Blood transfusions: good or bad?

C onfounding by indication is a serious potential problem in clinical observational research and can easily lead to unjustified conclusions, as has also been described previously. In transfusion medicine such a conclusion could be “blood transfusions kill,” since patients receiving more transfusions are almost invariably more likely to die. Even though most would agree that blood transfusions save lives, this erroneous conclusion did find its way into the literature. Although this example might seem overly obvious, confounding by indication can be indirect and much more subtle and difficult to detect. It is therefore of the utmost importance to thoroughly understand the nature of confounding by indication, to be able to recognize it and avoid unjustified conclusions. We introduce the problem of confounding by indication with examples from clinical transfusion research and provide a general explanation to help identify this form of bias in the literature and in the every day clinical research settings (for guidelines on detection and handling, see Table 1).