From evidence-based medicine to personalized medicine, with particular emphasis on drug-safety monitoring

Summary Nowadays, guidelines are derived from the findings of randomized controlled therapeutic trials. However, an overall significant P value does not exclude that some patients may be harmed by or will not respond to the therapeutic agent being studied. Trials in patients with a low risk of events and/or a limited chance of providing significant differences in therapeutic effects require a large patient population to demonstrate a beneficial effect. Composite efficacy endpoints are often employed to obviate the need for a large patient population when low rates of events or limited therapeutic efficacy are anticipated. Results of randomized controlled therapeutic trials are commonly expressed in terms of relative risk reduction, whereas absolute risk reduction allows the calculation of the “number needed to treat” to prevent an adverse outcome. The number needed to treat is a far more clinically relevant variable than relative risk reduction. The clinician's mission is to match treatment to patient with the goal of achieving optimal therapeutic response. Drug-safety monitoring is also of major importance to avoid exposing patients to irreversible adverse effects. Unfortunately, drug-safety monitoring is often overlooked in routine clinical practice. Finally, the lack of long-term therapeutic data (> 5–10 years) is an unsolved dilemma, as most trials are limited to a duration of a few months or years.