With the implementation of the European Union (EU) In Vitro Diagnostic Devices Regulations (IVDR) 2017/746, the Performance Evaluation Report (PER) has changed dynamically in terms of its requirements and approach.
The PER is built based on the three pillars of data demonstration: the Scientific Validity Report (SVR), Analytical Performance Report (APR), and Clinical Performance Report (CPR). The SVR highlights the association of the analyte with the clinical condition or physiological state; the APR is required to demonstrate the IVD’s capability to measure and detect the analyte/s; and the CPR demonstrates the ability of the IVD to yield results for the targeted patient population and/or users’ basis the clinical performance study.
Article 2 of EU IVDR 2017/746 describes the clinical performance 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.” As the CPR provides a comprehensive and evidence-based analysis of IVDs, it is potentially a key point in determining the safety/efficacy of the IVDs and meets Regulatory requirements. Annex XIII outlines detailed requirements for drawing up the CPR.
Now that we have established a basic understanding of CPR, let’s look at some key practices that can be used to develop it. They are as follows:
- Developing a Clear and Comprehensive Study Protocol: The key here is to establish a clear and concise Clinical Investigation Plan (CIP) and then ensure appropriate implementation of the same. The document should cover the objectives and the analysis (statistical method to be used) for the clinical investigation plan that will be included in the CPR. As data analysis will further act as the backbone of the CPR, it is of utmost importance that you begin correctly!
- Using Appropriate Data Sources: Clinical performance can be demonstrated via (in combination or individually) clinical performance studies, scientific peer-reviewed literature, and published experience gathered through routine diagnostic testing. Performing a clinical performance study is mandatory unless an appropriate justification is provided for relying on other sources for the clinical performance data. However, when it comes to novel and innovative devices, collecting clinical data can be challenging, as they may not have a well-established clinical use. In these cases, it is essential to gather data from clinical trials. Conduct a comprehensive literature review to identify the existing clinical data on the device and similar devices. This can help inform the study design and identify gaps in the available evidence. The data generated should be based on a robust, systematic, and unbiased literature review.
- Considering the Intended Use of IVD/s: When deducing CPR, the trivial but often overlooked aspect is considering the intended use of the device. The intended use will further form the basis for developing the study design and data points such as factors like diagnostic sensitivity, diagnostic specificity, positive predictive value, negative predictive value, likelihood ratio, and expected values in normal and affected populations in the CPR. The data points should be measurable, well-defined, and aligned with the study objectives.
- Carrying Out Regular Updation of the CPR: The frequent updation of the CPR has also become an obligatory step in the Post-market Surveillance (PMS) system. Regularly reviewing and updating the CPR is quite essential to ensure that the data provided in it is relevant and up to This may include incorporating new data or changing the study design in response to new information.
To develop a robust CPR, it is important to follow best practices, as discussed above, such as developing a clear and comprehensive study protocol, using appropriate data sources, considering the intended use of IVDs, and regularly updating the CPR. The best practices will help ensure that the CPR provides a comprehensive and accurate analysis of the IVD’s clinical performance, which can help meet Regulatory requirements and ensure patient safety.
With over a decade of experience, Freyr has built a robust model for tackling such crucial aspects of the Regulatory approval process. Do you require any support on PERs? Contact us today!