An adverse drug reaction differs from an adverse event in that it implies a suspected causal relationship between the medicinal product and the observed harm. While adverse events encompass all untoward medical occurrences temporally associated with drug use regardless of causality, adverse drug reactions represent the subset of events where evidence supports a reasonable possibility that the product contributed to or caused the effect. This distinction has significant regulatory implications, as adverse drug reactions trigger different reporting requirements and inform the product's characterized safety profile.

For premarketing clinical trials of investigational products, regulatory guidance defines an adverse drug reaction as any adverse event for which there is a reasonable possibility of a causal relationship with the medicinal product. This determination considers factors such as temporal relationship, known pharmacological properties of the product, biological plausibility, and the results of dechallenge or rechallenge when applicable. For marketed products, the definition expands to include adverse events occurring at any dose used in medical practice, including overdose, off-label use, and medication errors.

The aggregate of adverse drug reactions identified during clinical development and post-marketing surveillance constitutes the product's known safety profile, which forms the basis for labeling and prescribing information. Expected adverse drug reactions are those already identified in the reference safety information, while unexpected reactions represent new information that may require expedited regulatory reporting. Understanding the distinction between adverse events and adverse drug reactions is essential for clinical research professionals involved in safety data collection, assessment, and reporting.