Expert panel opinions on clinical evaluations: procedure and synthesis of consultations
[article first published on 6 july 2021]
The “Clinical Evaluation Consultation Procedure (CECP) for Certain DMs” is an additional requirement for clinical evaluations of implantable and IIb DM IIIs delivering/withdrawing a medicinal product, according to Article 54 of Regulation (EU) 2017/745.
This article explains the procedure for consultation, details the content of an opinion, and summarizes published opinion. It is updated when new publications are made.
Expert group consultation procedure
Below is a reminder of the regulatory process, repeated ad-libitum:
- The manufacturer produces a clinical evaluation report
- The notified body of the manufacturer produces an evaluation of the clinical evaluation report (per MDCG 2020-13)
- The European Expert Group:
- Assesses the need to produce an opinion (“screening” stage, by the “Preliminary Review” expert group)
- When appropriate: produced an opinion on the NB report (“opinion” step, by the expert group most appropriate for the MD being evaluated)
- The notified body shall take into account the opinion of the expert panel
- The manufacturer takes into account that the NB takes into account the opinion of the expert panel
An aid for your clinical evaluations
It can be important, even critical, to take into account published opinions, even if they don’t directly relate to your products. This is all the more necessary :
- If you are subject to the panel consultation process, to understand their expectations and angles of approach
- If you are equivalent to the target device: to benefit from the state of the art study included in the report (publications and issues in the field)
- (If you are not too confident in your NB)
👉 In general, these opinions provide a better understanding of the purposes of clinical studies.
Content of an expert panel opinion
The following §s outline an opinion
Part 1: Decision of the screening experts
Here, the need to produce an opinion is evaluated according to 3 criteria:
- Novelty of device and/or of related clinical procedure and associated risks;
- Health concerns identified in the literature;
- Significant increase of serious incident (relevant for the assessment).
Summary of selection
- Date of decision
- If applicable: summary of reasons if the information is deemed insufficient to reach a decision.
- Summary of reasons for producing an opinion. This may be motivated by relative uncertainties:
- to the intended use
- to the performance of the device
- to the quality of the clinical data, including:
- duration of studies
- completeness, relative to indications for use
- Other comments: this is to elaborate on the reasons that confirmed/infirmed the need for opinion.
The three selection criteria
Criterion 1: Novelty and clinical impact
Novelty may relate to the devices and/or the associated procedure for use.
- Description of novelty:
- indications for use
- procedures for uses
- principle of operation
- physical composition
- manufacturing process
- Level of Novelty:
- Incertainties related to novelty, e.g., long-term clinical validity
- Possible negative health impacts associated with novelty
- Severity of negative impacts, on 4 levels:
- Incertainties related to clinical impact, e.g., uncertainties about duration, clinical protocol, indications …
Criterion 2: Health concerns
Or, in the long version, “Scientifically valid health concerns leading to significantly adverse changes in the benefit/risk profile.”
- Bibliography : the list of publications used for making an opinion
- MD group/category: presumably according to the EMDN nomenclature
- Source of health concerns: likely to relate to
- the materials;
- health impact in the event of device failure;
- Description of concerns and health impact
- Quality and relevance of data used
Criterion 3: Significant increase of serious incidents
- Relevance of the data
- Summary of information used
Selection of the expert panel
If applicable, an experts panel is selected to formulate an opinion, from the ten existing panels.
Part 2: Expert panel opinion
👉 Status opinion on the adequacy of the study, caution: the opinion is very clear-cut, it will quickly be unfavorable if there are too many risks or uncertainties in the case.
- Device description: identification and medical indications
- Novelty of the device: identification and degree of novelty
- Evaluation assessment: type of clinical evaluation (new data, literature); adequacy of study (duration, indication, relevance of equivalence…); adequacy of planned PMCF
- Adaptation of clinical evidence: identification of clinical data gaps, related to both risks and benefits, based on intended uses
- Estimation of B/R: judges whether conclusions about B/R are admissible, given the above
- Clinical evidence vs. medical indications: status if evidence is sufficient, based on indications
- Planning for PMCF: assesses whether the PMCF plan is appropriate
- Conclusions and recommendations: if applicable, lists advice for resuming clinical assessment, phrased in the conditional tense but to be taken in the imperative
This is where the NB assessment is really critiqued, according to five criteria:
- An opinion on the NB’s assessment of the adequacy of the manufacturer’s clinical evaluation report.
- Advice on the NB’s assessment of the sufficiency of the clinical evidence provided by the manufacturer.
- Advice on the NB’s assessment of the adequacy of the manufacturer’s determination of the benefit/risk ratio.
- Advice on the NB’s assessment of the consistency of the manufacturer’s clinical evidence with the intended purpose, including the medical indication(s)
- Notice on the NB’s assessment of the consistency of the manufacturer’s clinical evidence with the PMCF plan.
👉 Note that the list of publications used to forge the opinion is provided.
General conclusions and recommendations
A summary of the expert panel’s opinion, you may want to start with this summary to get an idea of the opinion.
Divergences in the expert panel
Where applicable, differences among the experts are explained.
List of published opinions
The table below provides a synthesis of published opinions, a link is provided to each of the reports.
|MD type||bone graft material||acetabular inserts/cup||artificial plumonary heart valve||transcatheter heart valves||tricuspid valve replacement system||Resorbable mesh with a resorbable hydrogel coating|
|Expert planel||General and plastic surgery dentistry||Orthopaedics, traumatology,
|Circulatory system||Circulatory system||Circulatory system||General and plastic surgery and dentistry|
|Competence area||Maxillofacial surgery & Dentistry||Joint replacements (hip, knee, shoulder)||Prosthetic heart valves and devices for heart valve repair||Prosthetic heart valves and devices for heart valve repair||Prosthetic heart valves and devices for heart valve repair||Surgical implants and general surgery|
|NB||MDC MEDICAL DEVICE CERTIFICATION GMBH||BSI Group The Netherlands B.V.||DEKRA Certification B.V.||DEKRA Certification B.V.||DEKRA Certification B.V.||BSI Group The Netherlands B.V.|
|Novelty Type||Device||Device||Device||Procedure||Device and Procedure||None|
|Overall conclusions and recommendations||Presented clinical data for one indication (#4) are presently insufficient and should be extended to include at least the healing phase for the implant (additional 4 months) and the results can then also be used for a positive clinical assessment for indication #3 and #5. For the other indications data from clinical studies are missing and therefore the evidence for these indications in insufficient. Literature survey is flawed by the fact that the new device is similar but not equivalent to market products. The PMCF plan needs to be extended and specified e.g. to cover in detail the other claimed indications. If relevant data are available, the indications can be accordingly extended.||The expert panel concurs with the NB’s assessment of the manufacturer’s conclusions on benefit-risk determination for the change in PMMA spacer material grade. Longitudinal monitoring of clinical outcomes as proposed in the manufacturer’s PMCF plan is considered adequate to detect unexpected mechanisms of failure, insufficient performance, and a survival rate below the acceptable rate for clinical excellence.||The manufacturer should review the clinical and market availability of similar devices for the same indications as expressed in the Valve System IFU. Specifically, the expert panel identified one medical device approved by the U.S. Food and Drug Administration for clinical use. The CER should discuss differences and similarities of the devices and include another device clinical evidence into the CER discussion.
Misinformation on Valve System generations should be clarified, with specific indications on which generation types have been used in studies presented in CER, the reasons for generation improvements and the existence of the 4th device generation for clinical use in a clinical research study published in 2021
|Patients at high risks : The panels agrees with the NB
Patients at low to intermediate risks : The panel considers that the benefit/risk balance of alves for this subpopulation is not sufficiently supported by evidence in terms of amount and quality. The panel recommends that more prolonged follow-up from AVIV is reported (especially as the database extract was last performed in August 2020) and that additional studies are conducted so as to confirm external validity of the first registry.
|A positive benefit-risk ratio is not sufficiently demonstrated. A randomized controlled trial with comparison to optimized medical therapy alone would be relevant to properly assess the efficacy and safety of this novel technology.||Expert panel agrees with the NB’s assessment on the benefit-risk ratio of this device for the clinical indications currently under scrutiny in the early postoperative period. Further long-term studies with appropriate follow-up strategies are needed to draw definitive conclusions.|
|Conclusions of the notified body validated ?||no||yes||?||no||no||yes|