tetano
Editor, Senior Moderator
Am J Epidemiol. 2019 Oct 10. pii: kwz227. doi: 10.1093/aje/kwz227. [Epub ahead of print] [h=1]Distinguishing Causation from Correlation in the Use of Correlates of Protection to Evaluate and Develop Influenza Vaccines.[/h]
Lim WW[SUP]1[/SUP], Leung NHL[SUP]1[/SUP], Sullivan SG[SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Tchetgen Tchetgen EJ[SUP]5[/SUP], Cowling BJ[SUP]1[/SUP].
[h=3]Author information[/h] 1 WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region, China. 2 WHO Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia. 3 Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, California. 4 Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia. 5 Statistics Department, The Wharton School, University of Pennsylvania, Philadelphia, Pennsylvania.
[h=3]Abstract[/h] There is increasing attention on the need to identify new immune markers for the evaluation of existing and new influenza vaccines. Immune markers that could predict individual protection against infection and disease, commonly called "correlates of protection" (CoPs), play an important role in vaccine development and licensing. Here, we discuss the epidemiological considerations when evaluating immune markers as potential CoPs for influenza vaccines and emphasize the distinction between correlation and causation. While an immune marker that correlates well with protection from infection may be used as a predictor of vaccine efficacy, it should be distinguished from an immune marker that plays a mechanistic role in conferring protection against a clinical endpoint, as the latter may be a more reliable predictor of vaccine efficacy and a more appropriate target for rational vaccine design. To clearly distinguish mechanistic and non-mechanistic CoPs, we suggest using the term "correlates of protection" for non-mechanistic CoPs, and "mediators of protection" for mechanistic CoPs. Furthermore, as the interactions among and relative importance of correlates or mediators of protection may vary according to age or prior vaccine experience, the effect sizes and thresholds for protective effects for CoPs may also vary in different segments of the population.
? The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
[h=4]KEYWORDS:[/h] Biomarkers; Causality; Influenza Vaccines; Influenza, Human; Terminology as Topic; immune correlates of protection; immune markers; immune mediators of protection
PMID: 31598648 DOI: 10.1093/aje/kwz227
Lim WW[SUP]1[/SUP], Leung NHL[SUP]1[/SUP], Sullivan SG[SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Tchetgen Tchetgen EJ[SUP]5[/SUP], Cowling BJ[SUP]1[/SUP].
[h=3]Author information[/h] 1 WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region, China. 2 WHO Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia. 3 Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, California. 4 Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia. 5 Statistics Department, The Wharton School, University of Pennsylvania, Philadelphia, Pennsylvania.
[h=3]Abstract[/h] There is increasing attention on the need to identify new immune markers for the evaluation of existing and new influenza vaccines. Immune markers that could predict individual protection against infection and disease, commonly called "correlates of protection" (CoPs), play an important role in vaccine development and licensing. Here, we discuss the epidemiological considerations when evaluating immune markers as potential CoPs for influenza vaccines and emphasize the distinction between correlation and causation. While an immune marker that correlates well with protection from infection may be used as a predictor of vaccine efficacy, it should be distinguished from an immune marker that plays a mechanistic role in conferring protection against a clinical endpoint, as the latter may be a more reliable predictor of vaccine efficacy and a more appropriate target for rational vaccine design. To clearly distinguish mechanistic and non-mechanistic CoPs, we suggest using the term "correlates of protection" for non-mechanistic CoPs, and "mediators of protection" for mechanistic CoPs. Furthermore, as the interactions among and relative importance of correlates or mediators of protection may vary according to age or prior vaccine experience, the effect sizes and thresholds for protective effects for CoPs may also vary in different segments of the population.
? The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
[h=4]KEYWORDS:[/h] Biomarkers; Causality; Influenza Vaccines; Influenza, Human; Terminology as Topic; immune correlates of protection; immune markers; immune mediators of protection
PMID: 31598648 DOI: 10.1093/aje/kwz227