Establishing the generally acknowledged state of the art is a key aspect of the clinical evaluation process for any medical device. Even though the MDR does not define what the state of the art encompasses or provide guidance on the methodology for its establishment, it is evident that state of the art considerations form the basis for the demonstration of conformity.
The MDR requires that state of the art (SOTA) considerations are taken into account when demonstrating the safety and performance of a device and also mentions it in context with the clinical evaluation procedure and risk management activities. However, the regulation does not provide a definition of the term. Under the Medical Device Directive (MDD), some guidance on what the SOTA should encompass was provided in the MEDDEV 2.7/1 Rev. 4. The MEDDEV specified that applicable standards and guidance documents should be consulted, as well as information on the target medical condition, benchmark devices, other devices, and medical alternatives. The goal of the SOTA is not only to establish the clinical background and current knowledge in the corresponding medical field, but also to identify potential clinical hazards and justify criteria used for the clinical evaluation of a specific device.
Further guidance was provided by the complete revision of the ISO 14971 standard in 2019, when a new definition of SOTA as “developed stage of technical capability at a given time as regards products, processes and services, based on the relevant consolidated findings of science, technology and experience” was added. Importantly, it is noted that the SOTA embodies what is currently and generally accepted as good practice in technology and medicine and does not necessarily imply the most technologically advanced solution.
The SOTA provides valuable inputs for product development
Establishing the SOTA early in the life cycle of a device can provide valuable inputs for product design and data collection. Reviewing data relating to similar or benchmark devices can help identify design features that are considered safe and established, and vice versa, show what features may be associated with an increased risk profile or require additional validation. Similar device data should also be considered for the specification of the intended purpose and the necessary preclinical and clinical testing. If there is a well-established similar device on the market, it generally makes sense to align the intended purpose of a new device with the available clinical evidence for the similar device and perform comparative (pre-)clinical testing to establish the safety and performance. For well-established technologies, the SOTA and similar device data can also be used to support confirmation of conformity with relevant requirements.
Finally, relevant safety and performance outcomes for a device should always be based on the SOTA and benchmark data. The SOTA establishes which clinical outcomes are most frequently used to evaluate treatment safety and effectiveness for a specific medical condition, while benchmark data specify acceptance criteria for each outcome. The most appropriate data collection strategy comprising preclinical and clinical testing can then be developed, taking into account the nature of relevant outcomes and accepted methodology to measure these outcomes.
The SOTA is indispensable when determining the benefit-risk ratio
One of the aims of the MDR and the 2019 revision of ISO 14971 was to emphasize the interface between risk management and clinical evaluation activities. The benefit-risk determination is the key conclusion from these activities, since confirmation of conformity requires that any risks which may be associated with the use of a device constitute acceptable risks when weighed against the benefits to the patient. The MDR demands that the SOTA be taken into account for the adoption of risk control measures and for the determination of the acceptability of the benefit-risk ratio. ISO 14971 also specifies that risk management should consider the generally acknowledged SOTA. In practice, these requirements translate to a crucial role of the SOTA in risk management activities throughout the device life cycle. In early stages of product development, SOTA inputs are needed to identify potential clinical hazards, associated safety outcomes, acceptance criteria, as well as appropriate mitigation measures.
As per MDR Annex XIV on clinical evaluation, an indicative list and specification of parameters to be used to determine the acceptability of the benefit-risk ratio of a device based on the SOTA in medicine is an integral part of the clinical evaluation plan. Therefore, clinical benefit outcomes and respective acceptance criteria must also be defined in the early planning phase and based on the current SOTA. In addition to individual clinical benefit and risk parameters, the overall appropriateness of a device for the intended medical indications needs to be evaluated based on the SOTA, taking into consideration up-to-date alternative treatment options and, in particular, the benefit-risk profile of the currently accepted most effective treatment option for the intended purpose relevant to a device.
Once a device has been placed on the market, the SOTA must be updated regularly to ensure the continuing acceptability of the benefit-risk ratio. Both the MDR and ISO 14971 demand procedures to review potential changes in the SOTA that can be relevant to the benefit-risk ratio, such as alternative medical devices and/or therapies becoming available on the market, as well as changes in risk perception or risk acceptability. Even for well-established devices, it may be necessary for the manufacturer to generate new clinical data to enable an evaluation of their safety and clinical performance in relation to an evolving SOTA. The SOTA often evolves rapidly for novel and innovative device technology, and frequent SOTA updates may be required.
There is a close link between the SOTA and clinical data collection
The purpose of the clinical evaluation of a medical device is to demonstrate conformity of the device with relevant general safety and performance requirements (GSPRs), and to evaluate any undesirable side-effects and as well as the acceptability of the benefit-risk-ratio. As outlined above, the SOTA should already be established at the stage of clinical evaluation planning to define relevant parameters and criteria for the clinical evaluation. In addition, the SOTA is also relevant for specifying the level of clinical evidence necessary to demonstrate conformity with relevant GSPRs. According to MDR Article 61(1), demonstration of GSPR conformity must be based on clinical data providing sufficient clinical evidence, and it lies within the responsibility of the manufacturer to specify and justify the necessary level of clinical evidence given the characteristics of a device and its intended purpose. Relating device characteristics and intended purpose to the current SOTA is an important step in determining the required level of clinical evidence. Data on benchmark and similar devices provide guidance on appropriate methods for data collection. Information on the technical and clinical SOTA can be used to determine whether a device can be considered a well-established technology, and a lower level of clinical evidence may thus be justified.
The SOTA further plays a role in the planning of clinical data collection. A description of the SOTA in clinical care in the relevant field of application is a mandatory part of every clinical investigation plan, as is the description of the proposed benefits of a new device in the context of the clinical SOTA. Analogous to clinical evaluation planning, relevant clinical outcomes and acceptance criteria for a clinical investigation should be identified based on the SOTA assessment. After completion of a clinical investigation, the relevance of the results must be discussed in the context of the SOTA of clinical practice.
Conclusion – the SOTA plays a crucial role throughout the medical device life cycle
Although the MDR provides only a few specific requirements for establishing the SOTA, it plays a key role in ensuring conformity throughout the device life cycle. SOTA inputs should be considered early during device development and are indispensable for the planning of risk management activities, the clinical evaluation process, and clinical data collection. Keeping the SOTA up to date is crucial for any marketed device in order to ensure the continuing acceptability of the benefit-risk ratio. The importance of the SOTA is also reflected in the MDCG clinical evaluation assessment report template for notified bodies (MDCG 2020-13), which puts a strong emphasis on the appropriate description of the SOTA and the relevance of device safety and performance outcomes in relation to the SOTA.
Kathrin Abegg, DVM PhD
Team Leader Medical Writing ISS AG