A Clinical Evaluation remains one of the most scrutinised elements of EU MDR submissions and is a leading cause of Notified Body deficiencies.
Irrespective of whether manufacturers are well-established or new to the market, they often face severe consequences, such as costly rework of submissions, delayed market access, and even device rejection, due to avoidable gaps in meeting MDR compliance requirements.
Notified Bodies consistently highlight that the Clinical Evaluation and clinical investigation are the most common areas of MDR non-conformities across all device classes. A review of recent deficiency letters and white papers shows the same pattern. Notified-Body reviewers are still flagging predictable, repeatable weaknesses in Clinical Evaluation.
The five most commonly identified deficiencies are as follows:
1. Insufficient clinical evidence
Common Issues Observed
- Device specific claims made in the Clinical Evaluation are not supported by data.
- Clinical data has not been appropriately connected against the intended patient populations, treatment indications, and device variants.
- Overreliance on literature or equivalence data without proper justification.
What does a Notified Body expect?
- Manufacturers must develop robust, high quality clinical evidence aligned with the device’s intended purpose and risk class.
- Whenever feasible, generate manufacturer-led clinical investigation data or implement a comprehensive post-market data collection plan.
- Provide Specific and Measurable Outcomes (SMOs) data for each indication and patient population, and each device variant.
- If evidence gaps exist, justify with risk-based arguments and outline corresponding PMCF activities.
2. Incomplete or improper appraisal criteria and exclusion rationale
Common Issues Observed
- Literature search not systematic, transparent, or reproducible.
- Lack of clarity on how literature was screened and selected for inclusion.
- Poorly defined appraisal criteria for analysing clinical evidence.
What does a Notified Body expect?
- Implement a systematic, well-documented literature search strategy that specifies databases, timeframes, search strings, and inclusion/exclusion criteria.
- Maintain an audit trail of excluded records with clear exclusion criteria.
- Define appraisal criterion for determining the methodological quality of a study. Evaluate the completeness and transparency of disclosures related to study design and methods, products or interventions used, patient population characteristics, subject numbers and attrition, clinical outcomes, adverse events, statistical analyses, and specification of intention-to-treat versus per-protocol populations.
3. Failure to identify safety and performance objectives from the State-of-the-Art (SOTA) review
Common Issues Observed
- Safety and performance objectives are too generic or lack SMOs.
- Clinical claims not benchmarked against the SOTA performance and safety outcomes.
- Missing justification for clinical endpoints or acceptance criteria.
What does a Notified Body expect?
- Define specific and measurable outcomes early, based on intended purpose (performance) and device risk profile (safety).
- Clearly state which outcomes will be used to assess safety and performance.
- Establish a quantitative threshold or acceptance criteria for each outcome, justified with appropriate SOTA or clinical data sources.
4. Poor Integration of Risk Management with the Clinical Evaluation
Common Issues Observed
- Disconnect between the Clinical Evaluation and the manufacturer’s risk management process.
- Benefit–risk justification not supported by clinical data.
- Unverified risk mitigations or unaddressed residual risks.
What does a Notified Body expect?
- Presenting quantitative comparisons against the SOTA outcomes.
- Verify that all residual risks have corresponding clinical data to support.
- Use a traceability matrix showing clinical evidence for each identified risk.
5. Inadequate Post-Market Surveillance (PMS) / Post-Market Clinical Follow up (PMCF)
Common Issues Observed
- PMS and PMCF were treated as post-approval tasks rather than part of evidence generation.
- Lack of ongoing evidence refinement based on real-world data.
What does a Notified Body expect?
- Show that the PMCF activity endpoints mirror the outcomes needing confirmation.
- Develop a targeted PMCF plan based on identified clinical gaps and residual risks.
How manufacturers could be proactive: Clinical Evaluation - pre-submission review
At Mantra Systems, our new service “Clinical Evaluation - pre-submission review” has been designed to support medical device manufacturers in identifying the gaps before EU MDR submission by simulating a Notified Body review.
How does this service work?
The review tool has been developed in line with key EU MDR and MDCG guidance documents, including Annex XIV (Parts A and B) of the EU MDR, MDCG 2020-6, and MedDev 2.7/1 rev 4. The tool incorporates an expert document review to ensure the Clinical Evaluation is complete, consistent, and fully prepared for submission.
Within seven days of submitting your prepared Clinical Evaluation, you receive a clear, actionable report that enhances confidence in the robustness of your Clinical Evaluation. Each report includes a comprehensive gap analysis mapped against EU MDR requirements, along with detailed recommendations to strengthen clinical justifications and confirm that the level of evidence is appropriate for the device’s intended purpose and risk classification. A concise guidance summary also highlights critical versus minor findings, enabling effective prioritisation and targeted follow-up actions. This process enables early identification of weaknesses in your Clinical Evaluation strategy, ensuring targeted improvements before submission.
Why Use a Pre-Submission Review?
By proactively addressing potential deficiencies, manufacturers can:
- Shorten Notified Body review cycles by one to two rounds
- Reduce costly rework and avoid submission delays
- Accelerate CE marking and market access timelines by months
- Support a smoother path to patient safety and regulatory compliance
- Improve internal quality and regulatory confidence before submission.
The Clinical Evaluation - pre-submission review offers manufacturers a practical, fast-turnaround solution to validate their Clinical Evaluation Report against regulatory expectations before submission. By identifying and resolving issues early, it safeguards timelines, reduces rework costs, and strengthens the overall quality and defensibility of clinical evidence.
Contact us today to learn more about our pre-submission review service to ensure your Clinical Evaluation is robust, as early as possible.
