[Challenges on off label medicine use].

p After the Second World War, the so-called pharmacological explosion took place, leading to major advances in the treatment of diseases that were once inevitably fatal or disabling. This pharmacological expansion contributed to the occurrence of catastrophic incidents, such as the phocomelia epidemic attributed to thalidomide. Since then, concerns about drug safety have contributed to the development and application of clinical and epidemiological methods to assess the benefits and potential risks of any type of therapeutic intervention, whether pharmacological or not.1 Indisputably, the administration of a medication aims to obtain a beneficial effect for those who take it. Nonetheless, it is important that the assumptions arising from the analysis of scientific evidence are not forgotten: firstly, some drugs do not have the desired efficacy, and secondly, regardless of their beneficial effects, every medication may produce undesired effects. When a drug is launched on the market, all the knowledge about it is based on pre-marketing studies: during the development of the molecule, experimental studies on its effects and toxicity are conducted in animals (pre-clinical studies). If no unacceptable toxic effects are observed, the first clinical trials in humans are conducted. These are termed phase I, II, and III studies, which investigate aspects of the pharmacokinetics, toxicity, and efficacy in humans. In clinical trials, several factors may interfere with the results, such as inclusion and exclusion criteria, sample sizes, and even ‘‘apparently ethical’’ criteria, which,