Estimating potency for the Emax-model without attaining maximal effects

Area of Science:

• Pharmacology
• Biostatistics

Background:

• The Emax model is widely used to link drug concentrations to effects.
• Concentration-effect relationships can deviate from linearity without reaching a maximum due to side effects.
• Estimating Emax model parameters (EC50, Emax) is imprecise when a maximum effect is not observed.

Purpose of the Study:

• To introduce a novel parameter (S0 = Emax/EC50) for characterizing drug potency.
• To provide an adequate measure of potency even when concentration-effect curves do not clearly reach a maximum.
• To address the imprecision in EC50 and Emax estimates in such scenarios.

Main Methods:

• Introduction of a new parameter, S0, defined as the ratio of Emax to EC50.
• Use of simulations to investigate the properties of the S0 parameter.
• Illustration using published examples of concentration-effect relationships.

Main Results:

• The S0 parameter adequately characterizes potency even without a clear maximum in the concentration-effect curve.
• Simulations demonstrate the utility and nature of the S0 parameter.
• Published examples validate the application of S0 in real-world scenarios.

Conclusions:

• The S0 parameter offers a robust solution for potency characterization when Emax model assumptions are not met.
• This approach enhances the precision of potency estimation in drug development.
• The S0 parameter provides valuable insights into concentration-effect dynamics, especially in the presence of limiting side effects.