The Three Pillars of Clinical Evidence Under the IVDR

The IVDR raises the bar. Many in vitro diagnostic (IVD) medical device manufacturers still underestimate how significantly the IVDR (EU) 2017/746 has raised the bar for generating, documenting, and maintaining evidence of device performance compared with the former Directive 98/79/EC (IVDD).

Under the IVDD, most devices were self-certified. There was no independent scrutiny of the evidence behind most devices. IVDR changes that fundamentally: every device, regardless of class, now needs a documented, defensible performance evaluation — and for higher-risk devices, that means a structured, continuous, evidence-based process with formal reporting and lifecycle follow-up that must evolve with the device for as long as it is on the market.

Performance evaluation under the IVDR is built on three pillars, each of which must be substantiated separately:

· Scientific validity — the association of an analyte with a clinical condition or physiological state.

· Analytical performance — the ability of a device to correctly detect or measure a particular analyte.

· Clinical performance — the ability of a device to yield results that are correlated with a particular clinical condition or a physiological or pathological process or state, in accordance with the target population and intended user.

Together, these three pillars establish the clinical evidence base and ground the conformity assessment process. The depth of evidence required for each pillar depends on the device classification. Class D devices, which carry the highest risk, are subject to the most demanding requirements, while Class A devices face the least. Even lower-risk devices, however, must be supported by a genuine evidence base.

The three pillars are closely connected, build on one another, and must be addressed in the Performance Evaluation Plan (PEP) and critically analyzed in the Performance Evaluation Report (PER).

Performance evaluation is a continuous process. Performance evaluation is not a one-time exercise that you finalize and archive once CE mark is achieved. Under the IVDR, it must remain current throughout the lifetime of the device — a requirement that applies just as much to self-declared Class A devices as to those certified by a Notified Body — which in practice means:

• A living PER, not a static report. Every time new evidence emerges — from literature, post-market data, or a shift in the state of the art — the PER must be revisited. A PER that has not been updated since CE certification is itself a red flag to a Notified Body.
• Link to PMS and risk management, feeding back into the evidence base. Post-market performance follow-up (PMPF), as a systematic and proactive component of the post-market surveillance (PMS) system, exists specifically to generate real-world performance data that keeps the PER current and valid, while also feeding back into the risk management process to confirm that risk controls remain effective and to detect emerging risks on the basis of factual evidence. Without proper integration, the benefit-risk analysis may be incomplete.
• Traceability between intended purpose, performance claims, and evidence. Every statement in the intended purpose — every performance claim — needs a direct line back to specific evidence in the underlying scientific validity, analytical performance, and clinical performance documentation, as consolidated and critically analyzed in the PER. Notified Bodies increasingly probe this link directly: a claim without a clear traceable evidence source is treated as unsupported.

The challenges manufacturers are running into. A few recurring patterns:

• Data gaps for legacy devices. Many devices that were self-certified under the IVDD don't have evidence that meets the IVDR's higher bar, particularly for clinical performance.
• Internal resourcing. Many companies, especially smaller ones, don't have regulatory and clinical affairs teams sized for the scale of evidence generation the IVDR requires. This challenge is often compounded by a broader underestimation of just how extensive the requirements are.
• Timeline mismatch. Evidence generation across all three pillars takes longer than manufacturers expect. Scientific validity is often underestimated in scope, not just time — a poorly defined intended purpose can force a literature search to be repeated from scratch. For novel analytes lacking certified reference materials, analytical performance may be harder to establish through standard methods, sometimes requiring additional studies. If a dedicated clinical performance study is required, as is usually the case under the IVDR unless other clinical performance data can be justified, the process can take well over 12 months when factoring in ethics approval, protocol design, recruitment, and data collection.
• Notified Body capacity. With a limited number of designated Notified Bodies facing a substantial and growing pipeline of pending applications, and conformity assessment timelines averaging 12-18 months, manufacturers who apply late risk being caught in the backlog — with real risk to market access in the gap between expiring legal status and IVDR certification.

Worth watching. In December 2025, the EU Commission proposed amendments to MDR and IVDR aimed at easing the administrative burden — including fixed Notified Body assessment timelines, more flexible clinical evidence pathways, and a shift away from fixed five-year recertification toward continuous risk-based surveillance. However, the amendments have not yet been adopted into law.

The proposal still needs approval from the European Parliament and the Council through the EU's ordinary legislative procedure. Importantly, core safety, clinical evidence, or post-market surveillance requirements will not be reduced, but it may ease the administrative process for meeting them. For manufacturers navigating the IVDR today, building rigorous performance evaluation and PMS systems now is a strategy well worth pursuing — not waiting for simplifications that may or may not arrive.

Need support with your IVDR transition?

IVDR transition deadlines are approaching quickly, and navigating IVDR requirements is complex. At Aurevia, we guide manufacturers through every step — from device classification, clinical evidence, technical documentation, and Notified Body submission to quality management systems and post-market surveillance. Learn more

In case you missed it

In our previous article, we explored the ongoing IVDR transition, highlighting key regulatory deadlines, common compliance pitfalls, and practical considerations for IVD manufacturers navigating the changing regulatory landscape.

Read the article: The IVDR Transition Is Not Over: Key Deadlines and Common Pitfalls