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Detecting bliss synergy in in vivo combination studies with a tumor kinetic model
Authors:Wei Zhao  Paolo Vicini  Steven Novick  Judith Anderton  Gareth Davies  Gina DAngelo  Terrance O'Day  Binbing Yu  Jay Harper  Rajesh Narwal  Lorin Roskos  Harry Yang
Abstract:Linear models are generally reliable methods for analyzing tumor growth in vivo, with drug effectiveness being represented by the steepness of the regression slope. With immunotherapy, however, not all tumor growth follows a linear pattern, even after log transformation. Tumor kinetics models are mechanistic models that describe tumor proliferation and tumor killing macroscopically, through a set of differential equations. In drug combination studies, although an additional drug‐drug interaction term can be added to such models, however, the drug interactions suggested by tumor kinetics models cannot be translated directly into synergistic effects. We have developed a novel statistical approach that simultaneously models tumor growth in control, monotherapy, and combination therapy groups. This approach makes it possible to test for synergistic effects directly and to compare such effects among different studies.
Keywords:bliss independence  drug combination  tumor kinetics
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