The greater reliability of randomised controlled trials (RCTs) over non-randomised studies to objectively assess efficacy and/or safety of new therapeutic interventions is one of the main paradigms which sustains the evidence-based decision process in clinical practice. This assumption is primarily based on the hypothesis that randomisation, and particularly blinding procedure, drastically reduces the potential bias related to the preferences of patients and physicians. However, from non-randomised studies to double-blind, placebo-controlled RCTs, the preferences of patients and physicians can impact the evaluation of treatment effectiveness. Both internal validity and external validity of RCTs are impacted by various biases related to patient and physician preferences. Thus, influence of patient and physician expectations on trial outcomes might be much less trivial than expected, both in open-label and double-blind, placebo-controlled, randomised trials. Accordingly, it might be interesting to systematically collect information about patient preferences before randomisation, using dedicated questionnaires, in order to be able to evaluate the impact of non-preferred allocation on trial results.