Incorporating Resource Constraints in Health Economic Evaluations: Overview and Methodological Considerations.

It is well known that healthcare resource constraints influence the capacity to deliver care, affecting both the costs and outcomes of medical interventions. If these constraints are not adequately accounted for in economic evaluations, there may be a lack of understanding regarding the full impact of implementing health technologies, leading to decisions being made with suboptimal information. This paper offers an overview of the types of healthcare resource constraints and their potential effects, and introduces a framework grounded in operations research and health economics principles, outlining the methodological considerations for incorporating resource constraints into economic evaluations.

Decision analytical modelling of strategies for investigating suspected acute aortic syndrome.

Background: Acute aortic syndrome (AAS) requires urgent diagnosis with computed tomographic angiography (CTA). Diagnostic strategies need to weigh the benefits of detecting AAS against the costs of using CTA with a low yield of AAS when the prevalence of AAS is low. We aimed to estimate the cost-effectiveness of diagnostic strategies using clinical probability scoring and D-dimer to select patients with potential symptoms of AAS for CTA.

Systematic Review of Presymptomatic Treatment for Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) causes the degeneration of motor neurons in the spinal cord. Treatments including nusinersen, risdiplam, and onasemnogene abeparvovec have been shown to be effective in reducing symptoms, with recent studies suggesting greater effectiveness when treatment is initiated in the presymptomatic stage. This systematic review synthesises findings from prospective studies of presymptomatic treatment for 5q SMA published up to December 2023.

Systematic Review of Newborn Screening Programmes for Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder causing the degeneration of motor neurons in the spinal cord. Recent studies suggest greater effectiveness of treatment in the presymptomatic stage. This systematic review synthesises findings from 37 studies (and 3 overviews) of newborn screening for SMA published up to November 2023 across 17 countries to understand the methodologies used; test accuracy performance; and timing, logistics and feasibility of screening.

Understanding breast cancer patient pathways and their impact on survival in Mexico.

Background: Understanding patient pathways from discovery of breast symptoms to treatment start can aid in identifying ways to improve access to timely cancer care. This study aimed to describe the patient pathways experienced by uninsured women from detection to treatment initiation for breast cancer in Mexico City and estimate the potential impact of earlier treatment on patient survival.

Methods: We used process mining, a data analytics technique, to create maps of the patient pathways.

Issues, Challenges and Opportunities for Economic Evaluations of Orphan Drugs in Rare Diseases: An Umbrella Review.

Background And Objectives: There are significant challenges when obtaining clinical and economic evidence for health technology assessments of rare diseases. Many of them have been highlighted in previous systematic reviews but they have not been summarised in a comprehensive manner. For all stakeholders working with rare diseases, it is important to be aware and understand these issues.

Flexor Injury Rehabilitation Splint Trial (FIRST): protocol for a pragmatic randomised controlled trial comparing three splints for finger flexor tendon repairs.

Background: Without surgical repair, flexor tendon injuries do not heal and patients' ability to bend fingers and grip objects is impaired. However, flexor tendon repair surgery also requires optimal rehabilitation. There are currently three custom-made splints used in the rehabilitation of zone I/II flexor tendon repairs, each with different assumed harm/benefit profiles: the dorsal forearm and hand-based splint (long), the Manchester short splint (short), and the relative motion flexion splint (mini).

Cost-effectiveness of spinal muscular atrophy newborn screening based on real-world data in Belgium.

The objective of the study was to assess the cost-effectiveness of real-world spinal muscular atrophy newborn screening followed by treatment. We modeled the lifetime cost-effectiveness of the spinal muscular atrophy newborn screening followed by treatment (screening) compared to treatment without screening (no screening) from the Belgian healthcare perspective. Real-world data, including quality of life, costs, and motor development data, were collected on 12 patients identified by screening and 43 patients identified by their symptoms.

Gene therapies for sickle cell disease: Effectiveness and value.

Drs. Nikitin, McKenna, Rind, Nhan, and Pearson report grants from Arnold Ventures, grants from Blue Cross Blue Shield of MA, grants from California Healthcare Foundation, grants from The Commonwealth Fund, grants from The Patrick and Catherine Weldon Donaghue Medical Research Foundation, during the conduct of the study; other from America's Health Insurance Plans, other from Anthem, other from AbbVie, other from Alnylam, other from AstraZeneca, other from Biogen, other from Blue Shield of CA, other from CVS, other from Editas, other from Express Scripts, other from Genentech/Roche, other from GlaxoSmithKline, other from Harvard Pilgrim, other from Health Care Service Corporation, other from Kaiser Permanente, other from LEO Pharma, other from Mallinckrodt, other from Merck, other from Novartis, other from National Pharmaceutical Council, other from Premera, other from Prime Therapeutics, other from Regeneron, other from Sanofi, other from United Healthcare, other from HealthFirst, other from Pfizer, other from Boehringer-Ingelheim, other from uniQure, other from Envolve Pharmacy Solutions, other from Humana, other from Sunlife, outside the submitted work.

Relationship Between Standardized Measures of Chronic Kidney Disease-associated Pruritus Intensity and Health-related Quality of Life Measured with the EQ-5D Questionnaire: A Mapping Study.

Chronic kidney disease-associated pruritus is linked with decreased health-related quality of life assessed using disease-specific instruments. The extent to which worsening pruritus reduces generic quality of life assessed using the EQ-5D instrument is unknown. Prevalent kidney failure patients receiving in-centre haemodialysis from 5 centres completed the EQ-5D-5L quality of life measure, worst Itching Intensity Numerical Rating Scale and 5-D itch pruritus instruments.

Real-time pulmonary artery pressure monitoring in heart failure patients: an updated cost-effectiveness analysis.

Aims: Previous cost-effectiveness analysis suggests that CardioMEMS is cost-effective compared with usual care for patients with persistent New York Heart Association class III symptoms and at least one heart failure (HF) hospitalization within 12 months. The aim of the paper is to perform an update of the cost-effectiveness analysis of CardioMEMS using the most recent data from the published literature.

Methods And Results: A Microsoft Excel Markov model from a previous UK cost-effectiveness study of CardioMEMS was updated using the clinical effectiveness of pulmonary artery pressure (PAP)-guided treatment derived from the pivotal trials.

Cost comparison of oral, transnasal and magnet assisted capsule endoscopy in the examination of the upper gastrointestinal tract in patients with dyspepsia.

Introduction: Conventional oral upper gastrointestinal (GI) endoscopy can obe uncomfortable. By comparison, transnasal endoscopy (TNE) and magnet assisted capsule endoscopy (MACE) have superior tolerability. A cost comparison of competing upper GI endoscopic modalities have yet to be performed.

Troponin in acute chest pain to risk stratify and guide effective use of computed tomography coronary angiography (TARGET-CTCA): a randomised controlled trial.

Background: The majority of patients with suspected acute coronary syndrome presenting to the emergency department will be discharged once myocardial infarction has been ruled out, although a proportion will have unrecognised coronary artery disease. In this setting, high-sensitivity cardiac troponin identifies those at increased risk of future cardiac events. In patients with intermediate cardiac troponin concentrations in whom myocardial infarction has been ruled out, this trial aims to investigate whether outpatient computed tomography coronary angiography (CTCA) reduces subsequent myocardial infarction or cardiac death.

Quantitative Benefit-Risk Assessment in Medical Product Decision Making: A Good Practices Report of an ISPOR Task Force.

Benefit-risk assessment is commonly conducted by drug and medical device developers and regulators, to evaluate and communicate issues around benefit-risk balance of medical products. Quantitative benefit-risk assessment (qBRA) is a set of techniques that incorporate explicit outcome weighting within a formal analysis to evaluate the benefit-risk balance. This report describes emerging good practices for the 5 main steps of developing qBRAs based on the multicriteria decision analysis process.

Multicentre open label randomised controlled trial of immediate enhanced ambulatory ECG monitoring versus standard monitoring in acute unexplained syncope patients: the ASPIRED study.

Introduction: Diagnosing underlying arrhythmia in emergency department (ED) syncope patients is difficult. There is a evidence that diagnostic yield for detecting underlying arrhythmia is highest when cardiac monitoring devices are applied early, ideally at the index visit. This strategy has the potential to change current syncope management from low diagnostic yield Holter to higher yield ambulatory monitoring, reduce episodes of syncope, reduce risk of recurrence and its potential serious consequences, reduce hospital admissions, reduce overall health costs and increase quality of life by allowing earlier diagnosis, treatment and exclusion of clinically important arrhythmias.

Illustrating Emerging Good Practices for Quantitative Benefit-Risk Assessment: A Hypothetical Case Study of Systemic Biologic Treatments for Plaque Psoriasis.

Objectives: Quantitative benefit-risk assessment (qBRA) is a structured process to evaluate the benefit-risk balance of treatment options to support decision making. The ISPOR qBRA Task Force was recently established to provide recommendations for the design, conduct, and reporting of qBRA. This report presents a hypothetical case study illustrating how to apply the Task Force's recommendations toward a qBRA to inform the benefit-risk assessment of brodalumab at the time of initial marketing approval.

Cost Effectiveness of Difelikefalin Compared to Standard Care for Treating Chronic Kidney Disease Associated Pruritus (CKD-aP) in People with Kidney Failure Receiving Haemodialysis.

Background: Chronic kidney disease-associated pruritus (CKD-aP) is associated with an increased risk of depression, poor sleep and reduced health-related quality of life. Two phase III studies (KALM-1 and KALM-2) of difelikefalin showed reduced CKD-aP severity and improved itch-related health-related quality of life in patients with moderate and severe CKD-aP receiving haemodialysis for kidney failure.

Objective: We aimed to estimate the cost effectiveness of difelikefalin for patients with CKD-aP receiving haemodialysis for kidney failure compared to standard care from a UK National Health Service perspective.

Effectiveness of iodine-impregnated incise drapes for preventing surgical site infection in patients with clean or clean contaminated wounds: A systematic literature review and cost-consequence analysis.

Background: Surgical site infection is a serious complication associated with significant morbidity, mortality and health care expenditure.

Aims: To determine the clinical effectiveness and economic impact of using iodine-impregnated incise drapes for preventing surgical site infection.

Methods: MEDLINE, Embase, Cochrane Library and CINAHL databases were systematically searched.

Cost-effectiveness of rapid assessment of potential ischaemic heart disease with CT coronary angiography.

Objectives: To estimate the cost-effectiveness of early CT coronary angiography (CTCA) for intermediate risk patients with suspected acute coronary syndrome (ACS), compared with standard care METHODS: We performed within-trial economic analysis using data from the RAPID-CTCA randomised trial, and long-term modelling of cost-effectiveness using secondary data sources to estimate the cost-effectiveness of early CTCA compared with standard care for patients with suspected ACS attending acute hospitals in the UK. Cost-effectiveness was estimated as the incremental cost per quality-adjusted life year (QALY) gained, and the probability of each strategy being cost-effective at varying willingness-to-pay per QALY gained.

Results: The within-trial analysis showed that there were no demonstrable differences in costs or QALYs between early CTCA and standard care, with point estimates suggesting higher costs (£7414 vs £6845: mean difference £569, 95% CI -£208 to £1335; p=0.

Living Health Technology Assessment: Issues, Challenges and Opportunities.

Health technology assessments (HTAs) are typically performed as one-off evaluations and can potentially become out-of-date due to the availability of new data, new comparators, or other factors. Recently, living approaches have been applied to systematic reviews and network meta-analyses to enable evidence syntheses to be updated more easily. In this paper, we provide a definition for 'Living HTA' where such a living approach could be applied to the entire HTA process.

Early treatment of corneal abrasions and ulcers-estimating clinical and economic outcomes.

Background: In low-and-middle income countries, corneal abrasions and ulcers are common and not always well managed. Previous studies showed better clinical outcomes with early presentation and treatment of minor abrasions, however, there have been no formal studies estimating the financial impact of early treatment of abrasions and ulcers compared to delayed treatment.

Methods: We used the LV Prasad Eye Institute's (LVPEI's) electronic health record system (eyeSmart) to estimate the impact of early presentation on clinical outcomes associated with abrasions and ulcers.

Early computed tomography coronary angiography in adults presenting with suspected acute coronary syndrome: the RAPID-CTCA RCT.

Background: Acute coronary syndrome is a common medical emergency. The optimal strategy to investigate patients who are at intermediate risk of acute coronary syndrome has not been fully determined.

Objective: To investigate the role of early computed tomography coronary angiography in the investigation and treatment of adults presenting with suspected acute coronary syndrome.

Presentation cardiac troponin and early computed tomography coronary angiography in patients with suspected acute coronary syndrome: a pre-specified secondary analysis of the RAPID-CTCA trial.

Aims: To evaluate the potential associations between presentation cardiac troponin and the clinical impact of early computed tomography coronary angiography (CTCA) in intermediate-risk patients with suspected acute coronary syndrome.

Methods And Results: In a large multicentre randomized controlled trial of patients with intermediate-risk chest pain due to suspected acute coronary syndrome, early CTCA had no effect on the primary outcome-death or subsequent Type 1 or 4b myocardial infarction-but reduced the rate of invasive coronary angiography. In this pre-specified secondary analysis, cardiovascular testing and clinical outcomes were compared between those with or without cardiac troponin elevation at presentation.

ENTIMOS: A Discrete Event Simulation Model for Maximising Efficiency of Infusion Suites in Centres Treating Multiple Sclerosis Patients.

Background: Improved multiple sclerosis (MS) diagnosis and increased availability of intravenous disease-modifying treatments can lead to overburdening of infusion centres. This study was focused on developing a decision-support tool to help infusion centres plan their operations.

Methods: A discrete event simulation model ('ENTIMOS') was developed using Simul8 software in collaboration with clinical experts.

Carbon footprint and associated costs of asthma exacerbation care among UK adults.

Introduction: Asthma exacerbations are a primary driver of costs and health impacts from asthma. Despite research suggesting that asthma care has a disproportionate carbon footprint, emissions costs are not considered when evaluating its societal burden. To advance the understanding of greenhouse gas (GHG) emissions associated with asthma, we estimated the carbon footprint and associated costs of asthma exacerbation care by severity level among UK adults.