Understanding Clinical Performance Reports(CPR) under the IVDR: A Guide for IVD Manufacturers

‘Clinical performance’ is not a novel concept in the transition from the IVDD to the IVDR; however, the applicability of clinical performance and content of the Clinical Performance Report (CPR) appear to be some of the most misunderstood requirements of the IVDR.  Due to the lack of specific, sufficiently detailed guidance, the content of the CPR under the IVDR, and inconsistency in the expectations of Notified Bodies during performance evaluation review, ‘clinical performance’ is somewhat of a mystery.

Importance of demonstrating clinical performance parameters for IVDs under IVDR

‘Clinical performance’ is defined under the IVDR as ‘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.’ Furthermore, GSPR 9.1(b) of the IVDR lists the following specific clinical performance parameters:

• • Diagnostic sensitivity
  • Diagnostic specificity
  • Positive predictive value (PPV)
  • Negative predictive value (NPV)
  • Likelihood ratio
  • Expected value in normal and affected populations

Under Section 1.2.3, Annex XIII of the IVDR, the clinical performance of an IVD in relation to all of the above parameters, shall be demonstrated in the CPR, unless any omission can be justified as not applicable. For Class A devices, and calibrators/control materials, as they do not possess any of these specific clinical performance characteristics based upon their intended purpose, it is relatively straight forward to justify such omissions. However, most manufacturers believe that this is therefore a sufficient justification for the non-applicability of a CPR, forgetting that the first sentence of Section 1.2.3, Annex XIII of the IVDR states that “The manufacturer shall demonstrate the clinical performance of the device in relation to all of the parameters described in point (b) of Section 9.1 of Annex I, unless any omission can be justified as not applicable.” In other words, these specific clinical performance parameters are only part of the scope of clinical performance.

Sources for demonstrating clinical performance parameters for IVDs under IVDR.

The IVDR also establishes that clinical performance of a device shall be based on one or a combination of the following sources:

• • Clinical performance studies
  • Scientific peer-reviewed literature (refer to our article on best practices for performance evaluation literature searches here)
  • Published experience gained by routine diagnostic testing

Clinical performance studies are typically expected for IVDs measuring analytes/markers that have critical medical decision points and are certainly an expectation of Class D IVDs that fall within the scope of the Common Specifications in Commission Implementing Regulation (EU) 2022/1107, as indicated. However, it is also important to remember that the IVDR establishes a definition for ‘clinical evidence’ which means ‘clinical data and performance evaluation results, pertaining to a device of a sufficient amount and quality to allow a qualified assessment of whether the device is safe and achieves the intended clinical benefit(s), when used as intended by the manufacturer.’

As is the case for scientific validity (refer to our article on establishing scientific validity here), literature searches should be performed following an established methodology supported by both a literature search protocol and report, both annexes to the Performance Evaluation Report (PER).

References to ‘clinical data’ in IVDR and its relation to PMS and PMPF

While no definition for ‘clinical data’ is established under the IVDR, the following important references to ‘clinical data’ exist in the regulation:

• • Section 4.11, Annex VII: “…clinical data from post-market surveillance and PMPF activities…”
  • Section 2.4, Annex XIV: “Existing clinical data, in particular:
    • from relevant peer-reviewed scientific literature and available consensus expert opinions or positions from relevant professional associations relating to the safety, performance, clinical benefits to patients, design characteristics, scientific validity, clinical performance and intended purpose of the device and/or of equivalent or similar devices;
    • other relevant clinical data available relating to the safety, scientific validity, clinical performance, clinical benefits to patients, design characteristics and intended purpose of similar devices, including details of their similarities and differences with the device in question.”

Post-market surveillance (PMS) is mandatory for all IVDs under the IVDR (and is also applicable to all IVDD ‘legacy’ devices per the IVDR transitional provisions); therefore manufacturers of ‘legacy’ devices CE marked under the IVDD will have clinical data from PMS available for the devices which should be described and assessed within the scope of the CPR. Additionally, while many IVD manufacturers applied MEDDEV 2.12/2 rev. 2 to justify the non-applicability of PMPF studies under the IVDD, it is important to remember that under the IVDR there are both general and specific PMPF procedures/methods. In many cases, given the strong overlap with PMS activities, it will be challenging for IVD manufacturer to justify the non-applicability of general PMPF procedures/methods.

Incorporating ‘other’ clinical data in the CPR under IVDR

Therefore, while not specifically called out among the three clinical data sources listed under Section 1.2.3, Annex XIII, ‘other’ clinical data such as PMS/PMPF data generated by the manufacturer which includes sales/usage data, customer feedback/complaints, reports of serious incidents/adverse events, field safety corrective actions (FSCA) or testing of clinical specimens that are not in the public domain, can be gathered and assessed in the CPR. For those manufacturers placing their devices for the first time on the EU market, for which the IVD has an established marketing history in non-EU markets, the post-market data on such devices should not be described as PMS data but instead as ‘clinical experience’ in the CPR. ‘Other’ clinical data to be described in the CPR is particularly of note for IVDD ‘legacy’ devices, as studies that do not meet the requirements of Annex XIII or BS ISO 20916:2019 (not harmonized under the IVDR) do not fulfill the ‘clinical performance studies’ data source described under the IVDR.

Importance of CPR in NB review and increased scrutiny with higher risk classification

Manufacturers should expect the CPR to be a strong area of focus during NB review as this is fundamental in demonstrating the clinical safety and performance of the device when used as intended by the manufacturer and goes to heart of demonstrating the clinical benefits (and risks) or the device. Furthermore, the level of scrutiny of the NB over the CPR increases substantially as the risk classification increases from Class B through Class D.

Learn more about CPR’s under the IVDR with MedEnvoy

If you have any additional questions regarding performance evaluation or require relevant training / consulting services, get in touch.

Explore similar topics

• • Best Practices for Conducting Literature Searches in IVDR Performance Evaluation
  • Understanding the Specific Evaluation Documentation Required for IVD Performance Under Article 56 of the IVDR
  • Planning Performance Evaluation Under the IVDR
  • Analytical Performance Characteristics for IVDs: What Manufacturers Need to Know