Assessing Causality of Adverse Drug Reactions: Global Introspection and Its Limitations

Abstract

In assessing the probability of drug causation in individual cases of suspected adverse drug reaction (ADR), global introspection represents the oldest and most popular strategy. The assessor attempts to consider each factor that could possibly affect the causal link between one or more administered drugs and a subsequently observed adverse event. He or she makes a mental list of these factors, weighs them according to some sense of their relative importance, and then makes a decision about the probability of drug causation. Unfortunately, considerable evidence exists to show that global introspection, even by experts, is neither reproducible, valid, nor accountable. A variety of complicating issues and questions concerning persons, drugs, and events are grouped into seven general categories to facilitate presentation. These complicating factors are then illustrated using a case of methyldopa-associated pancreatitis.