Journal of Clinical Epidemiology
Volume 54, Issue 1 , Pages 68-85, January 2001

Sieve analysis:

methods for assessing from vaccine trial data how vaccine efficacy varies with genotypic and phenotypic pathogen variation

  • Peter Gilbert

      Affiliations

    • Department of Biostatistics, Harvard School of Public Health, 655 Huntington Ave., Boston, MA 02115, USA
    • Corresponding Author InformationCorresponding author. Tel.: (617) 432-2899; fax: (617) 739-7181. E-mail address:
    • ,
  • Steve Self

      Affiliations

    • Fred Hutchinson Cancer Research Center, Seattle, WA, USA
    • ,
  • Malla Rao

      Affiliations

    • National Institute of Child Health and Human Development, Bethesda, MD, USA
    • ,
  • Abdollah Naficy

      Affiliations

    • National Institute of Child Health and Human Development, Bethesda, MD, USA
    • ,
  • John Clemens

      Affiliations

    • National Institute of Child Health and Human Development, Bethesda, MD, USA

Received 3 February 1999; received in revised form 29 March 2000; accepted 10 April 2000.

Abstract 

A key component in the evaluation of efficacy of a vaccine to protect against disease caused by an antigenically diverse infectious pathogen in a preventative vaccine trial is assessing how vaccine-induced protection depends on genotypic and phenotypic variations of the exposing pathogen. This assessment is made by comparing pathogen isolates between infected vaccinated subjects and infected unvaccinated subjects. A survey of efficacy trial reports reveals a lack of systematic, quantitative investigation in this question. Analysis tools for testing if vaccine protection against disease is superior against some pathogen strains, and for estimating the magnitude of this differential vaccine protection, are described. The broad applicability of the methods is illustrated through analysis of isolates taken from persons infected while participating in vaccine trails for cholera, HIV-1, hepatitis B, rotavirus, and pneumococcus. These analyses reveal intriguing trends for Genentech's monovalent rgp120 HIV-1 vaccine, for two whole-killed-cell oral cholera vaccines, and for other vaccines.

Keywords:  Clinical trials, Genetic sequence variation, Human immunodeficiency virus, Molecular epidemiology, Sieve analysis, Statistical methods

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PII: S0895-4356(00)00258-4

Journal of Clinical Epidemiology
Volume 54, Issue 1 , Pages 68-85, January 2001

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