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THE STATISTICAL ANALYSIS OF DISCRETE AND CONTINUOUS OUTCOMES USING DESIRABILITY FUNCTIONS.
Citation:
COFFEY, T., C. GENNINGS, AND V. C. MOSER. THE STATISTICAL ANALYSIS OF DISCRETE AND CONTINUOUS OUTCOMES USING DESIRABILITY FUNCTIONS. REGULATORY TOXICOLOGY AND PHARMACOLOGY. Elsevier Science Ltd, New York, NY, 48:51-58, (2007).
Impact/Purpose:
To describe a method for deriving a composite score for a dose-response experiment that combines information from discrete and continuous outcomes through the use of desirability functions
Description:
Multiple types of outcomes are sometimes measured on each animal in toxicology dose-response experiments. In this paper we introduce a method of deriving a composite score for a dose-response experiment that combines information from discrete and continuous outcomes through the use of desirability functions. Desirability functions are commonly used in engineering to optimize multiple responses resulting from a manufacturing process, but they have not been applied to toxicology. These functions transform observed responses of any type to a 0-to-1 unitless scale, where smaller scores indicate less desirable responses (e.g., increased toxicity). The geometric mean is used to combine the scores and then a statistical model can be fit to the single dose-response curve of the overall score. Using data from five outcomes (a combination of ordinal, count, and continuous responses) from a recent neurotoxicity experiment, we demonstrate the use of desirability functions to derive a composite score. We analyze the overall score using a nonlinear exponential model with a threshold parameter. In this example, the threshold parameter was statistically significant and its estimate was less than the lowest dose. Compared to the vehicle control, the lower overall scores at this dose group were due to lower levels of brain and blood cholinesterase (90% and 82% of control, respectively) whereas other endpoints were not altered, thus demonstrating the sensitivity of the desirability function to detect low levels of toxicity in a small number of outcomes.