To perform performance evaluation within the framework of risk management of in vitro diagnostic devices based on IVDR 2017/746, it is important to provide sufficient clinical evidence.As defined in IVDR, performance evaluation is the assessment and analysis of data to establish or verify the scientific validity, the analytical and where applicable the clinical performance of the device under evaluation as per Article 2.
It is an important aspect of IVDR as it ensures the device under evaluation’s safety and effectiveness. As per Article 56 (1) of IVDR it is expected from the manufacturer to define and justify the level of clinical evidence necessary for performance evaluation for the device under evaluation. MDCG 2022-2 (Guidance on general principles of clinical evidence for In Vitro Diagnostic medical devices (IVDs)), provides further light to the clinical evidence required for IVD devices on showing compliance to the relevant General Safety and Performance Requirements through performance evaluation process. It should be noted that risk management process is strongly intertwined with performance evaluation process as per MDCG 2022-2 and IVDR 2017/746. Clinical evidence should be aligned and addressed with clinical risks present for the device.
The performance evaluation process starts with intended use. All activities to verify and validate the performance of the device are determined by each clinical benefits and intended use as defined in the instruction for use. With the introduction of IVDR 2017/746 providing sufficient clinical evidence through performance evaluation process for the demonstration of compliance with GSPRs became more important. It is required to be planned, documented and justified with the frame work of performance evaluation plan as per Annex XIII Part A.
As it has been described in IVDR Annex XIII Part A Performance evaluation should follow methodological procedures for the demonstration of scientific validity, analytical performance, clinical performance for the device under evalution.
As the initial step, scientific validity of the device under evaluation should be established. The manufacturer should create the link between the analyte and clinical condition or physiological state as defined Article 2(38) of IVDR. To create that link systematic literature search and review available to the device should be performed using appropriate appraisal techniques to establish the safety and the performance of the device. In order to demonstrate Scientific Validity of the device;
· Information on scientific validity of the devices measuring the same analyte or marker
· Peer-reviewed literature
· Consensus documents / expert opinions
· Results from proof-of-concept studies
· Results from clinical performance studies
Can be used. For well-established assays the description of guidelines or published literature might be sufficient whereas for newly developed novel assays if the existing published evidence is limited a gap analysis should be performed and manufacturer might need to create more evidence through proof-of-concept studies and/or clinical performance studies.
The following step of the data gathering for performance evaluation is the establishment of Analytical Performance of the device under evaluation. As per Article 2(40) of IVDR and MDCG 2022-2 analytical performance should focus on showing the IVD device reliably, accurately and consistently measures and/or detects an analyte(s) through analytical performance studies. When there is a need for clinical performance study to be conducted, first it is expected that analytical performance should be demonstrated taking into account the state of the art.
The third step of clinical evidence gathering is clinical performance of the device under evaluation. It is expected from manufacturer to demonstrate clinical performance of the IVD for performance evaluation through;
· Clinical performance studies
· Scientific peer-reviewed literature
· Published experience gained by routine diagnostic testing.
The necessity for clinical performance studies is dependent on the intended purpose and clinical claims of the device as well as the extend of analytical performance and scientific validity demonstrated for the device. For the devices measuring analytes that are associated with a clinical condition that have a medical decision point clinical performance study is mostly required. One of the important roles of the clinical performance studies is to confirm device performance when it cannot be demonstrated by analytical performance studies, literature review and previous experience gained by routine diagnosing testing.
As the data gathering for scientific validity, analytical and clinical performance to provide clinical evidence for performance evaluation is completed the results should be analyzed and concluded for the device under evaluation for performance and safety considering benefit / risk analysis and the state of the art in Performance Evaluation Report as per Section 1.3.2 of Part A of Annex XIII.
