Why Is Continuous Clinical Evaluation Necessary?

Introduction

Medical devices are used in human subjects; therefore, clinical evaluation is mandatory. Manufacturers must submit the results of clinical evaluation when applying for regulatory approval or certification. The clinical evaluation conducted during the design and development phase serves as the foundation for the device’s regulatory approval, but this is only the beginning of a comprehensive clinical evidence strategy.

Clinical Evaluation During Design and Development

Clinical evaluation during the design and development phase is conducted as part of design validation activities. Manufacturers conduct risk analysis at this stage and evaluate the balance between the benefits (advantages) and risks (harms) of the medical device. This pre-market clinical evaluation is based on a limited scope of evidence, including published literature, bench testing, non-clinical studies, and clinical investigations.

The Need for Post-Market Clinical Follow-Up (PMCF)

Under the European Medical Device Regulation (MDR), Post-Market Clinical Follow-Up (PMCF) is necessary to ensure the continued safety and performance of medical devices after they are placed on the market. PMCF involves the systematic and proactive collection of clinical data to monitor how devices perform in real-world clinical environments—information that is often unavailable during pre-market clinical trials.

The Fundamental Purpose of PMCF

The most important reason for continuous clinical evaluation is to verify that the benefit-risk ratio identified during the design and development risk management process remains valid and acceptable in actual clinical use. The balance between anticipated benefits and risks can change due to real-world clinical experience, emerging scientific evidence, and evolving standards of care. Therefore, continuous monitoring is essential.

The pre-market clinical evaluation process, while rigorous, operates within inherent limitations. Clinical trials typically involve selected patient populations, controlled settings, and relatively limited durations of follow-up. In contrast, real-world clinical environments encompass diverse patient demographics, variable clinical practices, and extended periods of device use. These real-world conditions may reveal risks or performance characteristics that were not apparent in controlled pre-market investigations.

The Dynamic Nature of Hazards and Benefits

A critical observation is that post-market experience often reveals new hazards while simultaneously eroding relative benefits. This phenomenon highlights why continuous vigilance is necessary throughout a device’s lifecycle.

Regarding hazard discovery, unanticipated use patterns may reveal new risks that were not foreseen during device development. For example, consumer misuse incidents—such as placing living animals in microwave ovens—illustrate how unpredictable user behavior can create hazard scenarios. Similarly, medical devices may encounter unexpected use patterns among certain patient populations or in particular healthcare settings, leading to the discovery of previously unknown risks or adverse effects post-market.

From a benefits perspective, the relative clinical value of a medical device can diminish as the healthcare landscape evolves. A device that represented the only therapeutic option at the time of market introduction may become less attractive once similar competing devices are launched or more effective treatment options become available. For instance, when famotidine (marketed as Gaster), an H2-receptor antagonist, was introduced in 1985 as Japan’s first H2-receptor antagonist for treating gastric ulcers, it represented a significant therapeutic advance. However, with the subsequent development of more potent proton pump inhibitors (PPIs), the relative clinical position and benefit profile of H2-receptor antagonists evolved. This dynamic shift in the therapeutic landscape demonstrates that the clinical context in which a device operates is not static but continuously evolving.

PMCF Requirements Under the MDR

Under the MDR, manufacturers bear the responsibility for ensuring that devices maintain their performance after market introduction and for taking prompt corrective actions when problems arise. Medical technology advances continuously, and new clinical applications or associated risks may be discovered. Through PMCF, manufacturers can identify emerging risks early, re-evaluate the benefit-risk ratio as necessary, and implement appropriate risk control measures to maintain the safety and effectiveness of their devices throughout the entire device lifecycle.

Principles of PMCF Implementation

PMCF implementation is mandatory for most medical devices because risk management conducted during the design phase may be incomplete. Medical devices can be affected by “real-world use conditions” that are not apparent from laboratory testing or controlled clinical trials alone. Because clinical investigations are conducted in controlled environments with selected patient populations and limited timeframes, it is difficult to anticipate all situations that may arise in actual clinical practice.

As experience accumulates with new patient groups and with increasing real-world clinical exposure, previously unknown risks and opportunities for improvement become apparent. Medical devices may experience performance changes or unexpected effects when used for extended periods. Continuous evaluation enables manufacturers to confirm the device’s durability and reliability and to understand the long-term effects of extended use. Such information is critical for validating the appropriateness of the anticipated benefit-risk ratio as the device matures in the clinical marketplace.

Additionally, this ongoing evaluation serves to detect any emergent risks that may not have been fully characterized during risk management activities, to monitor the frequency and severity of known adverse effects, and to identify possible systematic misuse or off-label use patterns.

When PMCF May Not Be Required

Exemption from PMCF is limited to a narrow set of circumstances. According to the MDR and related guidance documents (particularly MDCG 2020-6), PMCF may be omitted or simplified only when a device meets all of the following criteria: it qualifies as “Well-Established Technology (WET),” represents a low-risk medical device with a long history of safe use, has not undergone substantial design or manufacturing changes, exhibits no identifiable residual risks in the risk management file, and benefits from extensive long-term clinical safety data. For example, certain orthopedic prosthetic materials or orthodontic appliances that have been used safely in clinical practice for decades without technological innovation and possess a well-characterized safety profile may qualify. However, such exemptions are strictly exceptional. The vast majority of manufacturers must provide documented justification for why PMCF is or is not applicable to their specific devices.

Notably, the presence of long-term clinical history does not automatically exempt a device from PMCF under the MDR. Legacy devices based on equivalency arguments or those with limited pre-market clinical data will typically require PMCF. A thoughtful, evidence-based approach to determining PMCF applicability is a critical component of regulatory strategy.

Data Collection and Analysis from Real-World Clinical Settings

When medical devices are used in actual clinical environments, previously unknown risks may be discovered, or conversely, previously unrecognized benefits may become apparent. Feedback from healthcare professionals who use the devices is a valuable source of information for product improvement. By incorporating findings from PMCF data into the risk management process, manufacturers can determine whether the originally anticipated benefit-risk ratio remains acceptable or whether modifications are necessary.

The advancement of medical technology also introduces new clinical applications and therapeutic approaches. In such circumstances, reassessing the positioning and clinical utility of existing medical devices becomes important. PMCF data provides the scientific foundation necessary to respond to such market and clinical environment changes.

Medical professionals and patients may identify use cases or benefits that were not anticipated during pre-market investigations. Such discoveries enrich the clinical evidence base and contribute to optimizing the device’s role within the broader therapeutic landscape.

The Essential Nature of Continuous Clinical Evaluation

Continuous clinical evaluation should not be viewed merely as a regulatory requirement. Rather, it is a critical activity for confirming that the benefit-risk ratio identified during device development remains valid in real-world clinical practice and for taking appropriate measures to maintain the safety and effectiveness of medical devices. By ensuring that devices continue to perform as intended and that emerging risks are detected promptly, continuous monitoring guarantees that medical devices remain safe for users and patients and that anticipated clinical benefits are delivered to the fullest extent possible.

This ongoing process reflects the fundamental principle that regulatory oversight does not end at market approval. Instead, the regulatory system acknowledges that comprehensive evidence of device safety and performance accumulates over the entire lifecycle of a medical device.

Conclusion

Continuous clinical evaluation constitutes a crucial undertaking for continuously validating the acceptability of the device’s benefit-risk ratio and ensuring the safety and effectiveness of medical devices. Through long-term observation in real-world clinical settings, manufacturers, healthcare providers, and regulators work collaboratively to protect patient safety and advance the delivery of better medical care.