Why wound healing endpoints fail clinical evaluation review

Written by HATEM RABEH, MD, MSc Ing

Your Clinical Evaluation Expert And Partner

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This is not a drafting issue. It is a fundamental misunderstanding of how clinical outcomes must be defined, measured, and interpreted in the context of MDR Article 61 and MDCG 2020-5.

Wound care devices present a unique challenge in clinical evaluation. The claimed benefits often involve complex biological processes. Healing is not a single event. It is a cascade of cellular responses, tissue remodeling, and functional recovery. Yet many clinical evaluation reports treat wound healing as if it were a binary outcome.

The gap between what is claimed and what is measured becomes visible during regulatory review. And that gap is not easy to close once the file is submitted.

The problem starts with how outcomes are defined

Most wound care devices claim to support healing, reduce infection risk, manage exudate, or improve patient comfort. These are clinical benefits. Under MDR, clinical benefits must be demonstrated through clinical data that uses appropriate endpoints.

But here is what happens in practice. A manufacturer claims the device accelerates healing. The clinical evaluation includes studies that measure “percentage of wound area reduction at 4 weeks.” The Notified Body asks: does this endpoint reflect the clinical benefit you claim?

And often, the answer is no.

Wound area reduction is a surrogate endpoint. It suggests progress, but it does not confirm healing. A wound can shrink and still fail to close. It can close and still leave impaired tissue function. It can appear closed and reopen weeks later.

The clinical evaluation must explain why the chosen endpoint is clinically relevant for the claimed benefit. This explanation is often missing.

What makes an endpoint appropriate for wound care?

An appropriate endpoint must be clinically meaningful, objectively measurable, and directly related to the claimed benefit.

For a device claiming to accelerate healing, time to complete wound closure is more appropriate than percentage area reduction. For a device claiming to reduce infection, incidence of clinical infection with microbiological confirmation is more appropriate than colony counts from swabs.

But even when the endpoint seems appropriate, the way it is measured matters.

Consider complete wound closure. It sounds clear. But how is closure defined? Is it epithelialization without drainage? Is it absence of dressing requirement? Is it maintained closure at follow-up? Different studies use different definitions. If your clinical evaluation pools data from studies with inconsistent definitions, the evidence base weakens.

MDCG 2020-5 requires that clinical data be adequate to demonstrate conformity with General Safety and Performance Requirements. That adequacy depends on the quality, relevance, and consistency of outcome measurement.

Timing of outcome measurement

When the outcome is measured also matters. A wound care device used for acute wounds may show benefit within days. A device for chronic wounds may require weeks or months. If the clinical data reports outcomes at timepoints that do not reflect the intended use, the relevance of the data is questioned.

I have seen clinical evaluation reports where the device is intended for chronic venous leg ulcers, but the pivotal study reported outcomes at 2 weeks. Chronic wounds do not behave like acute wounds. The biological context is different. The timeframe for meaningful clinical benefit is different.

The clinical evaluation must justify why the timepoints used in the clinical data are appropriate for the device and indication.

Composite endpoints and their interpretation

Some wound care devices claim multiple benefits. Accelerated healing and improved comfort. Reduced infection risk and better exudate management. The temptation is to use composite endpoints that capture several outcomes at once.

Composite endpoints can be useful. But they create interpretation problems.

If a composite endpoint includes “complete closure OR 50% area reduction,” what does it mean when the device meets the endpoint? Did it accelerate complete healing? Or did it just reduce area without achieving closure? The clinical significance is not the same.

Notified Bodies are trained to ask: what is the clinical benefit when the composite endpoint is met? If the answer is unclear, the clinical data is considered insufficient.

The solution is not to avoid composite endpoints. It is to explain what each component means clinically and to report the components separately in the clinical evaluation.

Patient-reported outcomes in wound care

Many wound care devices claim to improve quality of life or reduce pain. These are subjective outcomes. They require patient-reported outcome measures.

But patient-reported outcomes are not soft data. They are valid clinical endpoints when measured with validated instruments.

The problem is that many clinical evaluation reports include studies that use non-validated questionnaires or single-item pain scales without demonstrating reliability or responsiveness. The Notified Body will question whether the outcome is truly measured or just reported anecdotally.

If your device claims comfort improvement, the clinical evaluation must include data from studies using validated wound-specific quality of life tools or validated pain assessment instruments. Generic quality of life tools may not be sensitive enough to detect changes related to wound care.

The role of surrogate endpoints

Surrogate endpoints are used when the ultimate clinical outcome is difficult to measure or takes too long to observe. In wound care, biomarkers such as inflammatory markers, bacterial load, or tissue perfusion are sometimes used as surrogates for healing.

The challenge is that surrogate endpoints must be shown to correlate with the clinical outcome. That correlation must be demonstrated in the clinical data, not assumed.

I have reviewed clinical evaluations where the manufacturer used reduction in bacterial load as evidence of healing benefit. But bacterial load reduction does not always lead to faster healing. Some wounds heal despite bacterial colonization. Others fail to heal despite low bacterial counts.

If you rely on a surrogate endpoint, the clinical evaluation must include evidence that changes in the surrogate predict changes in the clinical outcome. If that evidence is not available, the surrogate cannot support the claimed benefit.

How outcome measurement affects equivalence claims

Wound care devices often rely on equivalence to a predicate device. Equivalence under MDR requires clinical, technical, and biological equivalence. But equivalence in outcome measurement is often overlooked.

If your device claims equivalence to a predicate, the clinical data for both devices must use comparable endpoints. If the predicate studies measured complete closure and your data measures area reduction, equivalence is not demonstrated.

This becomes critical when the predicate device has strong clinical evidence but uses endpoints that differ from the studies available for your device. You cannot claim equivalence in clinical benefit if the outcomes measured are not equivalent.

The clinical evaluation must address this explicitly. If the endpoints differ, you must explain why the difference does not undermine the equivalence claim. Often, that explanation requires additional data or bridging evidence.

What reviewers look for

When a Notified Body or competent authority reviews a clinical evaluation for a wound care device, they ask a series of questions about outcome measurement:

Is the endpoint clinically meaningful for the claimed benefit? Is it objectively measured? Is the measurement method validated? Is the timing appropriate for the indication? Are the definitions consistent across studies? Are composite endpoints clearly explained? Are surrogate endpoints supported by correlation data?

If any of these questions cannot be answered from the clinical evaluation report, the file is insufficient.

The problem is not that the data does not exist. The problem is that the clinical evaluation does not explain how the data supports the claim.

How to address outcome measurement in your clinical evaluation

Start by defining the claimed clinical benefit precisely. Then identify the clinical endpoints that directly measure that benefit. Justify why those endpoints are appropriate for the device, indication, and patient population.

If the available clinical data uses different endpoints, explain the relationship between the measured endpoints and the claimed benefit. If surrogate endpoints are used, provide evidence of their predictive value. If patient-reported outcomes are included, confirm that the instruments are validated.

When you appraise individual studies, assess not only the study design and risk of bias, but also the appropriateness of the endpoints. A well-designed study with irrelevant endpoints does not contribute to your evidence base.

In your clinical evaluation conclusion, state clearly which endpoints were used across the clinical data and how they support each claimed benefit. If gaps exist, acknowledge them and address them in your PMCF plan.

What this means for PMCF

Outcome measurement does not stop at market entry. PMCF must continue to assess whether the claimed benefits are realized in real-world use. That requires defining PMCF endpoints that align with the claims made in the clinical evaluation.

If your clinical evaluation claimed accelerated healing based on time to closure, your PMCF plan should measure time to closure in the post-market setting. If the endpoints differ, the PMCF data cannot confirm the clinical evaluation conclusions.

This alignment is often missing. The clinical evaluation uses one set of endpoints. The PMCF plan measures something else. When the PSUR or clinical evaluation update is prepared, the PMCF data cannot be integrated because the endpoints do not match.

The continuity of outcome measurement from pre-market to post-market is a regulatory expectation. It is also the only way to confirm that your device performs as claimed.

Outcome measurement is not a technical detail. It is the foundation of clinical evaluation. When the endpoints do not align with the claimed benefits, the entire evidence base is questioned.

This is not something you can fix with better writing. It requires rethinking how clinical data is selected, appraised, and interpreted in the context of MDR.

If your clinical evaluation for a wound care device has been challenged on outcome measurement, the issue is not likely to resolve through clarification. It requires re-evaluation of the evidence base and, in many cases, additional clinical data.

The next post will address how to structure the clinical evaluation appraisal when the available data is limited but the device is still considered low risk.