Medical Device       
Medical Device Coordination Group Document         MDCG  2020-1  
  
 
 
 
 
 
MDCG  2020-1  
       Guidance on Clinical Evaluation (MDR) 
      / Performance Evaluation (IVDR) of  
      Medical Device Software              
 
             March 2020 
 
 
  
 
This document has been endorsed by the Medical Device Coordination Group (MDCG) 
established by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of 
representatives of all Member States and it is chaired by a representative of the European 
Commission. 
The document is not a European Commission document and it cannot be regarded as reflecting 
the official position of the European Commission. Any views expressed in this document are not 
legally binding and only the Court of Justice of the European Union can give binding 
interpretations of Union law.  
 
  
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  Guidance on 
Clinical Evaluation/  
Performance 
Evaluation of 
Medical Device 
Software 
March 2020  
 
Guidance on Clinical Evaluation 
(MDR) / Performance Evaluation 
(IVDR) of Medical Device Software  
  
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 Table of Contents 
 
1. Purpose ............................................................................................................................................ 3 
2. Scope ............................................................................................................................................... 3 
3. Background ..................................................................................................................................... 4 
3.1. Abbreviations ........................................................................................................................... 5 
3.2. Formats used within this document........................................................................................... 5 
3.3. Definitions ............................................................................................................................... 5 
4. General principles of the MDSW CLINICAL EVALUATION  (MDR) / PERFORMANCE EVALUATION  
(IVDR) process ....................................................................................................................................... 9 
4.1. Introduction ............................................................................................................................. 9 
4.2. Determination of the valid clinical association / scientific validity .......................................... 12 
4.3. Technical Performance /Analytical Performance .................................................................... 12 
4.4. Clinical Performance .............................................................................................................. 13 
4.4.1. Clinical investigations and clinical performance studies .................................................. 14 
4.4.2. Where demonstration of conformity based on clinical data is not deemed appropriate ..... 15 
4.5. Final analysis and conclusion of the clinical evaluation (MDR) / performance evaluation 
(IVDR) .............................................................................................................................................. 15 
4.6. Continuous update of the clinical evaluation (MDR) / performance evaluation (IVDR)........... 15 
Annex I – Methodological principle for generation of CLINICAL EVIDENCE  ........................................ 17 
Annex II – Examples of CLINICAL EVALUATION (MDR) /  PERFORMANCE EVALUATION  (IVDR) 
strategies ........................................................................................................................................... 18 
a) MDSW intended to analyse sleep quality data .................................................................... 18 
b) MDSW intended for image segmentation ............................................................................ 19 
c) MDSW intended to detect inflammatory bowel diseases (IBD) .......................................... 20 
d) Active devices containing MDSW to enable their intended purpose .................................. 21 
e) MDSW which provides an additional user-interface to control an insulin pump ............... 21 
f) MDSW intended to analyse exhaled CO2 in a life-sustaining device in order to control 
ventilator settings ......................................................................................................................... 21 
 
   
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 1. Purpose 
The purpose of this guidance is to provide a framework for the determination of the appropriate level of 
CLINICAL EVIDENCE  required for MEDICAL DEVICE SOFTWARE  (MDSW) to fulfil the requirements set out 
in Regulation (EU) 2017/745 – Medical Devices Regulation (MDR) and Regulation (EU) 2017/746 – In 
Vitro Diagnostic Medical Devices Regulation (IVDR).1  
In order to promote global convergence, this document takes into account certain concepts outlined in 
International Medical Device Regulators Forum (IMDRF) guidance documents (such as N41).2 
2. Scope 
This guidance should be applied to MDSW. For the purpose of this guidance, MDSW is software that is 
intended to be used, alone or in combination, for a purpose as specified in the definition of a “medical 
device” in the medical devices regulation or in vitro diagnostic medical devices regulation.  
It should be noted that software can be associated3 with another medical device, by driving or influencing 
its use. The guideline MDCG 2019-11 clarifies that software which is driving or influencing is covered by 
the medical devices regulations4 either as a part/component of a device or as an accessory for a medical 
device.  
Software developers should refer to MDCG 2019-11 for guidance on the appropriate qualification and 
classification of software prior to such software being introduced into the market. The same principles of 
CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) apply to all MDSW. Conceptually, 
the following models of software can be understood (whereas combinations may be possible, refer to Table 
1):  
a) Software for which the manufacturer claims a specific medical intended purpose. Such software 
has a CLINICAL BENEFIT  and requires CLINICAL EVIDENCE  within its own conformity assessment. 
b) Software for which the manufacturer does not claim any medical intended purpose. Such software 
is intended to drive or influence a medical device. The CLINICAL EVIDENCE  is provided within the 
context of the driven or influenced device and is therefore out of the scope of this document. 
It should be recognised that the concept of a CLINICAL BENEFIT  for MDSW may deviate from that which 
applies in the case of pharmaceuticals or other medical devices, since the benefit of MDSW may lie in 
providing accurate medical information on patients, where appropriate, assessed against medical 
information obtained through the use of other diagnostic options and technologies, whereas the final clinical 
outcome for the patient is dependent on further diagnostic and/or therapeutic options which could be 
available. 
                                                
1 Depending on the device in question, the level of Clinical Evidence may differ and shall be assessed on a case by case basis.  
2 International Medical Device Regulators Forum – IMDRF/SaMD WG/N41FINAL:2017 – Guidance on Software as a Medical 
Device (SaMD): Clinical Evaluation  
3 Associated medical device may be software or hardware. 
4  The use of “The Medical Devices Regulations” from here on out refers to both Regulation (EU) 2017/745 – MDR and Regulation 
(EU) 2017/746 – IVDR.   
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 Model of Software CLINICAL EVALUATION (MDR) / 
PERFORMANCE EVALUATION 
(IVDR)  - scope 
MDSW 
(with independent intended purpose and claimed CLINICAL 
BENEFIT)  MDSW only 
MDSW 
(with intended purpose and claimed CLINICAL BENEFIT  related 
to driving or influencing a medical device for a medical 
purpose) MDSW and the driven or influenced 
medical device Notes 1,2 
Software driving or influencing the use of a medical device 
(with no independent intended purpose or independent claimed 
CLINICAL BENEFIT ) Driven or influenced medical device 
including the software (component or 
accessory) 
Table 1 Different MDSW and CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION  (IVDR) 
requirements 
Note 1: If a software is driving/ influencing more than one medical device, an independent CLINICAL 
EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) is required for each foreseen and clinically 
viable software – device combination. 
Note 2: Out of scope of this guidance (See MDCG 2019-11 for examples). 
3. Background 
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  
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 horizontal guidance for the CLINICAL EVALUATION  of medical devices or PERFORMANCE EVALUATION  of 
in vitro diagnostic medical devices.5 
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 
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 
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. 
                                                
5 These guidance documents are under development and will be published on the Commission’s Medical Devices website.   
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 CLINICAL BENEFIT  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.6 
Source: EU 2017/745 (MDR), Article 2 (53); EU 2017/746 (IVDR), Article 2 (37) and IVDR recital (64)   
CLINICAL DATA  (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;  
Source: EU 2017/745 (MDR)  
(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; 
Source: Adopted from EU 2017/746 (IVDR) Annex XIV (2.4) and Annex VII (4.10) and (4.1 1) 
                                                
6 IVDR recital (64) states : It should be recognised that the concept of clinical benefit for in vitro diagnostic medical devices is 
fundamentally different from that which applies in the case of pharmaceuticals or of therapeutic medical devices, since the benefit 
of in vitro diagnostic medical devices lies in providing accurate medical information on patients, where appropriate, assessed 
against medical information obtained through the use of other diagnostic options and technologies, whereas the final clinical 
outcome for the patient is dependent on further diagnostic and/or therapeutic options which could be available.   
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 CLINICAL DEVELOPMENT PLAN 
(MDR) 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. 
Source: EU 2017/745 (MDR), Annex XIV, part A  
CLINICAL EVALUATION (MDR) 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. 
Source: EU 2017/745 (MDR), Article 2 (44) 
CLINICAL EVIDENCE  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. 
Source: EU 2017/745 (MDR), Article 2 (51)); EU 2017/746 (IVDR), Article 2 (36) 
CLINICAL INVESTIGATION 
(MDR) Any systematic investigation involving one or more human subjects, 
undertaken to assess the safety or performance of a device. 
Source: EU 2017/745 (MDR), Article 2 (45) 
CLINICAL PERFORMANCE  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.  
Source: EU 2017/745 (MDR), Article 2 (52); EU 2017/746 (IVDR), Article 2 (41)  
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.  
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 HUMAN FACTORS ENGINEERING  Human factors engineering refers to the a pplication 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) An assessment and analysis of data to establish or verify the 
SCIENTIFIC VALIDITY , the ANALYTICAL  and, where applicable, the 
CLINICAL PERFORMANCE  of a device. 
Source: EU 2017/746 (IVDR), Article 2 (44) 
PERFORMANCE STUDY (IVDR) A study undertaken to establish or confirm the analytical or CLINICAL 
PERFORMANCE  of a device. 
Source: EU 2017/746 (IVDR), Article 2 (42) 
REAL-WORLD PERFORMANCE  Information on real -world device use and performance from a wider 
patient population than a controlled study.  
Source: Definition derived from IMDRF/SaMD WG/N41FINAL:2017  
STATE-OF-THE-ART 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” 
Source: Modified from IMDRF/GRRP WG/N47 FINAL:2018  
TECHNICAL PERFORMANCE 
(MDR) /ANALYTICAL (IVDR))  
PERFORMANCE  Capability of a MDSW to accurately and reliably generate the 
intended technical/analytical output from the input data.  
Source:  IMDRF/SaMD WG/N41FINAL:2017 
Source: EU 2017/746 (IVDR) Article 2 (40)  
 
USABILITY For the purpose of this document, usability refers to the c haracteristic 
of the user interface that establishes effectiveness, efficiency and ease 
of user learning and user satisfaction.   
VALID CLINICAL ASSOCIATION 
(MDR) / SCIENTIFIC VALIDITY 
(IVDR) Means the association of an MDSW output with a clinical condition 
or physiological state. 
Source: Derived from IMDRF/SaMD WG/N41FINAL:2017 
Source: EU 2017/746 (IVDR), Article 2 (38) 
 
  
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 4. General principles of the MDSW CLINICAL EVALUATION  (MDR) / 
PERFORMANCE EVALUATION  (IVDR) process 
4.1. Introduction 
CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) is an ongoing process, conducted 
throughout the life cycle of a MDSW. It is a structured, transparent, iterative and continuous process which 
is part of the quality management system for a device. Software that qualifies as a MD or an IVD is subject 
to the same general CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) principles, laid 
down in the applicable guidelines and regulatory documents, as other MDs/ IVDs, such as: 
- Establishing and maintaining a CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION 
(IVDR) plan and criteria applied to generate the necessary CLINICAL EVIDENCE  based on the 
characteristics of the device; 
- Identification of the relevant data pertaining to performance and/ or safety of the device and any 
remaining unaddressed issues or gaps in the data; 
- Appraisal of the relevant data in terms of quality and its contribution to the CLINICAL EVALUATION 
(MDR) / PERFORMANCE EVALUATION (IVDR); 
- Analysis of the available data and its relevance with regard to demonstrating conformity with the 
relevant General Safety and Performance Requirements (GSPRs); 
- Documenting the relevant data, their assessment and the CLINICAL EVIDENCE  derived therefrom, in 
the CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) report; 
- Updating the CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) and its 
documentation throughout the life cycle of the MDSW concerned with data obtained from 
implementation of the manufacturer's Post Market Clinical Follow-up / Post Market Performance 
Follow-up (PMCF /PMPF) plan. 
These methodological principles are depicted in Figure 1. 
 
Figure 1 Overview of the stages of the CLINICAL  EVALUATION (MDR) / PERFORMANCE  EVALUATION (IVDR) 
 
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 The requirements for CLINICAL EVALUATION  and PERFORMANCE EVALUATION are outlined in Article 61 of 
the MDR (including Annex XIV) and Article 56 of the IVDR (including Annex XIII), respectively. 
While the definition of CLINICAL EVALUATION  in the MDR and PERFORMANCE EVALUATION  in the IVDR 
are not identical (see section 0), there is a shared expectation for providing sufficient CLINICAL EVIDENCE  
to demonstrate conformity with relevant GSPRs under the normal conditions of the device’s intended use. 
CLINICAL EVIDENCE  should be sufficient and appropriate in view of the characteristics of the device, clinical 
risks and its intended purpose. The level of CLINICAL EVIDENCE  necessary should be specified and justified 
by the manufacturer.  
Three key components should be taken into account when compiling CLINICAL EVIDENCE  for every MDSW 
(Figure 1), and each is described below in further detail.  
VALID CLINICAL ASSOCIATION / SCIENTIFIC VALIDITY is understood as  the extent to which, the MDSW’s 
output (e.g. concept, conclusion, calculations) based on the inputs and algorithms selected, is associated 
with the targeted physiological state or clinical condition. This association should be well founded or 
clinically accepted (e.g. existence of a scientific framework or sufficient level of evidence as further 
elaborated in section 4.2 of this document). The V ALID CLINICAL ASSOCIATION / SCIENTIFIC VALIDITY  of 
a MDSW should demonstrate that it corresponds to the clinical situation, condition, indication or parameter 
defined in the intended purpose of the MDSW.  
NOTE: The VALID CLINICAL ASSOCIATION / SCIENTIFIC VALIDITY  seeks to establish that there are sound 
scientific principles underpinning the use of the MDSW in question. The information provided for the 
establishment of the V ALID CLINICAL ASSOCIATION / SCIENTIFIC VALIDITY  should put forward the case that 
the MDSW has an association with a clinical condition or physiological state. This association may not 
always be readily established. Thus, the C LINICAL PERFORMANCE  can serve as an additional input to the 
VALID CLINICAL ASSOCIATION / SCIENTIFIC VALIDITY  from a clinical perspective for the specific intended 
purpose (see Annex I).    
Example: MDSW that detects heart arrhythmia by analysing auscultation sound obtained by a digital 
stethoscope requires demonstrating VALID CLINICAL ASSOCIATION of the association between abnormal 
cardiac sounds and heart arrhythmia. 
Evidence supporting VALID CLINICAL ASSOCIATION / SCIENTIFIC VALIDITY  can be generated e.g. through 
literature research, professional guidelines, proof of concept studies, or manufacturer’s own clinical 
investigations/clinical performance studies. 
Validation of the  TECHNICAL PERFORMANCE / ANALYTICAL PERFORMANCE is the demonstration of the 
MDSW’s ability to accurately, reliably and precisely generate the intended output, from the input data. 
Evidence supporting T ECHNICAL PERFORMANCE  / ANALYTICAL PERFORMANCE can be generated through 
verification and validation activities, e.g. unit-level, integration, and system testing or by generating new 
evidence through use of curated databases, curated registries, reference databases or use of previously 
collected patient data. 
Validation of the  CLINICAL PERFORMANCE  is the demonstration of a MDSW’s ability to yield clinically 
relevant output in accordance with the intended purpose. The clinical relevance of a MDSW’s output is a 
positive impact  
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 - on the health of an individual expressed in terms of measurable, patient-relevant clinical 
outcome(s), including outcome(s) related to diagnosis, prediction of risk, prediction of 
treatment response(s), or 
- related to its function, such as that of screening, monitoring, diagnosis or aid to diagnosis 
of patients, or 
- on patient management or public health. 
Evidence supporting C LINICAL PERFORMANCE can be generated by testing the MDSW under evaluation, 
or an equivalent device, in the target population and for the intended use. The applied methodology should 
be appropriate in light of the device characteristics and intended purpose and may include pre-clinical 
testing, a clinical investigation or a clinical performance study. 
Specifically, for MDSW not claiming C LINICAL BENEFITS that can be specified through measurable, 
patient-relevant clinical outcome(s), clinically relevant outputs are achieved through demonstrated 
predictable and reliable use and USABILITY  (please refer to section 4.2 of this document).  
In addition, CLINICAL EVALUATION  or PERFORMANCE EVALUATION  of MDSW must consider the benefit-
risk ratio in light of the STATE-OF-THE-ART related to practice of medicine for diagnosis, treatment or patient 
management. It is further expected that the assessment of MDSW considers all components of the CLINICAL 
EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) (see Figure 1 and Annex 0). 
The three components described above do not represent a distinct stepwise approach but rather portray a 
methodological principle for the generation of CLINICAL EVIDENCE .  
To determine and justify the level of CLINICAL EVIDENCE , both amount and quality of supporting data 
should be evaluated. This assessment may be guided by the following non-exhaustive questions: 
Sufficient amount 
- Does the data support the intended use, indications, target groups, clinical claims and 
contraindications? 
- Have the clinical risks and analytical performance/ clinical performance been investigated? 
- Have relevant MDSW’s characteristics, such as the data input and output, the applied algorithms 
or type of interconnection been considered when generating the data to support the performance of 
the device? 
- What is the grade of innovation/ history on the market (how big is the body of scientific evidence)? 
- Other, as applicable. 
Sufficient quality 
- Were the type and the design of the study/ test appropriate to meet the research objectives? 
- Was the data set appropriate and actual (state of the art)? 
- Was the statistical approach appropriate to reach a valid conclusion? 
- Were all ethical, legal and regulatory considerations/ requirements taken into account? 
- Is there any conflict of interest?  
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 - Other, as applicable. 
4.2. Determination of the valid clinical association / scientific validity 
In the first step, the manufacturer should verify the association between the output of the MDSW (based on 
the inputs and algorithms selected) and the targeted physiological/ clinical condition, clinical situation or 
clinical parameter, as defined in the intended purpose of the MDSW. MDSW may include a multitude of 
clinical features governed by its intended purpose which require individual assessment.  
This association should be clinically accepted or well founded, which means accepted by the broad medical 
community and/or described in scientific (peer-reviewed) literature.  
VALID CLINICAL ASSOCIATION / SCIENTIFIC VALIDITY can be demonstrated through the use of existing 
CLINICAL PERFORMANCE DATA  while taking into account the generally acknowledged STATE-OF-THE-ART. 
VALID CLINICAL ASSOCIATION  / SCIENTIFIC VALIDITY may further be demonstrated by the creation of new 
CLINICAL PERFORMANCE DATA  in the cases where existing data is not sufficient. For example, as a result 
of a gap analysis, the manufacturer could conclude that additional data may be required. 
Examples of existing data (in no particular order) 
- Technical standards 
- Professional medical society guidelines 
- Systematic scientific literature review  
- CLINICAL INVESTIGATION s/ CLINICAL PERFORMANCE  STUDIES 
- Published CLINICAL DATA  (e.g. Summary of Safety and Clinical Performance (SSCP) / Summary 
of Safety and Performance (SSP), Registries and databases from authorities)  
Examples of generating new evidence (in no particular order) 
- Secondary data analysis (Analysis of real-world data) 
- Perform CLINICAL INVESTIGATION / CLINICAL PERFORMANCE  STUDY 
4.3. Technical Performance /Analytical Performance 
The manufacturer should verify that the MDSW reliably, accurately and consistently meets the intended 
purpose in real-world usage.  
The relevant performance characteristics, as part of the GSPRs and linked to the analytical and / or clinical 
features, should be supported by evidence generated during verification and validation activities as part of 
good manufacturing practices for software, or by generating new evidence through the use of curated 
databases, curated registries, reference databases or use of previously collected patient data.   
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 TECHNICAL PERFORMANCE  / ANALYTICAL PERFORMANCE  is confirmed by the examination and provision 
of objective evidence that the MDSW specifications conform to user needs and intended uses, and that the 
requirements implemented can be consistently fulfilled.7 
For example, performance verification and validation in the intended computing8 and use environments9,10 
can be characterised by the demonstration of  
- availability, 
- confidentiality, 
- integrity, 
- reliability, 
- accuracy (resulting from trueness and precision),  
- analytical sensitivity,  
- limit of detection,  
- limit of quantitation,  
- analytical specificity,  
- linearity,  
- cut-off value(s),  
- measuring interval (range),  
- GENERALISABILITY , 
- expected data rate or quality,  
- absence of inacceptable cybersecurity vulnerabilities,  
- HUMAN FACTORS ENGINEERING .  
Identification of gaps during the validation of the T ECHNICAL PERFORMANCE /ANALYTICAL 
PERFORMANCE  could require generation of new evidence, for example, to demonstrate generalisability with 
real-life datasets or to extend the usability evaluation to omitted user groups.  
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 C LINICAL 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 C LINICAL PERFORMANCE , it is demonstrated that users can achieve clinically relevant 
outputs through predictable and reliable use of the MDSW.  
                                                
7 Derived from Source: GHTF/SG3/N18:2010. 
8 Computing environment: e.g., hardware, memory size, processing unit, time zone, network infrastructure) under which the 
software is to perform. 
9 Use environment: actual conditions and setting in which users interact with the medical device.  
10 Example on operating environments with distinct requirements are cloud or remote networks.   
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 The manufacturer should consider the intended use(s), indication(s), desired clinical output(s) expressed as 
claims, leading to expected CLINICAL BENEFIT s 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 C LINICAL 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 C LINICAL PERFORMANCE  can be characterised by 
the demonstration of applicable C LINICAL 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, C LINICAL EVALUATION  of class III and implantable devices 
(MDR), shall include data from a C LINICAL 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 C LINICAL 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.  
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 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 PERFORMANCE s 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. 
4.5. Final analysis and conclusion of the clinical evaluation (MDR) / 
performance evaluation (IVDR) 
The manufacturer should compile evidence, perform the benefit-risk analysis and document the CLINICAL 
or PERFORMANCE EVALUATION and its output in the CLINICAL EVALUATION (MDR) / PERFORMANCE 
EVALUATION (IVDR)  report.  
4.6. Continuous update of the clinical evaluation (MDR) / performance 
evaluation (IVDR) 
The safety, effectiveness and performance of the MDSW should be actively and continuously monitored 
by the manufacturer.   
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 Such data may include, but is not limited to post-market information such as complaints, PMCF/ PMPF 
data, REAL-WORLD PERFORMANCE  data, direct end-user feedback or newly published research / guidelines 
and should be subject to the CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) 
principles depicted in Figure 1. 
The unique level of connectivity of MDSW facilitates access to REAL-WORLD PERFORMANCE  data, which 
can be used for multiple purposes, including, but not limited to 
- timely detection and correction of malfunctions; 
- detection of systematic misuse; 
- understanding user interactions; 
- to conduct ongoing monitoring of CLINICAL PERFORMANCE ; 
- to improve effectiveness; 
- develop the claims in the CLINICAL DEVELOPMENT PLAN (MDR) or future releases. 
MDSW can be released for CE marking with initially claimed and validated CLINICAL BENEFITS . 
Monitoring of REAL-WORLD PERFORMANCE  data can help formulate hypotheses about future MDSW 
functionalities and intended use(s).   
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 Annex I – Methodological principle for generation of CLINICAL EVIDENCE  
 
 
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 Annex II – Examples of CLINICAL EVALUATION (MDR) /  PERFORMANCE 
EVALUATION  (IVDR) strategies  
The high-level examples provided here are for guidance purposes only and aim to provide general 
indications on how to develop a CLINICAL EVALUATION / PERFORMANCE EVALUATION  strategy. The 
strategy presented in each example is not a confirmation  of the pathway for a CLINICAL EVALUATION / 
PERFORMANCE EVALUATION  of the device, as other factors need to be considered.  
Moreover, the proposed pathway reflects the specific intended purpose, or the healthcare context or 
situation, in which the device is used as described in the example itself. Any change to the intended purpose 
or the healthcare context / situation in which that same device is used might result in a different approach. 
Data source Examples 
Peer-reviewed, relevant scientific literature  - Existing data from studies conducted 
with the subject device or equivalent 
device 
CLINICAL INVESTIGATION / CLINICAL 
PERFORMANCE  STUDIES - Prospective or retrospective studies 
- Existing manufacturer data  
- Data from equivalent devices 
- Data from curated 
databases/registries/reference databases 
- Data from outside the EU with 
justification on applicability 
 
Published experience gained by routine 
diagnostic testing - REAL-WORLD PERFORMANCE DATA  
- Data obtained from PMPF/ PMCF 
 
 
a) MDSW intended to analyse sleep quality data 
An independent MDSW intended to take into account accelerometer and microphone data to determine 
quality of sleep and to estimate the expected success rate of CPAP (continuous positive airway pressure) 
treatment for sleep apnoea.  
The Manufacturer claims that the MDSW 
- determines the quality of sleep that impacts the general well-being. 
- monitors quality of sleep in patients with sleep disorders such as sleep apnoea (using phone 
sensors/wearable devices) 
- estimates the expected success rate of CPAP therapy. 
Valid Clinical Association  
To establish VALID CLINICAL ASSOCIATION , review literature. 
- Objective quality of sleep is measured by sleep duration, efficiency and fragmentation.  It is further 
well-established that quality of sleep impacts general well-being such as concentration, risk-factors 
for cardiovascular disease, mood, cognitive abilities, etc.   
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 - It is not well-established that the success of CPAP therapy can be predicted by monitoring the 
quality of sleep. 
- Address the association of accelerometer and microphone data to established quality of sleep 
parameters (e.g. sleep duration, efficiency and fragmentation). 
The VALID CLINICAL ASSOCIATION  has been not established without gaps for prediction of success of CPAP 
therapy, which requires generation of missing clinical data. 
Technical Performance  
- Confirm with verification and validation tests that the app can reliably and reproducibly calculate 
sleep quality scoring. 
- Confirm compatibility between the MDSW and the device equipped with the sensors to ensure data 
can be utilised in the intended way.  
Clinical Performance  
- In addition to the USABILITY  assessment, the manufacturer would perform a retrospective study on 
previously obtained data to confirm that success of CPAP therapy can be predicted based on the 
quality of sleep.  
b) MDSW intended for image segmentation 
An independent MDSW intended to allow automatic detection of organs and anatomical structures (such 
as the aorta) in CT scans with the accuracy of a radiologist. 
The Manufacturer claims that the MDSW: 
- detects abdominal aortic aneurisms on abdominal CT scans, 
- detects compression fractures on vertebrae,  
- detects liver cysts. 
Valid Clinical Association  
To establish VALID CLINICAL ASSOCIATION , review literature. 
- The normal shape and size of anatomy is well established. 
- Segmentation techniques on cross-sectional images correlates well with the actual size and shape. 
The VALID CLINICAL ASSOCIATION  has been established without gaps identified.  
Technical Performance  
- Confirm with verification and validation tests the basic technical performance such as display, 
modification, window levelling of images, measurements including confirmation of accuracy, 
sensitivity and reliability of the MDSW as per the expected performance. 
   
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 Clinical Performance  
- USABILITY  assessment including the intended user groups in conjunction with the VALID CLINICAL 
ASSOCIATION  and validation of T ECHNICAL PERFORMANCE  results has been determined as 
sufficient to demonstrate conformity with relevant GSPRs. 
- In cases where data is available, a retrospective analysis can be performed. In cases where data 
does not represent the variability of input parameters, for the CLINICAL PERFORMANCE  of the 
segmentation algorithm, the missing data could be generated in a prospective CLINICAL 
INVESTIGATION .  
c) MDSW intended to detect inflammatory bowel diseases (IBD) 
Self-testing independent MDSW intended for the semi-quantitative detection of calprotectin from a faecal 
sample. Reagents are added to the sample resulting in a colour change. The sample is then photographed 
on a smartphone, and the image is evaluated by an MDSW application (app) running on the phone. The 
MDSW app detects the colour change in the sample and interprets the concentration of calprotectin. The 
test is intended as an aid in monitoring and staging of patients with inflammatory bowel disease (IBD). 
Manufacturer’s claims that the MDSW app 
- aids in monitoring and staging the disease level of patients with inflammatory bowel diseases 
(IBD). 
- aids in differentiation between IBD and functional bowel disorders.  
- helps patients avoid unnecessary clinical visits.  
Scientific Validity  
To establish S CIENTIFIC VALIDITY, review literature.  
- The SCIENTIFIC VALIDITY could address how the calprotectin level corresponds to the IBD level 
and stages. Furthermore, it should address, whether calprotectin levels are suitable to differentiate 
between IBD and functional bowel disorders. 
- It is well-established that calprotectin concentration in faecal matter can be reliably measured in 
test strips by change of colour.  
- The colour intensity is directly representative of the concentration of calprotectin.  
Analytical Performance  
- Confirm the MDSW app can detect reliably and accurately the colour of the test strip compared to 
human observation, taking into account environmental factors.  
Clinical Performance  
- The manufacturer should assess the initial performance and feasibility by creating CLINICAL 
PERFORMANCE  metrics, taking into account sensitivity, specificity and confidence intervals. 
- Any claims regarding CLINICAL BENEFIT  should be supported by sufficient clinical performance 
data.   
- USABILITY  should be confirmed by the manufacturer.   
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 d) Active devices containing MDSW to enable their intended purpose  
Active devices, such as diagnostic or therapeutic devices, that include MDSW which drives the device in a 
way that, without the software it would not be able to fulfil its intended purpose. This software does not 
perform a medical purpose on its own.    
The CLINICAL EVALUATION  of the MDSW should not be performed independently but should be performed 
together with the driven device.  
e) MDSW which provides an additional user-interface to control an insulin pump 
A MDSW intended to virtualise controls of an insulin pump additionally on a smartphone app by connecting 
to it.  
As the software is driving the insulin pump, it is not performing a medical purpose on its own, nor is it 
creating information on its own for medical purposes.  
The CLINICAL EVALUATION  of the MDSW app should not be performed independently but should be 
performed together with the driven insulin pump.  
f) MDSW intended to analyse exhaled CO2 in a life-sustaining device in order to control 
ventilator settings 
The MDSW uses physiological data of the patient (e.g. exhaled CO 2, blood oxygen saturation) to control a 
ventilation device (e.g. frequency, volume and pressure). 
The MDSW allows the device to maintain the pre-set value at a desired target (defined by the clinician) 
without periodic user adjustments needed. This MDSW is part of a closed-loop system.  
The CLINICAL EVALUATION  should not be limited to the MDSW and should include pre-clinical and clinical 
investigations, encompassing the entire closed-loop system.