from reducing common, morbid and preventable T2DM complications when considering the cost of diabetes medications.

Cost-effectiveness of dapagliflozin as an adjunct to insulin for the treatment of type 1 diabetes mellitus in the United Kingdom.

AIMS: To assess the cost-effectiveness of dapagliflozin, a sodium-glucose co-transporter-2 (SGLT2) inhibitor, as an adjunct to insulin in adults with type 1 diabetes mellitus (T1DM) inadequately controlled by insulin alone in the UK setting. METHODS: A cost-utility analysis was conducted to compare dapagliflozin (5 mg or 10 mg) added to insulin versus insulin monotherapy (standard of care) over a lifetime horizon. Treatment efficacy and safety data were obtained from 52-week results of the DEPICT-1 and DEPICT-2 trials and a network meta-analysis of SGLT2 inhibitors in T1DM. Direct healthcare costs, life-years, and quality-adjusted life-years (QALYs) were estimated from a UK payer perspective and discounted at 3.5% annually, using the Cardiff T1DM Model. Sensitivity analyses assessed uncertainty in estimated incremental cost-effectiveness ratios (ICERs). RESULTS: Dapagliflozin 5 mg was associated with gains of 0.23 life-years and 0.42 QALYs, at an additional cost of £4240 per person; corresponding to an ICER of £10 143 versus standard of care. For dapagliflozin 10 mg, incremental life-years, QALYs and costs were 0.24, 0.49 and £2964, respectively; corresponding to an ICER of £6103 versus standard of care. In probabilistic sensitivity analysis, ICER estimates fell below £20 000/QALY in 78% to 90% of simulations. Cost-effectiveness results were sensitive to changes in baseline patient characteristics and treatment effects on glycated haemoglobin; however, ICERs remained below £20 000. CONCLUSIONS: At cost-effectiveness thresholds conventionally applied in the UK, dapagliflozin as an adjunct to insulin appears to be a cost-effective treatment option for people with T1DM inadequately controlled by insulin alone.

The value of maintaining normokalaemia and enabling RAASi therapy in chronic kidney disease.

BACKGROUND: People with chronic kidney disease (CKD) are at an increased risk of developing hyperkalaemia due to their declining kidney function. In addition, these patients are often required to reduce or discontinue guideline-recommended renin-angiotensin-aldosterone system inhibitor (RAASi) therapy due to increased risk of hyperkalaemia. This original research developed a model to quantify the health and economic benefits of maintaining normokalaemia and enabling optimal RAASi therapy in patients with CKD. METHODS: A patient-level simulation model was designed to fully characterise the natural history of CKD over a lifetime horizon, and predict the associations between serum potassium levels, RAASi use and long-term outcomes based on published literature. The clinical and economic benefits of maintaining sustained potassium levels and therefore avoiding RAASi discontinuation in CKD patients were demonstrated using illustrative, sensitivity and scenario analyses. RESULTS: Internal and external validation exercises confirmed the predictive capability of the model. Sustained potassium management and ongoing RAASi therapy were associated with longer life expectancy (+ 2.36 years), delayed onset of end stage renal disease (+ 5.4 years), quality-adjusted life-year gains (+ 1.02 QALYs), cost savings (£3135) and associated net monetary benefit (£23,446 at £20,000 per QALY gained) compared to an absence of RAASi to prevent hyperkalaemia. CONCLUSION: This model represents a novel approach to predicting the long-term benefits of maintaining normokalaemia and enabling optimal RAASi therapy in patients with CKD, irrespective of the strategy used to achieve this target, which may support decision making in healthcare.

Pro-equity climate change and environmental sustainability action by district health boards in Aotearoa/New Zealand.

AIM: With current health ministerial directives to prioritise actions on reducing health inequities and district health board (DHB) greenhouse gas (GHG) emissions, we argue that all climate change and environmental sustainability actions by DHBs must be pro-equity, and explore how the two priorities can be addressed concurrently. METHOD: Building on prior knowledge of climate change and environmental sustainability action in the health and disability sector, we undertook a visioning exercise to generate ideas for pro-equity GHG emissions reduction initiatives in the DHB context. Visioning was further informed by presentation and feedback discussion at an Annual Scientific Meeting of the New Zealand College of Public Health Medicine. RESULTS: Three scenarios were envisioned in the areas of DHB energy use, transport and procurement where GHG emissions could be reduced, and health determinants and outcomes for Maori and Pacific peoples improved. CONCLUSION: Current ministerial directives to address both health inequities and DHB greenhouse gas emissions present DHBs with the opportunity to ensure they systematically address both priorities at the same time. In doing so, Aotearoa/New Zealand has the potential to lead the world in demonstrating pro-equity climate change and sustainability action in health systems.

Development of a health economic model to evaluate the potential benefits of optimal serum potassium management in patients with heart failure.

AIMS: Patients with heart failure are at increased risk of hyperkalemia, particularly when treated with renin-angiotensin-aldosterone system inhibitor (RAASi) agents. This study developed a model to quantify the potential health and economic value associated with sustained potassium management and optimal RAASi therapy in heart failure patients. MATERIALS AND METHODS: A patient-level, fixed-time increment stochastic simulation model was designed to characterize the progression of heart failure through New York Heart Association functional classes, and predict associations between serum potassium levels, RAASi use, and consequent long-term outcomes. Following internal and external validation exercises, model analyses sought to quantify the health and economic benefits of optimizing both serum potassium levels and RAASi therapy in heart failure patients. Analyses were conducted using a UK payer perspective, independent of costs and utilities related to pharmacological potassium management. RESULTS: Validation against multiple datasets demonstrated the predictive capability of the model. Compared to those who discontinued RAASi to manage serum potassium, patients with normokalemia and ongoing RAASi therapy benefited from longer life expectancy (+1.38 years), per-patient quality-adjusted life year gains (+0.53 QALYs), cost savings (£110), and associated net monetary benefit (£10,679 at £20,000 per QALY gained) over a lifetime horizon. The predicted value of sustained potassium management and ongoing RAASi treatment was largely driven by reduced mortality and hospitalization risks associated with optimal RAASi therapy. LIMITATIONS: Several modeling assumptions were made to account for a current paucity of published literature; however, ongoing refinement and validation of the model will ensure its continued accuracy as the clinical landscape of hyperkalemia evolves. CONCLUSIONS: Predictions generated by this novel modeling approach highlight the value of sustained potassium management to avoid hyperkalemia, enable RAASi therapy, and improve long-term health economic outcomes in patients with heart failure.

Hepatitis C disease transmission and treatment uptake: impact on the cost-effectiveness of new direct-acting antiviral therapies.

BACKGROUND: Hepatitis C virus (HCV) treatment can reduce the incidence of future infections through removing opportunities for onward transmission. This benefit is not captured in conventional cost-effectiveness evaluations of treatment and is particularly relevant in patient groups with a high risk of transmission, such as those people who inject drugs (PWID), where the treatment rates have been historically low. This study aimed to quantify how reduced HCV transmission changes the cost-effectiveness of new direct-acting antiviral (DAA) regimens as a function of treatment uptake rates. METHODS: An established model of HCV disease transmission and progression was used to quantify the impact of treatment uptake (10-100%), within the PWID population, on the cost-effectiveness of a DAA regimen versus pre-DAA standard of care, conducted using daclatasvir plus sofosbuvir in the UK setting as an illustrative example. RESULTS: The consequences of reduced disease transmission due to treatment were associated with additional net monetary benefit of £24,304-£90,559 per patient treated at £20,000/QALY, when 10-100% of eligible patients receive treatment with 100% efficacy. Dependent on patient genotype, the cost-effectiveness of HCV treatment using daclatasvir plus sofosbuvir improved by 36-79% versus conventional analysis, at 10-100% treatment uptake in the PWID population. CONCLUSIONS: The estimated cost-effectiveness of HCV treatment was shown to improve as more patients are treated, suggesting that the value of DAA regimens to the NHS could be enhanced by improved treatment uptake rates among PWID. However, the challenge for the future will lie in achieving increased rates of treatment uptake, particularly in the PWID population.

A clinician's guide to the cost and health benefits of hepatitis C cure assessed from the individual patient perspective.

BACKGROUND AND AIMS: The hepatitis C virus (HCV) remains a considerable public health challenge. Novel direct-acting antiviral (DAA) regimens offer high cure rates and the promise of reduced HCV incidence and prevalence following the up-scaling of treatment. This has focused attention towards affordability. This study aimed to estimate the economic value of cure to evaluate the treatment costs justifiable from the patient perspective. PATIENTS AND METHODS: A published, validated HCV model was utilized to contrast clinical and cost outcomes for patients aged 30-70 years, stratified by METAVIR F0-F4, for (i) no treatment and (ii) successful treatment [i.e. sustained virologic response (SVR)] ignoring the cost of treatment. Regression equations were fitted and used to determine the financial expenditure justifiable to achieve a cost-neutral or a cost-effective [£20 000 per quality-adjusted life-year (QALY)] cure. Model inputs were derived from UK literature; costs and utilities were discounted at 3.5% over a lifetime horizon. RESULTS: To achieve cost-neutrality, the maximum discounted expenditure justifiable for SVR was £3774-43 607 across ages and fibrosis stages. Spending between £19 745 (70 years, F0) and £188 420 (30 years, F4) on SVR is expected to be cost-effective at £20 000/QALY willingness-to-pay threshold. CONCLUSION: Heterogeneity across HCV patients is considerable, which can obscure the relevance of conventional cohort-based economic models evaluated at the mean, particularly when considering the value of treatment at the individual patient level. By quantifying the full exposition of HCV cost-savings and health benefits realizable following HCV cure, this study provides insight into the economic value of successful treatment from the patient perspective.

Value of Sustained Virologic Response in Patients with Hepatitis C as a Function of Time to Progression of End-Stage Liver Disease.

BACKGROUND: Targeted intervention in patients with hepatitis C virus (HCV) closest to end-stage liver disease (ESLD) progression may offer an approach to treatment prioritisation whilst delivering benefits for patients and the healthcare system. In contrast to previous HCV economic analyses, this study aimed to estimate the health economic value of sustained virologic response (SVR) stratified by the patient's propensity to progress to ESLD. METHODS: An HCV natural history model was adapted to estimate the value of avoiding ESLD complications following SVR, assessed as cost offsets and quality-adjusted life year (QALY) gains, as a function of time to ESLD at treatment initiation. These outcomes were used to estimate the financial value of achieving SVR, defined as the maximum investment that could be allocated without exceeding a willingness-to-pay threshold of £20,000/QALY. RESULTS: Regardless of time to ESLD onset, achieving SVR was beneficial, resulting in cost offsets and QALY gains, due to avoidance of ESLD complications. The value of achieving SVR was greatest in patients closest to ESLD onset, resulting in increased cost offsets and QALY gains (up to £50,901 and 9.56 QALYs). In patients closest to ESLD onset, the financial value of achieving SVR was £242,051, compared with £127,116 in patients furthest from onset. CONCLUSIONS: Standard cost-effectiveness evaluations may underestimate the value of treatment in HCV patients closest to ESLD development. Targeted intervention would promote efficient allocation of limited healthcare resources and reconcile concerns surrounding the affordability of new direct-acting antivirals, by minimising the number-needed-to-treat to maximise health benefit, whilst minimising healthcare expenditure.

An alternative approach to modelling HbA1c trajectories in patients with type 2 diabetes mellitus.

AIMS: Time-dependent HbA1c trajectories in health economic models of type 2 diabetes mellitus (T2DM) are typically informed by the UK Prospective Diabetes Study (UKPDS). However, this approach may not accurately predict HbA1c progression in patients who do not conform to the demographic profile of the original UKPDS cohort. This study aimed to develop an alternative mathematical model (MM) to simulate HbA1c progression in T2DM. MATERIALS AND METHODS: A systematic literature review identified studies, published between 2005 and 2015, that reported HbA1c in adult T2DM patients over a minimum duration of 18 months. Pooled data from eligible studies were used to develop an alternative MM equation for HbA1c progression, which was then contrasted with the UKPDS 68 progression equation in illustrative scenarios. RESULTS: A total of 68 studies were eligible for data extraction (mean follow-up time 4.1 years). HbA1c progression was highly heterogeneous across studies, varying with baseline HbA1c, treatment group and patient age. The MM equation was fitted with parameters for mean baseline HbA1c (8.3%), initial change in HbA1c (-0.62%) and upper quartile of maximum observed HbA1c (9.3%). Differences in HbA1c trajectories between the MM and UKPDS approaches altered the timing of therapy escalation in illustrative scenarios. CONCLUSIONS: The MM represents an alternative approach to simulate HbA1c trajectories in T2DM models, as UKPDS data may not adequately reflect the heterogeneity of HbA1c profiles observed in clinical studies. However, the choice of approach should ultimately be determined by the characteristics of individual patients under consideration and the clinical face validity of the modelled trajectories.

The Health Economic Value of Changes in Glycaemic Control, Weight and Rates of Hypoglycaemia in Type 1 Diabetes Mellitus.

AIMS: Therapy-related consequences of treatment for type 1 diabetes mellitus (T1DM), such as weight gain and hypoglycaemia, act as a barrier to attaining optimal glycaemic control, indirectly influencing the incidence of vascular complications and associated morbidity and mortality. This study quantifies the individual and combined contribution of changes in hypoglycaemia frequency, weight and HbA1c to predicted quality-adjusted life-years (QALYs) within a T1DM population. MATERIALS AND METHODS: We describe the Cardiff Type 1 Diabetes (CT1DM) Model, originally informed by the Diabetes Control and Complications Trial (DCCT) and updated with the Epidemiology of Diabetes Interventions and Complications (EDIC) study and Swedish National Diabetes Registry for microvascular and cardiovascular complications respectively. We report model validation results and the QALY impact of HbA1c, weight and hypoglycaemia changes. RESULTS: Validation results demonstrated coefficients of determination for clinical endpoints of R2 = 0.863 (internal R2 = 0.999; external R2 = 0.823), costs R2 = 0.980 and QALYs R2 = 0.951. Achieving and maintaining a 1% HbA1c reduction was estimated to provide 0.61 additional discounted QALYs. Weight changes of ±1kg, ±2kg or ±3kg led to discounted QALY changes of ±0.03, ±0.07 and ±0.10 respectively, while modifying hypoglycaemia frequency by -10%, -20% or -30% resulted in changes of -0.05, -0.11 and -0.17. The differences in discounted costs, life-years and QALYs associated with HbA1c 6% versus 10% were -£19,037, 2.49 and 2.35 respectively. CONCLUSIONS: Using a model updated with contemporary epidemiological data, this study presents an outcome-focused perspective to assessing the health economic consequences of differing levels of glycaemic control in T1DM with and without weight and hypoglycaemia effects.

The cost-effectiveness of daclatasvir-based regimens for the treatment of hepatitis C virus genotypes 1 and 4 in the UK.

OBJECTIVE: This study aimed to determine the cost-effectiveness of daclatasvir in combination with other medicinal products for the treatment of patients with hepatitis C virus genotypes 1 and 4 and advanced liver disease in the UK. METHODS: A published and validated Markov model designed to simulate the natural history of chronic hepatitis C was used to compare daclatasvir with relevant treatment options for patients with hepatitis C virus genotypes 1 and 4 and a METAVIR score of F3-F4. Patients were defined according to their treatment status; that is, naive, experienced or interferon ineligible/intolerant. Data inputs for the analysis were derived from published sources, UK-specific where possible. A lifetime horizon was used, with costs and benefits discounted at 3.5%. RESULTS: Daclatasvir-based regimens are estimated to be cost-effective versus no treatment and established standard-of-care regimens, including telaprevir in combination with pegylated interferon-α+ribavirin (PR), boceprevir in combination with PR and PR alone (incremental cost-effectiveness ratio range: £3715-£15,408). The cost-effectiveness of daclatasvir-based regimens versus emerging regimens (sofosbuvir or simeprevir based) is less consistent, but was dominant or cost-effective (incremental cost-effectiveness ratio range: £1394-£28,393) in all except two scenarios. CONCLUSION: Daclatasvir-based regimens are expected to be highly cost-effective for the majority patients with advanced disease versus relevant comparator regimens, including newer direct-acting antiviral regimens.

Health, fairness and New Zealand's contribution to global post-2020 climate change action.

Health and wellbeing have been largely ignored in discussions around climate change targets and action to date. The current public consultation around New Zealand's post-2020 climate target is an opportunity for health professionals to highlight the health implications of climate change. Without urgent global efforts to bring down global GHG (greenhouse gas) emissions, the world is heading towards high levels of global warming, which will have devastating impacts on human health and wellbeing. New Zealand's action to bring down GHG emissions (as part of the global effort) has potential to improve health and reduce costs on the health sector, if health and fairness are put at the centre of policies to address climate change. New Zealand should commit to at least 40 % reductions in GHG emissions by 2030, and zero carbon emissions before 2050, with healthy and fair policies across sectors to enable reaching these targets.

Is antenatal screening for hepatitis C virus cost-effective? A decade's experience at a London centre.

BACKGROUND & AIMS: This study aims to assess the cost-effectiveness of a routine universal antenatal hepatitis C virus (HCV) screening programme at a London centre. METHODS: Ten years' retrospective antenatal screening and outcome data informed a cost-effectiveness analysis using the previously validated MONARCH model. The cost and quality of life outcomes associated with the screening and treatment of newly identified hepatitis C cases were used to generate cost-effectiveness estimates for the screening programme. RESULTS: A total of 35,355 women were screened between 1st November 2003 and 1st March 2013; 136 women (0.38%) were found to be HCV antibody positive. Of 78 (0.22%) viraemic cases, 44 (0.12%) were newly diagnosed. In addition, the screening programme identified three (6.8%) vertical transmissions in children of newly diagnosed mothers. Of 16 newly diagnosed mothers biopsied, all were in the F0-F2 METAVIR disease stages, and 50% had HCV genotype 1. Postnatal treatment with pegylated interferon and ribavirin was initiated in 19 women, with 14 (74%) achieving sustained virologic response. The total cost of screening and confirmation of diagnoses was estimated to be £240,641. This translates to £5469 per newly diagnosed individual. The incremental cost-effectiveness ratio of this screening and treatment strategy was £2400 per QALY gained. Treatment with newer direct-acting antiviral regimens would have a projected cost of £9139 per QALY gained, well below the £20,000-30,000/QALY gained willingness-to-pay threshold applied by policy advisory bodies. CONCLUSIONS: This study demonstrates that an antenatal screening and treatment programme is feasible and effective, at a cost considered acceptable.

Assessing the Long-Term Impact of Treating Hepatitis C Virus (HCV)-Infected People Who Inject Drugs in the UK and the Relationship between Treatment Uptake and Efficacy on Future Infections.

OBJECTIVE: The prevalence of the hepatitis C virus (HCV) remains high amongst people who inject drugs (PWID) and accounts for the majority of newly acquired infections. This study aims to quantify the value of treatment amongst PWID with more efficacious treatments and at increased uptake rates, with respect to the avoidance of future infections and subsequent long-term complications of HCV. METHODS: A dynamic HCV transmission and disease progression model was developed, incorporating acute and chronic infection and their long-term complications (decompensated cirrhosis, cancer, liver transplant and mortality), with the potential for HCV transmission to other PWID prior to successful treatment. The model was populated with prevalence and therapy data from a UK setting. Scenarios of current standard of care (SoC) treatment efficacy and uptake were compared to anticipated sustained virologic response (SVR) rates of 90-100% and increased uptake over varied horizons. RESULTS: SoC led to modest reductions in prevalence; >5% after 200 years. New treatments achieving 90% SVR could reduce prevalence below 5% within 60 years at current uptake rates or within 5 years if all patients are treated. Amongst 4,240 PWID, chronic HCV infections avoided as a result of increasing treatment uptake over the period 2015-2027 ranged from 20-580 and 34-912 with SoC and 90% SVR rates respectively. The reduction in downstream HCV infections due to increasing treatment uptake resulted in an approximate discounted gain of 300 life-years (from avoiding reduced life expectancy from HCV infection) and a gain of 1,700 QALYs (from avoiding the disutility of HCV infection and related complications), with a projected £5.4 million cost saving. CONCLUSION: While improved SVR profiles led to reductions in modelled prevalence, increased treatment uptake was the key driver of future infections avoided. Increased treatment among PWID with new more efficacious therapies could significantly change the future dynamics, cost and health burden of HCV-related disease.

Estimating the clinical and economic benefit associated with incremental improvements in sustained virologic response in chronic hepatitis C.

INTRODUCTION: Hepatitis C virus (HCV) infection is one of the principle causes of chronic liver disease. Successful treatment significantly decreases the risk of hepatic morbidity and mortality. Current standard of care achieves sustained virologic response (SVR) rates of 40-80%; however, the HCV therapy landscape is rapidly evolving. The objective of this study was to quantify the clinical and economic benefit associated with increasing levels of SVR. METHODS: A published Markov model (MONARCH) that simulates the natural history of hepatitis C over a lifetime horizon was used. Discounted and non-discounted life-years (LYs), quality-adjusted life-years (QALYs) and cost of complication management were estimated for various plausible SVR rates. To demonstrate the robustness of projections obtained, the model was validated to ten UK-specific HCV studies. RESULTS: QALY estimates ranged from 18.0 years for those treated successfully in fibrosis stage F0 to 7.5 years (discounted) for patients in fibrosis stage F4 who remain untreated. Predicted QALY gains per 10% improvement in SVR ranged from 0.23 (F0) to 0.64 (F4) and 0.58 (F0) to 1.35 (F4) in 40 year old patients (discounted and non-discounted results respectively). In those aged 40, projected discounted HCV-related costs are minimised with successful treatment in F0/F1 (at approximately £ 300), increasing to £ 49,300 in F4 patients who remain untreated. Validation of the model to published UK cost-effectiveness studies produce R2 goodness of fit statistics of 0.988, 0.978 and of 0.973 for total costs, QALYs and incremental cost effectiveness ratios, respectively. CONCLUSION: Projecting the long-term clinical and economic consequences associated with chronic hepatitis C is a necessary requirement for the evaluation of new treatments. The principle analysis demonstrates the significant impact on expected costs, LYs and QALYs associated with increasing SVR. A validation analysis demonstrated the robustness of the results reported.

Estimating Cost-Effectiveness in Type 2 Diabetes: The Impact of Treatment Guidelines and Therapy Duration.

OBJECTIVES: Type 2 diabetes mellitus (T2DM) clinical guidelines focus on optimizing glucose control, with therapy escalation classically initiated within a "failure-based" regimen. Within many diabetes models, HbA1c therapy escalation thresholds play a pivotal role, controlling duration of therapy and, consequently, incremental costs and benefits. The objective of this study was to assess the relationship between therapy escalation threshold and time to therapy escalation on predicted cost-effectiveness of T2DM treatments. METHODS: This study used the Cardiff Diabetes Model to illustrate the relationship between costs and health outcomes associated with first-, second-, and third-line therapy as a function of time on each. Data from routine clinical practice were used to contrast predicted costs and health outcomes associated with guideline therapy escalation thresholds compared with clinical practice. The impact of baseline HbA1c and therapy escalation thresholds on cost-effectiveness was investigated, comparing a sodium/glucose cotransporter 2 inhibitor v. sulfonylurea added to metformin monotherapy. RESULTS: Lower thresholds are associated with a shorter time spent on monotherapy, ranging from 1.1 years (escalation at 6.5%) to 13 years (escalation at 9.0%) and an increase in total lifetime cost of therapy. Treatment-related disutility is minimized with higher thresholds because progression to insulin is delayed. Using metformin combined with either dapagliflozin or a sulfonylurea to illustrate lower baseline HbA1c and/or higher therapy escalation thresholds was associated with increased cost-effectiveness ratios, driven by a longer duration of therapy. DISCUSSION: A marked difference in treatment cost-effectiveness was demonstrated when comparing routine clinical practice with guideline-advocated therapy escalation. This is important to both health care professionals and the wider health economic community with respect to understanding the true cost-effectiveness profile of any particular T2DM therapy option.