Causal Insights from Failure: Post-marketing Risk Assessment of Drugs as a Way to Uncover Causal Mechanisms

Abstract

In order to make predictions about potential harms and benefits of treatments for the single patient, pharmacology needs to gain deep causal knowledge. That is, one needs to understand the causal mechanism underlying a certain outcome. Here, we base our argument on a particular philosophical framework, causal dispositionalism, which urges that causes should be understood as complex, intrinsic, tendential and context-sensitive. Applied to pharmacology, dispositionalism suggests that it is by digging into contextual influence, and not by eliminating it, that we can learn more about the how and why the intervention does its causal work. When a treatment fails to give the expected outcome, therefore, it offers an opportunity to investigate the local context of failure and identify possible interferers. Potentially, this helps uncovering more of the causal nexus by which the outcome is produced. Both pre-clinical research and clinical experimentation alone are poorly fit for uncovering causal mechanisms through failure, since they are based on screening off, or disregard, of interferers. This leaves the post-marketing drug monitoring as the best scenario for systematically generating mechanistic hypotheses about a treatment through studying instances of causal failure of treatment in individuals. We suggest an integrated framework in which post market monitoring, through the study of treatment failure, feeds pre-clinical and clinical research with mechanistic hypothesis.