A statistical model for in-vitro assessment of patient sensitivity to cytotoxic drugs.
Formation of colonies in semisolid medium is an assay used for the study of stem cell characteristics in hematopoietic and solid tumors. Previous experience with leukemia patients failed to show an association between the reduction in colony formation observed when patient blast cells were exposed to increased concentrations of an anticancer agent, and the subsequent patient response to the agent. By introducing a model that takes into account the possibility of a resistant subpopulation of clonogenic cells, the paper demonstrates that the null result was due to an inadequate summarization of the dose-response curve, and in fact a statistically and biologically significant association exists between one of the parameters of the model and patient response. The properties, implementation, and interpretation of the model are discussed.
Minkin
S
S
Division of Epidemiology and Statistics, Ontario Cancer Institute, Toronto, Canada.
D001699:Biometry; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D006801:Humans; D066298:In Vitro Techniques; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D016015:Logistic Models; D008954:Models, Biological; D015233:Models, Statistical; D009010:Monte Carlo Method; D012044:Regression Analysis; D014410:Tumor Stem Cell Assay / Q000706:statistics & numerical data*