On Causal Inferences for Personalized Medicine: How Hidden Causal Assumptions Led to Erroneous Causal Claims About the D-Value

Abstract

Personalized medicine asks if a new treatment will help a particular patient, rather than if it improves the average response in a population. Without a causal model to distinguish these questions, interpretational mistakes arise. These mistakes are seen in an article by Demidenko that recommends the “D-value,” which is the probability that a randomly chosen person from the new-treatment group has a higher value for the outcome than a randomly chosen person from the control-treatment group. The abstract states “The D-value has a clear interpretation as the proportion of patients who get worse after the treatment” with similar assertions appearing later. We show these statements are incorrect because they require assumptions about the potential outcomes which are neither testable in randomized experiments nor plausible in general. The D-value will not equal the proportion of patients who get worse after treatment if (as expected) those outcomes are correlated. Independence of potential outcomes is unrealistic and eliminates any personalized treatment effects; with dependence, the D-value can even imply treatment is better than control even though most patients are harmed by the treatment. Thus, D-values are misleading for personalized medicine. To prevent misunderstandings, we advise incorporating causal models into basic statistics education.