Analytical Performance Report vs. Clinical Performance Report: What Each Demonstrates Under IVDR

Analytical Performance Report (APR): Can the device reliably detect or measure the analyte?

Clinical Performance Report (CPR): Do the device results meaningfully correlate with the intended clinical condition or physiological/pathological state?

Under the EU In Vitro Diagnostic Medical Devices Regulation (IVDR), demonstrating that an IVD performs as intended requires more than a single validation study or summary report. Manufacturers are expected to establish a body of clinical evidence addressing three interconnected elements: scientific validity, analytical performance, and clinical performance.

Two key documents within that evidence framework are the Analytical Performance Report (APR) and the Clinical Performance Report (CPR). Although the reports are closely related, they answer fundamentally different regulatory questions.

The IVDR Performance Evaluation Framework

Article 56 of Regulation (EU) 2017/746 establishes performance evaluation as the foundation for demonstrating conformity with relevant General Safety and Performance Requirements (GSPRs). Under Article 56(3), the performance evaluation must follow a defined and methodologically sound procedure addressing scientific validity, analytical performance, and clinical performance.

Together, the data and conclusions from these elements constitute the clinical evidence for the IVD. The evidence must provide scientifically valid assurance that the applicable Annex I requirements are fulfilled under normal conditions of use and demonstrate, with reference to the state of the art in medicine, that the intended clinical benefit will be achieved and the device is safe.

Annex XIII expands on this framework. It requires manufacturers to establish and maintain a Performance Evaluation Plan (PEP) and describes how scientific validity, analytical performance, and clinical performance should be demonstrated. The resulting Scientific Validity Report (SVR), Analytical Performance Report, and Clinical Performance Report are then brought together and assessed in the Performance Evaluation Report (PER).

BSI similarly describes performance evaluation as a critical component of IVD verification and validation and emphasizes that the IVDR requires clinical evidence supporting the device’s intended purpose.

What Does the Analytical Performance Report Demonstrate?

The IVDR defines analytical performance as the ability of a device to correctly detect or measure a particular analyte.

In practical terms, analytical performance is concerned with whether the test itself works reliably under its specified conditions of use.

Annex XIII, Section 1.2.2 requires the manufacturer to demonstrate analytical performance against the applicable parameters identified in Annex I, Section 9.1(a). As a general rule, the IVDR specifies that analytical performance should be demonstrated through analytical performance studies and documented in an Analytical Performance Report.

Depending on the type of IVD, relevant analytical performance characteristics may include:

• analytical sensitivity
• analytical specificity
• trueness or bias
• precision, including repeatability and reproducibility
• accuracy
• limits of detection and quantitation
• measuring range
• linearity
• cut-off determination
• specimen collection and handling criteria
• endogenous and exogenous interference
• cross-reactivity

The Regulatory Question Behind the APR

Does this IVD technically perform as claimed when detecting or measuring its target analyte?

Consider an assay intended to detect a particular biomarker. Analytical performance evidence might demonstrate that the assay can detect the biomarker at the claimed concentration, produces sufficiently precise results across runs and sites, appropriately manages interfering substances, and does not produce unacceptable cross-reactivity.

Those findings establish confidence in the measurement or detection capability of the device. They do not necessarily establish that the result correctly identifies patients with – or without – the clinical condition of interest. That is where clinical performance enters the evidence framework.

What Does the Clinical Performance Report Demonstrate?

The IVDR defines clinical performance as the ability of an IVD to yield results that correlate with a particular clinical condition or with a physiological or pathological process or state, taking into account the target population and intended user.

Annex XIII, Section 1.2.3 requires manufacturers to demonstrate clinical performance against applicable parameters identified in Annex I, Section 9.1(b). Those parameters can include:

• diagnostic sensitivity
• diagnostic specificity
• positive predictive value
• negative predictive value
• likelihood ratio
• expected values in normal and affected populations

The evidence may come from one or a combination of clinical performance studies, scientific peer-reviewed literature, and published experience gained through routine diagnostic testing. Importantly, the IVDR states that clinical performance studies should be performed unless reliance on other sources of clinical performance data is duly justified.

BSI’s IVDR performance evaluation guidance similarly treats clinical performance and clinical performance studies as distinct elements of the broader performance evaluation process.

The Regulatory Question Behind the CPR

Does the device’s result perform as intended in the relevant clinical context and target population?

For example, an assay could demonstrate excellent analytical sensitivity and precision but still require evidence that its results appropriately distinguish the clinically relevant populations described in its intended purpose.

Analytical performance demonstrates confidence in the test result as a measurement or detection result. Clinical performance demonstrates confidence in the relationship between that result and the relevant clinical condition or physiological/pathological state.

APR vs. CPR at a Glance

Why Strong Analytical Performance Does Not Replace Clinical Performance

One potential documentation pitfall is treating strong analytical validation as sufficient evidence of overall IVD performance. Under the IVDR framework, it generally is not.

Article 56 explicitly separates scientific validity, analytical performance, and clinical performance as components of performance evaluation. Annex XIII then establishes separate expectations for demonstrating and documenting each component.

TUV SUD’s presentation of the IVDR requirements makes the distinction particularly clear: analytical performance is documented in the Analytical Performance Report, while clinical performance is documented separately in the Clinical Performance Report. Both ultimately contribute to the Performance Evaluation Report.

There is also an important sequencing relationship between the two. Article 57 states that, in the case of clinical performance studies, analytical performance must have been demonstrated taking the state of the art into consideration. For interventional clinical performance studies, both analytical performance and scientific validity must be demonstrated, subject to the specific IVDR provision for companion diagnostics where scientific validity has not yet been established.

In other words, manufacturers should not think of analytical and clinical performance as competing evidence categories. They are complementary layers of evidence.

The Intended Purpose Connects the APR and CPR

One of the most important considerations when preparing APRs and CPRs is consistency with the device’s intended purpose.

The intended purpose defines what the manufacturer says the device does, for whom, under what conditions, and for what clinical purpose. The evidence strategy must then substantiate those claims.

For example, if the intended purpose identifies a specific analyte, specimen type, patient population, screening/diagnostic/monitoring/prognostic application, intended users, use setting, or specific clinical claims, the APR and CPR should collectively provide evidence appropriate to those elements.

This is one reason performance evaluation should not be treated as a collection of independent reports assembled at the end of product development. Annex XIII requires the Performance Evaluation Plan to identify the device’s intended purpose, analyte or marker, intended use, target patient groups, applicable GSPRs, methods for examining analytical and clinical performance, state of the art, acceptance criteria, and other elements that shape the evidence strategy.

A well-designed PEP therefore creates the regulatory and scientific thread connecting the intended purpose to the APR, CPR, SVR, and ultimately the PER.

Where Does the Performance Evaluation Report Fit?

The APR and CPR should not be confused with the Performance Evaluation Report. The PER is the overarching assessment.

Under Annex XIII, Section 1.3.2, the Performance Evaluation Report includes the Scientific Validity Report, the Analytical Performance Report, the Clinical Performance Report, and an assessment of those reports that allows the manufacturer to demonstrate the clinical evidence for the device.

Annex II reinforces this structure by requiring the technical documentation to contain the PER, including the scientific validity, analytical performance, and clinical performance reports together with their assessment.

This means that a strong PER should do more than concatenate three reports. It should explain how the evidence collectively supports the intended purpose, performance and safety claims, applicable GSPRs, and intended clinical benefit.

What Should Manufacturers Watch for When Preparing APRs and CPRs?

The most effective IVDR performance documentation usually begins with evidence planning rather than report writing. Before drafting an APR or CPR, manufacturers should be able to trace the applicable performance claims to the intended purpose, PEP, GSPRs, state of the art, study protocols, acceptance criteria, results, and conclusions.

1.Do the reports address all applicable performance characteristics?

Annex XIII requires analytical and clinical performance to be demonstrated against the applicable characteristics identified in Annex I Section 9.1. Where a characteristic is omitted because it is not applicable, the rationale should be scientifically and regulatorily defensible.

2. Were acceptance criteria established appropriately?

Performance results become considerably more meaningful when evaluated against predefined, scientifically justified acceptance criteria connected to the intended purpose and state of the art. The PEP itself is expected to address methods, statistical tools, state of the art, and parameters used to determine the acceptability of analytical and clinical performance.

3. Is there consistency across the technical documentation?

Intended purpose, specimen types, populations, performance claims, cut-offs, acceptance criteria, and conclusions should tell the same regulatory story across the PEP, SVR, APR, CPR, PER, risk documentation, labeling, and other relevant technical documentation.

4. Are evidence gaps clearly addressed?

Annex XIII requires manufacturers to identify available relevant data, appraise its suitability, identify unresolved issues or gaps, and generate additional data where necessary. A performance report therefore should not simply summarize favorable results. The broader performance evaluation must be thorough and objective and consider both favorable and unfavorable data.

5. Does the documentation remain current?

Performance evaluation does not end at CE marking. Article 56 requires the performance evaluation and associated documentation to be updated throughout the device lifecycle using information generated through Post-Market Performance Follow-up (PMPF) and post-market surveillance. For Class C and D devices, the PER must be updated when necessary and at least annually with the applicable data.

BSI also emphasizes the lifecycle nature of IVDR performance documentation and, in its educational materials, addresses PER best practices alongside PMPF and PMS.

Building a Coherent IVDR Performance Evidence Story

The distinction between an Analytical Performance Report and a Clinical Performance Report is ultimately straightforward:

The APR demonstrates that the IVD can reliably detect or measure what it claims to detect or measure.

The CPR demonstrates that the resulting information performs appropriately in relation to the relevant clinical condition or physiological/pathological state.

Neither report should exist in isolation. Together with scientific validity, these evidence streams form the foundation of the manufacturer’s clinical evidence and feed into the Performance Evaluation Report required by the IVDR.

For manufacturers, the challenge is often not simply producing each document. It is ensuring that the PEP, SVR, APR, CPR, PER, PMPF activities, and related technical documentation form a coherent and traceable evidence package aligned with the device’s intended purpose and the state of the art.

That is where thoughtful IVD writing services and evidence strategy can make a significant difference – particularly when complex study data, literature evidence, performance claims, and post-market findings must be translated into documentation that is both scientifically rigorous and straightforward for a Notified Body reviewer to navigate.

References

1. Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR) – particularly Article 56; Article 57; Annex I, Section 9; Annex II; and Annex XIII. Source
2. BSI, Performance Evaluation Under IVDR – guidance discussing performance evaluation, clinical evidence, scientific validity, analytical performance, and clinical performance under Regulation (EU) 2017/746. Source
3. BSI, Performance Evaluation Under the In Vitro Diagnostic Regulation – Part 2 – guidance addressing clinical performance, clinical performance studies, the Performance Evaluation Report, and PMPF. Source
4. TUV SUD, IVDR Annex XIII: Performance Evaluation, Performance Studies and Post-Market Performance Follow-up. Source
5. TUV SUD, IVDR Annex II: Technical Documentation. Source

This article is intended for informational purposes and does not constitute legal or regulatory advice.