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Bounding the Infectiousness Effect in Vaccine Trials

VanderWeele, Tyler J.; Tchetgen Tchetgen, Eric J.

doi: 10.1097/EDE.0b013e31822708d5
Infectious Disease

In vaccine trials, the vaccination of one person might prevent the infection of another; a distinction can be drawn between the ways such a protective effect might arise. Consider a setting with 2 persons per household in which one of the 2 is vaccinated. Vaccinating the first person may protect the second person by preventing the first from being infected and passing the infection on to the second. Alternatively, vaccinating the first person may protect the second by rendering the infection less contagious even if the first is infected. This latter mechanism is sometimes referred to as an “infectiousness effect” of the vaccine. Crude estimators for the infectiousness effect will be subject to selection bias due to stratification on a postvaccination event, namely the infection status of the first person. We use theory concerning causal inference under interference along with a principal-stratification framework to show that, although the crude estimator is biased, it is, under plausible assumptions, conservative for what one might define as a causal infectiousness effect. This applies to bias from selection due to the persons in the comparison, and also to selection due to pathogen virulence. We illustrate our results with an example from the literature.

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From the Departments of Epidemiology and Biostatistics, Harvard School of Public Health, Boston, MA.

Submitted 14 October 2010; accepted 31 May 2011; posted 13 July 2011.

Supported by National Institutes of Health (grant HD060696).

Supplemental digital content is available through direct URL citations in the HTML and PDF versions of this article (www.epidem.com).

Correspondence: Tyler J. VanderWeele, Harvard School of Public Health, Departments of Epidemiology and Biostatistics, 677 Huntington Avenue, Boston, MA 02115. E-mail: tvanderw@hsph.harvard.edu.

© 2011 Lippincott Williams & Wilkins, Inc.