Pascal's uncertainty principle: Managing drug–drug interactions when the risks are unclear

Therapeutic decision-making (TDM) often occurs under conditions of scientific uncertainty, including decisions on how to manage the majority of drug–drug interactions (DDIs). The existence of many DDIs is not firmly established, and there is an unfortunate tendency to make decisions based on the binary assessment of whether or not a particular DDI is real, rather than taking a more probabilistic and holistic approach to TDM. There also seems to be an undue fear of making a Type I error (assuming the DDI is real when it is not) while ignoring the often much greater risk of a Type II error (assuming the DDI is not real, when it is). Thus, a more rational TDM process for such DDIs is needed. In his famous “Wager,” philosopher-mathematician Blaise Pascal made a probabilistic argument for believing in God. Instead of considering probability in isolation, Pascal linked the probability of God's existence with the severity of the outcome (an eternity in Hell for non-believers) and also added a third factor—the ease with which the risk can be avoided. We propose a novel paradigm for TDM that uses all three of Pascal's steps: probability, severity, and avoidability. We present several specific DDI examples to demonstrate how Pascal's Uncertainty Principle can help pharmacists make clinical management decisions for these DDIs. We suggest that this process be called “Pascal's Uncertainty Principle” rather than “Pascal's Wager,” because it can be used to make rational decisions in the presence of uncertainty in many non-theological situations. This process reinforces the value of philosophical training for pharmacy students.