Statistical analysis of proliferative index data in clinical trials

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

Research output: Contribution to journalArticle


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
Publication statusPublished - 1994
Externally publishedYes


ASJC Scopus subject areas

  • Epidemiology
  • Statistics and Probability

Cite this

Grambsch, P., Louis, T., Bostick, R. M., Grandits, G. A., Fosdick, L., Darif, M., & Potter, J. D. (1994). Statistical analysis of proliferative index data in clinical trials. Statistics in Medicine, 13(16), 1619-1634.