Use of historical controls in time-adjusted trend tests for carcinogenicity
- Publication Type:
- Journal Article
- Biometrics, 1996, 52 (4), pp. 1478 - 1485
- Issue Date:
We develop a method for incorporating historical control information into time-adjusted tests for dose effects in carcinogenicity studies. After discretizing the time scale, we use a multinomial distribution to model the number of animals dying with tumor in each interval and specify a Dirichlet prior distribution on the control tumor death rates in each interval. Data from past studies are used to estimate the parameters characterizing the prior. A score test derived from the resulting Dirichlet-multinomial generalizes the test of Tarone (1982, Biometrics 38, 215 220) and reduces, in the limit, to the log-rank test in the case of a diffuse prior. The methodology is illustrated with data from a study of the fire retardant 2,2- Bis(bromomethyl)-1,3-propanediol.
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