Clinical Evaluations & Clinical Investigations for SaMD Development

Clinical evaluations and investigations form critical components of the medical device regulatory pathway, particularly for Software as a Medical Device (SaMD). This document provides a comprehensive overview of these processes within the UK regulatory framework.

Clinical Evaluations

A clinical evaluation is a systematic process used to assess clinical data that demonstrates a medical device’s safety and performance according to its intended use. This evaluation:

• Begins during device development
• Continues after market placement through post-market surveillance
• Provides evidence of device safety and functionality
• Must follow methodological guidance outlined in MEDDEV 2.7.1 (revision 4)

The clinical evaluation process involves collecting and analyzing relevant clinical data, evaluating potential risks against benefits, and documenting conclusions about the device’s clinical safety and performance. This forms a crucial part of the technical documentation required for regulatory approval.

Clinical Investigations

A clinical investigation becomes necessary when insufficient published evidence exists to demonstrate compliance with essential requirements. These investigations:

• Require MHRA approval before testing on humans
• Need a Letter of No Objection (LONO) from the MHRA
• Must be conducted according to ISO 14155 standards
• Demonstrate essential safety and performance aspects of the device

For SaMD specifically, clinical investigations help establish:

1. Analytical validity – How accurately the software measures or identifies what it claims to measure
2. Scientific validity – Whether the software’s output relates to the intended clinical condition
3. Clinical performance – The ability to achieve the intended purpose in the target population

Regulatory Requirements

Any medical device, including SaMD, that has not received regulatory approval cannot be tested on humans without specific approvals:

• MHRA approval is mandatory
• A Letter of No Objection must be obtained
• Testing must follow ISO 14155 guidelines where applicable to software
• For patient data access, additional MHRA approval is needed
• Patient consent is required for confidential data collection

Documentation and Guidance

The clinical evaluation and investigation processes are guided by several key documents:

• MEDDEV 2.7.1 (revision 4) – Provides detailed guidance on conducting and documenting clinical evaluations
• MEDDEV 2.7.4 – Outlines requirements for clinical investigations
• ISO 14155 – Establishes good clinical practice for medical device clinical investigations

Post-Market Surveillance

Clinical evaluation is an ongoing process that continues after market placement. Post-market surveillance data contributes to the overall clinical evaluation by providing real-world evidence of device performance and safety.

References

1. National Institute for Health and Care Research. (2023). Software as a Medical Device (SaMD) Regulatory Pathway. NIHR HealthTech Research Centre in Devices, Digital and Robotics.
2. Medicines and Healthcare products Regulatory Agency. (2021). Guidance for manufacturers on clinical investigations. https://www.gov.uk/government/publications/guidance-for-manufacturers-on-clinical-investigations
3. European Commission. (2016). MEDDEV 2.7.1 Rev.4: Clinical evaluation: A guide for manufacturers and notified bodies under directives 93/42/EEC and 90/385/EEC.
4. International Organization for Standardization. (2020). ISO 14155:2020 Clinical investigation of medical devices for human subjects — Good clinical practice. https://www.iso.org/standard/71690.html

For more information on clinical evaluations and investigations for medical devices in the UK, visit the MHRA website or contact the NIHR HealthTech Research Centre in Devices, Digital and Robotics at HealthTechDDR@uhb.nhs.uk.