Statistical analysis of proliferative index data in clinical trials

Patricia Grambsch, Thomas A. Louis, Roberd M. Bostick, Greg A. Grandits, Lisa Fosdick, Mohamed Darif, John D. Potter

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Measurements of proliferative activity in colonic epithelial cells are being used as surrogate endpoints in clinical trials for colon cancer prevention. Proliferative index data exemplify an important type of clinical trial endpoint. The outcome variable is a proportion in which the denominator is an ancillary statistic and in which measurement error and technician judgement are important sources of variability. The paper proposes a statistical model for a repeated measures clinical trial with this type of endpoint, in the context of proliferative activity data. The model is a two‐stage random effects linear model in the log scale. In addition to fixed effects covariates, it explicitly incorporates two major sources of variability: the number of epithelial cells counted and the reader effect. Although the resulting likelihood is complicated, one can fit an approximate likelihood with minimal loss of efficiency using standard packages. We apply the model to a pilot randomized clinical trial.

Original languageEnglish (US)
Pages (from-to)1619-1634
Number of pages16
JournalStatistics in Medicine
Issue number16
StatePublished - Aug 30 1994
Externally publishedYes

ASJC Scopus subject areas

  • Epidemiology
  • Statistics and Probability


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