Benefit-risk determination for medical devices according to MDR

Correct assessment of benefits and risks throughout the entire product life cycle

Benefit-risk determination is a key regulatory requirement of the Medical Devices Regulation (EU) 2017/745 (MDR) and is often challenging for manufacturers of medical devices. Dr. Grit Kasper, Team Lead Clinical Affairs at Metecon, explains which processes are involved in the benefit-risk determination, what role the state of the art (SotA) plays, and why mathematical models are often not applicable in practice.

You will learn what we have learned from numerous projects and feedback from notified bodies for benefit-risk determination and how to successfully start a new benefit-risk assessment.

Benefit-risk determination as a continuous process

Article 2(24) MDR defines benefit-risk determination as the analysis of all assessments of benefit and risk of possible relevance for the use of the device for the intended purpose, when used in accordance with the intended purpose given by the manufacturer.

From a regulatory perspective, this involves continuous evaluation and decision-making activities that span multiple processes.

The benefit-risk determination is anchored in several places for different processes in the MDR, including here:

• Annex I, Chapter I, Section 3(e) MDR (Risk Management)
  Obligation to evaluate the overall risk, the benefit-risk ratio, and risk acceptability.
• Annex XIV, Part A, Section 1(a) MDR (Clinical Evaluation)
  The Clinical Evaluation Plan must include parameters used to assess the acceptability of the benefit-risk ratio based on the State of the Art.
• Article 83(3)(a) MDR (Post-Market Surveillance)
  PMS data shall be used to update the benefit-risk determination and to improve risk management.
• Annex XIV, Part B, Section 6.1(d) MDR (PMCF)
  One objective of PMCF is to ensure the continued acceptability of the benefit-risk ratio.

The benefit-risk determination is therefore not a one-off activity within the framework of approval, but a continuously updated component of the entire product life cycle.

Benefit-risk determination: “Where do I start?”

You may now be asking yourself: “And where is the best place to start?”

Our clear answer: with the SotA (more on this below), because the SotA provides:

• Information on product risks for risk management

• Parameters to determine the acceptability of the benefit-risk determination for the clinical evaluation plan (see below)

• Benchmarks for the clinical evaluation report

• Information on medical alternatives 

Because the SotA is so important, it can be helpful to create it as a separate document.

Risk management and clinical evaluation for benefit-risk determination: similar, but not the same

Both risk management according to EN ISO 14971 and clinical evaluation according to MDR Article 61 and Annex XIV are intended to perform benefit-risk determination. There are many overlaps, but also some crucial differences.

A fundamental difference lies in the approach: risk management focuses on the causes of risks and their mitigation, while clinical evaluation records the effects in clinical use and assesses their acceptability.

This also results in differences in the type of risks to be considered. While both clinical evaluation and risk management examine the risks caused by the medical device, clinical evaluation also addresses risks arising from the necessary clinical procedure, and risk management additionally addresses risks to the environment and property.

This distinction is important because, on the one hand, inconsistencies between risk management and clinical evaluation should be avoided, but on the other hand, not all risks from risk management are relevant for clinical evaluation and vice versa.

What does “acceptability” mean? The state of the art (SotA) as a reference for the benefit-risk determination

The SotA plays a central role in the benefit-risk determination. Based on the SotA, the parameters and acceptance limits (benchmarks) for the benefits and risks of the product to be assessed are derived.

These parameters and acceptance limits can be derived on the basis of similar products or, if there are no similar products, from other medical options that are commonly used as alternatives to the product being evaluated.

The level of detail of the data collected can be based on the degree of innovation and the complexity of the product. For innovative products, for example, more detailed information on medical alternatives is necessary than for established technologies.

Important for the assessment of established products: According to MDCG 2020-6, the SotA describes what is currently and generally accepted as good practice in technology and medicine. It does not necessarily imply the most technologically advanced solution. The last sentence is particularly important if there is an innovative competitor product on the market that may have a higher benefit or lower risk than the product being evaluated. This does not automatically mean that the product being evaluated no longer has an acceptable benefit-risk profile – as long as the competitor product does not yet represent “good practice”.

Important for product development: It is advisable to consider the acceptability of the benefit-risk profile early on in development in order to gather information for product design and also to set up V&V activities as efficiently as possible.

Methodological approaches to benefit-risk assessment

Checklists

Checklists that compare the data determined for the product with the acceptance criteria for each parameter can create structure and facilitate comparisons. However, they reach their limits when not all acceptance criteria are met, i.e., when benefits and risks (simultaneously) deviate from the acceptance limit. Or if there are no clear quantitative acceptance criteria from the state of the art (SotA).

This means that a direct weighing of benefits against risks is required.

Quantitative models

Ideally, one would like to have a figure for the benefits, which ideally should be greater than the overall risk.

Unfortunately, this is often difficult to implement in reality. Quantitative approaches in which benefits and risks are categorized and weighted can help to present data clearly. Typically, the frequency and severity of risks and benefits are taken into account. And even if a figure for the risk-benefit ratio can be derived from this in theory, such models have significant limitations.

The limitations of quantitative models for benefit-risk determination

• In most cases, it is not possible to map benefit or risk categories on linear scales.
• Models greatly simplify clinical reality, so that, for example, individual patient preferences or the duration of risks or benefits are not taken into account.
• Different data qualities are mixed and used without weighting.

This is also reflected in regulatory requirements.

For example, ISO/TR 24971 states: “The decision as to whether risks are outweighed by benefits is essentially a matter of judgment by experienced and knowledgeable individuals.”

The Team NB position paper “Best Practice Guidance for the Submission of Technical Documentation under Annex II and III of Medical Device Regulation (EU) 2017/745” (April 2025) also underscores this view: “At some point, a mathematical counterbalancing of what kind of benefits justify what kind of risks will not be possible anymore but rather must be assessed based on the clinical expertise of the evaluators.”

Argumentation as a central element of the benefit-risk determination

As a rule, clinical expertise and rigorous argumentation are therefore required.

Key factors for successful argumentation are:

• Transparency: Assumptions, uncertainties, and gray areas are openly stated.
• Clear presentation of the data basis: The origin, quality, and significance of the data are presented in a comprehensible manner.
• Consistency between documents: SotA, risk management, clinical evaluation, PMS, and PMCF use the same parameters and acceptance limits.
• Consideration of the reviewer's perspective: A comprehensible, logically structured, and clear line of argumentation greatly facilitates the assessment by the notified body.

A good benefit-risk determination does not tell a marketing story, but is a technically consistent and comprehensible regulatory argumentation.

Conclusion: Clarity, consistency, and clinical expertise

The benefit-risk determination is a central element in the conformity assessment of medical devices, involving several processes.

The key factors here are

• the smooth interlocking of processes,
• the consistent development and use of the SotA, and
• transparent, technically sound argumentation.

When performing the benefit-risk determination, clarity trumps complexity and clinical expertise trumps calculation.

How can the benefit-risk determination be carried out successfully in accordance with the MDR?

A robust benefit-risk determination is not a single step, but the result of consistent interaction between risk management, clinical evaluation, PMS, PMCF, and a well-founded analysis of the state of the art. It is therefore a central component for the MDR-compliant assessment of the safety and performance of medical devices throughout the entire product life cycle and requires experience, structure, and a deep understanding of the processes and regulatory context.

Metecon supports medical device manufacturers in the following areas:

• Developing strategies for the benefit-risk determination of their devices. Like our customers, you will find us to be an efficient sparring partner to discuss different approaches and quickly arrive at the right decision.
• Developing and revising benefit-risk arguments.
• Consistently and efficiently integrating risk management, clinical evaluation, PMS, and PMCF.
• Creating the state of the art for different product classes and levels of innovation.
• Preparing for audits and reviews by notified bodies.
• Determining the benefits and risks of product ideas so that their development is headed in the right direction from the outset.

Would you like to critically review your benefit-risk determination or set it up early on or from scratch?

Get in touch with us. We provide interdisciplinary, practical, and regulatory support.