Abstract
Evidence-based medicine (EBM) has created a revolutionary system for disseminating
a scientific method. However, the scientific rigor of early EBM did not demonstrate
any concern for ethics in the management of venous thromboembolism (VTE) and atrial
fibrillation (AF). We critically reviewed whether EBM and ethical principles have
always converged, focusing on the development and use of anticoagulants, by analyzing
key trials in the treatment and prevention of those conditions. Moreover, we aimed
to explore whether methodological rigor has sometimes overshadowed clinical ethics,
particularly in the context of placebo-controlled trials. In our opinion, even if
randomized clinical trials (RCTs) are considered the first step in the hierarchy of
EBM, several of these appear unjustified, as observational studies had already indicated
that anticoagulants (heparins and anti-vitamin K drugs [VKA]) were considered effective
in the treatment and prevention of thrombotic diseases, such as VTE and AF. The use
of a placebo was often unethical. This has caused unjustified mortality and morbidity
to many people when a placebo has been used as a control. Even the methodology in
favor of the non-inferiority margin is questionable, as it is considered satisfactory
to maintain at least half of the efficacy of the current drug. In other words, a bonus
for the new medicines seems to be always generous, and in the future, biocreep phenomenon is destined to be dangerous. The belief that only RCTs, even if of paramount
importance, produce trustworthy results and that observational studies are misleading
can lead to a disadvantage in patient care, clinical investigation, and the education
of health care professionals (visual abstract).
Keywords
venous thromboembolism - atrial fibrillation - randomized controlled trials - observational
studies - non-inferiority trials
