Post-Market Clinical Investigation | ISO 14155:2020 & MDR 2017/745

What is a Post-Market Clinical Investigation?

A post-market clinical investigation (PMCI) is a systematic investigation or study conducted on medical devices that have already been placed on

A post-market clinical investigation (PMCI) is a systematic investigation or study conducted on medical devices that have already been placed on the European market with CE marking. These investigations collect clinical data to evaluate device performance, safety, and effectiveness in real-world clinical settings, supporting ongoing regulatory compliance and post-market surveillance under EU MDR 2017/745.

Regulatory Framework: ISO 14155:2020 and MDR 2017/745

Post-market clinical investigations in Europe are governed by two key regulatory documents that work together to ensure scientific rigor and patient safety:

ISO 14155:2020

International standard for clinical investigations of medical devices for human subjects. Establishes requirements for study design, conduct, safety monitoring, and data management for all clinical investigations regardless of device type or therapeutic area.

MDR 2017/745

EU Medical Device Regulation establishing post-market surveillance and clinical follow-up requirements for manufacturers. Mandates systematic collection and evaluation of clinical data from devices in use, including PMCF plans and periodic safety update reports (PSURs).

MDCG Guidance Documents

Medical Device Coordination Group (MDCG) provides interpretive guidance on MDR implementation, including requirements for clinical investigations, safety reporting, and regulatory procedures. Key documents include MDCG 2020-7 on PMCF and MDCG 2020-10 on safety reporting.

Types of Post-Market Clinical Investigations

Post-market clinical investigations can take various forms depending on your clinical questions, resources, and regulatory objectives. Understanding the different types helps you select the most appropriate approach:

PMCI Study Types

Prospective PMCI Studies: Data collected after study initiation with subjects followed forward in time. Provides controlled data collection but requires more resources and time.
Retrospective PMCI Studies: Analysis of existing clinical data collected before study initiation. More cost-effective and faster but limited by data availability and quality.
Observational PMCI Studies: Passive observation of device use in routine clinical practice without intervention. Captures real-world performance but lacks control over data collection.
Comparative PMCI Studies: Comparison of the investigational device with alternative treatments or devices. Provides evidence of relative effectiveness but requires larger sample sizes.
Registry-Based PMCI: Systematic collection of standardized data from multiple sites using a centralized registry. Enables long-term monitoring and multi-center data collection.
Real-World Evidence (RWE) Studies: Analysis of data from electronic health records, claims databases, and other real-world sources. Provides population-level evidence but requires careful data validation.

PMCI vs. PMCF: Key Differences

It's important to understand the distinction between post-market clinical investigations (PMCI) and post-market clinical follow-up (PMCF), as they serve different regulatory purposes:

Aspect	PMCI (Clinical Investigation)	PMCF (Clinical Follow-Up)
Definition	Systematic investigation with defined protocol, objectives, and endpoints	Systematic collection of clinical data from routine device use
Study Design	Prospective or retrospective with controlled methodology	Typically observational without intervention
Protocol Required	Yes, detailed clinical investigation plan (CIP)	Yes, PMCF plan outlining methods and procedures
Ethics Approval	Required for prospective studies with human subjects	May not be required for passive data collection
Regulatory Authority Notification	Required; formal approval from competent authority	Included in technical documentation; no separate approval
Data Collection	Active, structured collection with defined procedures	Passive collection from routine clinical practice
Duration	Defined study period (typically 1-3 years)	Ongoing throughout device lifecycle
Purpose	Answer specific clinical questions; generate evidence	Monitor safety and performance; detect signals

PMCI Study Design and Protocol Development

A well-designed PMCI study requires careful planning and comprehensive documentation. The Clinical Investigation Plan (CIP) is the cornerstone document that guides all study activities:

Define Study Objectives

Clearly articulate specific clinical questions the investigation will answer. Objectives should address identified gaps in clinical data or safety concerns relevant to the device.

Select Study Design

Choose appropriate study design (prospective, retrospective, observational, comparative) based on objectives, resources, and regulatory requirements. Justify design selection.

Define Study Population

Specify inclusion/exclusion criteria, target population characteristics, and sample size with statistical justification. Consider representativeness of real-world users.

Identify Endpoints

Define primary and secondary endpoints that directly address study objectives. Endpoints should be measurable, clinically relevant, and achievable within study timeline.

Plan Data Collection

Specify data collection methods, visit schedule, assessments, and data sources. Ensure data collection procedures are feasible and minimize burden on sites and subjects.

Establish Safety Monitoring

Define procedures for identifying, reporting, and managing adverse events. Establish stopping rules and criteria for escalating safety concerns to regulatory authorities.

Plan Data Analysis

Develop statistical analysis plan specifying analysis populations, statistical methods, and interpretation criteria. Pre-specify analysis to avoid bias.

Document Quality and Risk

Provide quality overall summary of device manufacturing and quality assurance. Document risk management and mitigation strategies relevant to the investigation.

PMCI Regulatory Approval Process in Europe

Obtaining regulatory approval for a post-market clinical investigation in Europe involves coordination with national competent authorities and ethics committees. The process varies by member state but follows general principles:

Key Approval Steps

Step 1 - Pre-Submission: Contact your national competent authority to discuss investigation plan and clarify requirements. This helps identify potential issues early and streamlines the approval process.

Step 2 - Ethics Committee Review: Submit investigation plan to ethics committee for review of ethical and scientific aspects. Ethics approval is typically required before regulatory submission.

Step 3 - Regulatory Submission: Submit complete investigation dossier to national competent authority including CIP, ethics approval letter, device description, and quality documentation.

Step 4 - Regulatory Assessment: Competent authority reviews submission for compliance with MDR and ISO 14155 requirements. Assessment typically takes 30-60 days; may request additional information.

Step 5 - Approval Decision: Competent authority issues approval letter or requests modifications. Study cannot begin until formal approval is received.

ISO 14155:2020 Key Requirements

ISO 14155:2020 establishes comprehensive requirements for clinical investigations. Key requirements include:

Essential ISO 14155:2020 Elements

Study Protocol: Comprehensive protocol describing all aspects of the investigation including objectives, design, procedures, and safety monitoring.
Informed Consent: Written informed consent required from all study subjects with clear explanation of risks, benefits, and rights.
Ethics Review: Independent ethics committee review and approval of protocol, informed consent form, and investigator qualifications.
Investigator Qualifications: Principal investigators must have appropriate qualifications, training, and experience for the investigation.
Safety Monitoring: Systematic procedures for identifying, documenting, and reporting adverse events and serious adverse reactions.
Data Management: Secure data collection, storage, and management systems with appropriate access controls and audit trails.
Quality Overall Summary: Documentation of device quality, manufacturing controls, and quality assurance relevant to the investigation.
Risk Management: Comprehensive risk analysis and mitigation strategies to protect subject safety and data integrity.
Statistical Analysis: Pre-specified statistical analysis plan with defined populations, methods, and interpretation criteria.
Reporting: Comprehensive investigation report documenting methodology, results, conclusions, and implications for device safety and performance.

MDR 2017/745 Post-Market Clinical Investigation Requirements

MDR 2017/745 establishes specific requirements for post-market clinical investigations as part of the overall post-market surveillance and clinical follow-up strategy:

MDR Requirements for PMCI

Manufacturers must include PMCI activities in their PMCF plan when appropriate to address identified clinical data gaps or safety concerns. PMCI activities must be proportionate to the device's risk class and intended use. Results of PMCI studies must be analyzed and incorporated into periodic safety update reports (PSURs) and clinical evaluation updates. Any significant safety findings must be reported to competent authorities within specified timeframes.

Proportionality Principle

MDR emphasizes that PMCI activities must be proportionate to the device's risk profile. Higher-risk devices (Class IIb, III) typically require more robust PMCI activities, while lower-risk devices may require minimal or no PMCI. The choice of PMCI methods should be justified based on the device's risk class, clinical context, and identified data gaps.

Safety Monitoring and Adverse Event Reporting

Robust safety monitoring is essential for protecting study subjects and ensuring data integrity. All adverse events must be properly documented and reported according to regulatory requirements:

Adverse Event (AE) Definitions

→ Any untoward medical occurrence in a subject
→ May or may not be related to device
→ Includes device malfunctions
→ Includes lab abnormalities

Serious Adverse Event (SAE) Criteria

→ Results in death
→ Is life-threatening
→ Requires hospitalization
→ Results in persistent disability
→ Other medically important events

Reporting Requirements

→ SAEs reported within 7-15 days
→ Annual safety reports required
→ Ethics committee notification
→ Competent authority notification
→ Investigator safety updates

Informed Consent and Subject Protection

Obtaining valid informed consent is a fundamental ethical and legal requirement for clinical investigations. ISO 14155:2020 establishes specific requirements for the informed consent process:

Informed Consent Requirements

Written Consent: Informed consent must be documented in writing and signed by the subject before any study procedures begin.

PMCI findings must be analyzed and incorporated into periodic updates of the Clinical Evaluation Report (CER). Results should be used to update the benefit-risk determination, identify new risks or contraindications, and inform risk management activities. Significant safety findings must be reported in Periodic Safety Update Reports (PSURs) and communicated to competent authorities within specified timeframes.

Need Expert Support for Your Post-Market Clinical Investigation?

Our team of regulatory and clinical experts specializes in designing, implementing, and managing post-market clinical investigations that comply with ISO 14155:2020 and MDR 2017/745. We help sponsors and manufacturers generate robust clinical evidence to support regulatory compliance and device commercialization.

Schedule Your Consultation

Key Takeaways

Post-market clinical investigations (PMCI) are systematic studies conducted on CE-marked devices to evaluate performance, safety, and effectiveness in real-world settings
PMCI is regulated by ISO 14155:2020 (international standard) and MDR 2017/745 (EU regulatory requirement) working together to ensure scientific rigor and patient safety
PMCI differs from PMCF in that it involves active, structured data collection with defined protocol, objectives, and endpoints, while PMCF is passive collection from routine use
Common PMCI types include prospective studies, retrospective studies, observational studies, comparative studies, registry-based studies, and real-world evidence studies
A comprehensive Clinical Investigation Plan (CIP) is required, addressing study design, objectives, population, endpoints, procedures, safety monitoring, and data analysis
Regulatory approval from national competent authorities and ethics committee approval are required before PMCI initiation
ISO 14155:2020 establishes requirements for study protocol, informed consent, ethics review, investigator qualifications, safety monitoring, data management, and reporting
MDR 2017/745 requires that PMCI activities be proportionate to device risk class and included in the PMCF plan when appropriate to address clinical data gaps
Informed consent must be obtained from all study subjects with clear explanation of risks, benefits, data protection, and voluntary nature of participation
Robust safety monitoring with systematic adverse event identification, documentation, and reporting is essential for protecting study subjects
Serious adverse events must be reported to competent authorities within 7-15 days and to ethics committees according to regulatory requirements
Electronic data capture (EDC) systems with validation rules, audit trails, and secure access controls ensure data quality and regulatory compliance
Regular monitoring visits verify protocol compliance, data accuracy, safety monitoring adherence, and proper documentation at study sites
A pre-specified statistical analysis plan must define analysis populations, statistical methods, primary and secondary endpoints, and success criteria
Principal investigators must have appropriate qualifications, training in GCP, and demonstrated experience conducting clinical research
Study sites must have appropriate facilities, trained personnel, and experience conducting clinical investigations with proper subject protection measures
PMCI results must be systematically integrated into Clinical Evaluation Report updates and Periodic Safety Update Reports (PSURs)
Common challenges include recruitment difficulties, protocol deviations, data quality issues, regulatory changes, safety signal management, and resource constraints
Best practices include early planning, clear objectives, appropriate study design, experienced team, robust protocol, quality systems, thorough training, and proactive monitoring
GDPR compliance is required for all personal data collection, processing, storage, and protection throughout the investigation
Data integrity and security must be maintained with encryption, access controls, audit trails, and regular security audits
Multi-center investigations require coordination across sites with standardized procedures, training, and monitoring to ensure consistency
Independent Data Safety Monitoring Boards (DSMB) are recommended for high-risk investigations to provide objective safety oversight
Study stopping rules and interim safety analyses protect subjects and ensure investigation integrity when safety concerns emerge
Comprehensive documentation of all study activities, decisions, and communications is essential for regulatory inspection and audit readiness

Conclusion

Post-market clinical investigations are critical tools for generating robust clinical evidence that supports regulatory compliance, device safety assurance, and long-term commercialization success. By following ISO 14155:2020 requirements and MDR 2017/745 principles, you can conduct investigations that satisfy regulatory expectations, protect study subjects, and generate meaningful clinical data.

Success in PMCI requires careful planning, comprehensive documentation, experienced personnel, robust quality systems, and proactive regulatory engagement. The investment in well-designed and properly conducted post-market clinical investigations pays dividends through enhanced regulatory credibility, improved device performance understanding, and stronger clinical evidence supporting your device's benefit-risk profile.

Whether you're planning a prospective clinical study, analyzing real-world evidence, or establishing a device registry, our team of regulatory and clinical experts can guide you through every step of the process. From protocol development through regulatory submission and study conduct, we help ensure your post-market clinical investigation meets all regulatory requirements and generates the high-quality clinical evidence needed for sustained regulatory success.

Ready to strengthen your post-market clinical evidence strategy? Contact us today to discuss your PMCI needs and how our comprehensive CRO services can support your clinical investigation objectives across Europe.