Manager
Regulatory Affairs | 10+ Years of Experience Medical device
Under modern regulatory frameworks such as the EU Medical Device Regulation (EU MDR 2017/745) maintaining a clear distinction between “clinical data” and “clinical evidence” is a critical requirement for compliance.
Having large volumes of clinical data doesn’t always equate to having enough clinical evidence to prove the safety, performance and benefit risk profile of your medical device. One of the most common reasons for Notified Body rejection, delayed market access and expensive post market actions is the lack of understanding and addressing of clinical data gaps when producing/updating your Clinical Evaluation Report.
Understanding the Difference Between Clinical Data and Clinical Evidence
To build a strong Clinical Evaluation Report, it is important to understand how regulatory bodies globally distinguish between clinical data and clinical evidence.
What Is Clinical Data?
Clinical data refers to all raw or structured safety and performance information derived from the use of a medical device. According to EU MDR Article 2(48), clinical data is sourced from:
- Clinical investigations of the device concerned.
- Clinical investigation or clinical study data from equivalent device.
- Peer reviewed scientific literature
What Is Clinical Evidence?
According to Article 2(51) of the EU MDR, clinical evidence means clinical data and clinical evaluation results pertaining to a device of a sufficient amount and quality to allow a qualified assessment of whether the device is safe and achieves the intended clinical benefits when used as specified by the manufacturer.
It is the synthesized outcome of critically appraising all available clinical data to scientifically demonstrate that:
- The device achieves its intended purpose and clinical benefits.
- The device is clinically safe, with acceptable side effects.
- The benefit-risk ratio is favorable.
Key Takeaway: Clinical data represents the raw ingredients, whereas clinical evidence is the evaluated, scientifically justified outcome documented in your Clinical Evaluation Report (CER).
Also Read: Clinical Evaluation Report (CER) for Medical Devices: EU MDR Compliance Guide
What are Clinical Data Gaps?
Clinical data gaps are where there is insufficient clinical data to fully demonstrate conformity with GSPRs.
Common reasons for clinical data gaps:
- Moving from MDD to EU MDR Many devices have been cleared under MDD and do not include state of the art clinical trial data.
- Unsubstantiated claims within IFU Including claims in IFU that are not supported by clinical studies.
- Equivalency claims Not meeting the strict requirements of EU MDR for technical, biological and clinical equivalence.
- No data across demographics or subgroups No data available for various demographics such as paediatrics, geriatrics or high-risk patients.
- Late safety data: This is where there is insufficient post market data to demonstrate long term safety and longevity of the device.
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Clinical Data vs. Clinical Evidence: Key Differences
Feature / Metric | Clinical Data | Clinical Evidence |
Regulatory Definition | Raw or structured safety and performance information generated from the use of a medical device (EU MDR Art. 2(48)). | Clinical data and evaluation results of sufficient amount and quality to assess device safety and intended clinical benefits (EU MDR Art. 2(51)). |
Stage in Evaluation | Input: Unprocessed “raw material” gathered from various scientific and post-market sources. | Output: Refined, synthesized outcome after critical appraisal and scientific evaluation. |
Primary Sources | Clinical investigations, scientific literature, PMCF surveys, complaint files, and PMS registry data. | Compiled Clinical Evaluation Report (CER), SOTA analysis, and benefit-risk justification files. |
Core Objective | To capture real-world performance metrics, user feedback, and adverse event data. | To scientifically prove compliance with GSPRs (EU MDR) or Valid Scientific Evidence standards. |
Reviewer Focus | Notified Bodies check for data completeness, statistical power, and source relevance. | Notified Bodies evaluate the logical strength of the clinical argument and validity of benefit claims. |
Sufficiency Criterion | Determined by data volume, sample size, study endpoints, and the clinical relevance/quality of individual data sources. | Depends not only on data volume or sample size, but on the quality and relevance of available data, and whether the overall clinical evaluation robustly supports conclusions on device safety and intended clinical benefits. |
Step-by-step approach to identifying and addressing gaps
To address data gaps prior to submission of technical documentation to a Notified Body follow the below approach.
Define State-of-the-Art (SOTA)
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Review & Appraise Available Clinical Data
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Identify clinical evidence gaps
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Develop an Evidence Generation Strategy
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Update the CER
- Define State of the Art (SOTA)
Understand what the current standard of care is for clinical performance, alternatives and safety by undertaking a literature search.
- Review & Appraise Available Clinical Data
Identify relevant data and assess its quality, relevance and suitability for the device’s intended purpose. - Identify clinical evidence gaps
Determine whether the available evidence adequately supports the relevant GSPRs, intended clinical benefits and safety conclusions. - Develop an Evidence Generation Strategy
Determine how each identified gap should be addressed. PMCF may be appropriate, but additional literature evaluation, a clinical investigation or other suitable approaches may be needed, depending on the gap. - Update the CER
Document the appraisal, identified gaps, actions taken and conclusions on the sufficiency of the clinical evidence.
Regulatory Requirements
Clinical Evidence requirements under EU MDR
The clinical evaluation is an ongoing process under EU MDR. Manufacturers will need to continually update their CER using PMCF Reports, PSURs and SSCP for Class III implantable devices.
Clinical Evidence expectations from the FDA (510(k), PMA & De Novo)
The FDA requires data to be gathered using Valid Scientific Evidence (21 CFR 860.7) to support submissions to the US Market. Under 510(k) there is a large emphasis on substantial equivalence, however if the technology is novel (De Novo) or high risk (PMA) clinical investigations will be required to show safety and efficacy.
Read Next: Clinical Study vs. Clinical Evaluation: Key Differences in Medical Device Regulation
How can Operon Strategist help with your CER?
Operon Strategist offers an end-to-end approach to clinical evaluation, clinical research and regulatory strategy to meet global requirements. We offer a complete range of clinical evidence generation and clinical studies to medical device manufacturers worldwide including:
- Clinical Strategy & Feasibility: We develop clinical evidence strategies, study designs, site selection and investigator selection. We will also provide budgets and timelines.
- Study Design & Documentation: We draft compliant clinical study documents including Clinical Investigation Plans (CIP), Informed Consent Forms (ICF), Case Report Forms (CRF) and Investigators Brochures (IB). We will also gain ethics approval, CTRI registration and CDSCO clinical investigation approval (Form MD-22 / MD-23).
- Study Execution & Monitoring: We will manage site initiation, clinical monitoring, investigator and vendor coordination and will report Serious Adverse Events (SAE) and device deficiencies.
- CER Gaps & Literature Review: We will review technical files to identify any clinical data gaps. We will then perform a State of the Art (SOTA) search to identify literature according to MEDDEV 2.7/1 Rev 4 and EU MDR.
- Reporting & PMCF: We will write final Clinical Investigation Reports, Clinical Evaluation Reports (CER) and will produce targeted PMCF plans, registries and surveys.
- Quality Management System (QMS): We will ensure your clinical evaluation and investigation processes are integrated into your ISO 13485 Quality Management System (QMS). We can ensure alignment with FDA and EU MDR, De Novo, PMA).
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FAQ's
What is the difference between clinical data and clinical evidence?
Clinical data refers to raw data collected from studies, registries, literature or PMS. Clinical evidence is when you have critically appraised and interpreted this data to demonstrate the safety, performance and benefit risk profile of your device within a CER.
Are legacy devices able to use literature and PMS data alone to meet the clinical evidence requirements?
No, under EU MDR legacy devices cannot assume they can use literature or sales data. If the quality of data is poor and you cannot show equivalence based on the strict requirements of the MDR, then you may need to carry out a prospective PMCF study or clinical investigation.
How do I know if there is a clinical data gap in my CER?
If your current data set does not justify all intended uses, patient sub-populations, clinical benefit claims or state of the art requirements requested by Notified Bodies then you have a clinical data gap.
What happens if my Notified Body finds a clinical data gap?
A major non-conformity will be issued by your Notified Body meaning your device could be halted from receiving CE marking or the manufacturer will need to initiate a PMCF study.
Can I use a PMCF to address any clinical data gaps?
Yes, using a good PMCF plan (registries, surveys, PMCS etc.) you are able to gather clinical data to address any gaps identified.
Manager – Regulatory Affairs | 10+ Years of Experience
Medical device regulatory professional specializing in US FDA 510(k), EU MDR CE marking, Software as a Medical Device (SaMD), regulatory strategy, technical documentation, and risk management. Her expertise includes regulatory submissions, device classification, and regulatory gap assessments.
