CE Marking Meets Reimbursement: Aligning Clinical Evaluation and EU Health Technology Assessment Requirements

CE Certification vs EU HTA: Different Objectives, Shared Evidence

In the EU, CE certification of medical devices and Health Technology Assessment (HTA) have long served different purposes: notified bodies verify safety and performance for CE‑certification, while HTA bodies assess a technology’s added clinical value compared with existing alternatives to determine its reimbursement value. This division is often mirrored within manufacturers, with separate teams managing regulatory submissions and reimbursement strategies. 

Growing awareness of the need to align clinical evidence for both processes, now reinforced by mandatory Joint Clinical Assessments (JCAs) under the EU HTA Regulation (HTAR 2021/2282) alongside MDR/IVDR, has highlighted the importance of coordinated data generation and internal communication. Adopting a holistic approach early in development can streamline evidence planning, reduce duplication, and ensure scientific consistency. Effective clinical data generation is central to meeting requirements for both CE‑certification and JCAs, and early alignment helps bridge differences in methodology, evidence expectations, and timelines.

Timing and Applicability

From a timeline perspective, the clinical (or performance) evaluation is the first major step in generating, analysing, and appraising clinical evidence. It is mandatory for CE certification for all device classes. Although it is a continuous process, the initial evaluation must be completed before CE certification. 

JCAs, by contrast, apply only to: 

• Medical devices of class IIb or III under MDR-Article 51 for which the relevant expert panels have provided a scientific opinion in the clinical evaluation consultation procedure.
• Class D invitro diagnostics for which expert panels have provided views.

Not all eligible devices undergo JCAs. Devices may be selected based on criteria in Art. 7(4) HTAR, including: 

• unmet medical need 
• first in class 
• potential impact on patients, public health, or healthcare systems 
• significant crossborder dimension 
• major Unionwide added value 
• inclusion of artificial intelligence or machine learning software 

The European Commission designates devices for JCA through an Implementing Decision.

MDR, IVDR and the EU HTA Regulation Framework

CE certification under the framework of the MDR or IVDR requires demonstration of compliance with general safety and performance requirements through structured clinical or performance evaluation that draws conclusions about benefit–risk.  

The EU HTA Regulation, on the other hand, introduces a structured, collaborative approach meant to harmonise clinical assessments across Member States. Medical devices/IVDs may be selected for JCAs by Commission Implementing Decisions from 2026 onward. These assessments aim to determine relative clinical effectiveness and safety compared to relevant alternatives, while enabling Member States to maintain full autonomy over pricing, reimbursement, and non‑clinical evaluation domains. JCAs and JSCs are HTACG‑run HTA procedures under the HTA Regulation (with a secretariat provided by EMA). This framework is expected to accelerate access by reducing redundancy in national evaluations and promoting more consistent use of evidence across Europe. 

Clinical Data Generation for CE Marking and HTA

In addition to regulatory and HTA structural changes, scholarly work has examined why clinical trials designed for regulatory submissions often fall short of meeting HTA expectations. Comparative evidence is a central concern. HTA bodies frequently find that pivotal clinical investigations rely on comparator arms that do not adequately represent regional standard of care, limiting conclusions about relative benefit in real-world clinical practice. A recent review of Joint Clinical Assessment implementation describes how variations in comparator selection and PICO frameworks across countries create uncertainty and require early and transparent agreement between developers and evaluators. As the PICO framework for the JCA is specified by the HTA body, early application for Joint Scientific Advice (JSC) might be helpful in strategy planning. Often times, CE-certification often relies on smaller datasets and short follow‑up periods, pushing further data evidence generation into the post market clinical follow-up phase. Sometimes ethical limitations prevent clinical investigation design requirements, especially around randomisation or placebo/sham groups. 

Patient-Relevant Outcomes and Clinical Benefit in HTA

Another challenge relates to outcomes. While clinical evaluation focuses predominantly on safety and performance endpoints established from state of the art literature review, HTA bodies prioritise outcomes that matter to patients and health systems, such as quality of life, functional improvement, caregiver burden, treatment convenience, and long‑term real‑world effectiveness. Research on patient involvement in HTA emphasises that patient‑reported outcomes (PROMs), qualitative studies, and patient preference research can meaningfully inform both the design and assessment of health technologies. Such evidence helps to articulate unmet needs, identify relevant endpoints, and contextualise benefits in real-world settings. This form of patient-generated evidence is increasingly seen as essential for HTA appraisal, especially within new EU-level frameworks urging greater transparency, stakeholder engagement, and incorporation of patient perspectives. Integrating these dimensions early in clinical development can reduce the risk of HTA‑identified “uncertainties” that might otherwise delay reimbursement or restrict access. This can mainly be addressed through a careful clinical patient benefit statement selection. The patient clinical benefit is already an essential part of the clinical evaluation and defined by the MDR as “positive impact of a device on the health of an individual, expressed in terms of a meaningful, measurable, patient-relevant clinical outcome(s), including outcome(s) related to diagnosis, or a positive impact on patient management or public health” and in the IVDR as “positive impact of a device related to its function, such as that of screening, monitoring, diagnosis or aid to diagnosis of patients, or a positive impact on patient management or public health”.

Why Early Alignment Matters

The following fictional scenario demonstrates how misalignment in evidence planning can create real‑world consequences for manufacturers. A manufacturer developing a novel Class III cardiac monitoring device completes its pivotal study using a comparator common in North America but rarely used in most EU healthcare systems. While the data fully satisfies MDR requirements for CE‑certification, the HTA body preparing the Joint Clinical Assessment will most likely that the chosen comparator does not reflect EU clinical practice, making the relative effectiveness difficult to assess. As a result, additional real‑world data collection is requested, delaying reimbursement decisions in several Member States. Had the company engaged early in Joint Scientific Consultation, the appropriate EU‑relevant comparator and outcomes could have been integrated into the initial study design, avoiding months of downstream uncertainty. 

Strategic Approach

In light of these expectations, early alignment within the different departments at manufacturers and potential engagement between manufacturers, Notified bodies and HTA bodies is the most effective mechanism for aligning evidence requirements. 

Joint Scientific Consultations, now supported through coordinated activities between EMA and the HTA Coordination Group, provide a single forum for discussing clinical trial design elements, study endpoints, comparator selection, and use of real‑world data. EMA guidance stresses that such interactions are increasingly important for technologies with substantial uncertainty at launch, enabling developers to anticipate both regulatory and HTA needs and to generate evidence that minimises gaps at the reimbursement stage. Early engagement also allows patient communities to provide structured input on meaningful outcomes and care pathways, which can be incorporated into trial protocols and contribute to stronger evaluative consistency across the technology lifecycle.

Lifecycle Evidence Planning Under MDR and HTA

The efforts for clinical data collection have shifted towards consideration of the complete lifecycle of a device – which needs to be accounted for in the initial Clinical Development Plan. Although the Clinical Development Plan is a requirement from MDR/IVDR, it lays down the efforts on clinical evidence generation over the complete life cycle of the device. Therefore, clinical data generation strategies should consider requirements from all regulations, including:

• Appropriate endpoint selection.
• Appropriate clinical investigation design.
• Appropriate comparator groups.
• Appropriate timing.

Key Strategic Questions for Evidence Planning

A number of questions and approaches can help planning when asked early on: 

• What is the clinical benefit of my device? 
• How can I support this benefit, what should therefore be my clinical investigation endpoints? These need to be quantifiable, patient oriented and supportive of the clinical benefit. Both safety and performance of the device need to be considered. 
• Which (regionally relevant) comparator group is appropriate? What is the current standard of care, which similar devices are on the market? 

 The foundation to answer these questions is profound research of the current state of the art in the relevant medical field – including standard diagnostic or treatment approaches. It is important to account for geographic applicability. Focusing on the EU market might not be sufficient, regional differences in health care systems might need to be accounted for and guidelines from relevant expert societies should be consulted. 

Aligning CE Marking and EU Reimbursement Strategy

Overall, aligning clinical evaluation with HTA requirements is not simply a matter of harmonising regulatory and reimbursement terminology. It represents a shift toward integrated, anticipatory, and patient-centred evidence planning across the full lifecycle of a health technology.

References

• Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices (EU MDR), OJ L 117, 5.5.2017, p. 1–175.
• Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices (IVDR), OJ L 117, 5.5.2017, p. 176–332.
• Regulation (EU) 2021/2282 of the European Parliament and of the Council of 15 December 2021 on health technology assessment (HTAR), OJ L 458, 22.12.2021, p. 1–70.
• European Commission. Joint Clinical Assessments. Available at: https://health.ec.europa.eu/health-technology-assessment/implementation-regulation-health-technology-assessment/joint-clinical-assessments_en (accessed 13-FEB-2026)
• European Medicines Agency. New EU rules for health technology assessments become effective. 10 January 2025. Available at: https://www.ema.europa.eu/en/news/new-eu-rules-health-technology-assessments-become-effective (accessed 13-FEB-2026)
• Medical Device Coordination Group (MDCG). MDCG 2020‑6: Guidance on Sufficient Clinical Evidence for Legacy Devices. April 2020. Available at: https://health.ec.europa.eu/system/files/2020-09/md_mdcg_2020_6_guidance_sufficient_clinical_evidence_en_0.pdf (accessed 13-FEB-2026).
• Directorate‑General for Health and Food Safety. Guidance on Outcomes for Joint Clinical Assessments. 13 June 2024. Available at: https://health.ec.europa.eu/document/download/a70a62c7-325c-401e-ba42-66174b656ab8_en?filename=hta_outcomes_jca_guidance_en.pdf (accessed 13-FEB-2026).
• Facey, K. M., Holtorf, A.-P., & Single, A. N. V. (Eds.). (2026). Patient Involvement in Health Technology Assessment (2nd ed.). Springer Nature Switzerland AG. https://doi.org/10.1007/978-3-032-11284-2

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