Dose-response curves - in which the effect of varying the concentration of a chemical compound on the activity of a biochemical assay is measured - are widely analyzed to determine IC50 values that quantify the potency of the compound. National Center for Advancing Translational Sciences (NCATS) guidelines specify that readouts should be normalized by the controls before fitting the curves, but that the control data are not used in fitting. Here, we introduce a fitting procedure that includes the control data in the fitting. Simulations indicate that the proposed procedure provides more precise estimates of parameters compared to previously recommended procedures. Analysis of experimental datasets suggest that the proposed procedure provides a lower asymptotic standard error (ASE) for estimated parameters. We also describe an outlier detection method that appears to determine parameters more accurately and precisely.

Inclusion of control data in fitting to dose-response curves

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ACS Fall 2022

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