2023 White Paper on Recent Issues in Bioanalysis: EU IVDR 2017/746 Implementation/Impact, IVD/CDx/CLIA Approved Assays, High Dimensional Cytometry, Multiplexing Technologies, LBA Tissue Analysis, Vaccine Study Endpoints, Cell-Based Assays for Biomarkers, Cell Therapy and Vaccines ( - Recommendations on Development & Validation of Biomarkers, IVD, CDx, Cell-Based, Flow Cytometry, Ligand-Binding and Enzyme Assays; Advanced Critical Reagents Strategies).

The 17 Workshop on Recent Issues in Bioanalysis (17 WRIB) took place in Orlando, FL, USA on 19-23 June 2023. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 17 WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

Urinary Proteomics and Outcomes in Heart Failure With Preserved Ejection Fraction.

Background: Although several studies have addressed plasma proteomics in heart failure with preserved ejection fraction, limited data are available on the prognostic value of urinary proteomics. The objective of our study was to identify urinary proteins/peptides associated with death and heart failure admission in patients with heart failure with preserved ejection fraction.

Methods And Results: The study population included participants enrolled in TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial).

A Primary Care-Based Quality Improvement Project to Reduce Asthma Emergency Department Visits.

Background And Objectives: Asthma exacerbation is a common and often preventable cause of Emergency Department (ED) utilization. Children eligible for Medicaid are at increased risk of poor asthma control and subsequent ED visits. In 2010, we implemented a multicomponent longitudinal quality improvement project to improve pediatric asthma care for our primary care population, which was 90% Medicaid-eligible.

Predicting emergency department visits among children with asthma in two academic medical systems.

To develop and validate a predictive algorithm that identifies pediatric patients at risk of asthma-related emergencies, and to test whether algorithm performance can be improved in an external site via local retraining. In a retrospective cohort at the first site, data from 26 008 patients with asthma aged 2-18 years (2012-2017) were used to develop a lasso-regularized logistic regression model predicting emergency department visits for asthma within one year of a primary care encounter, known as the Asthma Emergency Risk (AER) score. Internal validation was conducted on 8634 patient encounters from 2018.

A Novel BCMA Immunohistochemistry Assay Reveals a Heterogenous and Dynamic BCMA Expression Profile in Multiple Myeloma.

B-cell maturation antigen (BCMA) is a promising target for the treatment of multiple myeloma (MM) because the expression of this protein is largely limited to B-cell sets, plasma cells, MM, and other B-cell malignancies. Early studies assessing BCMA protein expression and localization have used insufficiently qualified immunohistochemistry assays, which have reported broad ranges of BCMA expression. As a result, our understanding of BCMA tissue expression derived from these data is limited, specifically the prevalence of BCMA expression on the cell surface/membrane, which has mechanistic relevance to the antimyeloma activity of several novel biotherapeutics.

Autoimmune gene expression profiling of fingerstick whole blood in Chronic Fatigue Syndrome.

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition that can lead to severe impairment of physical, psychological, cognitive, social, and occupational functions. The cause of ME/CFS remains incompletely understood. There is no clinical diagnostic test for ME/CFS.

Direct comparison of circulating tumor DNA sequencing assays with targeted large gene panels.

Next generation sequencing (NGS) assays with large targeted gene panels can comprehensively profile cancer somatic mutations in a tumor sample. Given the rapid adoption of such assays for circulating tumor DNA (ctDNA) analysis in clinical oncology, it is essential for the community to understand their analytical performance in liquid biopsy settings. Here, we directly compared five ctDNA NGS assays, most of which having a panel of 400 or more genes, with simulated samples harboring mutations relevant to solid tumors or myeloid malignancy.

Biological impact of iberdomide in patients with active systemic lupus erythematosus.

Objectives: Iberdomide is a high-affinity cereblon ligand that promotes proteasomal degradation of transcription factors Ikaros () and Aiolos (). Pharmacodynamics and pharmacokinetics of oral iberdomide were evaluated in a phase 2b study of patients with active systemic lupus erythematosus (SLE).

Methods: Adults with autoantibody-positive SLE were randomised to placebo (n=83) or once daily iberdomide 0.

A randomized crossover trial of HEPA air filtration to reduce cardiovascular risk for near highway residents: Methods and approach.

Background: Near highway residents are exposed to elevated levels of traffic-related air pollution (TRAP), including ultrafine particles, which are associated with adverse health effects. The efficacy of using in-home air filtration units that reduce exposure and potentially yield health benefits has not been tested in a randomized controlled trial.

Methods: We will conduct a randomized double-blind crossover trial of portable air filtration units for 200 adults 30 years and older who live in near-highway homes in Somerville, MA, USA.

The all-on-4 concept in the maxilla-A biomechanical analysis involving high performance polymers.

A finite element analysis was used to determine the loading behavior of a full "All-on-4" bridge in the maxilla made from different framework materials. The model was generated based on data from an edentulous maxilla. Four implants were positioned according to the All-on-4 concept and a full arch restoration was created on top of the implants.

ROBUST: A Phase III Study of Lenalidomide Plus R-CHOP Versus Placebo Plus R-CHOP in Previously Untreated Patients With ABC-Type Diffuse Large B-Cell Lymphoma.

Purpose: Patients with the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) historically showed inferior survival with standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Phase II studies demonstrated that adding the immunomodulatory agent lenalidomide to R-CHOP improved outcomes in ABC-type DLBCL. The goal of the global, phase III ROBUST study was to compare lenalidomide plus R-CHOP (R2-CHOP) with placebo/R-CHOP in previously untreated, ABC-type DLBCL.

Effect of Reducing Ambient Traffic-Related Air Pollution on Blood Pressure: A Randomized Crossover Trial.

Exposure to traffic-related air pollution (TRAP) may contribute to increased prevalence of hypertension and elevated blood pressure (BP) for residents of near-highway neighborhoods. Relatively few studies have investigated the effects of reducing TRAP exposure on short-term changes in BP. We assessed whether reducing indoor TRAP concentrations by using stand-alone high-efficiency particulate arrestance (HEPA) filters and limiting infiltration through doors and windows effectively prevented acute (ie, over a span of hours) increases in BP.

Data on the implementation of VaxTrac electronic immunization registry in Sierra Leone.

Following the piloting of VaxTrac, an electronic immunization registry (EIR), we conducted a rapid assessment in November-December 2017 to evaluate the use of the EIR in 10 health facilities in Western Area Urban district in Sierra Leone [1]. In this data-in-brief report, we provide additional descriptive data from the assessment of the VaxTrac EIR in Sierra Leone. The assessment comprised aggregate data on vaccine doses administered that were abstracted from VaxTrac and three paper-based sources (daily tally sheets, register of children under the age of 2 years, and a summary form of doses administered).

Assessment of VaxTrac electronic immunization registry in an urban district in Sierra Leone: Implications for data quality, defaulter tracking, and policy.

Background: In 2016, the Sierra Leone Ministry of Health and Sanitation (MoHS) piloted VaxTrac, an electronic immunization registry (EIR), in an urban district to improve management of vaccination records and tracking of children who missed scheduled doses. We aimed to document lessons learned to inform decision-making on VaxTrac and similar EIRs' future use.

Methods: Ten out of 50 urban health facilities that implemented VaxTrac were purposively selected for inclusion in a rapid mixed-method assessment from November to December 2017.