Precision medicine has transformed the landscape of cancer treatment by shifting from histology-based to biomarker-driven therapies and enabling targeted interventions within molecularly defined patient populations. This paradigm shift has incorporated adaptive clinical trial designs and companion diagnostic (CDx) devices for participant selection, treatment assignment and response monitoring. However, CDx devices present distinct regulatory and ethical challenges. Institutional Review Boards (IRBs) are pivotal in systematically identifying CDx utilisation within clinical protocols, evaluating device-associated risks and ensuring adherence to regulatory compliance, ultimately safeguarding the rights and welfare of trial participants.