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Statistical analysis of proliferative index data in clinical trials
Author(s) -
Grambsch Patricia,
Louis Thomas A.,
Bostick Roberd M.,
Grandits Greg A.,
Fosdick Lisa,
Darif Mohamed,
Potter John D.
Publication year - 1994
Publication title -
statistics in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.996
H-Index - 183
eISSN - 1097-0258
pISSN - 0277-6715
DOI - 10.1002/sim.4780131603
Subject(s) - covariate , statistics , clinical trial , type i and type ii errors , context (archaeology) , random effects model , surrogate endpoint , statistic , ancillary statistic , clinical endpoint , medicine , statistical model , computer science , statistical hypothesis testing , mathematics , test statistic , biology , meta analysis , paleontology
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.