Clinical performance and health equity implications of the American Diabetes Association’s 2023 screening recommendation for prediabetes and diabetes

• Type of Material: Article
• Authors: Ying Huang, University of Washington; Nima S. Hejazi, Harvard University; bryan Blette, University of Pennsylvania; Lindsay N. Carpp, Fred Hutchinson Cancer Center; David Benkeser, Emory University; David C. Montefiori, Duke University; Adrian B. McDermott, National Institutes of Health; Youyi Fong, Fred Hutchinson Cancer Center; Holly E. Janes, Fred Hutchinson Cancer Center; Weiping Deng, Moderna, Inc.; Honghong Zhou, Moderna, Inc.; Christopher R. Houchens, Biomedical Advanced Research and Development Authority; Karen Martins, Biomedical Advanced Research and Development Authority; Lakshmi Jayashankar, Biomedical Advanced Research and Development Authority; Britta Flach, National Institutes of Health; Bob c. Lin, National Institutes of Health; Sarah O'Connell, National Institutes of Health; Charlene McDanal, Duke University; Amanda Eaton, Duke University; Marcella Sarzotti-Kelsoe, Duke University; Yiwen Lu, Fred Hutchinson Cancer Center; Chenchen Yu, Fred Hutchinson Cancer Center; Avi Kenny, University of Washington; Marco Carone, University of Washington; Chuong Huynh, Biomedical Advanced Research and Development Authority; Jacqueline Miller, Moderna, Inc.; Hana M. El Sahly, Baylor College of Medicine; Lindsey R. Baden, Brigham and Women's Hospital; Lisa A. Jackson, Kaiser Permanente Washington Health Research Institute; Thomas B. Campbell, University of Colorado, Anschutz; Jesse Clark, University of California, Los Angeles; Michele P. Andrasik, Fred Hutchinson Cancer Center; James G. Kublin, Fred Hutchinson Cancer Center; Lawrence Corey, Fred Hutchinson Cancer Center; Kathleen M. Neuzil, University of Maryland, Baltimore; rolando Pajon, Moderna, Inc.; Dean Follmann, National Institutes of Health; ruben O. Donis, Biomedical Advanced Research and Development Authority; Richard A. Koup, National Institutes of Health; Peter B. Gilbert, Fred Hutchinson Cancer Center
• Language: English
• Date: 2023-09-29
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2023 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): https://doi.org/10.3390%2Fv15102029
• Title of Journal or Parent Work: Viruses
• Volume: 15
• Issue: 10
• Start Page: 2029
• Grant/Funding Information: This work was supported by awards R37AI054165 and UM1AI068635 to investigator PBG from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health. This work was supported in whole or part with federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response, Biomedical Advanced Research and Development Authority, under Contract No. 75A50120C00034 (P3001 study). This work was also supported by award R01CA277133 to investigator YH from the National Cancer Institute of the National Institutes of Health.
• Keywords: stochastic interventional vaccine efficacy; neutralizing antibody assay; principal surrogate; modified treatment policy; principal stratification; stochastic intervention; binding antibody assay; immune correlates of protection; SARS-CoV-2
• Research Categories: Health Sciences, Immunology; Biology, Virology

Abstract

The COVE trial randomized participants to receive two doses of mRNA-1273 vaccine or placebo on Days 1 and 29 (D1, D29). Anti-SARS-CoV-2 Spike IgG binding antibodies (bAbs), anti-receptor binding domain IgG bAbs, 50% inhibitory dilution neutralizing antibody (nAb) titers, and 80% inhibitory dilution nAb titers were measured at D29 and D57. We assessed these markers as correlates of protection (CoPs) against COVID-19 using stochastic interventional vaccine efficacy (SVE) analysis and principal surrogate (PS) analysis, frameworks not used in our previous COVE immune correlates analyses. By SVE analysis, hypothetical shifts of the D57 Spike IgG distribution from a geometric mean concentration (GMC) of 2737 binding antibody units (BAU)/mL (estimated vaccine efficacy (VE): 92.9% (95% CI: 91.7%, 93.9%)) to 274 BAU/mL or to 27,368 BAU/mL resulted in an overall estimated VE of 84.2% (79.0%, 88.1%) and 97.6% (97.4%, 97.7%), respectively. By binary marker PS analysis of Low and High subgroups (cut-point: 2094 BAU/mL), the ignorance interval (IGI) and estimated uncertainty interval (EUI) for VE were [85%, 90%] and (78%, 93%) for Low compared to [95%, 96%] and (92%, 97%) for High. By continuous marker PS analysis, the IGI and 95% EUI for VE at the 2.5th percentile (519.4 BAU/mL) vs. at the 97.5th percentile (9262.9 BAU/mL) of D57 Spike IgG concentration were [92.6%, 93.4%] and (89.2%, 95.7%) vs. [94.3%, 94.6%] and (89.7%, 97.0%). Results were similar for other D29 and D57 markers. Thus, the SVE and PS analyses additionally support all four markers at both time points as CoPs.