AJP - Regulatory, Integrative and Comparative Physiology, Vol 240, Issue 5 259-R265, Copyright © 1981 by American Physiological Society
Optimized blood sampling protocols and sequential design of kinetic experiments
J. J. DiStefano 3rd
Design of optimal blood sampling protocols for kinetic experiments is
discussed and evaluated, with the aid of several examples--including an
endocrine system case study. The criterion of optimality is maximum
accuracy of kinetic model parameter estimates. A simple example illustrates
why a sequential experiment approach is required; optimal designs depend on
the true model parameter values, knowledge of which is usually a primary
objective of the experiment, as well as the structure of the model and the
measurement error (e.g., assay) variance. The methodology is evaluated from
the results of a series of experiments designed to quantify the dynamics of
distribution and metabolism of three iodothyronines, T3, T4, and
reverse-T3. This analysis indicates that 1) the sequential optimal
experiment approach can be effective and efficient in the laboratory, 2) it
works in the presence of reasonably controlled biological variation,
producing sufficiently robust sampling protocols, and 3) optimal designs
can be highly efficient designs in practice, requiring for maximum accuracy
a number of blood samples equal to the number of independently adjustable
model parameters, no more or less.
