3. Background, abbreviations, and definitions
Source: MDCG 2020-1 (March 2020), pages 4-8
Article 61 (1) of the MDR and Article 56 (1) of the IVDR state the following:
'The manufacturer shall specify and justify the level of CLINICAL EVIDENCE necessary to demonstrate conformity with the relevant general safety and performance requirements. That level of CLINICAL EVIDENCE shall be appropriate in view of the characteristics of the device and its intended purpose.'
Article 2 (51) of the MDR and Article 2 (36) of the IVDR define 'CLINICAL EVIDENCE' as:
'clinical data and CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) results pertaining to a device of a sufficient amount and quality to allow a qualified assessment of whether the device is safe and achieves the intended CLINICAL BENEFIT(S), when used as intended by the manufacturer.'
In order to provide guidance relating to the level of CLINICAL EVIDENCE required for MDSW and as set out in recital (5) of the MDR and IVDR, this guidance takes into account internationally converged principles adopted by an international group of regulators, IMDRF (http://www.imdrf.org). Adoption of these principles provides European regulators an initial framework when further developing MDR/ IVDR-specific regulatory approaches and expectations for regulatory oversight.
While this document describes a converged approach to CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) for MDSW, it should be read in conjunction with other documents that aim to provide
horizontal guidance for the CLINICAL EVALUATION of medical devices or PERFORMANCE EVALUATION of in vitro diagnostic medical devices.1
Note: Please be advised that this document is subject to revision upon the publication of the aforementioned horizontal guidance.
Clinical expertise and judgments are required at every step of the CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR), including literature search and appraisal. Each indication and claimed CLINICAL BENEFIT that is part of the intended purpose should be assessed individually and have the supporting CLINICAL EVIDENCE. Systematic and explicit approach for the appraisal of supporting data allows achieving confident, scientifically substantiated conclusions and facilitates transparency of these judgments.
3.1 Abbreviations
| Abbreviation | Definition |
|---|---|
| GSPR | General Safety and Performance Requirements |
| IMDRF | International Medical Device Regulators Forum |
| IVDR | In Vitro Diagnostic Medical Devices Regulation; EU 2017/746 |
| MDCG | Medical Device Coordination Group |
| MDR | Medical Devices Regulation; EU 2017/745 |
| MDSW | Medical Device Software |
| PMCF | Post Market Clinical Follow-up |
| PMPF | Post Market Performance Follow-up |
| PMS | Post Market Surveillance |
| RWE | Real-World Evidence |
| SaMD | Software as a Medical Device |
| SOTA | State-of-the-Art |
| SSCP | Summary of Safety and Clinical Performance |
| SSP | Summary of Safety and Performance |
3.2 Formats used within this document
| Format | Meaning |
|---|---|
| Cursive | A note to a text |
| CAPITALIZED | Terms defined in this document or the Regulations |
| subscript | References |
3.3 Definitions
The definitions elaborated within this section and utilised within this document are intended to apply solely to Medical Device Software (MDSW) according to the MDR and IVDR.
CLINICAL BENEFIT Source: EU 2017/745 (MDR), Article 2 (53); EU 2017/746 (IVDR), Article 2 (37) and IVDR recital (64)
Article 2 (53) MDR defines CLINICAL BENEFIT as the positive impact of a device on the health of an individual, expressed in the terms of a meaningful, measurable, patient-relevant clinical outcome(s), including outcome(s) related to diagnosis, or a positive impact on patient management or public health; whereas
Article 2 (37) IVDR defines CLINICAL BENEFIT as the positive impact of a device related to its function, such as that of screening, monitoring, diagnosis or aid to diagnosis of patients, or a positive impact on patient management or public health.2
CLINICAL DATA Source: EU 2017/745 (MDR); Adopted from EU 2017/746 (IVDR) Annex XIV (2.4) and Annex VII (4.10) and (4.11)
(MDR) Information concerning safety or performance that is generated from the use of a device and is sourced from the following:
- clinical investigation(s) of the device concerned,
- clinical investigation(s) or other studies reported in scientific literature, of a device for which equivalence to the device in question can be demonstrated,
- reports published in peer reviewed scientific literature on other clinical experience of either the device in question or a device for which equivalence to the device in question can be demonstrated,
- clinically relevant information coming from post-market surveillance, in particular the post-market clinical follow-up;
(IVDR) Clinical Data, in particular:
- from relevant peer-reviewed scientific literature and available consensus expert opinions or positions from relevant professional associations relating to the safety, performance, clinical benefits to patients, design characteristics, scientific validity, clinical performance and intended purpose of the device and/or of equivalent or similar devices; or
- other relevant clinical data available relating to the safety, scientific validity, clinical performance, clinical benefits to patients, design characteristics and intended purpose of similar devices, including details of their similarities and differences with the device in question
- clinically relevant information coming from post-market surveillance, in particular the post-market performance follow-up;
CLINICAL DEVELOPMENT PLAN (MDR) Source: EU 2017/745 (MDR), Annex XIV, part A
A plan indicating progression from exploratory investigations, such as first-in-man studies, feasibility and pilot studies, to confirmatory investigations, such as pivotal clinical investigations and a PMCF with an indication of milestones and a description of potential acceptance criteria.
CLINICAL EVALUATION (MDR) Source: EU 2017/745 (MDR), Article 2 (44)
A systematic and planned process to continuously generate, collect, analyse and assess the clinical data pertaining to a device in order to verify the safety and performance, including CLINICAL BENEFITS, of the device when used as intended by the manufacturer.
CLINICAL EVIDENCE Source: EU 2017/745 (MDR), Article 2 (51)); EU 2017/746 (IVDR), Article 2 (36)
Clinical data and CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) results pertaining to a device of a sufficient amount and quality to allow a qualified assessment of whether the device is safe and achieves the intended CLINICAL BENEFIT(S), when used as intended by the manufacturer.
CLINICAL INVESTIGATION (MDR) Source: EU 2017/745 (MDR), Article 2 (45)
Any systematic investigation involving one or more human subjects, undertaken to assess the safety or performance of a device.
CLINICAL PERFORMANCE Source: EU 2017/745 (MDR), Article 2 (52); EU 2017/746 (IVDR), Article 2 (41)
Article 2 (52) MDR defines clinical performance as the ability of a device, resulting from any direct or indirect medical effects which stem from its technical or functional characteristics, including diagnostic characteristics, to achieve its intended purpose as claimed by the manufacturer, thereby leading to a CLINICAL BENEFIT for patients, when used as intended by the manufacturer; whereas
Article 2 (41) IVDR defines clinical performance as the ability of a device to yield results that are correlated with a particular clinical condition or a physiological or pathological process or state in accordance with the target population and intended user.
CURATED DATABASE/ CURATED REGISTRY
For the purpose of this document, a curated database/curated registry is any kind of structured repository such as a traditional database, an ontology or an XML file, that is created and updated with a great deal of human effort through the consultation, verification, and aggregation of existing sources, and the interpretation of new (often experimentally obtained) raw data.
GENERALISABILITY
Generalisability refers to the ability of a MDSW to extend the intended performance tested on a specified set of data to the broader intended population.
HUMAN FACTORS ENGINEERING
Human factors engineering refers to the application of knowledge about human behaviour, abilities, limitations, and other characteristics to the design of and interactions with a MDSW to achieve adequate USABILITY.
PERFORMANCE EVALUATION (IVDR) Source: EU 2017/746 (IVDR), Article 2 (44)
An assessment and analysis of data to establish or verify the SCIENTIFIC VALIDITY, the ANALYTICAL and, where applicable, the CLINICAL PERFORMANCE of a device.
PERFORMANCE STUDY (IVDR) Source: EU 2017/746 (IVDR), Article 2 (42)
A study undertaken to establish or confirm the analytical or CLINICAL PERFORMANCE of a device.
REAL-WORLD PERFORMANCE Source: Definition derived from IMDRF/SaMD WG/N41FINAL:2017
Information on real-world device use and performance from a wider patient population than a controlled study.
STATE-OF-THE-ART Source: Modified from IMDRF/GRRP WG/N47 FINAL:2018
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.
Note: The STATE-OF-THE-ART embodies what is currently and generally accepted as good practice in technology and medicine. The state-of-the-art does not necessarily imply the most technologically advanced solution. The STATE-OF-THE-ART described here is sometimes referred to as the "generally acknowledged STATE-OF-THE-ART"
TECHNICAL PERFORMANCE (MDR) / ANALYTICAL (IVDR) PERFORMANCE Source: IMDRF/SaMD WG/N41FINAL:2017; EU 2017/746 (IVDR) Article 2 (40)
Capability of a MDSW to accurately and reliably generate the intended technical/analytical output from the input data.
USABILITY
For the purpose of this document, usability refers to the characteristic of the user interface that establishes effectiveness, efficiency and ease of user learning and user satisfaction.
VALID CLINICAL ASSOCIATION (MDR) / SCIENTIFIC VALIDITY (IVDR) Source: Derived from IMDRF/SaMD WG/N41FINAL:2017; EU 2017/746 (IVDR), Article 2 (38)
Means the association of an MDSW output with a clinical condition or physiological state.