Cost-Effectiveness Analysis of Empagliflozin for Treatment of Patients With Heart Failure With Reduced Ejection Fraction in the United States.

Background: In the EMPEROR-Reduced trial (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction), empagliflozin plus standard of care reduced the composite of cardiovascular death or hospitalization for heart failure versus standard of care in adults with heart failure with reduced ejection fraction. This analysis investigated the cost-effectiveness of the 2 regimens from the perspective of US payors.

Methods And Results: A Markov cohort model was developed based on Kansas City Cardiomyopathy Questionnaire Clinical Summary Score quartiles and death.

Health state utilities associated with weight loss: preferences of people with type 2 diabetes and obesity in Japan.

Aims: Health state utilities associated with weight change are needed for cost-utility analyses (CUAs) examining the value of treatments for type 2 diabetes and obesity. Previous studies have estimated the utility benefits associated with various amounts of weight reduction in the US and Europe, but preferences for weight change in Asian cultures may differ from these published values. The purpose of this study was to estimate utilities associated with reductions in body weight based on preferences of individuals with type 2 diabetes and obesity in Japan.

Applying the win ratio method in clinical trials of orphan drugs: an analysis of data from the COMET trial of avalglucosidase alfa in patients with late-onset Pompe disease.

Background: Clinical trials for rare diseases often include multiple endpoints that capture the effects of treatment on different disease domains. In many rare diseases, the primary endpoint is not standardized across trials. The win ratio approach was designed to analyze multiple endpoints of interest in clinical trials and has mostly been applied in cardiovascular trials.

A European multinational cost-effectiveness analysis of empagliflozin in heart failure with reduced ejection fraction.

Purpose: This research examined the cost-effectiveness of adding empagliflozin to standard of care (SoC) compared with SoC alone for treatment of heart failure with reduced ejection fraction (HFrEF) from the perspective of healthcare payers in the United Kingdom (UK), Spain and France.

Methods: A lifetime Markov cohort model was developed to simulate patients' progression through health states based on Kansas City Cardiomyopathy Questionnaire Clinical Summary Score. The model predicted risk of death, hospitalisation for worsening heart failure (HHF), treatment-related adverse events, and treatment discontinuation each monthly cycle.

Health state utilities associated with weight loss in type 2 diabetes and obesity.

Introduction: Health state utilities associated with weight change are needed as inputs for cost-utility analyses (CUAs) examining the value of treatments for obesity and type 2 diabetes (T2D). Although some pharmaceutical treatments currently in development are associated with substantial weight loss, little is known about the utility impact of weight decreases greater than 10%. The purpose of this study was to estimate utilities associated with body weight decreases up to 20% based on preferences of individuals with obesity, with and without T2D.

How Assessment-Schedule Matching Limits Bias When Comparing Progression-Free Survival in Single-Arm Studies: An Application in Second-Line Urothelial Carcinoma Treatments.

Objectives: Population-adjusted comparisons of progression-free survival (PFS) from single-arm trials of cancer treatments can be derived using matching-adjusted indirect comparisons (MAICs); however, results are still susceptible to bias, particularly if the trials had different tumor assessment schedules. This study aims to assess the effects of assessment-schedule matching (ASM) on the relative effectiveness on the PFS of avelumab versus approved comparator immunotherapies or chemotherapy after population matching in the second-line (2L) setting for metastatic urothelial carcinoma.

Methods: The MAIC used patient-level data for avelumab from the JAVELIN Solid Tumor trial (NCT01772004).

Assessing patient PREFERence between the dulaglutide pen and the semaglutide pen: A crossover study (PREFER).

Aim: When selecting treatments for type 2 diabetes (T2D), it is important to consider not only efficacy and safety, but also other treatment attributes that have an impact on patient preference. The objective of this study was to examine preference between injection devices used for two weekly GLP-1 receptor agonists.

Materials And Methods: The PREFER study was an open-label, multicentre, randomized, crossover study assessing patient preference for dulaglutide and semaglutide injection devices among injection-naïve patients receiving oral medication for type 2 diabetes.

Assessment-Schedule Matching in Unanchored Indirect Treatment Comparisons of Progression-Free Survival in Cancer Studies.

Background: The timing of efficacy-related clinical events recorded at scheduled study visits in clinical trials are interval censored, with the interval duration pre-determined by the study protocol. Events may happen any time during that interval but can only be detected during a planned or unplanned visit. Disease progression in oncology is a notable example where the time to an event is affected by the schedule of visits within a study.

Modeling long-term health outcomes of patients with cystic fibrosis homozygous for F508del-CFTR treated with lumacaftor/ivacaftor.

Background: Lumacaftor/ivacaftor combination therapy is efficacious and generally safe for patients with cystic fibrosis (CF) homozygous for the F508del-CF transmembrane conductance regulator (CFTR) mutation. However, long-term survival benefits of lumacaftor/ivacaftor (LUM/IVA) cannot yet be quantified. Simulation models can provide predictions about long-term health outcomes.

Relative effectiveness of sunitinib versus everolimus in advanced pancreatic neuroendocrine tumors: an updated matching-adjusted indirect comparison.

Aim: A matching-adjusted indirect comparison (MAIC) of sunitinib and everolimus has been previously reported based on the RADIANT-3 everolimus trial. We performed an analysis using updated overall survival (OS) data based on sunitinib's trial (A6181111).

Methods: The MAIC matched on all baseline characteristics available from both studies.

Alzheimer's disease Archimedes condition-event simulator: Development and validation.

Introduction: Several advances have been made in Alzheimer's Disease (AD) modeling, however, there remains a need for a simulator that represents the full scope of disease progression and can be used to study new disease-modifying treatments for early-stage and even prodromal AD.

Methods: We developed AD Archimedes condition-event simulator, a patient-level simulator with a focus on simulating the effects of early interventions through changes in biomarkers of AD. The simulator incorporates interconnected predictive equations derived from longitudinal data sets.

Additivity of nebivolol/valsartan single-pill combinations versus other single-pill combinations for hypertension.

The single-pill combination (SPC) comprising nebivolol (5 mg), a vasodilatory β -selective antagonist/β -agonist, and valsartan (80 mg), a renin-angiotensin-aldosterone system inhibitor, is the only Food and Drug Administration-approved β-blocker/renin-angiotensin-aldosterone system inhibitor SPC for hypertension. Additive effects of four nebivolol/valsartan SPC doses (5 mg/80 mg, 5/160 mg, 10/160 mg, 10/320 mg nebivolol/valsartan) were compared with five Food and Drug Administration-approved non-β-blocker/renin-angiotensin-aldosterone system inhibitor SPCs (aliskiren/hydrochlorothiazide, aliskiren/amlodipine, valsartan/amlodipine, aliskiren/valsartan, and telmisartan/amlodipine). Additivity is the ratio of placebo-adjusted SPC blood pressure (BP) reduction to the placebo-adjusted monotherapy component BP reduction sums.

The effect of lomitapide on cardiovascular outcome measures in homozygous familial hypercholesterolemia: A modelling analysis.

Background Patients with homozygous familial hypercholesterolemia are at high risk of cardiovascular disease due to high low-density lipoprotein (LDL)-cholesterol levels. Cardiovascular disease outcome studies are impossible to conduct, due to the rarity of homozygous familial hypercholesterolemia. We modelled the potential efficacy of lomitapide, a microsomal transfer protein inhibitor, on major adverse cardiovascular events (MACEs) and survival.

Using Bayesian Adaptive Trial Designs for Comparative Effectiveness Research: A Virtual Trial Execution.

Background: Bayesian and adaptive clinical trial designs offer the potential for more efficient processes that result in lower sample sizes and shorter trial durations than traditional designs.

Objective: To explore the use and potential benefits of Bayesian adaptive clinical trial designs in comparative effectiveness research.

Design: Virtual execution of ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) as if it had been done according to a Bayesian adaptive trial design.

Deriving health utility values from a randomized, double-blind, placebo-controlled trial of siltuximab in subjects with multicentric Castleman's disease.

Purpose: To estimate health utility values, explore predictors of utility values, and estimate the quality-adjusted life years (Q.A.L.

Simulation and matching-based approaches for indirect comparison of treatments.

Estimates of the relative effects of competing treatments are rarely available from head-to-head trials. These effects must therefore be derived from indirect comparisons of results from different studies. The feasibility of comparisons relies on the network linking treatments through common comparators; the reliability of these may also be impacted when the studies are heterogeneous or when multiple intermediate comparisons are needed to link two specific treatments of interest.

Mapping EORTC QLQ-C30 and QLQ-MY20 to EQ-5D in patients with multiple myeloma.

Background: In oncology, health-related quality of life (HRQoL) data are often collected using disease-specific patient questionnaires while generic, patient-level utility data required for health economic modeling are often not collected.

Methods: We developed a mapping algorithm for multiple myeloma that relates HRQoL scores from the European Organization for Research and Treatment of Cancer (EORTC) questionnaires QLQ-C30 and QLQ-MY20 to a utility value from the European QoL-5 Dimensions (EQ-5D) questionnaire. Data were obtained from 154 multiple myeloma patients who had participated in a multicenter cohort study in the UK or Germany.

Methods for adjusting for bias due to crossover in oncology trials.

Trials of new oncology treatments often involve a crossover element in their design that allows patients receiving the control treatment to crossover to receive the experimental treatment at disease progression or when sufficient evidence about the efficacy of the new treatment is achieved. Crossover leads to contamination of the initial randomized groups due to a mixing of the effects of the control and experimental treatments in the reference group. This is further complicated by the fact that crossover is often a very selective process whereby patients who switch treatment have a different prognosis than those who do not.

Effect of general symptom level, specific adverse events, treatment patterns, and patient characteristics on health-related quality of life in patients with multiple myeloma: results of a European, multicenter cohort study.

Purpose: Novel multiple myeloma (MM) therapies have increased patient longevity but are often associated with notable symptom burden. This study quantified the effect of general symptom level, specific symptoms, and treatment-related adverse events (AEs) on MM patients' health-related quality of life (HRQoL).

Methods: The European Organization for Research and Treatment of Cancer (EORTC) generic cancer questionnaire (Quality of Life Questionnaire Core 30) and MM-specific questionnaire (QLQ-MY20) were used in this study to assess patients' HRQoL.

Do Bayesian adaptive trials offer advantages for comparative effectiveness research? Protocol for the RE-ADAPT study.

Background: Randomized clinical trials, particularly for comparative effectiveness research (CER), are frequently criticized for being overly restrictive or untimely for health-care decision making.

Purpose: Our prospectively designed REsearch in ADAptive methods for Pragmatic Trials (RE-ADAPT) study is a 'proof of concept' to stimulate investment in Bayesian adaptive designs for future CER trials.

Methods: We will assess whether Bayesian adaptive designs offer potential efficiencies in CER by simulating a re-execution of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study using actual data from ALLHAT.

Smoking cessation treatment and outcomes patterns simulation: a new framework for evaluating the potential health and economic impact of smoking cessation interventions.

Background: Most existing models of smoking cessation treatments have considered a single quit attempt when modelling long-term outcomes.

Objective: To develop a model to simulate smokers over their lifetimes accounting for multiple quit attempts and relapses which will allow for prediction of the long-term health and economic impact of smoking cessation strategies.

Methods: A discrete event simulation (DES) that models individuals' life course of smoking behaviours, attempts to quit, and the cumulative impact on health and economic outcomes was developed.

Overview of parametric survival analysis for health-economic applications.

Health economic models rely on data from trials to project the risk of events (e.g., death) over time beyond the span of the available data.

Improved perioperative blood pressure control leads to reduced hospital costs.

Background: Perioperative hypertension affects 80% of cardiac surgery patients and is associated with an increased risk of complications.

Objective: To determine the relationship between perioperative blood pressure (BP) control and hospital costs for cardiac surgery in the United States (US) and estimate the potential cost reductions associated with effective therapies.

Methods: The analysis estimated hospitalization costs (2011 US dollars (USD)) for cardiac surgery when BP was controlled with intravenous (IV) antihypertensives.

Accounting for the relationship between per diem cost and LOS when estimating hospitalization costs.

Background: Hospitalization costs in clinical trials are typically derived by multiplying the length of stay (LOS) by an average per-diem (PD) cost from external sources. This assumes that PD costs are independent of LOS. Resource utilization in early days of the stay is usually more intense, however, and thus, the PD cost for a short hospitalization may be higher than for longer stays.

Optimizing the design of pragmatic trials: key issues remain.

Clinical trials have largely focused on whether an intervention can work. To ensure valid and powerful testing of this hypothesis, trials attempt to maximize the effect of the intervention of interest, controlling other factors that can confound comparisons. The benefits observed in these studies are often not sustained once the treatment is used in routine care, leaving regulators, practitioners and patients with a paucity of reliable evidence to assist decision-making.