Beyond hazard ratios: appropriate statistical methods for quantifying the clinical effectiveness of immune-oncology therapies - the example of the Netherlands.

Background: The Dutch Committee for the Evaluation of Oncological Drugs evaluates the effectiveness of new oncological treatments. The committee compares survival endpoints to the so-called PASKWIL-2023 criteria for palliative treatments, which define if treatment effects are considered clinically relevant. A positive recommendation depends on whether the median overall survival (OS) is below or above 12 months in the comparator arm.

The Cost-Effectiveness of Seizure Dogs for Persons Living With Severe Refractory Epilepsy: Results From the EPISODE Study.

Objectives: The Epilepsy Support Dog Evaluation study was commissioned by the Dutch Ministry of Health, Welfare and Sports to inform a reimbursement decision on seizure dogs. The randomized trial found that seizure dogs reduce seizure frequency and improve health-related quality of life of persons with severe refractory epilepsy (PSREs). This article examined the cost-effectiveness (CE) of adding seizure dogs to usual care for PSREs in The Netherlands.

A cloud-based medical device for predicting cardiac risk in suspected coronary artery disease: a rapid review and conceptual economic model.

Background: The CaRi-Heart® device estimates risk of 8-year cardiac death, using a prognostic model, which includes perivascular fat attenuation index, atherosclerotic plaque burden and clinical risk factors.

Objectives: To provide an Early Value Assessment of the potential of CaRi-Heart Risk to be an effective and cost-effective adjunctive investigation for assessment of cardiac risk, in people with stable chest pain/suspected coronary artery disease, undergoing computed tomography coronary angiography. This assessment includes conceptual modelling which explores the structure and evidence about parameters required for model development, but not development of a full executable cost-effectiveness model.

A blueprint for health technology assessment capacity building: lessons learned from Malta.

Objectives: The development and strengthening of health technology assessment (HTA) capacity on the individual and organizational level and the wider environment is relevant for cooperation on HTAs. Based on the Maltese case, we provide a blueprint for building HTA capacity.

Methods: A set of activities were developed based on Pichler et al.

Effectiveness of Seizure Dogs for People With Severe Refractory Epilepsy: Results From the EPISODE Study.

Background And Objectives: The aim of this study was to evaluate whether people living with severe medically refractory epilepsy (PSRE) benefit from a seizure dog.

Methods: An individual-level stepped-wedge randomized controlled trial was conducted. The study was conducted in the Netherlands among adults with daily to weekly seizures.

Home Telemonitoring and a Diagnostic Algorithm in the Management of Heart Failure in the Netherlands: Cost-effectiveness Analysis.

Background: Heart failure is a major health concern associated with significant morbidity, mortality, and reduced quality of life in patients. Home telemonitoring (HTM) facilitates frequent or continuous assessment of disease signs and symptoms, and it has shown to improve compliance by involving patients in their own care and prevent emergency admissions by facilitating early detection of clinically significant changes. Diagnostic algorithms (DAs) are predictive mathematical relationships that make use of a wide range of collected data for calculating the likelihood of a particular event and use this output for prioritizing patients with regard to their treatment.

The Net Benefit of Personalized Medicine: A Systematic Literature Review and Regression Analysis.

Objectives: Amidst conflicting expectations about the benefits of personalized medicine (PM) and the potentially high implementation costs, we reviewed the available evidence on the cost-effectiveness of PM relative to non-PM.

Methods: We conducted a systematic literature review of economic evaluations of PM and extracted data, including incremental quality-adjusted life-years (ΔQALYs) and incremental costs (Δcosts). ΔQALYs and Δcosts were combined with estimates of national cost-effectiveness thresholds to calculate incremental net monetary benefit (ΔNMB).

Therapeutic Drug Monitoring-Guided Adjuvant Tamoxifen Dosing in Patients with Early Breast Cancer: A Cost-Effectiveness Analysis from the Prospective TOTAM Trial.

Background And Objectives: Endoxifen is the active metabolite of tamoxifen, and a minimal plasma concentration of 16 nM has been suggested as a threshold above which it is effective in reducing the risk of breast cancer recurrence. The aim of the current analysis was to investigate the cost-effectiveness of therapeutic drug monitoring (TDM)-guided tamoxifen dosing.

Methods: A cost-effectiveness analysis was performed from a Dutch healthcare perspective, using a partitioned survival model and a lifetime horizon.

Four Aspects Affecting Health Economic Decision Models and Their Validation.

Health care decision makers in many jurisdictions use cost-effectiveness analysis based on health economic decision models for policy decisions regarding coverage and price negotiation for medicines and medical devices. While validation of health economic decision models has always been considered important, many reviews of model-based cost-effectiveness studies report limitations regarding their validation. The current opinion paper discusses four aspects of current health economic decision modeling with relevance for future directions in model validation: increased use of complex models, international cooperation, open-source modeling, and stakeholder involvement.

Modeling Early Warning Systems: Construction and Validation of a Discrete Event Simulation Model for Heart Failure.

Objectives: Developing and validating a discrete event simulation model that is able to model patients with heart failure managed with usual care or an early warning system (with or without a diagnostic algorithm) and to account for the impact of individual patient characteristics in their health outcomes.

Methods: The model was developed using patient-level data from the Trans-European Network - Home-Care Management System study. It was coded using RStudio Version 1.

Cost-effectiveness of the fixed-dose combination tiotropium/olodaterol versus tiotropium monotherapy or a fixed-dose combination of long-acting β2-agonist/inhaled corticosteroid for COPD in Finland, Sweden and the Netherlands: a model-based study.

Objectives: Chronic obstructive pulmonary disease (COPD) guidelines advocate treatment with combinations of long-acting bronchodilators for patients with COPD who have persistent symptoms or continue to have exacerbations while using a single bronchodilator. This study assessed the cost-utility of the fixed dose combination of the bronchodilators tiotropium and olodaterol versus two comparators, tiotropium monotherapy and long-acting β2 agonist/inhaled corticosteroid (LABA/ICS) combinations, in three European countries: Finland, Sweden and the Netherlands.

Methods: A previously published COPD patient-level discrete event simulation model was updated with most recent evidence to estimate lifetime quality-adjusted life years (QALYs) and costs for COPD patients receiving either tiotropium/olodaterol, tiotropium monotherapy or LABA/ICS.

Cost-utility analysis of four common surgical treatment pathways for breast cancer.

Background: The aim was to evaluate the cost-utility of four common surgical treatment pathways for breast cancer: mastectomy, breast-conserving therapy (BCT), implant breast reconstruction (BR) and autologous-BR.

Methods: Patient-level healthcare consumption data and results of a large quality of life (QoL) study from five Dutch hospitals were combined. The cost-effectiveness was assessed in terms of incremental costs and quality adjusted life years (QALYs) over a 10-year follow-up period.

How to Address Uncertainty in Health Economic Discrete-Event Simulation Models: An Illustration for Chronic Obstructive Pulmonary Disease.

. Evaluation of personalized treatment options requires health economic models that include multiple patient characteristics. Patient-level discrete-event simulation (DES) models are deemed appropriate because of their ability to simulate a variety of characteristics and treatment pathways.

Evaluating the Effectiveness and Cost-Effectiveness of Seizure Dogs in Persons With Medically Refractory Epilepsy in the Netherlands: Study Protocol for a Stepped Wedge Randomized Controlled Trial (EPISODE).

Epilepsy is associated with a high disease burden, impacting the lives of people with epilepsy and their caregivers and family. Persons with medically refractory epilepsy experience the greatest burden, suffering from profound physical, psychological, and social consequences. Anecdotal evidence suggests these persons may benefit from a seizure dog.

Early cost-utility analysis of tissue-engineered heart valves compared to bioprostheses in the aortic position in elderly patients.

Objectives: Aortic valve disease is the most frequent indication for heart valve replacement with the highest prevalence in elderly. Tissue-engineered heart valves (TEHV) are foreseen to have important advantages over currently used bioprosthetic heart valve substitutes, most importantly reducing valve degeneration with subsequent reduction of re-intervention. We performed early Health Technology Assessment of hypothetical TEHV in elderly patients (≥ 70 years) requiring surgical (SAVR) or transcatheter aortic valve implantation (TAVI) to assess the potential of TEHV and to inform future development decisions.

Severity-Adjusted Probability of Being Cost Effective.

Background: In the context of priority setting, a differential cost-effectiveness threshold can be used to reflect a higher societal willingness to pay for quality-adjusted life-year gains in the worse off. However, uncertainty in the estimate of severity can lead to problems when evaluating the outcomes of cost-effectiveness analyses.

Objectives: This study standardizes the assessment of severity, integrates its uncertainty with the uncertainty in cost-effectiveness results and provides decision makers with a new estimate: the severity-adjusted probability of being cost effective.

Long-term cost-effectiveness of the fixed-dose combination of tiotropium plus olodaterol based on the DYNAGITO trial results.

Purpose: Combinations of long-acting bronchodilators are recommended to reduce the rate of COPD exacerbations. Evidence from the DYNAGITO trial showed that the fixed-dose combination of tiotropium + olodaterol reduced the annual rate of total exacerbations (<0.05) compared with tiotropium monotherapy.

Broadening the Perspective of Cost-Effectiveness Modeling in Chronic Obstructive Pulmonary Disease: A New Patient-Level Simulation Model Suitable to Evaluate Stratified Medicine.

Objectives: To develop a health economic model that included a great diversity of patient characteristics and outcomes for chronic obstructive pulmonary disease (COPD), which can be used to inform decisions about stratified medicine in COPD.

Methods: The choice of patient characteristics and outcomes to include in the model was based on 3 literature reviews on multidimensional prognostic COPD indices, COPD phenotypes, and treatment effects in subgroups. A conceptual model was constructed including 14 patient characteristics, 7 intermediate outcomes (lung function, physical activity, exercise capacity, symptoms, disease-specific quality of life, exacerbations, and pneumonias), and 3 final outcomes (mortality, quality-adjusted life-years [QALYs], and costs).

What Is the Potential of Tissue-Engineered Pulmonary Valves in Children?

Background: As a living heart valve substitute with growth potential and improved durability, tissue-engineered heart valves (TEHVs) may prevent reinterventions that are currently often needed in children with congenital heart disease. We performed early health technology assessment to assess the potential cost-effectiveness of TEHVs in children requiring right ventricular outflow tract reconstruction (RVOTR).

Methods: A systematic review and meta-analysis was conducted of studies reporting clinical outcome after RVOTR with existing heart valve substitutes in children (mean age ≤12 years or maximum age ≤21 years) published between January 1, 2000, and May 2, 2018.

Obinutuzumab in Combination with Chemotherapy for the First-Line Treatment of Patients with Advanced Follicular Lymphoma : An Evidence Review Group Evaluation of the NICE Single Technology Appraisal.

The National Institute for Health and Care Excellence (NICE), as part of the institute's single technology appraisal (STA) process, invited the company that makes obinutuzumab (Roche Products Limited) to submit evidence of the clinical and cost effectiveness of the drug in combination with chemotherapy, with or without obinutuzumab as maintenance therapy for adult patients with untreated, advanced follicular lymphoma (FL) in the UK. Kleijnen Systematic Reviews Ltd (KSR), in collaboration with Erasmus University Rotterdam, was commissioned to act as the Evidence Review Group (ERG). This paper describes the company's submission, the ERG review, and NICE's subsequent decisions.

The increasing importance of a continence nurse specialist to improve outcomes and save costs of urinary incontinence care: an analysis of future policy scenarios.

Background: In an ageing population, it is inevitable to improve the management of care for community-dwelling elderly with incontinence. A previous study showed that implementation of the Optimum Continence Service Specification (OCSS) for urinary incontinence in community-dwelling elderly with four or more chronic diseases results in a reduction of urinary incontinence, an improved quality of life, and lower healthcare and lower societal costs. The aim of this study was to explore future consequences of the OCSS strategy of various healthcare policy scenarios in an ageing population.

Cost Effectiveness of the Angiotensin Receptor Neprilysin Inhibitor Sacubitril/Valsartan for Patients with Chronic Heart Failure and Reduced Ejection Fraction in the Netherlands: A Country Adaptation Analysis Under the Former and Current Dutch Pharmacoeconomic Guidelines.

Objectives: To describe the adaptation of a global health economic model to determine whether treatment with the angiotensin receptor neprilysin inhibitor LCZ696 is cost effective compared with the angiotensin-converting enzyme inhibitor enalapril in adult patients with chronic heart failure with reduced left ventricular ejection fraction in the Netherlands; and to explore the effect of performing the cost-effectiveness analyses according to the new pharmacoeconomic Dutch guidelines (updated during the submission process of LCZ696), which require a value-of-information analysis and the inclusion of indirect medical costs of life-years gained.

Methods: We adapted a UK model to reflect the societal perspective in the Netherlands by including travel expenses, productivity loss, informal care costs, and indirect medical costs during the life-years gained and performed a preliminary value-of-information analysis.

Results: The incremental cost-effectiveness ratio obtained was €17,600 per quality-adjusted life-year (QALY) gained.

Faecal immunochemical tests (FIT) can help to rule out colorectal cancer in patients presenting in primary care with lower abdominal symptoms: a systematic review conducted to inform new NICE DG30 diagnostic guidance.

Background: This study has attempted to assess the effectiveness of quantitative faecal immunochemical tests (FIT) for triage of people presenting with lower abdominal symptoms, where a referral to secondary care for investigation of suspected colorectal cancer (CRC) is being considered, particularly when the 2-week criteria are not met.

Methods: We conducted a systematic review following published guidelines for systematic reviews of diagnostic tests. Twenty-one resources were searched up until March 2016.

A New Statistical Method to Determine the Degree of Validity of Health Economic Model Outcomes against Empirical Data.

Background: The validation of health economic (HE) model outcomes against empirical data is of key importance. Although statistical testing seems applicable, guidelines for the validation of HE models lack guidance on statistical validation, and actual validation efforts often present subjective judgment of graphs and point estimates.

Objectives: To discuss the applicability of existing validation techniques and to present a new method for quantifying the degrees of validity statistically, which is useful for decision makers.