Clinical Performance Reports (CPR) under the IVDR

What is a Clinical Performance Report (CPR)?

Clinical Performance, as per Article 2(41) of IVDR 2017/746, means the capacity of the device to produce findings in correlation with particular clinical conditions or physiological/pathological processes, as well as suitability for the intended user and patient group. After the performance characteristics of Analytical Performance have been demonstrated, the next step should be the Clinical Performance studies. Their purpose is to validate and demonstrate certain aspects of the performance of the device which cannot be evaluated with the help of laboratory evaluation, literature information, and normal diagnostic use.

According to EU In Vitro Diagnostic Medical Device Regulation (IVDR) [Regulation (EU) 2017/746], the CPR is an essential component of the more comprehensive Performance Evaluation Report (PER). The report contains information obtained from clinical performance studies, scientific references, and real world evidence, which proves that the device performs its intended function in the clinical environment.

Reference: Article 2(41), Article 56(1), Annex XIII Part A Section 1.3.2

Purpose of the Clinical Performance Report (CPR)

The CPR is an important document for:

• Providing evidence of clinical performance in support of the performance claim made about the IVD device.

• Providing validation of the intended use by providing quantifiable results of sensitivity, specificity, predictive values, negative predictive value, and likelihood ratios expected in the healthy and diseased populations.

• Showing evidence that the device fulfills the General Safety and Performance Requirements (GSPRs) outlined in Annex I of the IVDR.

The CPR can be considered as a document that provides the clinical rationale for determining whether the benefits of the device outweigh any associated risks.

Reference: Article 56(1), Annex I, Annex XIII Part A Section 1.3.2

What Makes a Clinical Performance Report (CPR) Mandatory Under the IVDR?

To ensure the safety and clinical reliability of the IVDs put on the EU market, the In Vitro Diagnostic Regulation (IVDR) has set some stringent conditions. A Clinical Performance Report (CPR) plays an important role in fulfilling these conditions, as it is the proof that a device works in the way it claims to work.

Reference: Article 5(3), Article 56(1), Annex XIII

Key Aspects of Safety, Performance, and Scientific Validity of Claims

The purpose of the CPR is to demonstrate that:

• The accuracy and reliability of the device are high enough to minimize the number of misdiagnoses.

• There is a scientific basis for the medical purpose of the device because there is a link between the analyte/biomarker and the clinical condition.

• In addition to being scientifically sound, the evidence about the device is clinically meaningful.

It means that all claims about the device are scientifically and clinically proven.

Reference: Article 56(1), MDCG 2022-2

Comparison with the Old Approach to IVDD

In accordance with the old In Vitro Diagnostic Directive 98/79/EC (IVDD), manufacturers possessed additional leeway and, in most instances, little need to present clinical evidence. In many cases, medical devices were able to obtain access to the market while having little information on their clinical performance, particularly when speaking of low risk and medium risk products.

When it comes to the IVDR, however, things have changed:

• CPR has become an obligatory part of the process of performance evaluation.

• Manufacturers should include in their CPR data obtained through clinical performance studies, scientific literature, and post market performance data.

• The CPR should be continually updated with post market performance data from Post Market Performance Follow up (PMPF).

Reference: Article 56(1), Annex XIII, MDCG 2022-2

This transition is a result of the EU's dedication to enhancing patient safety and reliability of data, among other things.

What Should Be Included in a Clinical Performance Report (CPR)?

A Clinical Performance Report (CPR), which is required by the IVDR, is not just a summary report. In fact, it is a report that provides evidence that an IVD device has clinical validity and reliability. 

The following should be included in a CPR:

1. Clinical Performance Study Description

The CPR should give a complete description of the clinical studies undertaken using the device. It should have:

• Objectives of the study

• Design and methodology used in the study

• Population studied

• Methods of testing and end points

• Data which shows the performance of the device in actual clinical practice

It helps to clarify the way in which data was collected and that the test was done under realistic conditions of device use.

2. Scientific Validity and Analytical Performance

In addition, the CPR should show that:

There is a scientific justification for the biomarker/analyte being tested and that it is related to a particular clinical condition.

There is adequate analytical performance of the device including accuracy, precision, reproducibility, detection limits and interference testing.

3. Statistical Analysis and Interpretation of Data

It is critical that the data contained within the CPR should be backed by proper statistical analysis. This normally consists of:

• Sensitivity, specificity, and predictive values

• Confidence intervals and errors

• Comparison to currently available tests and methods

• Rationale for acceptance criteria and levels

This will ensure that the claim of the device can withstand regulatory review based on evidence.

Reference: Annex XIII Part A Sections 1.2 and 1.3.2

What Is the Relationship between the CPR and the PEP and PER?

The CPR is not an independent document but rather a component of the broader framework for the performance evaluation procedure described under the IVDR. For this reason, it is essential to discuss its relationship to the Performance Evaluation Plan (PEP) and the Performance Evaluation Report (PER).

Integration within the Performance Evaluation Lifecycle

• Performance Evaluation Plan (PEP)

• This is where it all begins.

• It includes the methodology that the company plans to use to gather and evaluate data related to scientific validity, analytical performance, and clinical performance.

• This is the plan for gathering evidence that will be used for PER and CPR.

Performance Evaluation Report (PER)

• This is the main document that covers the whole process of the evaluation.

• It brings together all the evidence gathered according to the PEP, including literature review, clinical investigation, and post market information.

• In the PER, the CPR deals with the clinical performance aspect only.

Clinical Performance Report (CPR)

• A targeted report that puts emphasis on the clinical aspect of the performance evaluation.

• It proves the safety and effectiveness of the device from a clinical perspective.

• It is an attachment to or an essential part of the PER and ensures that the clinical information is clearly identifiable in accordance with Annex XIII of IVDR.

Reference: Article 56(1), Annex XIII Part A 1.2 – 1.3

Frequency of Updating the Clinical Performance Report (CPR)

The Clinical Performance Report (CPR) is not a once only document. According to the IVDR, manufacturers need to think of CPR as a dynamic document that should be constantly updated with new information to guarantee continued compliance with safety and performance criteria.

CPR Frequency Depending on the Device Classification

Class C and Class D Devices

• Such IVDs are considered to have high risk levels and are usually applied in critical fields of diagnostics, like infections, cancer or blood. In case of class C and class D devices, it is necessary to revise CPR no less than once a year.

Class A and Class B Devices

• The frequency of revising the IVD can be lower than once a year depending on risk assessment, post market surveillance and clinical importance of the product. Although there is no obligation of an annual revision as in the case with class C and class D, the manufacturer has to give justifications for the update schedule.

 Reference: Article 10(9), Article 56(1), Annex XIII Part A Section 1.3.2, Annex III Section 1

 Connection Between PMS & PMPF Actions and the CPR

• CPR update is directly associated with the Post Market Surveillance (PMS) and Post Market Performance Follow up (PMPF):

• Information from PMS activities, such as complaints, vigilance reports, and users' feedback can point to trends which might necessitate the update of the CPR.

• Evidence on device performance in actual clinical practice, gathered during PMPF actions needs to be reflected in the CPR for the demonstration of the clinical relevance of its performance.

The connection between PMS & PMPF allows maintaining the CPR up to date, evidence based, and relevant to the purpose of the medical device.

Reference: Article 78, Article 79, Annex III Section 1, Annex XIII Part A Section 1.3.2

Typical Errors in the Drafting of a Clinical Performance Report (CPR)

Creating a CPR can be complicated and a lot of manufacturers make errors which are easily avoidable. Identifying these typical errors can significantly improve your chances of drafting an adequate report.

1. Insufficient Scientific Data

The lack of robust scientific evidence is one of the most common errors that are made in the creation of a CPR. The report must contain clear and traceable data that will prove the diagnostic claims of the IVD device. Without a strong scientific base, reviewers will doubt the conclusions made in the report. The evidence can be taken either from the research study, scientific literature, or real world performance data but not just general assumptions.

2. Lack of a Systematic Literature Review

A literature review is included in a CPR in order to prove the scientific validity. However, in practice, many CPRs fail to include a systematic review process. It is possible to overlook some relevant studies, not to follow inclusion and exclusion criteria properly, or not to analyze a wide range of references. Thus, the review must be documented and organized properly in order to prove that all relevant data was taken into consideration.

3. Weak Relation to Intended Use

If you have managed to provide a good amount of strong scientific evidence, yet another error that is often made is not connecting the data to the intended use. Your performance results must prove that the device is suitable for its use as well as for the targeted population. Even with strong scientific evidence, your CPR will not pass if there is no link to the intended use.

Reference: MDCG 2022-2, Annex XIII Part A Section 1.3.2

Tips on How to Make a Good Clinical Performance Report (CPR)

The quality of your CPR can be the key to a smooth regulatory process or endless discussions with notified bodies. Not only does it matter what kind of data you have collected but how you present it as well.

1. Employ Different Sources of Credible Data

To prepare a good CPR, you need to gather evidence from different credible sources like:

• Clinical performance study findings conducted according to the IVDR regulations.

• Peer reviewed scientific literature that confirms the claims of your device.

• Registries and clinical databases.

Evidence gathered from different sources proves the validity of the results received.

2. Utilize Real World Evidence (RWE)

Besides controlled clinical studies, it is beneficial to provide regulators with information on the performance of your device in actual clinical practice. Such evidence can come from:

• Post market surveillance (complaints, vigilance data, user feedback).

• Post market performance follow up (PMPF) activities, which provide evidence based on daily practice.

• Clinical use registries and large scale data gathering efforts.

It will demonstrate that your device works well in the real world as well.

3. Utilize Clinical Studies

Clinical studies are at the core of your CPR. In order to utilize them correctly, you need to:

• Outline your study design with all details (goals, sample size, endpoints).

• Show how your findings relate to the purposes of your device.

• Analyze your findings statistically providing information about sensitivity, specificity, predictive values, and confidence intervals.

• Provide an explanation of limitations of your studies.

In such a way, you demonstrate to regulators that your evidence is solid and relevant.

Reference: MDCG 2022-2, Article 56(1), Annex XIII

IVDR CPR Requirements Versus Other Regions: EU, India, US

IVDR CPR versus clinical evidence from CDSCO (India)

• The IVDR specifies structured CPR, which includes scientific validity, analytical performance, and clinical performance.

• The CDSCO (India) mandates clinical evidence but provides the freedom of dependency on foreign data in case the medical device has already been approved elsewhere.

FDA expectation comparison

• The FDA mandates the validation of analytical performance and in many cases clinical performance as evidenced through summaries such as 510(k) or PMA.

• Unlike the IVDR, the FDA cares more about demonstrating substantial equivalence or safety and effectiveness evidence rather than structured CPR.

Steps for aligning the global data for EU submission

• Aligning study protocols for both FDA and IVDR requirements.

• Performance data collection from different geographies to cover global marketplaces.

Regulatory References

The CPR is directly referenced in the following parts of the IVDR:

• Article 56(1) – Outlines the need for a documented performance evaluation plan and report, including clinical performance aspects.

• Annex XIII, Part A, Section 1.3.2 – Specifies the structure and content required in a clinical performance study report and its integration into the overall performance evaluation.

• MDCG 2022-2 - Guidance on general principles of clinical evidence for In Vitro Diagnostic medical devices (IVDs) 

• Article 2 of Regulation (EU) 2017/745 

• MDCG 2022-2: General principles of clinical evidence for IVDs

• Article 2(41): Defines clinical performance

In summary, the CPR consolidates all clinical data that confirms the real-world diagnostic value of an IVD device, ensuring transparency, traceability, and scientific rigor in compliance with the IVDR.

How We Can Help

Here at Morulaa HealthTech, we focus on providing consultation services for medical devices and IVDs, helping you navigate the necessary regulations for entering international markets. Although preparing a Clinical Performance Report (CPR) is not easy, thanks to our experience, you can expect an organized, compliant, and efficient procedure.

Consulting Support from Our Team

• Full Fledged CPR Development – We prepare, review, and revise Clinical Performance Reports according to IVDR regulations.

• Gap Analysis – The missing information or weaknesses in your existing documents are identified by our specialists along with ways to improve them.

• Lifecycle Compliance – We provide you with assistance regarding preparation for market introduction and post market performance follow up (PMPF) of your CPR.

• Tailored Approach – The customized solution for your specific device, classification, and target audience.