An Adaptive Three-Arm Comparative Clinical Endpoint Bioequivalence Study Design With Unblinded Sample Size Re-Estimation and Optimized Allocation Ratio.

A three-arm comparative clinical endpoint bioequivalence (BE) study is often used to establish bioequivalence (BE) between a locally acting generic drug (T) and reference drug (R), where superiority needs to be established for T and R over Placebo (P) and equivalence needs to be established for T vs. R. Sometimes, when study design parameters are uncertain, a fixed design study may be under- or over-powered and result in study failure or unnecessary cost.

Exploring the relationship between condition severity and health-related quality of life in people with haemophilia A across Europe: a multivariable analysis of data from the CHESS II study.

Background: Haemophilia A (HA; Factor VIII deficiency) is a congenital X-linked bleeding disorder characterized by trauma-related or spontaneous bleeding events, most notably arising within the intraarticular space and resulting in chronic inflammation and degeneration of affected joints. Endogenous clotting factor activity relative to normal levels determines the severity of HA symptoms, as mild (> 5-40%), moderate (1-5%), or severe (< 1%). Within the current environment of rapid evolution in HA management, we seek to understand the interplay of condition severity and health-related quality of life (HRQoL) to characterise and differentiate unmet needs among people with HA (PwHA).

Comparative Effectiveness of Valoctocogene Roxaparvovec and Prophylactic Factor VIII Replacement in Severe Hemophilia A.

Introduction: A prospective, non-interventional study (270-902) followed 294 adults with severe hemophilia A (SHA) receiving prophylactic factor VIII (FVIII). From these participants, 112 rolled over into a single-arm, multicenter, phase 3 trial (GENEr8-1; NCT03370913) that evaluated efficacy and safety of valoctocogene roxaparvovec, a gene therapy that provides endogenous FVIII in individuals with SHA. Participants from 270-902 who did not roll over provide an opportunity for a contemporaneous external control.

Matching-adjusted indirect comparison of bleeding outcomes in severe haemophilia A: Comparing valoctocogene roxaparvovec gene therapy, emicizumab prophylaxis, and FVIII replacement prophylaxis.

Introduction: Head-to-head evaluation of valoctocogene roxaparvovec, the first gene therapy approved for haemophilia A, with emicizumab is not available. Therefore, phase 3 trial data were indirectly compared.

Aim: To compare bleeding rates in trials evaluating 6 × 10  vg/kg valoctocogene roxaparvovec (GENEr8-1; NCT03370913), 1.

Healthcare utilization of patients with hereditary angioedema treated with lanadelumab and subcutaneous C1-inhibitor concentrate.

New hereditary angioedema (HAE) treatments have become available in recent years for the treatment of HAE due to C1-inhibitor (C1-INH) deficiency, including two subcutaneous (SC) options: a monoclonal antibody (lanadelumab) and a plasma-derived C1-INH concentrate (SC-C1-INH). Limited real-world data on these therapies have been reported. The objective was to describe new users of lanadelumab and SC-C1-INH, including demographics, healthcare resource utilization (HCRU), costs, and treatment patterns before and after beginning treatment.

Asthma control among treated US asthma patients in Practice Fusion's electronic medical record research database.

This study investigated burden of 'not well-controlled' asthma, overall and by Global Initiative for Asthma (GINA) Step, among treated asthma patients in Practice Fusion's research database. Asthma control (Asthma Control Test [ACT]) was stratified by GINA Step; prevalence ratios were estimated using Poisson regression with robust variance controlled for confounders. ACT scores ≤19 reflect not well-controlled; >19 reflect 'well-controlled' asthma.

Genome-wide meta-analysis of insomnia prioritizes genes associated with metabolic and psychiatric pathways.

Insomnia is a heritable, highly prevalent sleep disorder for which no sufficient treatment currently exists. Previous genome-wide association studies with up to 1.3 million subjects identified over 200 associated loci.

Genome-wide association study of musical beat synchronization demonstrates high polygenicity.

Moving in synchrony to the beat is a fundamental component of musicality. Here we conducted a genome-wide association study to identify common genetic variants associated with beat synchronization in 606,825 individuals. Beat synchronization exhibited a highly polygenic architecture, with 69 loci reaching genome-wide significance (P < 5 × 10) and single-nucleotide-polymorphism-based heritability (on the liability scale) of 13%-16%.

Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals.

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.

Characterizing mood disorders in the AFFECT study: a large, longitudinal, and phenotypically rich genetic cohort in the US.

There has recently been marked progress in identifying genetic risk factors for major depression (MD) and bipolar disorder (BD); however, few systematic efforts have been made to elucidate heterogeneity that exists within and across these diagnostic taxa. The Affective disorders, Environment, and Cognitive Trait (AFFECT) study presents an opportunity to identify and associate the structure of cognition and symptom-level domains across the mood disorder spectrum in a prospective study from a diverse US population.Participants were recruited from the 23andMe, Inc research participant database and through social media; self-reported diagnosis of MD or BD by a medical professional and medication status data were used to enrich for mood-disorder cases.

Real-world Treatment Patterns, Outcomes, and Healthcare Resource Utilization in Newly Treated Korean Patients With Asthma: A Retrospective Cohort Study.

Purpose: Although asthma treatment guidelines recommend regular inhaled medication, real-world treatment patterns and outcomes in South Korea have not been examined. We examined real-world treatment patterns and outcomes among patients treated for asthma in South Korea.

Methods: This retrospective cohort study utilized data from the South Korean National Health Insurance database (2013-2016).

CCR5 and Biological Complexity: The Need for Data Integration and Educational Materials to Address Genetic/Biological Reductionism at the Interface of Ethical, Legal, and Social Implications.

In the age of genomics, public understanding of complex scientific knowledge is critical. To combat reductionistic views, it is necessary to generate and organize educational material and data that keep pace with advances in genomics. The view that CCR5 is solely the receptor for HIV gave rise to demand to remove the gene in patients to create host HIV resistance, underestimating the broader roles and complex genetic inheritance of CCR5.

A systematic literature review of burden of illness in adults with uncontrolled moderate/severe asthma.

Background: There are limited published data on the burden of moderate/severe uncontrolled asthma.

Methods: We conducted a systematic literature review to better understand the impact of moderate-to-severe asthma in the US, the UK, Germany, France, Italy, Spain, Canada, Japan, and Australia in terms of prevalence, clinical measures, health-related quality of life (HRQoL) and economic burden, for patients whose asthma is uncontrolled despite inhaled corticosteroid/long-acting β-agonist (ICS/LABA) therapy.

Results: The prevalence of uncontrolled asthma among patients with moderate/severe disease varied but was as high as 100% in some subgroups.

Characteristics of Treated Asthmatics Experiencing Exacerbations in a US Database: A Retrospective Cohort Study.

Rationale: The National Heart, Lung, and Blood Institute (NHLBI) recommend a stepwise approach to asthma management, with the goals of maintaining asthma control and reducing exacerbations. Although asthma treatments reduce the frequency of exacerbations, they still occur. We aimed to characterize the treated United States of America (US) adult asthma population, including those experiencing exacerbations, in terms of socio-demographics, clinical characteristics, and healthcare resource utilization (HRU).