Predicted clinical and economic burden associated with reduction in access to acute coronary interventional care during the COVID-19 lockdown in two European countries.

AIMS: As a consequence of untimely or missed revascularization of ST-elevation myocardial infarction (STEMI) patients during the COVID-19 pandemic, many patients died at home or survived with serious sequelae, resulting in potential long-term worse prognosis and related health-economic implications.This analysis sought to predict long-term health outcomes [survival and quality-adjusted life-years (QALYs)] and cost of reduced treatment of STEMIs occurring during the first COVID-19 lockdown. METHODS AND RESULTS: Using a Markov decision-analytic model, we incorporated probability of hospitalization, timeliness of PCI, and projected long-term survival and cost (including societal costs) of mortality and morbidity, for STEMI occurring during the first UK and Spanish lockdowns, comparing them with expected pre-lockdown outcomes for an equivalent patient group.STEMI patients during the first UK lockdown were predicted to lose an average of 1.55 life-years and 1.17 QALYs compared with patients presenting with a STEMI pre-pandemic. Based on an annual STEMI incidence of 49 332 cases, the total additional lifetime costs calculated at the population level were £36.6 million (€41.3 million), mainly driven by costs of work absenteeism. Similarly in Spain, STEMI patients during the lockdown were expected to survive 2.03 years less than pre-pandemic patients, with a corresponding reduction in projected QALYs (-1.63). At the population level, reduced PCI access would lead to additional costs of €88.6 million. CONCLUSION: The effect of a 1-month lockdown on STEMI treatment led to a reduction in survival and QALYs compared to the pre-pandemic era. Moreover, in working-age patients, untimely revascularization led to adverse prognosis, affecting societal productivity and therefore considerably increasing societal costs.

Evolving Use of Health Technology Assessment in Medical Device Procurement-Global Systematic Review: An ISPOR Special Interest Group Report.

OBJECTIVES: To review the current academic evidence describing how data from health technology assessments (HTAs) informs procurement decisions for medical devices. METHODS: A systematic literature review was performed to identify relevant studies and criteria used in medical device purchasing or procurement decisions. Included articles were screened for relevancy and risk of bias. The included studies were summarized qualitatively. RESULTS: A total of 292 studies were screened, of which 11 matched the inclusion criteria. Included studies' geographies and HTA maturity varied. Some studies described hospital-level HTA processes, whereas others focused on national-level recommendations. Criteria for procurement decisions included standard HTA factors, such as efficacy, cost, cost-effectiveness, and budget impact; broader issues were also noted, including impact on the organization, ethical aspects, staff workload, and volume. There was little consideration of device-specific characteristics, such as life cycle, learning curve, or incremental technical innovation. Few decisions referred to HTA reports as part of the procurement decision; similarly, few HTA reports included a procurement perspective to help guide the procurement bodies. CONCLUSIONS: There is minimal evidence that notes HTA influencing medical device procurement. Procurement bodies and hospitals may not be incentivized to publish their work and transparency could be improved; further research would better describe the link between HTA and procurement. Such research would enable the HTA agencies to meaningfully assess devices to target procurement bodies and allow device sponsors to prioritize evidence. This could limit redundancy, improve evidence, and ultimately promote savings to healthcare systems and expand access.

Cost-effectiveness of 4 mg dibotermin alfa/absorbable collagen sponge versus iliac crest bone graft for lumbar degenerative disc disease in the United Kingdom.

AIMS: To develop a model to evaluate the cost-effectiveness of 4 mg dibotermin alfa/absorbable collagen sponge (ACS) versus iliac crest bone graft (ICBG) in patients with lumbar degenerative disc disease in the United Kingdom. MATERIALS & METHODS: A Markov decision-analytic model was constructed to calculate costs and quality-adjusted life-years over a 4-year time horizon in each treatment group, from a United Kingdom National Health Service perspective. An individual patient data meta-analysis was undertaken to synthesize data from four randomized controlled trials and two single-arm studies concerning health-related quality of life and procedural resource use. Current cost data from the United Kingdom were then applied to determine the overall mean cost per patient in each group. One-way and probabilistic sensitivity analyses were undertaken to explore the impact of parameter uncertainty. RESULTS: The model predicted 4-year discounted cost savings of £192 per patient treated with dibotermin alfa/ACS, compared with ICBG, and a gain of 0.0114 QALYs per patient over the same time period. Sensitivity analyses indicated that the results were most sensitive to variability in the differences in health-related quality of life and secondary surgery rate, with dibotermin alfa/ACS having a 60% probability of being cost-effective at a willingness-to-pay threshold of £20,000 per QALY gained. LIMITATIONS: There is uncertainty in the difference in cost and QALYs between the two groups. However, comprehensive sensitivity analyses were undertaken to explore this and present the results in a transparent manner. CONCLUSIONS: Our results provide an economic case for the use of 4 mg dibotermin alfa/ACS versus iliac crest bone graft, with additional health benefits predicted at reduced overall cost.

Resource Use and Cost of Subcutaneous Nerve Stimulation Versus Optimized Medical Management in Patients With Failed Back Surgery Syndrome: An Analysis of the SubQStim Study.

OBJECTIVES: To undertake a detailed healthcare resource use and cost analysis of the SubQStim study, which randomized patients with failed back surgery syndrome (FBSS) with low back pain to receive subcutaneous nerve field stimulation in combination with optimized medical management (treatment) or optimized medical management alone (control). MATERIALS AND METHODS: Patient-level data from the SubQStim study were used to present descriptive analyses of healthcare resource use and estimated costs for pain medication, healthcare visits, adverse events, and device acquisition/implantation. A United Kingdom National Health Service perspective was adopted, using cost data from national tariffs, drug and device prices, and social care cost studies. Results were calculated as the mean cost per patient over the nine-month follow-up period. RESULTS: Mean cost per patient was £18,403 in the treatment group versus £1613 in the control group. Almost 90% of the cost in the treatment group consisted of device acquisition/implantation. Higher adverse event costs were observed for patients in the treatment group, but lower costs were observed for pain medication and healthcare visits. Over nine months, opioid use decreased in the treatment group and increased in the control group. Enrolment and follow-up were terminated early in the clinical study, leading to substantial between-patient variability in each cost category. CONCLUSIONS: Subcutaneous nerve field stimulation has the potential to offset the initial costs of the device by reducing analgesic medication and the number of healthcare visits in FBSS patients, alongside potential gains in health-related quality of life. There remains uncertainty in long-term costs and cost-effectiveness of stimulation and longer-term follow-up analyses are needed.

Burden of oral anticoagulation in embolic stroke of undetermined source without atrial fibrillation.

OBJECTIVE: Prevention of recurrent stroke in patients with embolic stroke of undetermined source (ESUS) is challenging. The advent of safer anticoagulation in the form of direct oral anticoagulants (DOACs) has prompted exploration of prophylactic anticoagulation for all ESUS patients, rather than anticoagulating just those with documented atrial fibrillation (AF). However, recent trials have failed to demonstrate a clinical benefit, while observing increased bleeding. We modeled the economic impact of anticoagulating ESUS patients without documented AF across multiple geographies. METHODS: CRYSTAL-AF trial data were used to assess ischaemic stroke event rates in ESUS patients confirmed AF-free after long-term monitoring. Anticipated bleeding event rates (including both minor and major bleeds) with aspirin, dabigatran 150 mg, and rivaroxaban 20 mg were sourced from published meta-analyses, whilst a 30% ischaemic stroke reduction for both DOACs was assumed. Cost data for clinical events and pharmaceuticals were collected from the local payer perspective. RESULTS: Compared with aspirin, dabigatran and rivaroxaban resulted in 17.9 and 29.9 additional bleeding events per 100 patients over a patient's lifetime, respectively. Despite incorporating into our model the proposed 30% reduction in ischaemic stroke risk, both DOACs were cost-additive over patient lifetime, as the costs of bleeding events and pharmaceuticals outweighed cost savings associated with the reduction in ischaemic strokes. DOACs added £5953-£7018 per patient (UK), €6683-€7368 (Netherlands), €4933-€9378 (Spain), AUD$5353-6539 (Australia) and $26,768-$32,259 (US) of payer cost depending on the agent prescribed. Additionally, in the U.S. patient pharmacy co-payments ranged from $2468-$12,844 depending on agent and patient plan. In all settings, cost-savings could not be demonstrated even when the modelling assumed 100% protection from recurrent ischaemic strokes, due to the very low underlying risk of recurrent ischaemic stroke in this population (1.27 per 100 patient-years). CONCLUSIONS: Anticoagulation of non-AF patients may cause excess bleeds and add substantial costs for uncertain benefits, suggesting a personalised approach to anticoagulation in ESUS patients.

An Epidemiological Model for First Stroke in Saudi Arabia.

BACKGROUND: The Kingdom of Saudi Arabia has a young but ageing population, leading to concerns for planning for future growth in the number of strokes to provide necessary care. An understanding of the expected evolution of stroke incidence is therefore necessary to plan infrastructure changes. Our aim was to predict the number of first strokes occurring in Saudi Arabia over a 10-year period. METHODS: An epidemiological model was developed, using local mortality and population data to model changes in the population. Gender- and age-specific stroke rates were then applied to the population projections to estimate the number of first strokes occurring over a 10-year period. Stroke incidence data from a range of sources were applied to obtain a plausible range for the change in expected number of first strokes. RESULTS: The model predicted population growth of 12.8% over the 10-year period. Depending on the stroke incidence data applied, the number of first strokes occurring during this time was predicted to increase within the range 57%-67%. CONCLUSIONS: A growing and ageing population is expected to lead to a substantial increase in the number of first strokes occurring in Saudi Arabia in the coming decade. Our results suggest that stroke care services will need to be expanded to continue to ensure high quality care, and that strategies for stroke prevention will play an important role in reducing the overall burden. This type of analysis can be applied to other countries' stroke policy planning.

Workforce requirements for comprehensive ischaemic stroke care in a developing country: the case of Saudi Arabia.

BACKGROUND: Ischaemic stroke care requires a co-ordinated multi-disciplinary approach to optimise patient outcomes. Current care provision in Saudi Arabia is below international recommendations, and with increasing patient numbers, variable access to new therapies, and sub-optimal co-ordination of staff, the Kingdom's Ministry of Health has prioritised strategies to develop stroke care. Our objective was to use local epidemiological data to predict stroke incidence and to combine this with international staffing recommendations to estimate future staff requirements and their costs over a 10-year period. METHODS: We researched existing stroke services and staff availability within Saudi Arabia to establish current provision, undertook epidemiological modelling to predict stroke incidence, and used international staffing recommendations for acute and rehabilitation services to develop a care pathway to provide state-of-the-art stroke services. This information was used to determine the additional staff requirements, and their costs, across the Kingdom. RESULTS: Our research concluded that current staff numbers and services are inadequate to cope with the projected increase in the number of stroke cases. In order to provide acute and rehabilitation services which use the latest technologies, re-organisation of existing staff and services would be required, together with significant investment in new staff across several disciplines. An estimated additional 43.8 full-time equivalent stroke neurologists would be required, plus 53.5 full-time equivalent interventional neuroradiologists in addition to expansion of occupational therapy and psychology services. The total cost of additional staff over 10 years was estimated to be 862 390 778 Saudi Riyals ($229 970 874). CONCLUSIONS: Providing high-quality care for ischaemic stroke patients would involve significant investment in new staff in Saudi Arabia. Further research is required on the applicability of international staffing ratios to countries where there is a significant workforce gap. Nevertheless, this analysis provides a framework to inform stroke care planning and can be adapted to other regions or countries.

Intrinsic properties of medical devices: considerations for economic evaluation.

Introduction: In recent decades, medical devices (MDs) have increasingly become an integral part of patient care. However, when it comes to designing and appraising economic models, researchers typically follow pharmaceutical templates (e.g. CHEERS) to assess their economic viability. This study evaluates the generalizability of four device-specific criteria, as recommended by the recent MedtechHTA project, of learning curve, incremental innovation, dynamic pricing, and organizational impact with a broader group of MDs including diagnostics and implantables. The purpose was to determine the applicability of these criteria to a broader range of MDs.Areas Covered: We determined the extent to which these criteria could be applied to each device type and attempted to identify common themes. We performed a literature search using PubMed and Google of a range of devices to understand the clinical significance, operation, and economic viability.Expert Opinion: Our findings suggest that the four characteristics are not applicable to all device types. Prior evaluation of a device's intrinsic properties (such as longevity and device location) and its FDA risk classification could help to indicate the applicability of the criteria. Documenting this process when assessing the additional four criteria on the CHEERS checklist would improve the transparency of future economic evaluations.

A national economic and clinical model for ischemic stroke care development in Saudi Arabia: A call for change.

BACKGROUND: Stroke is a significant burden in Saudi Arabia and the Saudi Ministry of Health's stroke committee has identified an urgent need to improve care. AIM: The purpose of this study was to undertake a health-economic analysis to quantify the impact of developing stroke care in the country. METHODS: An economic model was developed to assess the costs and clinical outcomes associated with an ischemic stroke care development program compared with current stroke care. Based on Saudi epidemiological data, cohorts of ischemic stroke patients enter the model each year for the first 10 years based on increasing incidence. Four treatment options were modeled including reperfusion and non-reperfusion treatments. The development scenario estimates the impact of gradually increasing uptake of more effective treatments over 10 years. Changes in the stroke care organization are considered along with resources required to increase capacity, allowing more patients to be admitted to stroke hospitals and access effective treatments. RESULTS: The stroke care development program is associated with an increase in functionally independent patients and a decrease in disabling strokes compared with current stroke care. Additionally, the development program is associated with estimated cost savings of $602 million over 15 years ($255 million direct costs, $348 million indirect costs). CONCLUSIONS: The model predicts that the stroke care development program is associated with improved patient outcomes and lower overall costs compared with the current stroke care program.

Cost-effectiveness of TYRX absorbable antibacterial envelope for prevention of cardiovascular implantable electronic device infection.

AIMS: Infection is a major complication of cardiovascular implantable electronic device (CIED) therapy that usually requires device extraction and is associated with increased morbidity and mortality. The TYRX Antibacterial Envelope is a polypropylene mesh that stabilizes the CIED and elutes minocycline and rifampin to reduce the risk of post-operative infection. METHODS: A decision tree was developed to assess the cost-effectiveness of TYRX vs standard of care (SOC) following implantation of four CIED device types. The model was parameterized for a UK National Health Service perspective. Probabilities were derived from the literature. Resource use included drug acquisition and administration, hospitalization, adverse events, device extraction, and replacement. Incremental cost-effectiveness ratios (ICERs) were calculated from costs and quality-adjusted life-years (QALYs). RESULTS: Over a 12-month time horizon, TYRX was less costly and more effective than SOC when utilized in patients with an ICD or CRT-D. TYRX was associated with ICERs of £46,548 and £21,768 per QALY gained in patients with an IPG or CRT-P, respectively. TYRX was cost-effective at a £30,000 threshold at baseline probabilities of infection exceeding 1.65% (CRT-D), 1.95% (CRT-P), 1.87% (IPG), and 1.38% (ICD). LIMITATIONS AND CONCLUSIONS: Device-specific infection rates for high-risk patients were not available in the literature and not used in this analysis, potentially under-estimating the impact of TYRX in certain devices. Nevertheless, TYRX is associated with a reduction in post-operative infection risk relative to SOC, resulting in reduced healthcare resource utilization at an initial cost. The ICERs are below the accepted willingness-to-pay thresholds used by UK decision-makers. TYRX, therefore, represents a cost-effective prevention option for CIED patients at high-risk of post-operative infection.

Global health resource utilization associated with pacemaker complications.

AIM: To estimate health resource utilization (HRU) associated with the management of pacemaker complications in various healthcare systems. METHODS: Electrophysiologists (EPs) from four geographical regions (Western Europe, Australia, Japan, and North America) were invited to participate. Survey questions focused on HRU in the management of three chronic pacemaker complications (i.e. pacemaker infections requiring extraction, lead fractures/insulation breaches requiring replacement, and upper extremity deep venous thrombosis [DVT]). Panelists completed a maximum of two web-based surveys (iterative rounds). Mean, median values, and interquartile ranges were calculated and used to establish consensus. RESULTS: Overall, 32 and 29 panelists participated in the first and second rounds of the Delphi panel, respectively. Consensus was reached on treatment and HRU associated with a typical pacemaker implantation and complications. HRU was similar across regions, except for Japan, where panelists reported the longest duration of hospital stay in all scenarios. Infections were the most resource-intensive complications and were characterized by intravenous antibiotics days of 9.6?13.5 days and 21.3?29.2 days for pocket and lead infections respectively; laboratory and diagnostic tests, and system extraction and replacement procedures. DVT, on the other hand, was the least resource intensive complication. LIMITATIONS: The results of the panel represent the views of the respondents who participated and may not be generalizable outside of this panel. The surveys were limited in scope and, therefore, did not include questions on management of acute complications (e.g. hematoma, pneumothorax). CONCLUSIONS: The Delphi technique provided a reliable and efficient approach to estimating resource utilization associated with chronic pacemaker complications. Estimates from the Delphi panel can be used to generate costs of pacemaker complications in various regions.

Financial impact of adopting implantable loop recorder diagnostic for unexplained syncope compared with conventional diagnostic pathway in Portugal.

BACKGROUND: To estimate the short- and long-term financial impact of early referral for implantable loop recorder diagnostic (ILR) versus conventional diagnostic pathway (CDP) in the management of unexplained syncope (US) in the Portuguese National Health Service (PNHS). METHODS: A Markov model was developed to estimate the expected number of hospital admissions due to US and its respective financial impact in patients implanted with ILR versus CDP. The average cost of a syncope episode admission was estimated based on Portuguese cost data and landmark papers. The financial impact of ILR adoption was estimated for a total of 197 patients with US, based on the number of syncope admissions per year in the PNHS. Sensitivity analysis was performed to take into account the effect of uncertainty in the input parameters (hazard ratio of death; number of syncope events per year; probabilities and unit costs of each diagnostic test; probability of trauma and yield of diagnosis) over three-year and lifetime horizons. RESULTS: The average cost of a syncope event was estimated to be between 1,760€ and 2,800€. Over a lifetime horizon, the total discounted costs of hospital admissions and syncope diagnosis for the entire cohort were 23% lower amongst patients in the ILR group compared with the CDP group (1,204,621€ for ILR, versus 1,571,332€ for CDP). CONCLUSION: The utilization of ILR leads to an earlier diagnosis and lower number of syncope hospital admissions and investigations, thus allowing significant cost offsets in the Portuguese setting. The result is robust to changes in the input parameter values, and cost savings become more pronounced over time.

Cost-effectiveness of cryoballoon ablation for the management of paroxysmal atrial fibrillation.

AIMS: Cryoballoon ablation is an established treatment option for the management of patients with atrial fibrillation. We sought to evaluate the cost-effectiveness of cryoablation, compared with second-line anti-arrhythmic drug (AAD) therapy in patients with paroxysmal atrial fibrillation (PAF), from a UK payer perspective. METHODS AND RESULTS: We developed a state-transition (Markov) model to calculate the total costs and quality-adjusted life-years (QALYs) associated with cryoablation and AAD therapy in patients with PAF. A 5-year horizon was used for the base-case. Data from a recent study of cryoballoon ablation in patients with PAF were used to model short-term health outcomes and costs, together with longer term external evidence to populate subsequent time periods. Total discounted costs were £21 162 and £17 627 for the cryoballoon ablation and AAD arms, respectively. Total QALYs of 3.565 and 3.404 therefore led to an incremental cost-effectiveness ratio of £21 957 per QALY gained. Sensitivity analysis suggested that the key drivers of the results were the model time horizon, the costs of follow-up care in patients with recurrent AF, and the costs of the ablation procedure. CONCLUSION: Cryoballoon ablation provides increased quality-adjusted life expectancy compared with AAD at reasonable additional cost, representing good value for money in patients with PAF.

The cost-effectiveness of deep brain stimulation in combination with best medical therapy, versus best medical therapy alone, in advanced Parkinson's disease.

Parkinson's disease (PD) is a complex progressive movement disorder leading to motor and non-motor symptoms that become increasingly debilitating as the disease advances, considerably reducing quality of life. Advanced treatment options include deep brain stimulation (DBS). While clinical effectiveness of DBS has been demonstrated in a number of randomised controlled trials (RCT), evidence on cost-effectiveness is limited. The cost-effectiveness of DBS combined with BMT, versus BMT alone, was evaluated from a UK payer perspective. Individual patient-level data on the effect of DBS on PD symptom progression from a large 6-month RCT were used to develop a Markov model representing clinical progression and capture treatment effect and costs. A 5-year time horizon was used, and an incremental cost-effectiveness ratio (ICER) was calculated in terms of cost per quality-adjusted life-years (QALY) and uncertainty assessed in deterministic sensitivity analyses. Total discounted costs in the DBS and BMT groups over 5 years were £68,970 and £48,243, respectively, with QALYs of 2.21 and 1.21, giving an incremental cost-effectiveness ratio of £20,678 per QALY gained. Utility weights in each health state and costs of on-going medication appear to be the key drivers of uncertainty in the model. The results suggest that DBS is a cost-effective intervention in patients with advanced PD who are eligible for surgery, providing good value for money to health care payers.

Option appraisal of population-based colorectal cancer screening programmes in England.

OBJECTIVES: To estimate the effectiveness, cost-effectiveness and resource impact of faecal occult blood testing (FOBT) and flexible sigmoidoscopy (FSIG) screening options for colorectal cancer to inform the Department of Health's policy on bowel cancer screening in England. METHODS: We developed a state transition model to simulate the life experience of a cohort of individuals without polyps or cancer through to the development of adenomatous polyps and malignant carcinoma and subsequent death in the general population of England. The costs, effects and resource impact of five screening options were evaluated: (a) FOBT for individuals aged 50-69 (biennial screening); (b) FOBT for individuals aged 60-69 (biennial screening); (c) once-only FSIG for individuals aged 55; (d) once-only FSIG for individuals aged 60; and (e) once-only FSIG for individuals aged 60, followed by FOBT for individuals aged 61-70 (biennial screening). RESULTS: The model suggests that screening using FSIG with or without FOBT may be cost-saving and may produce additional benefits compared with a policy of no screening. The marginal cost-effectiveness of FOBT options compared to a policy of no screening is estimated to be below pound3000 per quality adjusted life year gained. CONCLUSIONS: Screening using FOBT and/or FSIG is potentially a cost-effective strategy for the early detection of colorectal cancer. However, the practical feasibility of alternative screening programmes is inevitably limited by current pressures on endoscopy services.

Methodological issues in the economic analysis of cancer treatments.

Cost-effectiveness analysis may be applied to the full range of interventions that make up a cancer service, including screening programmes and early treatments, diagnostic test and referral processes, surgery, radiotherapy, chemotherapy and palliative care. Numerous methodologies have been employed within existing models of cancer interventions. However, not all methodologies are equal; inappropriate modelling approaches may bias cost-effectiveness results. Generic guidelines for good practice in decision-analytic modelling provide a useful basis for critically appraising cost-effectiveness models, yet explicit consideration of a range of cancer-specific issues is required to avoid bias in cost-effectiveness results. These cancer-specific issues include the appropriate representation of relevant costs and health effects associated with unplanned treatments for metastatic disease administered beyond disease progression, the appropriate extrapolation of long-term outcomes and resources from clinical trials, assumptions concerning the nature of the event hazard function beyond the duration of the trial, and relationships between surrogate outcomes and final outcomes.