Mixture-of-exponentials models to explain heterogeneity in studies of the duration of Chlamydia trachomatis infection

Malcolm J. Price*, A. E. Ades, Daniela De Angelis, Nicky J. Welton, John A A Macleod, Kate Soldan, Katy Turner, Ian Simms, Paddy J. Horner

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

26 Citations (Scopus)

Abstract

Published studies of the duration of asymptomatic Chlamydia trachomatis infection in women have produced diverse estimates, and most reviewers have not attempted an evidence synthesis. We review the designs of duration studies, distinguishing between the incident cases presenting soon after infection in clinic-based studies and prevalent cases ascertained in population screening studies. We combine evidence from all studies under fixed-effect (single clearance rate), random-effect (study-specific clearance rate), and mixture-of-exponentials models, in which there are either two or three classes of infection that clear at different rates. We can identify classes as passive' infection and fast-clearing and slow-clearing infections. We estimate models by Bayesian MCMC and compared them using posterior mean residual deviance and the deviance information criterion. The single fixed-effect clearance rate model fitted very poorly. The random-effect model was adequate but inferior to the two-class and three-class mixture of exponentials. According to the two-class model, the proportion in the first class was 23% (95% CI: 1631%), and the mean duration of C.trachomatis infection is 1.36years (95% CI: 1.131.63years). With the three-rate model, duration was similar, but identification of the proportions in each class (19%, 31%, and 49%) was poor. Although the random-effect model was descriptively adequate, the extreme degree of between-study variation in the clearance rate it predicted lacked biological plausibility. Differences in study recruitment and sampling mechanisms, acting through a mixture-of-exponentials model, better explains the apparent heterogeneity in duration. Copyright (c) 2012 John Wiley & Sons, Ltd.

Original languageEnglish
Pages (from-to)1547-1560
Number of pages14
JournalStatistics in Medicine
Volume32
Issue number9
DOIs
Publication statusPublished - 30 Apr 2013

Keywords

  • Chlamydia trachomatis
  • evidence synthesis
  • Bayesian
  • duration of infection
  • heterogeneity
  • mixture of exponentials
  • RANDOM-EFFECTS METAANALYSIS
  • COST-EFFECTIVENESS
  • FOLLOW-UP
  • GENITAL-INFECTION
  • SCREENING-PROGRAMS
  • UNTREATED PATIENTS
  • NATURAL-HISTORY
  • WOMEN
  • RESOLUTION
  • GONORRHEA

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  • Projects

    Malcolm Price Fellowship

    Price, M. J.

    1/09/111/09/12

    Project: Research

    CHLAMYDIA SYNTHESIS

    Ades, A. E.

    1/07/091/01/12

    Project: Research

    MRC METHODOLOGY RESEARCH FELLOWSHIP

    Welton, N. J.

    4/05/094/11/13

    Project: Research

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