Estimation of cancer drug potencies and relative potencies from in vitro data.

A method is proposed for the estimation of drug or toxicity potencies using in vitro data. A typical experiment in cancer research is presented where cells from a tumor-derived cell line were deposited as fixed volumes in 12-well cell culture plates. After waiting for 72 hours (for further growth), the wells were exposed to different concentrations of a drug and, at the end of the experiment, the numbers of surviving cells were counted. In this article, the "standard model" is extended to take explicit account of the error structure generated by the two experimental stages, namely, the cell deposition stage (and growth, prior to challenging by drug) and the cell counting stage (by hemacytometer) that are fundamental to the design but have usually been ignored in the modeling process. A simulation study illustrates substantial gains in efficiency in the estimation of the median effective dose.