Introduction: The Continuous Problem
Under the European Medical Device Regulation (EU MDR 2017/745), clinical evaluation is defined as a continuous process (Article 2(44)). This requirement reflects the need for ongoing assessment of clinical data throughout the lifecycle of a medical device, ensuring that safety, performance, and benefit–risk profiles remain up to date as new evidence emerges.
In practice, however, many manufacturers continue to rely on periodic literature reviews, conducted at predefined intervals to support updates to the Clinical Evaluation Report (CER) or Post-Market Clinical Follow-up (PMCF) activities. While this approach satisfies minimum compliance requirements, it does not fully align with the regulatory expectation of continuous evaluation.
This creates a clear operational gap between regulatory intent and real-world implementation. The challenge is not in interpreting the requirement, but in identifying a practical and scalable methodology to support it.
Living systematic reviews (LSRs) offer a structured solution to this challenge. By enabling continuous literature monitoring, ongoing evidence synthesis, and dynamic updating of clinical conclusions, LSRs provide a framework for operationalising continuous clinical evaluation under the EU MDR.
What Are Living Systematic Reviews?
A living systematic review (LSR) is a systematic review that is continually updated, incorporating new evidence as it becomes available. Unlike traditional systematic reviews, which represent a fixed snapshot of the literature at a specific point in time, LSRs are designed to evolve alongside the evidence base. The concept originated in clinical research, particularly in areas where evidence is rapidly changing and timely updates are critical for decision-making. In this context, LSRs enable the incorporation of newly published studies as they emerge, ensuring that conclusions remain current and relevant.
Key characteristics of living systematic reviews include:
- Continuous literature monitoring through automated searches and alerts
- Predefined update triggers, based on time intervals or the emergence of new evidence
- AÂ living protocol, with version control to track methodological changes
- Ongoing screening, inclusion, and synthesis of new data
- Regular updates to evidence summaries and conclusions
While originally developed for academic evidence synthesis, the principles of LSRs are highly applicable to medical device regulatory processes, particularly in the context of continuous clinical evaluation and PMCF literature review requirements.
Why Medical Device Teams Should Adopt Living Systematic Reviews
Medical device manufacturers are required to maintain up-to-date clinical evidence throughout the product lifecycle, particularly through post-market clinical follow-up (PMCF) and ongoing clinical evaluation activities. Under the EU MDR, PMCF requires continuous literature monitoring to identify new data relating to device safety, performance, and benefit–risk balance. Similarly, in the United States, regulatory frameworks such as 21 CFR 814.84(b) require periodic reporting, including annual literature summaries for certain devices.
Traditional approaches to literature review, which rely on periodic updates at fixed intervals, may not fully support these requirements. In contrast, living systematic reviews enable continuous literature monitoring, allowing manufacturers to identify and assess new evidence as it becomes available. This approach aligns more closely with the expectation that clinical evaluation be maintained as a continuous process.
One of the key advantages of adopting living systematic reviews is the ability to support earlier signal detection. Continuous screening of the literature can help identify emerging safety concerns, rare adverse events, or changes in clinical outcomes that may not be captured through periodic review cycles. This is particularly important in the context of PMCF, where timely identification of new risks contributes to proactive risk management and patient safety. For more information, check out systematic literature review software tools.
In addition to improving safety surveillance, LSRs can also reduce the operational burden associated with periodic literature reviews. Rather than conducting large, resource-intensive updates at defined intervals, manufacturers can distribute the workload over time through ongoing monitoring and incremental updates. This supports more efficient use of resources while maintaining regulatory compliance.
Living systematic reviews also provide a strong foundation for notified body (NB) audit readiness. By maintaining a continuous and well-documented record of literature monitoring, screening decisions, and evidence updates, manufacturers can demonstrate that clinical evaluation activities are actively managed and aligned with regulatory expectations. This level of transparency is particularly valuable during audits, where the ability to justify monitoring frequency, search strategies, and evidence inclusion decisions is critical.
Overall, living systematic reviews offer a practical and scalable approach for meeting regulatory requirements while improving the quality and responsiveness of clinical evidence generation for medical devices.
Adapting Living Systematic Reviews for Regulatory Compliance
Traditional systematic reviews are designed to answer a defined research question at a specific point in time. In contrast, living systematic reviews are designed to support ongoing evidence surveillance and repeated updates as new data becomes available. For medical device manufacturers, this distinction is particularly important because regulatory activities such as post-market surveillance (PMS), post-market clinical follow-up (PMCF), and clinical evaluation require evidence review processes that can be maintained over time.
Adapting a living systematic review methodology for regulatory compliance means moving from a static review model to a structured process for continuous literature monitoring, evidence reassessment, and documented update decisions. This approach better supports the EU MDR expectation that clinical evaluation remains current throughout the device lifecycle.
The table below highlights the main differences between a standard systematic review and a living review when applied to PMS and PMCF activities. In regulatory practice, these differences have direct implications for how literature review processes are designed and maintained.
Comparison table
In the regulatory context, the value of a living review lies not simply in more frequent updates, but in its ability to create a documented and repeatable framework for maintaining clinical evidence in a continuous, inspection-ready manner.
To implement a living systematic review approach effectively, manufacturers need a structured workflow that defines how searches are maintained, how new evidence is screened, and how update decisions are documented.
Implementation Components
Implementing a living systematic review (LSR) approach requires a structured and repeatable workflow that supports continuous literature monitoring, consistent evidence assessment, and clear documentation of decisions over time. For medical device manufacturers, this process must align with regulatory expectations for traceability, audit readiness, and ongoing clinical evaluation.
The key components of implementing an LSR in a regulatory context are outlined below.
Living Protocol Development
A living systematic review begins with the development of a robust and reusable search protocol. This protocol defines the research question, inclusion and exclusion criteria, search terms, and selected databases.
Unlike traditional systematic reviews, the protocol must be designed for long-term use, allowing it to be rerun consistently over time. Version control is essential to ensure that any updates to the search strategy are documented and justified, particularly for notified body review.
Update Triggers and Monitoring Frequency
A key feature of LSRs is the use of predefined update triggers. These may include:
- Time-based triggers (e.g. monthly or quarterly search reruns)
- Event-based triggers (e.g. publication of key studies or safety signals)
- Volume-based triggers (e.g. a threshold number of new articles identified)
Defining an appropriate monitoring frequency is critical and should be justified based on the device’s risk profile, clinical context, and expected rate of evidence generation.
Automated Alerting and Continuous Literature Monitoring
To support continuous literature monitoring, manufacturers can implement automated alerts and saved search strategies across multiple databases. This enables new publications to be identified in near real time, reducing the risk of missing emerging evidence.
Comprehensive database coverage is important to ensure that relevant studies, case reports, and safety data are captured across different sources.
Ongoing Screening Workflow
An effective LSR requires an ongoing screening process for newly identified records. This includes:
- Title and abstract screening
- Full-text review
- Application of predefined inclusion and exclusion criteria
Consistency in screening decisions is essential, and processes should be standardized to ensure reproducibility across update cycles.
Evidence Management and Audit Trail
A critical requirement in regulatory contexts is the ability to demonstrate traceability of decisions. LSR workflows should include a complete audit trail documenting:
- Search dates and databases used
- Screening decisions and exclusions
- Inclusion of new studies
- Updates to evidence synthesis
This level of documentation supports notified body audits and helps justify the completeness and rigor of literature monitoring activities.
Managing Cumulative Data and Duplicates
As literature searches are repeated over time, managing cumulative data becomes increasingly important. Systems should be in place to identify and remove duplicate records across multiple update cycles, ensuring that the dataset remains accurate and manageable.
Effective duplicate management also supports efficient screening and reduces the risk of inconsistencies in evidence assessment.
Transition Criteria and Review Updates
While LSRs are designed to be continuous, it is important to define criteria for when updates should lead to formal changes in clinical documentation. This may include:
- New evidence impacting safety or performance
- Changes in the benefit–risk profile
- Identification of new risks or indications
These triggers should be clearly defined to ensure that updates to the Clinical Evaluation Report (CER), PMCF documentation, or risk management files are made in a timely and justified manner.
While the implementation of living systematic reviews provides a structured framework for continuous clinical evaluation, practical considerations such as resource requirements, scalability, and technology infrastructure play a key role in determining how effectively this approach can be applied across a device portfolio.
Practical Considerations for Implementing Living Systematic Reviews
While living systematic reviews offer a structured approach to continuous clinical evaluation, their successful implementation depends on several practical considerations, including resource availability, scalability, and supporting technology.
Resource Requirements and Staffing Models
Implementing an LSR requires ongoing effort rather than periodic intensive review cycles. This shift changes how resources are allocated. Instead of large teams conducting infrequent literature reviews, smaller teams may perform continuous screening and incremental updates.
Organizations should consider:
- Availability of trained reviewers
- Allocation of time for ongoing monitoring
- Processes for quality control and consistency
Establishing clear roles and responsibilities helps ensure that the LSR process remains sustainable over time.
Scaling Across Device Portfolios
For manufacturers managing multiple products, scalability becomes a key consideration. While an LSR approach may be manageable for a small number of devices, maintaining continuous literature monitoring across large portfolios (e.g. 50–100+ devices) can be challenging without structured processes.
Scaling requires:
- Standardized workflows across products
- Reusable search strategies where appropriate
- Efficient handling of large volumes of literature
A portfolio-based approach can help ensure consistency while maintaining efficiency.
Technology Enablement
Technology plays a central role in enabling LSR implementation at scale. Manual processes alone may not be sufficient to support continuous literature monitoring and repeated screening cycles.
Key technological capabilities include:
- Automated literature alerts and saved searches
- Access to multiple databases for comprehensive coverage
- Tools to support efficient screening and prioritization of records
- Systems for maintaining an audit trail of decisions
These capabilities support both efficiency and regulatory compliance.
Search Strategy Evolution
Over time, search strategies may need to be refined to reflect:
- Changes in device indications or intended use
- Emerging terminology in the literature
- Newly identified relevant keywords or data sources
Any updates to the search strategy should be documented and justified, ensuring transparency for regulatory review.
Managing Duplicate Records Across Update Cycles
As literature searches are repeated, duplicate records will accumulate across update cycles. Effective duplicate management is essential to:
- Reduce unnecessary screening effort
- Maintain a clean and consistent dataset
- Avoid inconsistencies in evidence inclusion
Structured processes or automated tools can help identify and remove duplicates efficiently across cumulative datasets.
Beyond operational considerations, living systematic reviews also play an important role in supporting broader safety surveillance activities by enabling earlier identification of emerging risks and facilitating integration with vigilance processes.
Connecting Living Systematic Reviews to Safety Surveillance
Living systematic reviews not only support continuous clinical evaluation but also play a critical role in ongoing safety surveillance. By enabling continuous literature monitoring, LSRs provide an additional layer of insight into device performance and emerging risks in real-world clinical use.
One of the key advantages of LSRs is their ability to support earlier identification of safety signals. Continuous screening of published literature allows manufacturers to detect new case reports, adverse events, or trends in clinical outcomes as they emerge. This is particularly valuable in identifying rare or long-term complications that may not have been evident during pre-market evaluation or initial post-market assessments.
LSRs facilitate the integration of external evidence with internal data sources. Findings from the literature can be correlated with complaint data, vigilance reports, and post-market surveillance activities, providing a more comprehensive understanding of device performance. For example, recurring issues identified in published case reports may reinforce trends observed in internal complaint data, supporting earlier investigation and intervention.
In this way, living systematic reviews contribute to a bi-directional relationship between literature monitoring and risk management. Literature findings can inform updates to risk management files, clinical evaluation reports, and PMCF activities, while insights from internal surveillance processes can guide the focus of ongoing literature searches.
This integrated approach strengthens the overall safety surveillance system by ensuring that relevant evidence is identified, assessed, and incorporated into decision-making in a timely manner. As a result, manufacturers are better positioned to respond proactively to emerging risks and maintain a robust and up-to-date understanding of their device’s safety and performance profile.
Regulatory Expectations for Living Systematic Reviews
While the EU MDR does not explicitly mandate the use of living systematic reviews, regulatory requirements clearly support the need for continuous literature monitoring and ongoing clinical evaluation. As such, LSR methodologies align closely with existing expectations outlined in MDR and associated guidance documents.
MDCG guidance documents, including MDCG 2020-7 (Post-Market Clinical Follow-up) and MDCG 2020-13 (Clinical Evaluation Assessment), emphasize the importance of systematic and ongoing data collection, as well as the need to maintain up-to-date clinical evidence throughout the device lifecycle. These documents also highlight the expectation that manufacturers provide clear justification for their literature search strategies, monitoring frequency, and evidence selection processes.
In practice, this means that manufacturers must demonstrate that their literature review processes are:
- Systematic and reproducible
- Conducted at an appropriate and justified frequency
- Capable of identifying relevant new evidence in a timely manner
- Supported by clear documentation and traceability
Living systematic reviews provide a structured framework for meeting these expectations by enabling continuous literature monitoring and maintaining a documented record of search updates, screening decisions, and evidence inclusion.
Alignment between clinical documentation is also an important regulatory consideration. Updates to the Clinical Evaluation Report (CER) should be consistent with data collected through post-market surveillance activities, including Periodic Safety Update Reports (PSURs) and PMCF findings. A continuous literature review process helps ensure that these documents remain aligned and reflect the most current available evidence.
Ultimately, regulatory compliance under the EU MDR requires not only the collection of clinical data but also the ability to demonstrate that this process is ongoing, justified, and well-documented. Living systematic reviews support this requirement by providing a transparent and repeatable approach to maintaining up-to-date clinical evidence.
Conclusion
Living systematic reviews provide a practical and scalable solution to one of the central challenges of the EU MDR: maintaining clinical evaluation as a truly continuous process. By enabling ongoing literature monitoring, dynamic evidence synthesis, and structured documentation of updates, LSRs help bridge the gap between regulatory expectations and operational reality.
Beyond supporting compliance, this approach strengthens the overall quality of clinical evidence by allowing manufacturers to respond more rapidly to emerging data, identify safety signals earlier, and maintain a current understanding of device performance in real-world use.
As regulatory expectations continue to evolve, adopting methodologies that support continuous, transparent, and well-documented evidence generation will become increasingly important. Living systematic reviews represent a practical and scalable framework for achieving this goal.
Operationalising living systematic reviews at scale requires systems that support automated literature monitoring, structured screening workflows, and full audit traceability. As such, living systematic reviews are not only a methodological advancement, but a critical component of modern, lifecycle-based clinical evidence management.
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ATTNs Ethan Glasser Dover, Delaware, 19901, United States
