State of the Art

and EU-MDR

State of the Art  noun ISO 14971, 2019 MDCG 2020-6, according to IMDRF/GRRP WG/N47
VS.
State-of-the-art  adjective Developed stage of technical capability at a given time as Developed stage of current technical capability and/or
regards products, processes and services, based on the accepted clinical practice in regard to products, processes
relevant consolidated findings of science, technology and and patient management, based on the relevant
experience consolidated findings of science, technology and
STATE OF THE ART
Note 1 to entry: The state of the art embodies what is currently experience’.
≠ and generally accepted as good practice in technology and Note: The state of the art embodies what is currently and
STANDARDS OF CARE medicine. The state of the art does not necessarily imply the generally accepted as good practice in technology and
most technologically advanced solution. The state of the medicine. The state of the art does not necessarily imply the
art described here is sometimes referred to as the “generally most technologically advanced solution. The state of the
acknowledged state of the art. art described here is sometimes referred to as the “generally
❑ 12 mentions in EU-MDR
Taken from ISO/IEC Guide 63:2019, 3.18 acknowledged state of the art.
❑ 20 mentions in EU-IVDR
❑ 0 definitions

MEDDEV 2.7.1. rev4

State of the Art is NOT Includes applicable standards and guidance documents, data that relate to benchmark devices, other
❑ The most innovative devices, critical components and medical alternatives or to the specific medical conditions and patient
❑ The most technologically advanced populations intended to be managed with the device. The data are typically needed in order to -
❑ The most expensive describe the clinical background and identify the current knowledge/ state of the art in the
❑ The most frequently used corresponding medical field, - identify potential clinical hazards (including hazards due to substances
❑ The less ‘’dangerous’’ (use-associated risks) and technologies, manufacturing procedures and impurity profiles), - justify the validity of criteria used for
the demonstration of equivalence (if equivalence is claimed), - justify the validity of surrogate endpoints
(if surrogate endpoints are used). […] A review of the current knowledge/ the state of the art needed
for the proper conduct of the appraisal and analysis of the clinical data of the device under evaluation
State of the Art is bounded by and the equivalent device (i.e. applicable standards and guidance documents, information on the
-intended use medical conditions that are relevant to the clinical evaluation, therapeutic/ management/ diagnostic
-medical field options available for the intended patient population, etc.)

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State of the Art
and EU-MDR
State of the Art is expected to

❑ Frame the device in scope within the intended medical field AND respective alternative treatment
options
❑ Define quantifiable safety and performance endpoints to be used for the assessment of clinical data in
all relevant CER sections (including PMS + literature + RM)
❑ Provide evidence for the assessment of risk management data
❑ Provide criteria AND evidence for the acceptability of benefit-risk profile
❑ Explain/corroborate equivalence criteria

Sources of data for State of the Art

❑ Literature databases
❑ Manufacturer documentation (own device AND similar /benchmark / equivalent devices)
❑ Applicable Standards
❑ Up-to-date Guidelines applicable to the intended medical field
❑ External vigilance data

Steps for a comprehensive development of State of the Art

❑ Formulate the research questions to reflect the aspects to be discussed (see previous page). Find the
balance point between sensitivity and specificity
Note: Increasing search sensitivity tends to reduce specificity (search precision)
❑ Divide searches into concepts (e.g. use PICO model)
❑ Select databases and build a rationale for the selection
❑ Identify search terms and keywords. Combine concepts with Boolean operators (OR, AND, NOT) and
proximity operators (near /next) to build your final algorithm
❑ Include additional search options, e.g. filters such as dates of search, truncation, wildcards and build a
rationale for the selection
❑ Implement searches (you may need to run a few pilot searches to optimize results)
❑ Manage the retrieved results with reference management software
❑ Appraise search results based on data contribution, data suitability and levels of evidence

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State of the Art
and EU-MDR
What to discuss in the State of the Art section of a CER

Clinical background Identification of performance and safety endpoints

❑ Medical field concerned with the device(s) under evaluation:

❑ Use clinical practice guidelines to extract quantifiable
• An overview of the medical field(s) and/or relevant medical condition(s) to be
Safety and Performance Endpoints: identify them,
treated, managed or diagnosed.
discuss their clinical relevance and explain how they are
used to provide data for the safety/performance of
❑ Pathogenesis - clinical manifestations:
each therapeutic option. Focus on endpoints that can
▪ Pathogenesis and clinical manifestations of the medical conditions: natural
be used for the quantitative analysis of the target
course and clinical evolution of the condition and co-morbidities that may have
device's and similar/benchmark/equivalent device's
an impact; severity/ consequences of successful/unsuccessful
clinical data. Justify the validity of any potential
treatment/diagnostic methods, whenever relevant /prevention, if applicable;
surrogate endpoints, if applicable to the target
whether there are different clinical forms, stages and severities of the conditions.
device(s). Refer to the CEP's respective section and align
▪ Associated Medical Conditions: medical conditions that could derive from the
with it
condition for which our device(s) is/are used and could have a long-term impact
to the prognosis and/or management of the condition.
❑ The rationale for use of safety/performance endpoints
should include an assessment of their suitability for the
❑ Epidemiological data – prevalence and patterns of use/different
characterization of the performance of the target
populations/potential unmet needs/risk factors:
device(s) in the indicated population. Describe if, and
• Prevalence of the condition (frequency in the general population, by age group,
how, the endpoints can be objectively assessed and
gender, ethnicity, familiar predispositions, risk factors; prevalence and patterns of
determine if selected endpoints are subjective in nature
use).
or are dependent on investigator’s judgement.

❑ Historical aspects of the identified medical field:

❑ Historical context and developments of the identified medical field: to show
evolution of the intended medical field, how each treatment option has
impacted the therapeutic approaches, focusing on the category where the
device in scope belongs. This section must demonstrate the way the paradigm
shift has evolved in time and not attempt a historical throwback.

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State of the Art
and EU-MDR
What to discuss in the State of the Art section of a CER

Identification of alternative treatment options Identification of similar benchmark device(s)

❑ Discuss all currently available alternative treatment options for the indication of the target ❑ Identify medical devices belonging to the same
device(s). This may include not only medical technology options but also pharmaceutical category with the device(s) in scope and ensure they have
and/or conservative approaches. the same intended purpose.
❑ Describe the mechanism of action and main technical
features that have a clinical relevance. Use brand names
❑ Discuss the advantages and disadvantages of the different options, benefit/risk profiles and
when a device is standard of care/gold standard.
their acceptability and/or limitations from a clinical perspective, harms, management of side-
❑ Present and discuss evidence of clinical performance
effects stages, risk mitigation approaches, rationale for choice of each option based on patient
and safety, focusing on published clinical data for
profile, i.e. describe benefits and risks (nature, extent, probability, duration, frequency),
similar/benchmark devices.
acceptability of undesirable side-effects and other risks (including the nature, severity,
❑ When possible, add a table and/or a figure
probability and duration of acceptable harm).
summarizing/comparing clinical data for medical devices
that are similar/benchmark to the device(s) in scope.
❑ Summarize the findings in a comprehensive table, including the name of the therapeutic ❑ Include clinical data for the device(s) in scope, if
option, its main targeted population and main pros and cons. If applicable, add a second published and available. Discuss the level of available
table overviewing the available types of medicines and medical devices currently used. evidence, taking into account MDCG 2020-6.
Discuss available clinical practice guidelines and/or standards and whether there are
diverging opinions of professionals with respect to their use (if applicable).

❑ Use Guidelines pertinent to the intended medical field(s) to identify gold standards, devices,
technologies, invasive and/or non-invasive approaches, conservative and/or surgical options,
which are being used as alternative treatment options for some and/or all indications treated
by the target device(s). Analyze recent Guidelines and/or peer-reviewed meta-analyses
and/or reviews.

❑ Try to situate the target device(s) and/or the category it/they belong to into the algorithm of
the guidelines.
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State of the Art
and EU-MDR
What to discuss in the State of the Art section of a CER

Potential hazards/Complications Conclusion of the State of the Art

❑ Discuss hazards related to treatment options based on quantifiable ❑ Add a summary highlighting the main aspects of the Intended
safety/performance endpoints and qualitative data. Discuss clinical deficiencies medical fields, the main alternative options, an overview of the
associated with the use of similar/benchmark devices: are there any potential comparison of the target device's clinical safety and performance
safety/performance gaps for patients and/or physicians? (Including similar/benchmark device(s)).

❑ Discuss potential unmet needs and summarize complications and

❑ If the devices are WET with limited clinical data, focus on design aspects.
risks.

❑ Develop a table that outlines all identified risks/hazards and specify the target ❑ Add a statement on residual risks and the remaining overall risk.
population and occurrence/frequency rates.

❑ Highlight any potential emerging risks that may not be discussed previously in the
literature. This comparison aims to situate the device(s) in scope into the context of
the State of the Art.

❑ Present data accordingly without withholding unfavorable data and add a

conclusive statement on whether the target device(s) and its/their generic group
is/continues to be State of the Art.

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State of the Art
and EU-MDR

Identification and
historical
perspective of
the intended
medical field Identification and
discussion of the
Alternative medical condition
treatments (pathophysiology
options for the , clinical
Intended Use* manifestations,
epidemiology
etc.)
What to discuss in the
SoTA section of a MDR-
compliant CER

Unmet clinical
Identification of needs on the
Safety and intended medical
Performance field / intended
Endpoints use
Clinical data,
safety and
performance of
benchmark/simil
ar devices

We provide measurable actions and tailored solutions.

Let us be the bridge between your operational reality and current regulatory expectations. www.evnia.dk @Evnia_dk Linkedin.com/evnia