Streamlining Clinical Evaluation for Software as a Medical Device: Best Practices Under MDR 2017/745

Explore best practices for Clinical Evaluation for SaMD under MDR 2017/745 to streamline the process and ensure compliance.

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Streamlining Clinical Evaluation for Software as a Medical Device: Best Practices Under MDR 2017/745

The Medical Device Regulation (MDR) 2017/745 in the European Union (EU) governs medical devices, including Clinical Evaluation for Software as a Medical Device (SaMD).

This regulation classifies medical devices into four categories based on the significance of the information provided by SaMD to healthcare decisions and the patient’s healthcare condition. Clinical Evaluation for Software plays a crucial role in determining the safety, performance, and regulatory compliance of SaMD under the MDR framework.

The MDR requires software vendors to certify products through notified bodies, which assess conformity based on device classification. This article explains the clinical evaluation process for SaMD under MDR 2017/745, focusing on compiling clinical data for software.

Understanding Clinical Evaluation for SaMD

The FDA issued guidance titled “Software as a Medical Device (SaMD): Clinical Evaluation” for industry and FDA staff. Although this guidance does not impose regulatory requirements, it offers valuable insights into the process.

Key Components of SaMD Clinical Evaluation

Clinical Evaluation for Software involves assessing clinical safety, performance, and effectiveness based on clinical data. The process includes the following key components:

Valid Clinical Association (scientific validity)
Analytical / Technical Validation
Clinical Validation

Evaluate the amount and quality of supporting data to determine and justify the necessary level of clinical evidence.

Clinical Evaluation Process

The clinical evaluation process for SaMD typically involves the following steps:

Identifying intended use and user needs
Reviewing available clinical data
Identifying gaps
Planning clinical investigations if necessary

Special considerations for AI/ML-based SaMDs include algorithm opacity and continuous learning.

Compiling a Clinical Evaluation

When compiling a clinical evaluation for SaMD, it is important to consider the following:

Clinical data: This includes any information related to the safety, performance, and effectiveness of the SaMD, such as scientific literature, clinical investigations, and real-world evidence.
Algorithm transparency: Manufacturers should provide evidence of the scientific validity, technical performance, and clinical performance of the algorithms used in the SaMD.
Intended use characteristics: The clinical evaluation should be tailored to the specific intended use and user needs of the SaMD.
Scope of evaluation: The clinical evaluation should cover all aspects of the SaMD, including its design, development, and post-market surveillance.

Continuous Monitoring and Improvement

SaMD clinical evaluation should be an iterative and continuous process as part of the quality management system for medical devices. Real-world performance data can be used for multiple purposes, including monitoring clinical performance, improving effectiveness, and facilitating future releases.

Consideration	Description
Cybersecurity	Vulnerabilities may introduce risks during use of the medical device.
Standards and Best Practices	Development of standards and best practices to address cybersecurity risks is necessary.
Regulatory Convergence	Regulatory bodies like IMDRF, FDA, and Health Canada are working towards regulatory convergence and harmonization in the SaMD space.

In summary, clinical evaluation for SaMD is a comprehensive process that involves assessing the safety, performance, and effectiveness of the software based on clinical data.

By following the guidance provided by regulatory bodies and considering the unique aspects of SaMD, manufacturers can ensure that their products meet the necessary requirements and provide safe and effective healthcare solutions.

Key Requirements of MDR 2017/745 for SaMD

The Medical Device Regulation (MDR) 2017/745 introduces several key requirements for Software as a Medical Device (SaMD) to ensure safety, effectiveness, and continuous improvement throughout the product lifecycle. Here are the essential aspects manufacturers need to consider:

Clinical Evaluation Process: The clinical evaluation process for SaMD includes determining the valid clinical association, technical performance, and clinical performance. Continuous monitoring of safety, effectiveness, and real-world performance data is essential for detecting malfunctions, understanding user interactions, and improving effectiveness.
Classification and Conformity Assessment: SaMD is classified under MDR rules 2, 10, 15, or 22 based on its intended use and impact on patient health. Notified Bodies assess conformity before market placement, with higher scrutiny for higher-risk devices.
Technical Documentation and Standards: Manufacturers must maintain technical documentation, risk management records, and apply IEC 62304 standards. A gap analysis against IEC 62304 is necessary.
Unique Device Identification (UDI) System: The UDI system applies to all medical devices, including SaMD, except custom-made and investigational devices. Manufacturers must assign, label, and store unique UDIs for their devices.
Post-Market Surveillance and Vigilance: MDR introduces increased post-market surveillance requirements for medical devices, including SaMD. Manufacturers must actively monitor and report any incidents, malfunctions, or adverse events related to their SaMD. Post-market clinical follow-up and continuous clinical evaluation are essential to ensure the ongoing safety and effectiveness of the SaMD.

Requirement	Description
PRRC	Person Responsible for Regulatory Compliance ensures conformity of devices with MDR requirements.
EUDAMED	Manufacturers must register their SaMD in the EUDAMED database.
Labeling	SaMD must comply with the labeling requirements set forth in the MDR.
Transition Timelines	Transition periods for certain medical devices have been extended by the Transition Timelines Update (EU) 2023/607.

Clinical Evaluation Process for SaMD

The clinical evaluation process for MDSW in the European Union involves determining valid clinical association, technical performance, and clinical performance. This process is crucial for ensuring the safety, effectiveness, and performance of the software throughout its lifecycle.

Key Steps in the Clinical Evaluation Process

The clinical evaluation process for SaMD includes several steps:

Defining the intended use and identifying the patient population
Developing a study protocol and conducting the study
Analyzing the results and submitting regulatory filings
Generating and assessing evidence based on the maturity of the underlying clinical association and confidence in the evidence as applied to the specific SaMD
Establishing a valid clinical association, which refers to the extent to which the SaMD’s output corresponds accurately to the real-world healthcare situation and condition identified in the SaMD definition statement
Conducting analytical validation to measure the ability of the SaMD to accurately, reliably, and precisely generate the intended technical output from the input data
Performing clinical validation to measure the ability of the SaMD to yield a clinically meaningful output associated with the target use in the identified healthcare situation or condition

Compiling a Clinical Evaluation for SaMD

When compiling a clinical evaluation for SaMD, it is essential to consider the following:

Clinical data: This includes any information related to the safety, performance, and effectiveness of the SaMD, such as scientific literature, clinical investigations, and real-world evidence.
Specific considerations for software as a medical device: The clinical evaluation should take into account the unique aspects of SaMD, such as algorithmic complexity, evidence generation, technical and analytical validation, and clinical performance validation.

Regulatory Requirements and Standards

Adhering to the requirements outlined in the MDR or IVDR, following the IEC 62304 standard, and complying with the ISO 14155 standard for clinical investigations enhances the likelihood of market success and contributes to improved patient outcomes.

Device Class	Required Documentation
Class I	Clinical Evaluation Report (CER), Post-market Surveillance Plan (PMS Plan), Post-market Surveillance Report (PMS Report), Post-market Clinical Follow-up Plan (PMCF Plan), Post-market Clinical Follow-up Report (PMCF Report)
Class IIa – III	Clinical Evaluation Report (CER), Post-market Surveillance Plan (PMS Plan), Periodic Safety Update Report (PSUR), Post-market Clinical Follow-up Plan (PMCF Plan), Post-market Clinical Follow-up Report (PMCF Report), Summary of Safety and Clinical Performance (SSCP)

The Clinical Evaluation Report (CER) proves that the device performs as intended without compromising user safety and documents the clinical evaluation.

Post-market Surveillance (PMS) is a systematic and proactive process for collecting information, assessing collected data, and managing events subject to the trend report. Post-market Clinical Follow-up (PMCF) specifies methods and procedures used to proactively collect and evaluate clinical data on a device’s performance and safety.

Clinical investigations or clinical performance studies may be required to generate necessary data for compliance with General Safety and Performance Requirements (GSPRs). The importance of an independent review of a SaMD’s clinical evaluation is highlighted, with the recommendation that the level of clinical evaluation and importance of independent review should be commensurate with the risk posed by the SaMD.

Challenges and Considerations in Clinical Evaluation

Post-market surveillance and the Post-Market Surveillance Plan are crucial for monitoring the safety, effectiveness, and performance of the MDSW after it is placed on the market. However, healthcare facilities face increasing supply costs, with hospital executives frequently ranking these as primary concerns.

Between 1991 and 2004, the cost of orthopedic implant devices rose by 132%, while hospital reimbursement rose by only 16%.Hospitals are becoming more aware that cost-effectiveness is critical in device selection, in addition to safety or physician preference.

Challenges:

There is a growing demand for data on medical device efficacy and cost-effectiveness, but several obstacles prevent medical devices from undergoing the standard formulary committee review process. These challenges include:

Assessing product equivalencies for medical devices with different features developed by diverse manufacturers is problematic.
Cost comparisons or effectiveness evaluations are not always possible because manufacturers rarely reveal pricing voluntarily.
Surgeon preferences and vendor relationships significantly impact medical device selection.

Alternatives:

To address these challenges, alternative means of evaluating medical devices have been developed, such as:

Value analysis teams (VATs): Many hospitals are developing VATs to evaluate new technology and justify the purchase and expense of these products. VATs facilitate decision making and standardization regarding medical devices and other supplies.
Payment caps and group purchasing organizations.

Developers can pursue activities such as working with regulators early on, requesting to work with limited cases for rare conditions, and capturing user data as part of a quality management system. All SaMD need ongoing post-market surveillance, which can look at “real-world evidence” from the use of your device, including user data, complaints, and any adverse events.

Consideration	Description
Maintaining balance	Maintaining an appropriate balance between the costs and benefits of the physician–supplier relationship is important.
Real-world data (RWD)	A review highlights examples of RWD assisting in the regulation of IVDs and CDSS, while also addressing key challenges within the current healthcare system that hinder the potential of RWE.

In summary, clinical evaluation for SaMD presents unique challenges, including cost-effectiveness, product equivalency assessment, and the impact of surgeon preferences and vendor relationships. Strategies such as value analysis teams, post-market surveillance, and capturing user data can help address these challenges and ensure the safety and effectiveness of SaMD throughout its lifecycle.

A Comprehensive and Ongoing Process

The clinical evaluation process for Software as a Medical Device (SaMD) is a comprehensive and ongoing process that ensures the safety, effectiveness, and performance of the software throughout its lifecycle.

By following the guidance provided by regulatory bodies, such as the MDR 2017/745, and considering the unique aspects of SaMD, non-professionals can better understand the importance of compiling a thorough clinical evaluation.

This article has highlighted the key components of a clinical evaluation, including the assessment of clinical data, such as scientific literature, clinical investigations, and real-world evidence, as well as the specific considerations for SaMD, like algorithmic complexity and technical validation.

By adhering to these principles and continuously monitoring the performance of SaMD through post-market surveillance, manufacturers can ensure that their products meet the necessary requirements and provide safe and effective healthcare solutions.

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FAQs

1. What does clinical evaluation entail under the EU MDR?
Clinical evaluation under the EU MDR is an ongoing process that must be carried out over the entire lifespan of a medical device. It involves summarizing the clinical evaluation of each device periodically in a Clinical Evaluation Report (CER). The frequency of these reports depends on the risk classification of the device.

2. What is the fundamental principle of clinical evaluation for medical devices?
The clinical evaluation of medical devices is a systematic and planned process aimed at the ongoing generation, collection, analysis, and assessment of clinical data pertaining to a specific device. This process helps ensure the device’s efficacy and safety throughout its lifecycle.

3. Which guideline governs the clinical evaluation process?
The clinical evaluation process is governed by the MedDev 2.7.1 – 6.4 guideline. The guideline specifies that individuals performing the clinical evaluation should have at least 10 years of documented professional experience if a degree is not required for the task. Any deviations from this standard must be thoroughly documented and justified.

4. Are Class I medical devices subject to clinical evaluation?
Yes, manufacturers of Class I medical devices are required to prepare a formal Post-Market Surveillance (PMS) report. Additionally, while higher classes of medical devices must also prepare a Periodic Safety Update Report, all classes should have a post-market clinical follow-up (PMCF) plan. The PMCF is a proactive process that continually updates the clinical evaluation of the device.