Item 3: Clinical Data

Deficiency

Clinical assessment of the device is incomplete based on the requirements of Annex XIV and Article 61.

Requirements and references

• Article 2(48)
• Article 2(51)
• Article 61(1)
• Article 7
• GSPR 1
• Annex XIV (b), (c), and (e)
• Annex XIV (2)
• Annex XIV (3)

MDF reference

MDF4550 §3.1.3, 3.1.5, 3.2.1, 3.2.3

Context

Requirements

• Article 2 (48) defines clinical data
• Article 2 (51) defines clinical evidence
• Article 61 (1) 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 7 In the labelling, instructions for use, making available, putting into service and advertising of devices, it shall be prohibited to use text, names, trade marks, pictures and figurative or other signs that may mislead the user or the patient with regard to the device's intended purpose, safety and performance…
• GSPR 1 Devices shall achieve the performance intended by their manufacturer and shall be designed and manufactured in such a way that, during normal conditions of use, they are suitable for their intended purpose...
• Annex XIV b, c, and e discusses the requirements to identify and analyze all relevant clinical data in order to make conclusion about the benefit, safety and performance of the device
• Annex XIV (2) The clinical evaluation shall be thorough and objective, and take into account both favourable and unfavourable data. Its depth and extent shall be proportionate and appropriate to the nature, classification, intended purpose and risks of the device in question, as well as to the manufacturer's claims in respect of the device.
• Annex XIV (3) A clinical evaluation may be based on clinical data relating to a device for which equivalence to the device in question can be demonstrated. The following technical, biological and clinical characteristics shall be taken into consideration for the demonstration of equivalence…

Observations

See question 2. Appropriate device description, intended purpose/indications, and clinical benefit claims, outcomes and acceptance criteria and performance and safety objectives and acceptance criteria as based on SotA to meet the requirements of Annex XIV 1 (a) sub-bullets 2, 3, 4 and 6 have not been found.

The clinical evaluation does not provide sufficient analysis of evidence to support clinical benefits and outcomes, and safety and performance of the device under the intended purpose (including patient population, all indications/diseases, etc.):

For example:

As it pertains to the overall analysis:

• It is unclear how all clinical benefit claims have been met. The document entitled "Clinical Benefits" is difficult to follow, links to CIs do not work for traceability, it is unclear how/why data has been pooled or what the categories represent (e.g. many categories of specificity for 7GH, etc). An overall analysis including justifications and limitations is not found
• It is unclear how all safety and performance claims have been met. The document entitled "Performance Claims" is difficult to follow, links to CIs do not work for traceability, it is unclear how/why data has been pooled. Some acceptance criteria have not been met and further analysis/justification has not been performed. An overall analysis including justifications and limitations is not found

As it pertains to the Clinical Investigations:

For CIs MC DAO and IDEI, the following is not found:

• Communication with competent authority
• If the studies were publicly registered (and number if so)
• If the studies were published in a journal
• Any deviations from the protocol

Evidence of sufficient analysis is not found:

• How do the CIs sufficiently cover all/representative patient populations (age, pigment, sex, etc) and indications (including sufficient coverage of malignant/high risk conditions in particular)
• Sufficient traceability to clinical benefit, safety, and performance outcomes
• Justifications of methodology and analysis of limitations are incomplete (e.g. removal of data if photo quality was poor (as this may occur in clinical practice), photos taken with dermatoscopic camera only (is this representative of how the device will be used), why for MC DAO 200 patients were initially targeted but the study was stopped after 105, justification for sample sizes
• A discussion of if all acceptance criteria were met for each was not found

As it pertains to Equivalence:

• Equivalence assessment seems to be at a high level with a lack of detail
• It remains unclear if changes have been made to the device since the time of marketing. Although §17.8 of the CEP states that changes have not been made to the MDD/legacy device other than documentation compliance for MDR, §16.24 of the CER seems to state that improvements have been made. It is unclear what these changes are (a list is not found), and justification that these would not be expected to impact clinical safety and performance is not found.

As it pertains to clinical literature:

• §16.4.4 of the CER seems to state that there are no relevant articles identified on the subject device in the literature. §3.1 of the SotA document lists "clinical data" for each clinical application, however, these seem to be on alternative/similar devices rather than the subject device (note that tables are cut off)
• Additionally, it remains unclear if the same protocol (including appraisal methodology) as described for SotA applies to the clinical literature search (and any differences in keywords, etc do not seem to be identified)

As it pertains to PMS:

• Although this device seems to have been marketed since 2020 per §1 of the CER, with 21 contracts and 4500 reports, no discussion of data from the market, including any complaints, serious incidents, CAPAs, FSCAs, etc is found.