Beyond the guidance: clinical and performance evidence for IVDs

The Medical Device Coordination Group Document (MDCG) 2022-2 gave the industry something unique and valuable, clarifying expectations for clinical evidence under the In Vitro Diagnostic Regulation (IVDR). Titled Guidance on general principles of clinical evidence for In Vitro Diagnostic medical devices,¹ it laid out detailed principles around scientific validity, analytical performance, and clinical performance offering a structured foundation for manufacturers. However, guidance alone, regardless of how well-framed, cannot deliver the precise, context-driven evidence that IVDR demands.

In the early decades of modern diagnostics before reliable assays existed and systematic screening was established, contaminated blood products transmitted HIV and hepatitis to tens of thousands of patients with haemophilia and transfusion recipients across Europe leading to thousands of deaths. This travesty exposed the urgent need for reliable diagnostic screening and became one of the most sobering reminders of how essential timely, accurate testing is to public health.² While today’s regulatory landscape is far more structured, the underlying lesson remains unchanged: diagnostic evidence matters because real-world consequences are profound, and IVDR formalises this by requiring that performance claims are anchored in evidence that reflects clinical relevance and real-world use.

For regulatory affairs teams, diagnostic manufacturers, and clinical laboratory directors, translating guidance to evidence reveals a complex reality. It is often found in practice that the path to compliance is rarely linear but shaped by data limitations, operational constraints, and day-to-day realities of clinical environments. This article examines key tensions and offers a pragmatic view for manufacturers of in vitro diagnostics (IVDs) to align evidence generation with clinical relevance and regulatory expectations.