Translating the dose response into risk and benefit

Abstract

When choosing a medicine two aspects determine the balance between benefit and harm (risk–benefit), matching the medicine to the individual and the choice of dose. Knowing the relationship between dose and response allows a calculation of the dose that causes 50% of the maximal effect, the ED50. Rational drug dosing depends on defining the ratio of the dose to the ED50. The ED50 of each drug has two scales, whether the effect measured is for efficacy, or safety. Quantifying efficacy is comparatively straightforward. A fall in blood pressure, combined with a statistical and clinically significant reduction in cardiovascular events, might justify the efficacy of an antihypertensive. Measuring a drug's effect on safety is more complex, as this is so often a subjective assessment of a collection of adverse events. Though a science-based therapeutic window defined from in vitro efficacy and safety dose response curves is reassuring, this review discusses how to translate this into dose-dependent risk–benefit based on clinical trial data. Some of the limitations of our knowledge about the choice of dose that optimizes an individual's risk–benefit, or whether no drug is a better option, are discussed. It is important to define these limitations when educating the consumer/patient about the clinical pharmacology that justifies their treatment dose options.