4.4 Clinical Performance (Pillar 3)
Source: MDCG 2020-1 (March 2020), pages 13-15
4.4 Clinical Performance
For the validation of a MDSW's Clinical Performance, the manufacturer should demonstrate that the MDSW has been tested for the intended use(s), target population(s), use condition(s), operating- and use environment(s) and with all intended user group(s). Section 4.1 of this document further provides context that validation of Clinical Performance includes the assessment of clinical safety, effectiveness, performance and can support the demonstration of clinical benefit. Validation of the Clinical Performance should be considered at each change of the software to a new release. If no validation is performed, a justification should be stated in the technical documentation.
With a validation of Clinical performance, it is demonstrated that users can achieve clinically relevant outputs through predictable and reliable use of the MDSW.
The manufacturer should consider the intended use(s), indication(s), desired clinical output(s) expressed as claims, leading to expected clinical benefits as part of the Clinical performance validation.
A MDSW may have multiple features with only some features claiming a specific clinical benefit. Clinical performance is only applicable to those features. Since MDSW can be modular in nature, validation of the Clinical performance is also permissible on module level when the functionality of the modules is independent of the other modules. This would allow the confirmation of a continuous benefit / risk acceptability only for the MDSW modules that have changed. In cases where the final combination of modules changes product indications and intended purposes, the performance of that final product configuration should also be evaluated. Validation of the Clinical Performance can be characterised by the demonstration of applicable Clinical Data to the MDSW in question, such as (non-exhaustive):
- clinical/ diagnostic sensitivity,
- clinical/ diagnostic specificity,
- positive predictive value,
- negative predictive value,
- number needed to treat (average number of patients that need to be diagnosed/ treated in order to have an impact on one person),
- number needed to harm (number of patients that need to be diagnosed/ treated in order have an adverse effect on one patient),
- positive likelihood ratio,
- negative likelihood ratio,
- odds ratio,
- usability/ user interface,
- confidence interval(s).
Clinical data can be obtained by one or multiple methods such as those referred to in GHTF/SG5/N7:2012 and IMDRF/SaMD WG/N41FINAL:2017.
In addition to the considerations above, Clinical Evaluation of class III and implantable devices (MDR), shall include data from a Clinical Investigation unless the conditions of Article 61(4), (5) or (6) of the MDR have been fulfilled.
For MDSW falling under the IVDR, the evaluation of clinical performance requires the carrying out of clinical performance studies regardless of the classification of the device, unless due justification is provided for relying on other sources of clinical performance data.
Relevant common specifications should be taken into account.
4.4.1 Clinical investigations and clinical performance studies
The practical and achievable benefits of a Clinical Investigation / Clinical Performance Study should be considered as part of determining what data are needed for demonstrating the safety and performance of a new or modified MDSW. The investigation or study should account for potential risks, should follow appropriate ethical requirements, and should be compliant with all relevant legal and regulatory requirements.
MDSW has specific characteristics that should be considered when setting up a clinical investigation or clinical performance study. If the MDSW is used for the determination of a patient's future state (e.g. predisposition, prognosis, prediction) or if the output of the MDSW impacts clinical outcomes (e.g. treatment efficacy) or patient management decisions, then a prospective study may be required as part of the device's Clinical Evaluation (MDR) / performance evaluation (IVDR). In other situations, retrospective analysis may be more appropriate to generate the necessary data to support compliance with the GSPRs, as there is no impact on patient management and the research does not introduce any risks to the patients. Such an approach is only possible under condition that there is an adequate access to data sets of sufficient amount and quality and obtained from the target population.
Formal requirements of MDR Articles 62 (1), 74 and 82 need to be met as far as appropriate for pre-market retrospective studies of MDSW falling under the MDR.
4.4.2 Where demonstration of conformity based on clinical data is not deemed appropriate
In line with the provisions of MDR Article 61 (1) and IVDR Article 56(1), the level of clinical evidence required should be appropriate in view of the device claims and characteristics. For medical devices, where the demonstration of conformity with GSPRs based on clinical data is not deemed appropriate (MDR Article 61 (10)), the manufacturer shall duly substantiate in the technical documentation why it is adequate to demonstrate conformity based on the results of non-clinical testing methods alone, including performance evaluation, bench testing and preclinical evaluation, and usability assessment.
The justification must be based on the output of the risk management process. This should include an evaluation of clinical state-of-the-art, including alternative diagnostic and treatment options, including those identified from literature, and an appraisal of their relevance to the device under evaluation. The device / body interaction, the clinical performances intended, and the claims of the manufacturer should be specifically considered.
A clinical evaluation (MDR) is still required, and the above information and evidence-based justification should be presented in the clinical evaluation report.
Similarly for IVDs, where due to specific device characteristics, demonstration of conformity with GSPRs based on clinical data is not deemed appropriate, a performance evaluation (IVDR) is still required and a justification shall be provided and documented in the Performance Evaluation Plan and the corresponding Performance Evaluation Report.