Impact of eptinezumab on work productivity beyond reductions in monthly migraine days: post hoc analysis of the DELIVER trial.

Background: Eptinezumab's impact on self-reported work productivity in adults with migraine and 2‒4 prior preventive migraine treatment failures is not fully understood.

Methodology: Electronic diaries captured monthly migraine days (MMDs) reported by patients enrolled in the randomized, double-blind, placebo-controlled DELIVER trial (NCT04418765). The migraine-specific Work Productivity and Activity Impairment questionnaire, administered at baseline and each monthly visit, was a secondary outcome of DELIVER and used to model changes from baseline in self-reported monthly hours of absenteeism (decreased work attendance) and presenteeism (reduced work efficiency while at work with a migraine) in Canada, as the base case.

Assessment of patient life engagement in schizophrenia using items from the Positive and Negative Syndrome Scale.

Background: Improved patient life engagement is a meaningful treatment goal in schizophrenia that cannot be satisfactorily measured using existing tools. This research aimed to determine whether certain items from the Positive and Negative Syndrome Scale (PANSS) can assess patient life engagement in schizophrenia.

Methods: Three approaches were used to identify PANSS items that reflect patient life engagement: (1) a panel discussion with expert psychiatrists (n = 4); (2) interviews with patients with schizophrenia (n = 20); and (3) a principal component analysis to explore clustering of items (n = 954 from three randomized controlled trials).

Structural equation modeling for identifying the drivers of health-related quality of life improvement experienced by patients with migraine receiving eptinezumab.

Background: As new migraine therapies emerge, it is crucial for measures to capture the complexities of health-related quality of life (HRQoL) improvement beyond improvements in monthly migraine day (MMD) reduction. Investigations into the correlations between MMD reduction, symptom management, and HRQoL are lacking, particularly those that focus on improvements in canonical symptoms and improvement in patient-identified most-bothersome symptoms (PI-MBS), in patients treated with eptinezumab. This exploratory analysis identified efficacy measures mediating the effect of eptinezumab on HRQoL improvements in patients with migraine.

Meta-regression to explain the placebo effects in clinical trials of anti-CGRP monoclonal antibodies for migraine prevention.

Commonly used methods of comparison (e.g. network meta-analyses) require common comparator(s) across trials, such as placebo in placebo-controlled trials.

Persistence to anti-CGRP monoclonal antibodies and onabotulinumtoxinA among patients with migraine: a retrospective cohort study.

Background: To date, real-world evidence on persistence to anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAbs) or onabotulinumtoxinA have excluded eptinezumab. This retrospective cohort study was performed to compare treatment persistency among patients with migraine on anti-CGRP mAbs (erenumab, fremanezumab, galcanezumab, or eptinezumab) or onabotulinumtoxinA.

Methods: This retrospective study used IQVIA PharmMetrics data.

Estimating treatment effects on health utility scores for patients living with migraine: a post hoc analysis of the DELIVER trial.

Background: This post hoc analysis aimed to estimate eptinezumab's therapeutic effect on health utilities and determined to which extent monthly migraine days (MMDs) explain changes in health utilities.

Research Design/methods: DELIVER, a randomized, double-blind, placebo-controlled phase 3b trial (NCT04418765), investigated eptinezumab efficacy and safety in patients with 2-4 prior migraine treatment failures. Regression analysis explored the relationship between utility scores and MMDs, with eptinezumab treatment as a covariate along with MMDs to identify any MMD-independent effect on utilities.

Comparison of indirect treatment methods in migraine prevention to address differences in mode of administration.

Indirect treatment comparisons (ITCs) are anchored on a placebo comparator, and the placebo response may vary according to drug administration route. Migraine preventive treatment studies were used to evaluate ITCs and determine whether mode of administration influences placebo response and the overall study findings. Change from baseline in monthly migraine days produced by monoclonal antibody treatments (subcutaneous, intravenous) was compared using fixed-effects Bayesian network meta-analysis (NMA), network meta-regression (NMR), and unanchored simulated treatment comparison (STC).

NASHmap: clinical utility of a machine learning model to identify patients at risk of NASH in real-world settings.

The NASHmap model is a non-invasive tool using 14 variables (features) collected in standard clinical practice to classify patients as probable nonalcoholic steatohepatitis (NASH) or non-NASH, and here we have explored its performance and prediction accuracy. The National Institute of Diabetes and Digestive Kidney Diseases (NIDDK) NAFLD Adult Database and the Optum Electronic Health Record (EHR) were used for patient data. Model performance metrics were calculated from correct and incorrect classifications for 281 NIDDK (biopsy-confirmed NASH and non-NASH, with and without stratification by type 2 diabetes status) and 1,016 Optum (biopsy-confirmed NASH) patients.

Assessment of patient life engagement in major depressive disorder using items from the Inventory of Depressive Symptomatology Self-Report (IDS-SR).

Background: Patient-reported outcomes can measure domains that are personally meaningful, such as life engagement, which reflects motivation, pleasure, and well-being. This study explored whether certain items from the Inventory of Depressive Symptomatology Self-Report (IDS-SR) can capture patient life engagement in major depressive disorder (MDD).

Methods: IDS-SR life engagement items were identified by a) a panel of expert psychiatrists (n = 4), b) patient interviews (n = 20), and c) a principal component analysis (PCA) to explore clustering of items.

Mendelian randomization: estimation of inpatient hospital costs attributable to obesity.

Background: Mendelian Randomization is a type of instrumental variable (IV) analysis that uses inherited genetic variants as instruments to estimate causal effects attributable to genetic factors. This study aims to estimate the impact of obesity on annual inpatient healthcare costs in the UK using linked data from the UK Biobank and Hospital Episode Statistics (HES).

Methods: UK Biobank data for 482,127 subjects was linked with HES inpatient admission records, and costs were assigned to episodes of care.

Development of a novel machine learning model to predict presence of nonalcoholic steatohepatitis.

Objective: To develop a computer model to predict patients with nonalcoholic steatohepatitis (NASH) using machine learning (ML).

Materials And Methods: This retrospective study utilized two databases: a) the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) nonalcoholic fatty liver disease (NAFLD) adult database (2004-2009), and b) the Optum® de-identified Electronic Health Record dataset (2007-2018), a real-world dataset representative of common electronic health records in the United States. We developed an ML model to predict NASH, using confirmed NASH and non-NASH based on liver histology results in the NIDDK dataset to train the model.

Mapping the Kansas City Cardiomyopathy Questionnaire (KCCQ) Onto EQ-5D-3L in Heart Failure Patients: Results for the Japanese and UK Value Sets.

Health technology assessment bodies in several countries, including Japan and the United Kingdom, recommend mapping techniques to obtain utility scores in clinical trials that do not have a preference-based measure of health. This study sought to develop mapping algorithms to predict EQ-5D-3L scores from the Kansas City Cardiomyopathy Questionnaire (KCCQ) in patients with heart failure (HF). Data from the randomized, double-blind PARADIGM-HF trial were analyzed, and EQ-5D-3L scores were calculated using the Japanese and UK value sets.

Is the St. George's Respiratory Questionnaire an Appropriate Measure of Symptom Severity and Activity Limitations for Clinical Trials in COPD? Analysis of Pooled Data from Five Randomized Clinical Trials.

Purpose: The objective of this study was to examine the psychometric properties of the St. George's Respiratory Questionnaire (SGRQ) in patients with chronic obstructive pulmonary disease (COPD) using Rasch measurement theory (RMT) analyses.

Materials And Methods: RMT analysis was conducted on the baseline SGRQ data from five multi-national, Phase III randomized trials investigating a fixed-dose combination of a long-acting β2-agonist and a long-acting muscarinic antagonist in COPD patients.

Patient-reported outcomes are important elements of psoriasis treatment decision making: A discrete choice experiment survey of dermatologists in the United States.

Background: Psoriasis Area and Severity Index (PASI) response rates have been the benchmark for evaluating treatment efficacy in trials involving moderate-to-severe psoriasis.

Objective: To understand how dermatologists assess biologics and which trade-off rules they apply when planning psoriasis treatment.

Methods: Two online surveys of 130 and 129 US dermatologists (surveys 1 and 2, respectively) were conducted with use of direct and indirect elicitation via discrete choice experiment.

The Commercial Market For Priority Review Vouchers.

In 2007 the US Congress created the priority review voucher program to encourage the development of drugs for neglected diseases. Under the program, the developer of a drug that treats a neglected disease receives both a faster review of the drug by the Food and Drug Administration and a voucher for a faster review of a different drug. The developer can sell the voucher.

Review and comparison of methodologies for indirect comparison of clinical trial results: an illustration with ranibizumab and aflibercept.

Aim: To review and compare methods for indirect comparison of aflibercept and ranibizumab in patients with diabetic macular edema.

Methods: Post-stratification, inverse probability weighting based on simulated data, weight optimization, and regression model techniques were used to compare pooled individual patient-level data from the RESTORE and RESPOND (ranibizumab 0.5 mg as needed after 3 initial monthly doses) studies with summary-level data from the VIVID and VISTA (aflibercept 2.

Using Patient-Level Data to Develop Meaningful Cross-Trial Comparisons of Visual Impairment in Individuals with Diabetic Macular Edema.

Introduction: The aim of this study was to assess the impact of baseline characteristics on visual outcome of patients with diabetic macular edema and compare the results of clinical trials with different patient populations.

Methods: A model was created with patient-level data from the RESPOND/RESTORE trials to estimate the impact of baseline characteristics on increases in best-corrected visual acuity (BCVA) with anti-vascular endothelial growth factor therapies, measured by letters gained on the Early Treatment Diabetic Retinopathy Study scale from baseline to month 12. Mean BCVA gains with ranibizumab 0.

Comparative efficacy and safety of approved treatments for macular oedema secondary to branch retinal vein occlusion: a network meta-analysis.

Objective: To compare the efficacy and safety of approved treatments for macular oedema secondary to branch retinal vein occlusion (BRVO).

Design: Randomised controlled trials (RCTs) evaluating the efficacy and safety of approved treatments for macular oedema secondary to BRVO were identified from an updated systematic review.

Setting: A Bayesian network meta-analysis of RCTs of treatments for macular oedema secondary to BRVO.

Cost-effectiveness of ranibizumab versus aflibercept in the treatment of visual impairment due to diabetic macular edema: a UK healthcare perspective.

Background: Ranibizumab and aflibercept are alternative anti-vascular endothelial growth factor agents approved for the treatment of visual impairment (VI) due to diabetic macular edema (DME).

Objective: To estimate, from a UK healthcare perspective, the cost-effectiveness of ranibizumab 0.5 mg pro re nata (PRN) and ranibizumab 0.

Potential impact of vaccination against Neisseria meningitidis on Neisseria gonorrhoeae in the United States: results from a decision-analysis model.

Components in 4CMenB vaccine against Neisseria meningitidis serogroup B have shown to potentially cross-react with Neisseria gonorrhoeae. We modeled the theoretical impact of a US 4CMenB vaccination program on gonorrhea outcomes. A decision-analysis model was populated using published healthcare utilization and cost data.

How does drug coverage vary by insurance type? Analysis of drug formularies in the United States.

Objectives: To quantify how access to on-patent drugs by tier placement varies by insurance type and therapeutic area.

Study Design: Retrospective analysis of insurance plan drug coverage data.

Methods: Drug coverage information was collected from the Fingertip Formulary database in May 2011 for 3 drug classes (statins, angiotensin II receptor blockers, and protein-tyrosine kinase inhibitors) across 3 therapeutic areas with varying levels of generic drug availability.

Drug versus vaccine investment: a modelled comparison of economic incentives.

Background: Investment by manufacturers in research and development of vaccines is relatively low compared with that of pharmaceuticals. If current evaluation technologies favour drugs over vaccines, then the vaccines market becomes relatively less attractive to manufacturers.

Methods: We developed a mathematical model simulating the decision-making process of regulators and payers, in order to understand manufacturers' economic incentives to invest in vaccines rather than curative treatments.

Respiratory syncytial virus immunization program for the United States: impact of performance determinants of a theoretical vaccine.

Objectives: To inform strategic decisions on respiratory syncytial virus (RSV) vaccine development and identify critical endpoints likely to drive the vaccine's medical and economic impact.

Design: A decision-analysis model populated using healthcare utilization data and costs from the literature; vaccine efficacy and duration based on assumptions.

Setting: Vaccination in the physician office setting in the USA.

Association between respiratory syncytial virus hospitalizations in infants and respiratory sequelae: systematic review and meta-analysis.

Background: The association between hospitalization for respiratory syncytial virus (RSV) infection in infancy and asthma/wheezing in later life has long been studied. However, no published studies have combined systematic review and meta-analysis of existing evidence.

Purpose: To quantify the link between RSV hospitalization in early life and subsequent diagnosis of asthma.