The evolving role of disproportionality analysis in pharmacovigilance.

Introduction: From 2009 to 2015, the IMI PROTECT conducted rigorous studies addressing questions about optimal implementation and significance of disproportionality analyses, leading to the development of Good Signal Detection Practices. The ensuing period witnessed the independent exploration of research paths proposed by IMI PROTECT, accumulating valuable experience and insights that have yet to be seamlessly integrated.

Areas Covered: This state-of-the-art review integrates IMI PROTECT recommendations with recent acquisitions and evolving challenges. It deals with defining the object of study, disproportionality methods, subgrouping, masking, drug-drug interaction, duplication, expectedness, the debated use of disproportionality results as risk measures, integration with other types of data.

Expert Opinion: Despite the ongoing skepticism regarding the usefulness of disproportionality analyses and individual case safety reports, their ability to timely detect safety signals regarding rare and unpredictable adverse reactions remains unparalleled. Moreover, recent exploration into their potential for characterizing safety signals revealed valuable insights concerning potential risk factors and the patient's perspective. To fully realize their potential beyond hypothesis generation and achieve a comprehensive evidence synthesis with other kinds of data and studies, each with their unique limitations and contributions, we need to investigate methods for more transparently communicating disproportionality results and mapping and addressing pharmacovigilance biases.