R-TF-015-001 Clinical Evaluation Plan_2023_001

Scope

The Clinical Evaluation Plan defines methods for creating and updating the Clinical Evaluation Report. This plan is updated later by the post-market clinical follow-up, e.g., to include new search criteria for the literature search.

Medical device information

Manufacturer contact details

	Manufacturer data
Legal manufacturer name	AI Labs Group S.L.
Address	Street Gran Vía 1, BAT Tower, 48001, Bilbao, Bizkaia (Spain)
SRN	ES-MF-000025345
Person responsible for regulatory compliance	Alfonso Medela, María Diez, Giulia Foglia
E-mail	office@legit.health
Phone	+34 638127476
Trademark	Legit.Health

Product characterization

	Information
Device name	Legit.Health Plus (hereinafter, the device)
Model and type	NA
Version	1.0.0.0
Basic UDI-DI	8437025550LegitCADx6X
Certificate number (if available)	MDR 792790
EMDN code(s)	Z12040192 (General medicine diagnosis and monitoring instruments - Medical device software)
GMDN code	65975
Class	Class IIb
Classification rule	Rule 11
Novel product (True/False)	FALSE
Novel related clinical procedure (True/False)	FALSE
SRN	ES-MF-000025345

Intended use or purpose

Intended use

The device is a computational software-only medical device intended to support health care providers in the assessment of skin structures, enhancing efficiency and accuracy of care delivery, by providing:

• quantification of intensity, count, extent of visible clinical signs
• interpretative distribution representation of possible International Classification of Diseases (ICD) classes.

Quantification of intensity, count and extent of visible clinical signs

The device provides quantifiable data on the intensity, count and extent of clinical signs such as erythema, desquamation, and induration, among others; including, but not limited to:

• erythema,
• desquamation,
• induration,
• crusting,
• dryness,
• oedema,
• oozing,
• excoriation,
• swelling,
• lichenification,
• exudation,
• depth,
• edges,
• undermining,
• pustulation,
• hair loss,
• type of necrotic tissue,
• amount of necrotic tissue,
• type of exudate,
• peripheral tissue edema,
• peripheral tissue induration,
• granulation tissue,
• epithelialization,
• nodule count,
• papule count,
• pustule count,
• cyst count,
• comedone count,
• abscess count,
• draining tunnel count,
• lesion count

Image-based recognition of visible ICD classes

The device is intended to provide an interpretative distribution representation of possible International Classification of Diseases (ICD) classes that might be represented in the pixels content of the image.

Device description

The device is computational software-only medical device leveraging computer vision algorithms to process images of the epidermis, the dermis and its appendages, among other skin structures. Its principal function is to provide a wide range of clinical data from the analyzed images to assist healthcare practitioners in their clinical evaluations and allow healthcare provider organisations to gather data and improve their workflows.

The generated data is intended to aid healthcare practitioners and organizations in their clinical decision-making process, thus enhancing the efficiency and accuracy of care delivery.

The device should never be used to confirm a clinical diagnosis. On the contrary, its result is one element of the overall clinical assessment. Indeed, the device is designed to be used when a healthcare practitioner chooses to obtain additional information to consider a decision.

Intended medical indication

The device is indicated for use on images of visible skin structure abnormalities to support the assessment of all diseases of the skin incorporating conditions affecting the epidermis, its appendages (hair, hair follicle, sebaceous glands, apocrine sweat gland apparatus, eccrine sweat gland apparatus and nails) and associated mucous membranes (conjunctival, oral and genital), the dermis, the cutaneous vasculature and the subcutaneous tissue (subcutis).

Intended patient population

The device is intended for use on images of skin from patients presenting visible skin structure abnormalities, across all age groups, skin types, and demographics.

Intended user

The medical device is intended for use by healthcare providers to aid in the assessment of skin structures.

User qualification and competencies

In this section we specificy the specific qualifications and competencies needed for users of the device, to properly use the device, provided that they already belong to their professional category. In other words, when describing the qualifications of HCPs, it is assumed that healthcare professionals (HCPs) already have the qualifications and competencies native to their profession.

Healthcare professionals

No official qualifications are needes, but it is advisable if HCPs have some competencies:

• Knowledge on how to take images with smartphones.

IT professionals

IT professionals are responsible for the integration of the medical device into the healthcare organisation's system.

No specific official qualifications are needed, but it is advisable that IT professionals using the device have the following competencies:

• Basic knowledge of FHIR
• Understanding of the output of the device.

Use environment

The device is intended to be used in the setting of healthcare organisations and their IT departments, which commonly are situated inside hospitals or other clinical facilities.

The device is intended to be integrated into the healthcare organisation's system by IT professionals.

Operating principle

The device is computational medical tool leveraging computer vision algorithms to process images of the epidermis, the dermis and its appendages, among other skin structures.

Body structures

The device is intended to use on the epidermis, its appendages (hair, hair follicle, sebaceous glands, apocrine sweat gland apparatus, eccrine sweat gland apparatus and nails) and associated mucous membranes (conjunctival, oral and genital), the dermis, the cutaneous vasculature and the subcutaneous tissue (subcutis).

In fact, the device is intended to use on visible skin structures. As such, it can only quantify clinical signs that are visible, and distribute the probabilities across ICD classes that are visible.

Variants and models

The device does not have any variants.

Expected lifetime

Its expected lifetime is considered unlimited because the device will be updated with each improvement opportunity extracted from the information and analysis of the data provided by the continuous and systematic post-market data follow-up.

Clinical benefits

• Claim 1: Comprehensive Dermatological Data for Informed Clinical Decisions. Comprehensive Analysis for Informed Decision Making. Improvement in Dermatological Assessment Accuracy. Precise Detection of Dermatological Features. Empowerment of Health Care Practitioners.
• Claim 2: Faster Measurement of Clinical Signs. Accurate and Objective Measurement of Clinical Signs. Precise Quantification, Count and Extent measure of Skin Issues. Facilitation of Longitudinal Skin Condition Monitoring. Consistent Tracking of Patient Condition Over Time. More agile follow-up consultations.
• Claim 3: Targeted Analysis for Facial Palsy Evaluation. Support in Assessing Facial Palsy. Accurate Assessment for Facial Palsy.
• Claim 4: Improved Operational Efficiency for Healthcare Organizations. Streamlining Healthcare Operations. Data-Driven Insights for Workflow Optimization.
• Claim 5: Support in Preliminary ICD Classification through Image Analysis. Aiding in ICD Classification. Diagnostic Support.

Identification of General Safety and Performance Requirements (GSPR)

The table below indicates the General Safety and Performance Requirements (GSPR) that required support from relevant clinical data as well as the risks related to each applicable GSPR. The identification of the applicable GSPR for the device is the foundation of the clinical development plan based on the MDR (Article 61 and Annex XIV Part A) and the Guidelines MEDDEV 2.7/1, MDCG 2020-1 and MDCG 2020-5.

General requirements	Applicable?	Related hazard or hazardous situation risks
GSPR 1: The product shall achieve the intended performance and be suitable for its intended purpose. The product shall be safe and effective and shall not compromise the clinical condition or the safety of patients.	TRUE	5, 6, 7, 9, 20
GSPR 2: Eliminate or reduce risks as far as possible without adversely affecting the benefit-risk ratio.	TRUE	21
GSPR 3: Establish, implement, document and maintain a risk management system. Establish and document a risk management plan, identify and analyze the known and foreseeable hazards, estimate and evaluate the risks, eliminate or control the evaluated risks, and evaluate the impact of information from the production phase and post-market surveillance system and amend control measures if necessary.	TRUE	21, 27
GSPR 4: Manage risks so that the residual risk associated with each hazard as well as the overall residual risk is judged acceptable. eliminate or reduce risks as far as possible through safe design and manufacture, take protection measures in relation to risks that cannot be eliminated, provide information for safety and, when appropriate, training to users. Inform users of any residual risks.	TRUE	5, 6, 9, 21, 26, 28, 29, 30
GSPR 5: Eliminate or reduce risks related to use error.	TRUE	1, 2, 3, 4, 8, 16, 17, 18, 19, 31, 36
GSPR 6: The characteristics and performance shall not be adversely affected during the lifetime of the product.	TRUE	40, 48, 49, 50, 51
GSPR 7: The characteristics and performance shall not be adversely affected during transport and storage.	FALSE
GSPR 8: All known and foreseeable risks shall be acceptable when weighed against the evaluated benefits to the patient and/or user.	TRUE	9, 26, 41, 54
GSPR 9: For the devices referred to in Annex XVI, the general safety requirements set out in Sections 1 and 8 shall be understood.	FALSE
GSPR 10: Chemical, physical and biological properties.	FALSE
GSPR 11: Infection and microbial contamination.	FALSE
GSPR 12: Products incorporating a medicinal product absorbed by the human body.	FALSE
GSPR 13: Products incorporating materials of biological origin.	FALSE
GSPR 14: Construction of products and interaction with their environment.	TRUE	1, 2, 4, 11, 13, 16, 19, 23, 25, 31, 36
GSPR 15: Products with a diagnostic or measuring function.	TRUE	34, 35, 37, 38
GSPR 16: Protection against radiation.	FALSE
GSPR 17: Electronic programmable systems.	TRUE	25, 26, 29, 34, 35, 37, 38
GSPR 18: Active products and products connected to them.	TRUE	5, 6, 7, 11, 12, 13, 14, 15, 26, 29, 40
GSPR 19: Particular requirements for active implantable products.	FALSE
GSPR 20: Protection against mechanical and thermal risks.	FALSE
GSPR 21: Protection against risks posed by products supplying energy or substances.	FALSE
GSPR 22: Protection against risks posed by medical products intended by the manufacturer for use by lay persons.	FALSE
GSPR 23: General requirements regarding the information supplied by the manufacturer. Information on the label. Information on the packaging which maintains the sterile condition of a device (‘sterile packaging’). Information in the instructions for use.	TRUE	1, 2, 3, 4, 5, 7, 9, 10, 11, 12, 13, 14, 18, 19, 22, 23, 24, 25, 28, 29, 30, 36, 41, 43, 44, 45, 46, 48, 49, 51, 53, 54

Risk management

Methods to examine clinical safety

The methods used to evidence the medical device clinical safety are based on preclinical and clinical data analysis, and the acceptability of the benefit/risk ratio derived from this analysis.

The results obtained performing the activities described at the R-TF-007-002 PMCF plan are the inputs to analyse the clinical safety and the emerging risks that could be detected according to our GP-013 Risk management procedure.

Acceptability of the benefit-risk ratio

The risk/benefit acceptability is based on the analysis of the possible risks of the product in relation to its benefits.

Once per year, the conclusions extracted from the preclinical and clinical data analysis will be used to confirm the benefit/risk ratio of the device. This analysis will be drafted in the T-015-002 Preclinical and clinical evaluation record and T-015-003 Clinical evaluation report.

The parameters used to determine, based on the state of the art, the global acceptability of the benefit/risk ratio for the intended purpose of the device are:

• No adverse effects should be found in the preclinical data evaluation.
• Current literature should support the usage of AI on the manufacturing process and should evidence the clinical benefits of the use of the device.
• Current literature should also show the feasibility of the device in comparison with current alternatives and solutions. The advantages of the device (PMCF activity 2) should be clear.
• No significant risks should be identified in relation to patient safety.
• The positive impact of the device should be strongly evidenced on the performance and the feedback obtained (PMCF activities 2 and 4).
• The use of the device as a skin structure assessment support tool, should be proven necessary due to its multiple advantages. Based on the device's characteristics, the device should not have side-effects specifically related to its use and should have a high benefit/risk ratio.

Benefit-risk issues relating to specific components

This section does not apply to the device as there are no specific additional components on it.

Clinical development plan

As required by the MDR 2017/745, we continuously generate, collect, analyse and assess the clinical data related to the device in order to verify the safety and performance, evaluate the undesirable side-effects and the acceptability of the benefit-risk ratio throughout the device's life cycle. We plan, conduct and document a clinical evaluation in accordance with the requirements established in the MDR (Article 61 and Annex XIV Part A) and following the Guidelines MEDDEV 2.7/1, MDCG 2020-1 and MDCG 2020-5.

Data identification and selection

Sufficient amount and quality of data shall be identified and analyzed to build relevant evidence that allows performing a non-biased and objective assessment of whether the device under evaluation is safe and achieves the intended clinical benefits, when used as intended by the manufacturer. This is performed through:

• Analysis of preclinical data to identify:
  • Applicable and/or harmonized standards, according to the Technical File.
  • Related and/or governmental publications that may be observed in relation to the product.
  • Similar devices that provide data related to similar features, previous experience, and similar:
    • Intended use.
    • Principles of operation (safety & performance).
    • Functional elements.
  • State of the art publications about the related medical fields, medical conditions, technology and available alternative treatments.
• Analysis of clinical data relating to the safety, performance, design characteristics and intended purpose of the device under evaluation and/or an equivalent device:
  • Clinical investigation(s) of the device performed by the manufacturer.
  • Clinical investigation(s) or other studies reported in scientific and clinical literature, of a device for which equivalence to the device can be demonstrated.
  • Reports published in peer reviewed scientific and clinical literature on other clinical experience of either the device or a device for which equivalence to the device can be demonstrated.
  • Clinically relevant information coming from post-market surveillance, in particular the post-market clinical follow-up.

Responsible evaluators

The process of data identification and selection is developed and executed by professionals with expertise in information retrieval and understanding of the scope of the clinical evaluation set out by us. More details about the clinical team can be found below.

Data sources

The evaluation of data is based on a critical and analytical assessment of the available literature. The different sources utilized are:

• Preclinical data:
  • National and international institutions and medical devices regulatory bodies webs:
    • https://www.aemps.gob.es/
    • http://imdrf.org/safety/safety.asp
    • https://www.medtecheurope.org/
    • https://ec.europa.eu/growth/single-market/european-standards/harmonised-standards/medical-devices_en
    • https://ec.europa.eu/info/policies/public-health_en
    • https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfmaude/search.cfm
    • https://www.cisa.gov/cybersecurity
    • https://www.enisa.europa.eu/
    • https://www.nbog.eu/
  • Other manufacturers' similar devices websites.
  • State of the art publications in renowned journal databases.
• Information generated by the manufacturer.
• Clinical data:
  • Renowned journal databases to support scientific validity:
    • https://pubmed.ncbi.nlm.nih.gov/
    • https://onlinelibrary.wiley.com/
    • https://link.springer.com/
    • https://www.sciencedirect.com/
    • https://scholar.google.es/
  • Clinical trials registry platforms to identify relevant investigational studies:
    • https://www.who.int/clinical-trials-registry-platform/the-ictrp-search-portal
    • https://clinicaltrials.gov/

Search filters

When using the search tool of specific websites or when searching in journal databases, at least the first 5 pages are considered for their further evaluation. If the same scientific publication appears under different search characteristics, the repeated source is ignored and the following source is analysed instead. The scientific and clinical publications are already sorted out by relevance. Moreover, a time filter (last 3 years) is applied in order to ensure that the most recent information is evaluated. Relevant citations referenced in the scientific and clinical literature already selected from the previous sources might also be considered for evaluation.

Research questions and keywords

The technical documentation of the device as well as the state of the art is used to develop the clinical research questions and keywords. The method PICO is chosen to help breaking down into four components the research questions. These identify the key problem of the patient, what treatment or tests are available for the patient, what alternative treatment or tests are being considered (if any) and what is the desired outcome to promote or avoid.

• P = Patient Population: it describes the most important characteristics of the patient. This may include the primary problem, disease, or co-existing conditions.
• I = Intervention, prognostic factor or exposure: it describes the main intervention, prognostic factor, or exposure.
• C = Comparator: it describes the main alternative to compare with the intervention. This can be different devices, tests or placebo. Sometimes the clinical question may not always have a specific comparison.
• O = Outcomes: it describes performance and safety a) What intervention wants to accomplish, measure, improve or affect. This can be to relieve or eliminate the symptoms or reduce the number of adverse events. b) Currently known risks or evidence on safety of the intervention or comparators.

Database search steps

The defined research keywords are used and the search filters are applied in the clinical data sources previously specified to retrieve relevant information allowing a systematic assessment of the available literature.

Step 1: Use PICO to formulate the search strategy.

#		Selectet terms
1	Patient population	Dermatosis, Skin cancer, Chronic skin conditions, inflamatory skin diseases, malignant skin lesions, pigmented skin lesions, melanoma, basal cell carcinoma, squamous cell carcinoma, atypical nevus, acne, psoriasis, urticaria, atopic dermatitis, onychomycosis, melasma, solar lentigo, dermatofibroma
2	Intervention	Clinical image, digital imaging, web application, smartphone, dermatoscopy, camera
3	Comparator	Artificial intelligence, machine learning, deep learning, computer vision, deep neural networks, convolutional neural networks, molescope, metaoptima, dermengine
4	Outcomes	Diagnosis, diagnosis support, followup, segmentation, detection, estimation, classification

Description

Patient population AND Intervention AND Comparator AND Outcomes (Performance OR Safety)

Scheme

# 1 AND # 2 AND # 3 AND # 4

Search

The combination of terms used for the search will be detailed at the report with the corresponding findings.

Step 2: Search parameters.

Randomized Control Trials (RCTs) are often considered the gold standard and represents the cornerstone of Evidence-Based Medicine (EBM) due to the rigorous methodology used. RCTs allow avoidance of bias related to confounding factors (through a control group), selection bias (through randomization) and interpretation bias (through double blinding). Moreover, they elementary aspects of the scientific report are included such as adequate statistical methods and controls. Likewise, meta-analysis studies provide high evidence, and clinical trials are considered to report high-quality data. Therefore, the search parameters are:

• Type of trials: randomized controlled trials, meta-analysis and clinical trials.
• Publication time: last 3 years (since 2021).
• Species: humans.
• Number of publications: all the results of the first 5 pages.

Additionally it is required to look at search details to look for contraindications and adverse events reported, meaning that "contraindication" OR "adverse event" should be considered in the search parameters established.

info

It is worth mentioning that we performed a previous clinical evaluation and databases search covering the period from 2012 to 2020 for our medical device placed on the market following the 93/42/EEC MDD regulation that can be consulted within its corresponding technical file.

Device equivalence

As described at the corresponding Device equivalence section of the GP-015 Clinical evaluation procedure, the equivalence table from the Guideline MDCG 2020-5 is used to identify the supporting data to demonstrate device equivalence. We place emphasis on the differences between the device and an equivalent device rather than the similarities.

In line with the MDR 2017/745 requirements, we consider the following characteristics to claim device equivalence and compile them at the R-TF-015-003 Clinical evaluation report:

1. Technical Characteristics (add a separate row for each of the assessed characteristics)	Device 1 (under clinical evaluation) Description of characteristics and reference to specifying documents	Device 2 (marketed device) Description of characteristics and reference to specifying documents	Identified differences or conclusion that there are no differences in the characteristic
Device is of similar design			1.1
Used under similar conditions of use			1.2
Similar specifications and properties including software algorithms			1.3
Uses similar deployment methods where relevant			1.4
Has similar principles of operation and critical performance requirements			1.5

Scientific justification why there would be no clinically significant difference in the safety and clinical performance of the device, OR a description of the impact on safety and or clinical performance (use one row for each of the identified differences in characteristics, and add references to documentation as applicable)	Clinically significant difference Yes / No
1.1
1.2

2. Biological Characteristics (add a separate row for each of the assessed characteristics)	Device 1 (under clinical evaluation) Description of characteristics and reference to specifying documents	Device 2 (marketed device) Description of characteristics and reference to specifying documents	Identified differences or conclusion that there are no differences in the characteristic
Uses the same materials or substances in contact with the same human tissues or body fluids			(The characteristic must be the same for the demonstration of equivalence) 2.1

Scientific justification why there would be no clinically significant difference in the safety and clinical performance of the device, OR a description of the impact on safety and or clinical performance (use one row for each of the identified differences in characteristics, and add references to documentation as applicable)	Clinically significant difference Yes / No
2.1

3. Clinical Characteristics (add a separate row for each of the assessed characteristics)	Device 1 (under clinical evaluation) Description of characteristics and reference to specifying documents	Device 2 (marketed device) Description of characteristics and reference to specifying documents	Identified differences or conclusion that there are no differences in the characteristic
Same clinical condition or purpose, including similar severity and stage of disease			3.1
Same site in the body			(The characteristic must be the same for the demonstration of equivalence) 3.2
Similar population, including as regards age, anatomy and physiology			3.3
Same kind of user			(The characteristic must be the same for the demonstration of equivalence) 3.4
Similar relevant critical performance in view of the expected clinical effect for a specific intended purpose			3.5

Scientific justification why there would be no clinically significant difference in the safety and clinical performance of the device, OR a description of the impact on safety and or clinical performance (use one row for each of the identified differences in characteristics, and add references to documentation as applicable)	Clinically significant difference Yes / No
3.1
3.2

Summary

In the circumstance that more than one non-significant difference is identified, we will provide a justification whether the sum of differences may affect the safety and clinical performance of the device.

For every single characteristic incorporated in the table, scientific justification must be elaborated to show that there is no clinically significant difference in the safety and performance of the device. For the identification of characteristics that may affect safety and for the assessment of equivalence regarding safety, we implement a risk-based approach.

Both favorable and unfavorable data from the device as well as from the devices for which equivalence can be demonstrated must be identified. This data may come from:

• Scientific and clinical literature
• Common specifications
• Harmonized standards
• Other established technical specifications

All this data progresses to data appraisal and analysis in order to evaluate whether they are providing sufficient clinical evidence for the purpose of confirmation of conformity with the applicable GSPR.

Data appraisal

Once the data is identified in the current literature, the content is appraised to evaluate its suitability for establishing the safety and performance of the device. The manufacturer's clinical team evaluates each piece of information taking into consideration three parameters: the methodological quality of work and scientific validity of the information, the relevance to the device and its intended use, and the contribution to the overall evaluation. Then, the clinical team accepts or rejects the data after applying the following weight-based system:

Data characteristics	Methodological quality Q	Relevance, R	Contribution, C	Weighted value, W (W=Q+R+C)	Appraisal data	Notes
Very relevant information in relation with the product and its intended use	Up to 40	Up to 30	Up to 30	W ≥ 70	Accepted	Pivotal data
Relevant information in relation with the product and its intended use	Up to 40	Up to 30	Up to 30	30 < W < 70	Accepted	Other data
Little relevant information in relation with the product and its intended use	Up to 40	Up to 30	Up to 30	W ≤ 30	Rejected	No contribution, rejected

These three indicators allow a systematic weighted evaluation:

• Methodological quality and scientific validity: examination of the methods used to generate and collect the data, and evaluate to which extent the observed outcomes are the result of the device/technology under evaluation or are due to confounding influences, bias, random error, inadequate disclosure of information or misinterpretation. The methodology is accepted when:
  • Data is extracted from RCTs (Randomized Clinical Trials), meta-analysis and clinical trials, from publications based on scientific evidence or from previous experience on the market.
  • The study design is adequate in terms of type, sample size, relevance of endpoints, randomization of patients, inclusion and exclusion criteria, stratification of patients, prognostic factors, follow-up, recording and reporting of serious adverse events, reliability of the methods used for quantifying outcomes, or procedures for retrieving complete information.
  • Data consists of an adequate number of observations that can confirm or refute the claims of the device under evaluation.
  • The methods for data processing and statistics are suitable.
  • It complies with Good Clinical Practice (GCP) according to EN ISO 14155 or equivalent standards.
  • The information is disclosed in an adequate manner, including summary, introduction, methods, results, discussion and conclusions.
• Relevance: examination of whether the data directly demonstrates adequate clinical performance and clinical safety of the device under evaluation, or whether the data serves as indirect supportive role. The information is relevant when:
  • It is representative of the device under evaluation, including data concerning the medical conditions that are managed with the device, other devices and medical alternatives, or equivalent devices.
  • The aspects covered are related to clinical safety and performance, claims, hazards and hazardous situations, management of risks, establishment of current knowledge and state of the art, determination and justification of the benefit/risk ratio and the acceptability of undesirable side-effects, or the determination of equivalence.
  • It is representative to the intended purpose or claims of the device under evaluation.
  • It is representative to the user group, patient population, medical indication, age group, gender, type and severity of the medical condition, or range of time.
• Contribution:
  • Device and/or related techniques intended use. The contribution of the analyzed data in relation to the device or techniques features and in relation to the intended use must be strong and clear.
  • Device and/or related techniques risk analysis. The contribution of the analyzed data in relation to the device or techniques risk analysis must be strong and clear, based on keywords definition.

On the other hand, the information is rejected when:

• There is a lack of information (only the abstract is available).
• The information comes from reviews, editorials or opinion papers.
• The study design and/or statistical methods are inadequate.
• The topic discussed is not related to the device and/or technology under evaluation.
• Bias or influencing factors are present (conclusions are inconsistent and can lead to misinterpretations).
• The information is inaccessible or repetitive.

Therefore, the information meeting the inclusion criteria and obtaining a value W > 30 after going through the weighted-based system will be accepted. On the contrary, the information with a value W ≤ 30 will be rejected. Proper justification for the decisions made, whether the information is accepted or rejected, must be given under the column named “DATA ANALYSIS AND CHARACTERISTICS EXTRACTION” of the T-015-002 Preclinical and clinical evaluation record.

PMS and PMCF data appraisal

The PMS data will be analyzed according to the General Procedure GP-007 Post-market surveillance. The same criterion, which is documented and structured in the Preclinical and clinical evaluation record (T-015-002 Preclinical and clinical evaluation record), will be applied to identify, and select preclinical and clinical data from the available literature.

Periodically and according to the PMS and PMCF plans, the clinical evidence as well as new data will be revised, appraised, and evaluated objectively yearly to confirm the product's intended use, the acceptable benefit/risk ratio and the accomplishment of the GSPRs.

Clinical investigations

If necessary, generate, through properly designed clinical investigations in accordance with the MDR 2017/745 regulation and ISO 14155:2020 standard, any new or additional clinical data necessary to address outstanding issue.

As we explained at the GP-015 Clinical evaluation procedure, we will carry out a clinical investigation study based on a Clinical Investigation Plan or Protocol (T-015-004 Clinical Investigation Plan (CIP)) and a investigator brochure (T-015-005 Investigator's Brochure). The results will be documented in the Clinical Investigation Report (T-015-006 Clinical Investigation Report (CIR)).

As established in the Guideline MEDDEV 2.7/1, the clinical evaluation will identify aspects that need to be addressed systematically during post-market through the clinical investigations, as well as through the post-market surveillance and other post-market clinical follow-up studies. Aspects such as residual risks, any uncertainty or unanswered question, rare complications, uncertainties regarding long-term performance and/or safety under wide-spread use will be evaluated during post-market. Moreover, the planned clinical investigations will generate clinical evidence to support scientific validity and clinical performance, as stated in the Guideline MDCG 2020-1.

Proof of concept studies or other studies

Proof of concept studies will generate clinical evidence to support scientific validity and technical performance, as indicated in the Guideline MDCG 2020-1. The ones that are planned are detailed at the R-TF-015-008 Clinical development plan_2023_002.

Data analysis

The data accepted from the appraisal is analyzed in order to reach conclusions about the safety and clinical performance of the device including its clinical benefits and possible adverse events.

Data analysis is performed qualitatively, although some aspects can be analyzed quantitatively such as the number of incidents or serious adverse events. The appraised data is evaluated to find consistency of results related to performance and safety characteristics, risks and benefits to patients, users and other persons associated with the intended purpose of the device under evaluation, and the confirmation of usability.

Moreover, following the MDCG 2020-1, three key components are taken into consideration to analyze the clinical evidence of the device:

• Valid clinical association: the extent to which the software's output, based on the inputs and algorithms selected, is associated with the targeted physiological state or clinical condition defined in the intended purpose.
  • Evidence generated through the previous literature research, proof of concept studies or manufacturer's own clinical investigations/clinical performance studies.
• Technical performance: ability to accurately, reliably and precisely generate the intended output from the input data (principle of operation).
  • Evidence generated through verification and validation activities.
• Clinical performance: ability to yield clinically relevant output in accordance with the intended purpose. It assesses clinical safety, effectiveness and performance. It supports the demonstration of clinical benefits against foreseeable or known risks associated with the product (benefit/risk ratio acceptability) and compared with current processes, expected benefits and diagnostic/therapeutic/monitoring improvements.
  • Evidence generated through device equivalence in the target population and for the intended use, contraindications and undesirable effects, and through clinical investigations.

Lastly, it is analyzed the alignment and consistency between the current knowledge and state of the art, the clinical evaluation, the information materials supplied by the manufacturer, and the risk management documentation for the device under evaluation.

GAP analysis

We carry out a gap analysis to confirm whether the existing data are sufficient to verify that the device under evaluation is in conformity with the applicable GSPR. As a result of this gap analysis, the creation of new clinical data may be considered necessary. The manufacturer may conclude that additional data is required, for example, in the form of further clinical investigations studies.

Clinical Evaluation Report (CER)

A final T-015-003 Clinical Evaluation Report (CER) will be drafted. The essential content is:

• Summary
• Scope of the clinical evaluation
• Clinical background, current knowledge and state of the art
• Device under evaluation
• Analysis of the clinical data
• GAP analysis
• Conclusions
• Date of the next clinical evaluation
• Qualification of the responsible evaluators
• References

This report shall contain sufficient data and effective conclusions related to the safety and performance characteristics, the undesirable side-effects and the acceptability of the benefit-risk ratio of the device. Every year, said report (T-015-003 Clinical Evaluation Report (CER)) must be updated in relation to:

• Device intended use.
• Device characteristics.
• Safety and performance of the device. GSPR accomplishment and relationship.
• Users group, target population, and related medical fields and conditions.
• Side-effects and complications.
• Benefit/risk ratio.
• Applicable harmonized standards.

This update will be evidenced in the Preclinical and clinical evaluation record (T-015-002 Preclinical and clinical evaluation record).

Responsible evaluators

The qualifications and experience of the responsible evaluators are provided in the T-015-003 Clinical Evaluation Report (CER) to demonstrate that the responsible person(s) fulfil the requirements to evaluate the product clinical evaluation.

Name	Position	Company	Role in the evaluation	Declaration of interest	CV
María Diez	JD-004 Quality Manager and PRRC	AI Labs Group SL	Author	Yes	Yes
Alberto Sabater	JD-009 Medical Data Scientist	AI Labs Group SL	Author	Yes	Yes
Taig Mac Carthy	JD-003 Design and development Manager	AI Labs Group SL	Author	Yes	Yes
María Belén Hirigoity	Dermatologist and Medical Advisor to Legit.Health	Hospital 9 de Octubre and Alta Estética clinic	Reviewer	Yes	Yes
Constanza Balboni	Professor of Medicine (Dermatology) and Medical Advisor at Legit.Health	UBA School of Medicine	Reviewer	Yes	Yes
Alfonso Medela	Technical Responsible and PRRC	AI Labs Group SL	Approver	Yes	Yes

Record signature meaning

• Author: JD-004 María Diez
• Review: JD-003 Taig Mac Carthy
• Approve: JD-005 Alfonso Medela