Clinical Performance – The demonstration of clinical performance under the IVDR
With the entry into force of Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR), manufacturers are obliged to demonstrate not only the analytical performance of their products, but also – where applicable – their clinical performance. This proof is a central component of the technical documentation and the basis for the Clinical Performance Report (CPR) and the performance evaluation.
Overview and definition of clinical performance
According to IVDR, Article 2 (39), the performance of a device describes its ability to fulfil the intended purpose stated by the manufacturer. This performance includes:
- Analytical performance (e.g. sensitivity, specificity at analytical level)
- Clinical performance, where applicable
Further details on “analytical performance” can be found here.
The IVDR defines “clinical performance” as the ability of a device to provide reliable results that are clearly related to a specific clinical condition or physiological or pathological process. The decisive factor here is that this connection applies to the intended target group and the intended users.
According to IVDR Annex XIII Part A 1.2.3, the manufacturer must demonstrate the clinical performance of a device unless there is a valid justification for non-application. The evidence may be based on one or more of the following sources:
- Clinical performance studies
- Peer-reviewed scientific literature
- Published experience from routine diagnostic practice (e.g. databases such as BfArM, FDA MAUDE)
Clinical performance studies may only be omitted if there are valid reasons to use other reliable sources of clinical performance data instead. Data on equivalent or similar products may also be used if they are relevant.
Evidence and documentation of clinical performance is provided in the Clinical Performance Report (CPR).
Structured evidence: LSP & LSR
If no clinical performance study is required or feasible, literature data must be used systematically. The following documents are usually created for this purpose:
- Literature Search Protocol (LSP)
- Literature Search Report (LSR)
The LSP describes and documents the entire literature search process: from the definition of search terms, search details and evaluation criteria to the screening of abstracts and full texts and the final decision on which publications to include or exclude.
The LSR summarises the implementation and results of this search. It contains, among other things, the objectives, the scope of the search, the methodology used (e.g. PRISMA, PICO), the databases used, the selection criteria, the selection process and the final list of relevant literature.
Finally, the CPR evaluates the content of the relevant articles identified, interprets the results and presents them in a coherent report. In addition, it links all available sources, critically evaluates them and provides the official rationale why the product demonstrates clinical performance according to IVDR.
Relevant performance parameters
The clinical performance of a device can be demonstrated and evaluated according to IVDR Annex I 9.1(b) and the MDCG 2022-2 Guidance using various criteria applicable to the device, including (but not limited to):
- Diagnostic (clinical) sensitivity: sensitivity, detection rate of positive cases
- Diagnostic (clinical) specificity: accuracy, exclusion rate of negative cases
- Positive predictive value (PPV): Probability that a positive test result is correct
- Negative predictive value (NPV): Probability that a negative test result is correct
- Likelihood ratio: ratio of how much a test result changes the probability of the presence or absence of a disease
- Odds ratio: ratio between event occurrences in different groups
- Usability: user-friendliness/user interface
The key figures must fit the intended purpose in a comprehensible manner and come from valid sources.
Differentiation from analytical sensitivity/specificity
In contrast to analytical sensitivity and specificity, which evaluate the technical accuracy of a test in measuring an analyte, clinical performance focuses on the actual informative value in a diagnostic context: Does the test actually recognise sick people correctly (diagnostic sensitivity)? Does it correctly exclude healthy individuals (diagnostic specificity)?
Clinical performance therefore describes how well the test works in a real clinical setting – regardless of how precise the measurement was in the laboratory.
Does clinical performance apply to every IVD?
No. The need to demonstrate clinical performance must be assessed on a product-by-product basis. The MDCG 2022-2 “Guidance on general principles of clinical evidence for In Vitro Diagnostic medical devices (IVDs)” specifies that clinical performance data is not expected for certain products. Examples:
- Specimen containers, microscopy slides or some general reagents
- Calibrators and controls that are usually evaluated in the context of the complete test system and not in isolation
In such cases – and only if justified – a Clinical Performance Report is not required.
Important: even if no clinical performance evaluation is required for a product, the other components of the performance evaluation (e.g. analytical performance, scientific validity) must still be carried out unless there is also a justified exception.
Special challenges: Near Patient Testing (NPT)
For point-of-care devices, including self-tests, the range of use situations must be considered:
- Professional use
- Home use
- Different target groups
- Different clinical indications
The clinical performance data must cover all realistic scenarios – ideally through specifically designed studies or extensive literature data.
In addition, aspects such as user-friendliness, robustness under variable conditions, correct interpretation of results, necessary training and safety aspects should be included in the assessment, as they can significantly influence the actual clinical performance in the near-patient setting.
The clinical performance of an IVD is a central component of product safety and performance under the IVDR. Manufacturers must make a differentiated assessment:
- When is clinical performance data necessary?
- Which sources are permissible and reliable?
- How do I prove suitability for the intended purpose – even without a clinical study?
Only a carefully prepared Clinical Performance Report (CPR) – based on studies, literature and/or empirical data – can provide clear regulatory proof that a product fulfils its diagnostic purpose in everyday clinical practice.
seleon can support you in the planning and preparation of an IVDR-compliant performance evaluation!
Please note that all details and listings do not claim to be complete, are without guarantee and are for information purposes only.
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