Randomization and Additivity in the Two‐Period Crossover Clinicial Trial

Richard McHugh, Orlando Gomez‐Marin

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


In certain areas of medical research, the two‐period crossover design is a frequent choice for comparing treatments A and B in a randomized clinical trial. Earlier work by Grizzle and by Brown was based upon a parametric theory linear model. Recently, the present authors employed D. R. Cox's additive randomization models and, for the case of zero residual effect, found a discrepancy between it and the parametric model with respect to the precision of period effects. In the present note, this divergence is accounted for by allowing for the possibility of non‐additivity through the use of a completely general randomization model. It is concluded that the structure of the crossover design is such that use of the parametric theory linear model is required if a single, consistent model is desired.

Original languageEnglish (US)
Pages (from-to)961-970
Number of pages10
JournalBiometrical Journal
Issue number8
StatePublished - 1987
Externally publishedYes


  • Additive randomization model
  • Crossover trial
  • General randomization model
  • Parametric theory model

ASJC Scopus subject areas

  • Statistics and Probability
  • Statistics, Probability and Uncertainty


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