Figure 1 : Average benefit–risk of drugs as a function of treatment scenario.

From: Bridging the efficacy–effectiveness gap: a regulator's perspective on addressing variability of drug response

Figure 1

a | In the context of regulatory clinical trials (left-hand side), variability in drug response is deliberately kept to a minimum by enforced treatment conditions and narrow selection criteria, which aim to restrict the patient population to high-responders and good-toleraters. Criteria for treatment eligibility and treatment scenarios are usually less constrained in the authorized drug label (middle), and even less so after the drug comes to market and is partly prescribed and taken outside the label scenario (different populations, doses, patients with contraindications and comorbidities, poor adherence, and so on; right-hand side). As variability in drug response increases from left to right (red line), average benefit–risk deteriorates (blue line), giving rise to the efficacy–effectiveness gap. b | The deterioration in average benefit–risk is a result of the diminishing responsiveness to the beneficial effects (red line) and the increasing susceptibility to adverse drug effects (blue line), as more and different patient strata are added. Note that responsiveness to beneficial drug effects or susceptibility to adverse drug effects are not merely determined genetically but also by environmental and behavioural factors (for example, inappropriate prescribing or poor patient adherence to treatment regimens).