Benefits of a digital health technology for older nursing home residents. A de-novo cost-effectiveness model for digital health technologies to aid in the assessment of toileting and containment care needs.

The aim of this study was first, to introduce a comprehensive, de-novo health economic (HE) model incorporating the full range of activities involved in toileting and containment care (T&CC) for people with incontinence, capturing all the potential benefits and costs of existing and future Digital Health Technologies (DHT) aimed at improving continence care, for both residential care and home care. Second, to use this novel model to evaluate the cost-effectiveness of the DHT TENA SmartCare Identifi in the implementation of person-centred continence care (PCCC), compared with conventional continence care for Canadian nursing home residents. The de-novo HE model was designed to evaluate technologies across different care settings from the perspective of several stakeholders.

Being Transparent About Brilliant Failures: An Attempt to Use Real-World Data in a Disease Model for Patients with Castration-Resistant Prostate Cancer.

Background: Real-world disease models spanning multiple treatment lines can provide insight into the (cost) effectiveness of treatment sequences in clinical practice.

Objective: Our objective was to explore whether a disease model based solely on real-world data (RWD) could be used to estimate the effectiveness of treatments for patients with castration-resistant prostate cancer (CRPC) that could then be suitably used in a cost-effectiveness analysis.

Methods: We developed a patient-level simulation model using patient-level data from the Dutch CAPRI registry as input parameters.

Model-based cost-effectiveness analyses comparing combinations of urate lowering therapy and anti-inflammatory treatment in gout patients.

Objectives: To assess the cost-effectiveness of various combinations of urate lowering therapy (ULT) and anti-inflammatory treatment in the management of newly diagnosed gout patients, from the Dutch societal perspective.

Methods: A probabilistic patient-level simulation estimating costs and quality-adjusted life years (QALYs) comparing gout and hyperuricemia treatment strategies was performed. ULT options febuxostat, allopurinol and no ULT were considered.

Impact of hospitalisation on health-related quality of life in patients with chronic heart failure.

Background: Empirical identification of the direct impact of hospitalisation in the change in utility could provide an interpretation for some of the unexplained variance in quality of life responses in clinical practice and clinical trials and provide assistance to researchers in assessing the impact of a hospitalisation in the context of economic evaluations. This study had the goal of determining the impact of nonfatal hospitalisations on the quality of life of a cohort of patients previously diagnosed with heart failure by using their quality of life measurements before and after hospitalisation.

Methods: The impact of hospitalisation on health-related quality of life was estimated by calculating the difference in utility measured using the EQ-5D-3L in patients that were hospitalised and had records of utility before and after hospitalisation.

Cost-effectiveness analysis of the first-line EGFR-TKIs in patients with non-small cell lung cancer harbouring EGFR mutations.

Objectives: To compare the cost-effectiveness of first-line gefitinib, erlotinib, afatinib, and osimertinib in patients with non-small cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations.

Methods: A systematic review and network meta-analysis (NMA) were conducted to compare the relative efficacy of gefitinib, erlotinib, afatinib, and osimertinib in EGFR-mutated NSCLC. To assess the cost-effectiveness of these treatments, a Markov model was developed from Dutch societal perspective.

Phase I/II Clinical Trial-Based Early Economic Evaluation of Acalabrutinib for Relapsed Chronic Lymphocytic Leukaemia.

Objectives: The objective of this study was to construct an early economic evaluation for acalabrutinib for relapsed chronic lymphocytic leukaemia (CLL) to assist early reimbursement decision making. Scenarios were assessed to find the relative impact of critical parameters on incremental costs and quality-adjusted life-years (QALYs).

Methods: A partitioned survival model was constructed comparing acalabrutinib and ibrutinib from a UK national health service perspective.

First-line tyrosine kinase inhibitors in EGFR mutation-positive non-small-cell lung cancer: a network meta-analysis.

Background: EGFR-tyrosine kinase inhibitors (EGFR-TKIs) including afatinib, dacomitinib, erlotinib, gefitinib, and osimertinib have proven efficacy in terms of progression-free survival (PFS) in patients with non-small-cell lung cancer (NSCLC) harboring EGFR mutations. However, an overall view for comparing efficacy and toxicity on a meta-level is lacking. This study compared efficacy and toxicity of first-line treatment with five different EGFR-TKIs by conducting a network meta-analysis (NMA).

Conceptual model for the health technology assessment of current and novel interventions in rheumatoid arthritis.

The objective of this study was to evaluate current approaches to economic modeling in rheumatoid arthritis (RA) and propose a new conceptual model for evaluation of the cost-effectiveness of RA interventions. We followed recommendations from the International Society of Pharmacoeconomics and Outcomes Research-Society of Medical Decision Making (ISPOR-SMDM) Modeling Good Research Practices Task Force-2. The process involved scoping the decision problem by a working group and drafting a preliminary cost-effectiveness model framework.

Ribociclib with an Aromatase Inhibitor for Previously Untreated, HR-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

The National Institute for Health and Care Excellence, as part of the institute's single technology appraisal process, invited the manufacturer of ribociclib (Kisqali, Novartis) to submit evidence regarding the clinical and cost effectiveness of the drug in combination with an aromatase inhibitor for the treatment of previously untreated, hormone receptor-positive, human epidermal growth factor receptor 2-negative, locally advanced or metastatic breast cancer. Kleijnen Systematic Reviews Ltd and Erasmus University Rotterdam were commissioned as the Evidence Review Group for this submission. The Evidence Review Group reviewed the evidence submitted by the manufacturer, corrected and validated the manufacturer's decision analytic model, and conducted exploratory analyses to assess the robustness and validity of the presented clinical and cost-effectiveness results.

Cost-Effectiveness Analysis of Abatacept Compared with Adalimumab on Background Methotrexate in Biologic-Naive Adult Patients with Rheumatoid Arthritis and Poor Prognosis.

Objectives: To assess cost effectiveness of abatacept versus adalimumab, each administered with methotrexate, in treating patients with rheumatoid arthritis (RA) stratified according to baseline anticitrullinated protein antibody (ACPA) levels (marker of poor prognosis in RA).

Methods: A payer-perspective cost-effectiveness model simulated disease progression in patients with RA who had previously failed conventional disease-modifying antirheumatic drugs and were starting biologic therapy. Patients commenced treatment with abatacept or adalimumab plus methotrexate and were evaluated after 6 months.

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.

Pomalidomide with Dexamethasone for Treating Relapsed and Refractory Multiple Myeloma Previously Treated with Lenalidomide and Bortezomib: An Evidence Review Group Perspective of an 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 manufacturer of pomalidomide (POM; Imnovid, Celgene) to submit evidence regarding the clinical and cost effectiveness of the drug in combination with dexamethasone (POM + LoDEX) for the treatment of relapsed and refractory multiple myeloma (RRMM) after at least two regimens including lenalidomide (LEN) and bortezomib (BOR). Kleijnen Systematic Reviews Ltd (KSR) and Erasmus University Rotterdam were commissioned as the Evidence Review Group (ERG) for this submission. The ERG reviewed the evidence submitted by the manufacturer, validated the manufacturer's decision analytic model, and conducted exploratory analyses in order to assess the robustness and validity of the presented clinical and cost-effectiveness results.

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.

Ramucirumab for Treating Advanced Gastric Cancer or Gastro-Oesophageal Junction Adenocarcinoma Previously Treated with Chemotherapy: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

The National Institute for Health and Care Excellence (NICE) invited the company that manufactures ramucirumab (Cyramza, Eli Lilly and Company) to submit evidence of the clinical and cost effectiveness of the drug administered alone (monotherapy) or with paclitaxel (combination therapy) for treating adults with advanced gastric cancer or gastro-oesophageal junction (GC/GOJ) adenocarcinoma that were previously treated with chemotherapy, as part of the Institute's single technology appraisal (STA) process. 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.

Mix and match. A simulation study on the impact of mixed-treatment comparison methods on health-economic outcomes.

Background: Decision-analytic cost-effectiveness (CE) models combine many parameters, often obtained after meta-analysis.

Aim: We compared different methods of mixed-treatment comparison (MTC) to combine transition and event probabilities derived from several trials, especially with respect to health-economic (HE) outcomes like (quality adjusted) life years and costs.

Methods: Trials were drawn from a simulated reference population, comparing two of four fictitious interventions.

Cost Recommendation under Uncertainty in IQWiG's Efficiency Frontier Framework.

Background: The National Institute for Quality and Efficiency in Health Care (IQWiG) employs an efficiency frontier (EF) framework to facilitate setting maximum reimbursable prices for new interventions. Probabilistic sensitivity analysis (PSA) is used when yes/no reimbursement decisions are sought based on a fixed threshold. In the IQWiG framework, an additional layer of complexity arises as the EF itself may vary its shape in each PSA iteration, and thus the willingness-to-pay, indicated by the EF segments, may vary.

Lenalidomide for the Treatment of Low- or Intermediate-1-Risk Myelodysplastic Syndromes Associated with Deletion 5q Cytogenetic Abnormality: An Evidence Review of the NICE Submission from Celgene.

The National Institute for Health and Care Excellence (NICE) invited the manufacturer of lenalidomide (Celgene) to submit evidence of the clinical and cost effectiveness of the drug for treating adults with myelodysplastic syndromes (MDS) associated with deletion 5q cytogenetic abnormality, as part of the Institute's single technology appraisal (STA) process. 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 the NICE's subsequent decisions.

Effects of Achieving Target Measures in Rheumatoid Arthritis on Functional Status, Quality of Life, and Resource Utilization: Analysis of Clinical Practice Data.

Objective: To evaluate associations between achieving guideline-recommended targets of disease activity, defined by the Disease Activity Score in 28 joints using C-reactive protein level (DAS28-CRP) <2.6, the Simplified Disease Activity Index (SDAI) ≤3.3, or the Clinical Disease Activity Index (CDAI) ≤2.

Determining the impact of modeling additional sources of uncertainty in value-of-information analysis.

Background: The conditional reimbursement policy for expensive medicines in The Netherlands requires data collection on actual use and cost-effectiveness after the initial decision to reimburse a drug. This introduces new sources of uncertainty (less important in a randomized controlled trial than in daily practice), which may affect priorities for further research.

Objectives: This article focuses on determining the impact of including these uncertainties at the time a decision is made, and whether more complex models are always needed to address prioritization of additional research.

A choice that matters? Smulation study on the impact of direct meta-analysis methods on health economic outcomes.

Background: Decision-analytic cost-effectiveness (CE) models combine many different parameters like transition probabilities, event probabilities, utilities and costs, which are often obtained after meta-analysis. The method of meta-analysis may affect the CE estimate.

Aim: Our aim was to perform a simulation study that compares the performance of different methods of meta-analysis, especially with respect to model-based health economic (HE) outcomes.

Real-life compliance and persistence among users of subcutaneous and sublingual allergen immunotherapy.

Background: Subcutaneous allergen immunotherapy (SCIT) and sublingual allergen immunotherapy (SLIT) are safe and effective treatments of allergic rhinitis, but high levels of compliance and persistence are crucial to achieving the desired clinical effects.

Objective: Our objective was to assess levels and predictors of compliance and persistence among grass pollen, tree pollen, and house dust mite immunotherapy users in real life and to estimate the costs of premature discontinuation.

Methods: We performed a retrospective analysis of a community pharmacy database from The Netherlands containing data from 6486 patients starting immunotherapy for 1 or more of the allergens of interest between 1994 and 2009.

Continuous versus intermittent data collection of health care utilization.

Background: In economic evaluations, participants have to report their health care utilization continuously during follow-up. To unburden participants, researchers often collect data intermittently (i.e.

Cost-effectiveness acceptability curves revisited.

Since the introduction of the cost-effectiveness acceptability curve (CEAC) in 1994, its use as a method to describe uncertainty around incremental cost-effectiveness ratios (ICERs) has steadily increased. In this paper, first the construction and interpretation of the CEAC is explained, both in the context of modelling studies and in the context of cost-effectiveness (CE) studies alongside clinical trials. Additionally, this paper reviews the advantages and limitations of the CEAC.

The role of value-of-information analysis in a health care research priority setting: a theoretical case study.

Background: The Dutch reimbursement procedure for expensive drugs requires the submission of a baseline cost-effectiveness (CE) analysis and a research plan for the period of temporary reimbursement to estimate the real-life cost-effectiveness after 4 years. The Dutch guidelines recommend a value-of-information analysis to identify the critical parameters to be studied in such an outcome study.

Objectives: Identify situations where sensitivity analyses are sufficient to establish the need for additional data collection and priority setting.