More and more focus has been given to the state of the art in the process of clinical evaluation with the update of the regulations and the guidelines. But do you know what it means and how to make the best use of it in the process of getting your device CE marked?
1. Definition of the state of the art
The state of the art, frequently shortened as SOTA or SoA, went from being mentioned three times under the 93/42/EEC amended by the Council Directive 2007/47/EC (MDD) to being mentioned 12 times under the EU Medical Device Regulation 2017/745 (MDR). Similarly, it was mentioned four times in the MEDDEV 2.7.1 Rev 3 (2009) and 39 times (!!!) in the MEDDEV 2.7.1 Rev 4 (2016). Intriguingly, even with a growing interest in the SOTA, no definition was given until 2018, when the IMDRF/GRRP WG/N47 FINAL:2018 provided clarification of the term, which was reinforced two years later with the publication of the MDCG 2020-6. From this last reference, the current understanding is that the state of the art is a “developed stage of current technical capability and/or accepted clinical practice in regard to products, processes and patient management, based on the relevant consolidated findings of science, technology and experience. (…) It 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 state of the art (can also be) referred to as the ‘generally acknowledged state of the art’ ”.
2. How to make the best use of the state of the art
Analyzing the state of the art can be confusing and at times seems to be an “art” in itself. It is usually an activity that is neglected because it involves a well-structured systematic literature search process that is commonly performed only for the Clinical Evaluation Report (CER), at the very end of the project. However, this analysis contains information that is crucial early in the device development, such as understanding the current medical practice and treatment alternatives, knowing the potential competitors and being aware of all literature data that is available for equivalent and/or similar devices, and previous versions of the subject devices, if applicable. This is critical to the device development because it is a must to know what is out there in the market, what is feasible in terms of collecting clinical data, and what is the bare minimal acceptance criteria for performance and safety requirements. In order to be competitive, a new device should perform as well as competitors; or at least perform at the minimum accepted for the current medical practice and be associated with an acceptable level of complications or adverse effects when compared with alternatives.
An early establishment of the state of the art is valuable in defining risk management, device claims, endpoints (clinical outcome parameters), acceptance criteria, data collection plan and clinical evaluation strategy, as presented in Figure 1.
Figure 1: Proposed best use of the state of the art.
In practice, the SOTA often leads to edits to risk management documents after the clinical evaluation, but it would be much more productive to assess frequency of complications, side-effects, and adverse events based on the procedure independent of device use in order to fully understand the risks and benefits of the device in the current state of medical practice for the disease being treated. The data from the state of the art helps the manufacturer to understand in advance what is expected, acceptable or not for the device under development and therefore, should be used early as an input for the risk management.
Any device clinical claim should be linked to endpoints (clinical outcome parameters) and acceptance criteria and supported by clinical data. In this sense, the SOTA helps the manufacturer to understand what can be claimed for the device in terms of safety and performance, and what are the best endpoints to measure the achievement of such requirements in a clinical setting or technical requirements that can be met with pre-clinical data for Article 61(10) compliant devices. Being aware of the endpoints usually measured in clinical practice helps the manufacturer to design feasible pre-market and post- market data collection, facilitating the collection of appropriate clinical data that will support conformity to the MDR. And more than having the data, the manufacturer will know in advance where to set the acceptance bar to have a competitive device on the market.
Finally, a well-designed SOTA will present all clinical data available and, therefore, help the manufacturer of a new device to choose the most appropriated strategy for the clinical evaluation: if based on an data from an equivalent device that represents a previous generation, if the device can considered a well-established technology (WET) or standard of care, if no clinical claims will be made and MDR article 61(10) can be applicable, or if sufficient clinical data on the actual device mut be generated previous to CE mark.
3. Summary and conclusion
The analysis of the state of the art of the medical condition related to the subject device and of the general class of devices belonging to the same generic group is a requirement under MDR. Therefore, as it must be executed anyway, it would be more productive to perform it in the early development of the device, and then have data to substantiate risk management, device claims, endpoints, acceptance criteria, planning data collection for both pre-market and post-market phases (aka clinical development plan) and choosing the best clinical evaluation strategy. As the state of the art in medicine changes over time and Notify Bodies usually expect clinical data from the literature from the past six months, an update on the state of the art is expected in the end of the project, during completion of the CER.