During the conformity assessment, the manufacturer must submit the complete information material (labelling, IFU (Instructions for Use), any promotional materials and other relevant documents), Clinical evaluation plan & report with the available clinical data, which includes (General Safety and Performance Requirements) GSPR, intended target groups and purpose, qualitative and quantitative aspects of clinical safety, performance procedures and other risk factors involved. The manufacturer must carry out a gap analysis to fill the sufficient data according to the guidelines to meet the safety and performance of the device as in PART A Annex XIV in MDR 2017/745.
A clinical evaluation report (CER) is a technical document submitted by the manufacturer for the conformity of the devices. While updating the clinical evaluation, the manufacturer must consider,
Frequency of updates:
- If the device carries any frequency risk during the intended use
- If the device needs any changes like clinical sciences, materials, or other evaluation
- Consider the data available on the PMCF (Post Market Clinical Follow-up) reports, clinical investigations, and other studies which may influence the frequency of updates.
- Changes in the design or procedure
- For the showing of equivalency – technological, biological, and clinical criteria must be considered.
Some general considerations during the updates:
PMS (Post Market Surveillance) always gets updated with new data like safety reports, published literature, registries, PMCF reports and other data during the intended purpose. Those data should be fed into the clinical evaluation periodically. Also, check the benefit-risk ratios, undesirable side effects and other risk mitigations during the updates. This may result in changes in the risk management reports, IFUs (Instructions for Use) and PMS activities as in PART B Annex XIV in MDR 2017/745.
Before conducting clinical evaluation and/or investigation for all class III and class IIb devices, the manufacturer is permitted to consult the expert panel mentioned in Article 106 MDR to review the manufacturer’s intended clinical development strategy and proposals for clinical investigation. In particular, the criteria for an appropriate data set for assessment of the conformity of a device, regarding the clinical data necessary for clinical evaluation, physio-chemical characterization, and microbiological, biocompatibility, mechanical, and electrical considerations, shall be made available to the Member States, notified bodies, and manufacturers through the Commission.
The person who performs the clinical evaluation should know
- Research Methodology
- Information management
- Regulatory requirements
- Medical writing with a degree from higher education or 5 to 10 years of professional experience
- The technology of that device and complete information
- Diagnosis and management of medical alternatives with the standards
Stage 0 Define the scope.
Basic and various aspects of the scopes are
- Initial device description
- Design features, intended purpose, applications of the device and other equivalence
- Complete risk management documents which address clinical risks
- Any changes in the design, material, or procedures. Also, any changes in IFUs, labels or other promotional materials
- PMS aspects like new clinical data or knowledge which may change the state of the art and other aspects
It is crucial to acknowledge that there is a wide range of types, histories, and hazards associated with the technology employed in medical devices. Since many devices have undergone incremental development or modification, they are not unique. It might be possible to use the clinical reports of an equivalent device’s performance and safety from experience and literature to establish the requirement for clinical data acquired by clinical trials by utilizing the clinical evidence investigation of the experimental device.
Stage 1 Identification of Pertinent data
Manufacturer-generated and stored data:
All premarket clinical investigations, risk management activities and PMS programs like PMCF studies, vigilance reports, literature and compliance reports, field safety corrective actions, and other user reports.
Searching the literature reveals prospective sources of clinical data. The following aspects need to be considered.
- Identify all the relevant favourable and unfavourable data
- Obtain several types of searches like scientific literature databases, internet and non-published data and other literature that has a direct interest
- Literature search and other appraisals of clinical data
The literature search must be thoroughly documented so that the methodology can be evaluated critically, and the findings can be confirmed, and the search can be repeated as needed.
Stage 2 Appraisal of pertinent data
The appraisal/evaluation plan includes
- Criteria for judging the methodological quality and scientific validity of each data set
- Standards for establishing the device’s intended use relevance to the clinical evaluation
- Standards for weighing each data set’s contribution to the overall clinical assessment
The following section provides examples of factors that can be considered when assessing the methodological quality and scientific validity of the evidence, as in Article 61(3).
- Pre- and post-market clinical investigation study plans like adequacy of sample size, random or blinding of patients, adequacy of the follow-up period, serious adverse effects reports and other medical interventions
- Some additional aspects like a clinical investigation plan, case report form, audits, regulatory authority approvals, ongoing clinical investigation report which is conducted outside or in the territory and other gap analysis
- Data obtained from case studies, patient dossiers, device registries, vigilance data, and other useful data
- Data processing is like converting data to a standard format, and statistics
- Good clinical practice with all the legal requirements
- Sufficient description with proper disclosure of the report
When assessing the relevance of obtained data, we must consider whether the data are meant to directly demonstrate appropriate clinical performance and clinical safety of the device (commonly referred to as pivotal data) or whether they serve an indirect supportive role.
There is no one well-established approach for weighting clinical data due to the variety of medical devices. Instead, the evaluators should choose the best criteria to apply to each evaluation and adhere carefully to these pre-established criteria.
Stage 3 Analysis of Clinical Data
A device’s clinical efficacy and safety should not be demonstrated using data that are not methodologically sound (such as single patient reports). The evaluators should employ reliable methodologies, conduct a thorough study, decide whether more clinical research or other actions are required, and identify PMCF needs to establish compliance.
During the evaluation, the evaluator should include
- Pre-clinical testing
- Benefits-risks associated with the patients
- IFU correctly addresses risk mitigating methods
- Gap analysis like identifying the entire range of products used during evaluation, conditions of use, the number of patients exposed, severity of adverse events, hazard analysis, current standard of care and other profiles
- Some additional investigation into missing data and eradicating the issues of compliance.
- Determine medium or long-term PMCF needs
Stage 4 Clinical Evaluation Report (CER)
The manufacturer must demonstrate compliance with the general safety and performance requirements using clinical evidence, non-clinical data obtained from non-clinical testing methods, and other pertinent documentation. These materials must also be included in the technical documentation for the relevant device.
Cross-references between the clinical evaluation report’s contents and the pertinent documentation supporting them are required. Which claims are supported by which pieces of data, and which express the evaluators’ opinions should be clear? With cross-references to the location in the technical documentation from the manufacturer, the report should include references to literature-based data as well as the titles and investigational codes of any clinical investigation reports (if applicable and available).
What are CEP and CER?
The clinical evaluation plan (CEP) outlines the devices that will focus on the CER, including their dimensions, intended uses, target population, and patient clinical benefits. Every time brand-new medical equipment is put on the market, the manufacturer must prove that it conforms to all applicable Essential Requirements (ERs) by using the proper conformity assessment methods.
What is the demonstration of equivalence?
When proving equivalence to another device, the MDR stipulates those technical, biological, and clinical features. Although MEDDEV 2.7 Appendix 1 describes these general qualities and aligns them with the MDR Annex XIV Part A (3) requirement, the requirements for each of the three characteristics differ.
What do you mean by similar devices?
Similar devices are devices that fall within the same general device category. The MDR defines this as a group of devices with the same or comparable intended uses or a shared technology that enables them to be categorized in a general way without reflecting characteristics.
What are the available guidelines and guidance documents for clinical evaluation?
Please refer to the following link for more guidance
Guidance – MDCG endorsed documents and other guidance (europa.eu)
Also, refer to the MEDDEV 2.7/1 revision 4, June 2016 for any clarification.