Association Between Intermediate End Points, Progression-free Survival, and Overall Survival in First-line Advanced or Recurrent Endometrial Cancer.

Purpose: Advanced/recurrent endometrial cancer is associated with poor long-term outcomes. Clinical studies of novel regimens are ongoing, but given that data on overall survival (OS) take a long time to mature, surrogate end points are often used to support clinical-research interpretation. The aim of this study was to explore the correlation between progression-free survival (PFS)/time to progression (TTP) and OS across multiple time points in the first-line treatment of advanced/recurrent endometrial cancer.

Challenges in conducting fractional polynomial and standard parametric network meta-analyses of immune checkpoint inhibitors for first-line advanced renal cell carcinoma.

Network meta-analyses (NMAs) increasingly feature time-varying hazards to account for non-proportional hazards between different drug classes. This paper outlines an algorithm for selecting clinically plausible fractional polynomial NMA models. The NMA of four immune checkpoint inhibitors (ICIs) + tyrosine kinase inhibitors (TKIs) and one TKI therapy for renal cell carcinoma (RCC) served as case study.

Estimating and Extrapolating Survival Using a State-Transition Modeling Approach: A Practical Application in Multiple Myeloma.

Objectives: State-transition models (STMs) applied in oncology have given limited considerations to modeling postprogression survival data. This study presents an application of an STM focusing on methods to evaluate the postprogression transition and its impact on survival predictions.

Methods: Data from the lenalidomide plus dexamethasone arm of the ASPIRE trial was used to estimate transition rates for an STM.

An Innovative Approach to Modelling the Optimal Treatment Sequence for Patients with Relapsing-Remitting Multiple Sclerosis: Implementation, Validation, and Impact of the Decision-Making Approach.

Introduction: An innovative computational model was developed to address challenges regarding the evaluation of treatment sequences in patients with relapsing-remitting multiple sclerosis (RRMS) through the concept of a 'virtual' physician who observes and assesses patients over time. We describe the implementation and validation of the model, then apply this framework as a case study to determine the impact of different decision-making approaches on the optimal sequence of disease-modifying therapies (DMTs) and associated outcomes.

Methods: A patient-level discrete event simulation (DES) was used to model heterogeneity in disease trajectories and outcomes.

Identifying key factors for the effectiveness of pancreatic cancer screening: A model-based analysis.

Pancreatic cancer (PC) survival is poor, as detection usually occurs late, when treatment options are limited. Screening of high-risk individuals may enable early detection and a more favorable prognosis. Knowledge gaps prohibit establishing the effectiveness of screening.

What Did Time Tell Us? A Comparison and Retrospective Validation of Different Survival Extrapolation Methods for Immuno-Oncologic Therapy in Advanced or Metastatic Renal Cell Carcinoma.

Background: The immuno-oncologic (IO) mechanism of action may lead to an overall survival (OS) hazard that changes over time, producing shapes that standard parametric extrapolation methods may struggle to reflect. Furthermore, selection of the most appropriate extrapolation method for health technology assessment is often based on trial data with limited follow-up.

Objective: To examine this problem, we fitted a range of extrapolation methods to patient-level survival data from CheckMate 025 (NCT01668784, CM-025), a phase III trial comparing nivolumab with everolimus for previously treated advanced renal cell carcinoma (aRCC), to assess their predictive accuracy over time.

Mortality Prediction of the CHADS-VASc Score, the HAS-BLED Score, and Their Combination in Anticoagulated Patients with Atrial Fibrillation.

Background And Objectives: Atrial fibrillation (AF) is associated with increased mortality, predictors of which are poorly characterized. We investigated the predictive power of the commonly used CHADS-VASc score (congestive heart failure, hypertension, age ≥ 75 years [doubled], diabetes, stroke/transient ischemic attack/thromboembolism [doubled], vascular disease [prior myocardial infarction, peripheral artery disease, or aortic plaque], age 65-75 years, sex category [female]), the HAS-BLED score (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio [INR], elderly [age ≥ 65 years], drugs/alcohol concomitantly), and their combination for mortality in AF patients.

Methods: The PREvention oF thromboembolic events-European Registry in Atrial Fibrillation (PREFER in AF) was a prospective registry including AF patients across seven European countries.

The Impact of the Policy-Practice Gap on Costs and Benefits of Barrett's Esophagus Management.

Introduction: Clinical guidelines recommend surveillance of patients with Barrett's esophagus (BE). However, the surveillance intervals in practice are shorter than policy recommendations. We aimed to determine how this policy-practice gap affects the costs and benefits of BE surveillance.

Deep Vein Thrombosis in Europe-Health-Related Quality of Life and Mortality.

Objectives: Deep vein thrombosis (DVT) is a major health-care burden in Europe, but exact estimates are lacking. This study reports results from the PREFER venous thromboembolism (VTE) study concerning health-related quality of life (HrQoL) and mortality of patients with DVT.

Methods: PREFER VTE was a prospective, observational study, conducted in 7 European countries, designed to provide data concerning treatment patterns, resource utilization, mortality, and QoL.

Optimizing Management of Patients With Barrett's Esophagus and Low-Grade or No Dysplasia Based on Comparative Modeling.

Background & Aims: Endoscopic treatment is recommended for patients with Barrett's esophagus (BE) with high-grade dysplasia, yet clinical management recommendations are inconsistent for patients with BE without dysplasia (NDBE) or with low-grade dysplasia (LGD). We used a comparative modeling analysis to identify optimal management strategies for these patients.

Methods: We used 3 independent population-based models to simulate cohorts of 60-year-old individuals with BE in the United States.

Health-related quality of life and mortality in patients with pulmonary embolism: a prospective cohort study in seven European countries.

Purpose: Little is known about the quality of life following pulmonary embolism (PE). The aim of the study was to assess the 12-month illness burden in terms of health-related quality of life (HrQoL) and mortality, in relation to differences in patient characteristics.

Methods: The PREFER in VTE registry, a prospective, observational study conducted in seven European countries, was used.

Comparison of quality of life measurements: EQ-5D-5L versus disease/treatment-specific measures in pulmonary embolism and deep vein thrombosis.

Introduction: There is a lack of performance comparisons of the generic quality of life tool EQ-5D-5L against disease- and treatment-specific measures in venous thromboembolism (VTE). The aim of this study was to compare EQ-5D-5L against the pulmonary embolism (PE)-specific PEmb-QoL and the deep vein thrombosis (DVT)-specific VEINES-QOL/Sym, and PACT-Q2 (treatment-specific) questionnaires in five language settings.

Methods: PREFER in VTE was a non-interventional disease registry conducted between 2013 and 2014 in primary and secondary care across seven European countries with five languages, including English, French, German, Italian and Spanish.

The impact of co-morbidity on the disease burden of VTE.

Venous thromboembolism (VTE) is often accompanied by co-morbidities, which complicate and confound data interpretation concerning VTE-related mortality, costs and quality of life. We aimed to assess the contribution of co-morbidities to the burden of VTE. The PREFER in VTE registry, across seven European countries, documented and followed acute VTE patients over 12 months.

Pulmonary embolism in Europe - Burden of illness in relationship to healthcare resource utilization and return to work.

Objectives: Pulmonary embolism (PE) is associated with a substantial economic burden. However evidence from patients in Europe is scarce. The aim of this study was to report the impacts of PE on healthcare resource utilization (HCRU) and return to work using the PREFER in VTE registry.

Deep-vein thrombosis in Europe - Burden of illness in relationship to healthcare resource utilization and return to work.

Objectives: Deep-vein thrombosis (DVT) forms a major healthcare burden in Europe, but exact estimates concerning the economic burden on society are lacking. This study reports results from the PREFER in VTE study concerning resource utilization and absence from work in DVT patients.

Methods: The PREFER in VTE registry was a prospective, observational, multicenter study carried out in Europe (France, Italy, Spain, the UK, and DACH [Germany, Switzerland and Austria]), designed to provide data concerning treatment patterns, resource utilization, mortality and quality of life.

Harms, benefits and costs of fecal immunochemical testing versus guaiac fecal occult blood testing for colorectal cancer screening.

Background: The ColonCancerCheck screening program for colorectal cancer (CRC) in Ontario, Canada, is considering switching from biennial guaiac fecal occult blood test (gFOBT) screening between age 50-74 years to the more sensitive, but also less specific fecal immunochemical test (FIT). The aim of this study is to estimate whether the additional benefits of FIT screening compared to gFOBT outweigh the additional costs and harms.

Methods: We used microsimulation modeling to estimate quality adjusted life years (QALYs) gained and costs of gFOBT and FIT, compared to no screening, in a cohort of screening participants.

Cost Effectiveness of Screening Patients With Gastroesophageal Reflux Disease for Barrett's Esophagus With a Minimally Invasive Cell Sampling Device.

Background & Aims: It is important to identify patients with Barrett's esophagus (BE), the precursor to esophageal adenocarcinoma (EAC). Patients with BE usually are identified by endoscopy, which is expensive. The Cytosponge, which collects tissue from the esophagus noninvasively, could be a cost-effective tool for screening individuals with gastroesophageal reflux disease (GERD) who are at increased risk for BE.

Real-Time Monitoring of Results During First Year of Dutch Colorectal Cancer Screening Program and Optimization by Altering Fecal Immunochemical Test Cut-Off Levels.

Background & Aims: After careful pilot studies and planning, the national screening program for colorectal cancer (CRC), with biennial fecal immunochemical tests (FITs), was initiated in The Netherlands in 2014. A national information system for real-time monitoring was developed to allow for timely evaluation. Data were collected from the first year of this screening program to determine the importance of planning and monitoring for optimal screening program performance.

Calibrating Parameters for Microsimulation Disease Models: A Review and Comparison of Different Goodness-of-Fit Criteria.

Background: Calibration (estimation of model parameters) compares model outcomes with observed outcomes and explores possible model parameter values to identify the set of values that provides the best fit to the data. The goodness-of-fit (GOF) criterion quantifies the difference between model and observed outcomes. There is no consensus on the most appropriate GOF criterion, because a direct performance comparison of GOF criteria in model calibration is lacking.

An Accurate Cancer Incidence in Barrett's Esophagus: A Best Estimate Using Published Data and Modeling.

Background & Aims: Published estimates for the rate of progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) vary. We used simulation modeling to reconcile published data and more accurately estimate the incidence of EAC among people with BE.

Methods: We calibrated the ERASMUS/UW model (a collaboration between Erasmus Medical Center, Rotterdam, the Netherlands and the University of Washington, Seattle) for EAC to match the 0.

The Impact of Uncertainty in Barrett's Esophagus Progression Rates on Hypothetical Screening and Treatment Decisions.

Background: Estimates for the annual progression rate from Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) vary widely. In this explorative study, we quantified how this uncertainty affects the estimates of effectiveness and efficiency of screening and treatment for EAC.

Design: We developed 3 versions of the University of Washington / Microsimulation Screening Analysis-EAC model.