Design and analysis of intra-subject variability in cross-over experiments

Vernon M. Chinchilli, James D. Esinhart

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62 Scopus citations


Recently, interest has grown in the development of inferential techniques to compare treatment variabilities in the setting of a cross-over experiment. In particular, comparison of treatments with respect to intra-subject variability has greater interest than has inter-subject variability. We begin with a presentation of a general approach for statistical inference within a cross-over design. We discuss three different statistical models where model choice depends on the design and assumptions about carry-over effects. Each model incorporates t-variate random subject effects, where t is the number of treatments. We develop maximum likelihood (ML) and restricted maximum likelihood (REML) approaches to derive parameter estimators and we consider a special case in which closed-form expressions for the variance component estimators are available. Finally, we illustrate the methodologies with the analysis of data from three examples.

Original languageEnglish (US)
Pages (from-to)1619-1634
Number of pages16
JournalStatistics in Medicine
Issue number15
StatePublished - Aug 15 1996

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Statistics and Probability


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