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554 – Drug Combination Studies: From Discovery to Clinical

Experimental Design for In Vitro Drug Combination Studies

Sponsor: Biopharmaceutical Section
Keywords: drug combinations, experimental design, cell viability, synergy

Huaihou Chen

Columbia University

Gregory Hather

Millennium: The Takeda Oncology Company

Ray Liu

Millennium: The Takeda Oncology Company

In vitro drug combination studies typically involve a large number of wells with various concentrations of two drugs added together. To gain the most information from an experiment, what should the drug concentrations be? Here, we consider the case where the single drug response curves are known beforehand, but no previous data is available from the combination. We consider several designs, including C and D-optimal designs, and a factorial design. We evaluate these designs based on the expected variance of the synergy score for a large set of in vitro experiments performed at Millennium. Based on the results, we were able to identify which design was the most efficient and robust.

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