What is it? Why is it important?

Safety assessment (SA) of Investigational Medical Devices (IMD) is a standardised procedure used to evaluate the occurrence of Adverse Events (AEs) and other reportable events, such as Device Deficiency (DD) during study conduct.

In IMD studies, SA of AEs is based on 4 main criteria:

  • Severity: grades the intensity of an AE as mild, moderate, and severe
  • Seriousness: grades the effective harm of an AE to study participants, MD users, or other persons. The grading is based on clear regulatory definitions (e.g. serious / non-serious)
  • Causality: suspected relationship with
    • IMD exposure
    • Study procedures, or
    • Comparator (e.g. a licensed MD used as a control)
  • Anticipation / Expectedness: assess AE occurrence based on previously observed events in current risk assessment documents (e.g. risk analysis report and/or CIP, the “instruction for use” for licensed MDs, the IB for non-licenced MDs (IMD))

IMD safety assessment also includes the evaluation whether the AE was due to a device deficiency (DD), namely any inadequacy of the IMD itself.

More

A DD assessment includes:

  • The nature of the DD (i.e. malfunction, using error, inadequate labelling, or other)
  • The inadequacy type (i.e. related to the IMD identity, quality, durability, reliability, safety or performance)
  • If the DD has led to an AE, could it have led to an SAE?

Severity

Suggested ratings:

  • Mild: minor discomfort which does not interfere with normal daily activity
  • Moderate: discomfort which reduces or affects normal activity
  • Severe: incapacitating with the inability to work or perform normal daily activities

Seriousness

For IMD serious is defined as any adverse event that led to any of the following (MDCG and MDR):

  • Death
  • Serious deterioration in the health of the subject, that resulted in any of the following:
    • Life-threatening illness or injury
    • Permanent impairment of a body structure or a body function
    • Hospitalisation or prolongation of patient hospitalisation
    • Medical or surgical intervention to prevent life-threatening illness or injury or permanent impairment to a body structure or a body function
    • Chronic disease
  • Foetal distress, foetal death or a congenital physical or mental impairment or birth defect

Causality

The following grading system is required:

  • Not related: Relationship can be excluded
  • Possible: Weak relationship but cannot be ruled out completely. Alternative causes are also possible
  • Probable: Relationship with device relevant and/or AE cannot reasonably be explained by another cause
  • Causal relationship: Relationship with device, comparator or procedures beyond reasonable doubt

Expectedness

Refers to the previous occurrence of serious AE similar in nature and severity, based on RSI (e.g. in the “instruction for use” for licensed MDs, the IB for non-licenced MDs (IMD))

DD with an SAE potential

Is defined as a DD that might have led to an SAE if:

  • Appropriate action had not been taken
  • Intervention had not occurred, or
  • Circumstances had been less fortunate

What do I need to do?

As a Site-INV, assess each AE and:

  • Determine its severity (e.g. intensity) as defined in the study protocol
  • Determine whether the AE qualifies as serious. A serious AE is named a Serious Adverse Event (SAE)
  • Determine whether there is reason for causality. In the event of a possible causal relationship, the event is named an Adverse Device Effect (ADE)
  • An AE that is both serious and related is named Serious Adverse Device Effect (SADE)
  • Record and assess any DDs
  • Report all DDs and AEs to the SP-INV

As a SP-INV:

  • Re-assess each AE reported by the Site-INV(s) on severity, seriousness, and causality (relatedness)
  • Determine expectedness (in nature, intensity or frequency) based on current risk assessments
  • Events that are serious, related and not expected are named Unanticipated Serious Adverse Device Effect (USADE)
  • Inform the Site-INV
  • Re-assess each DD reported by the Site-INV and determine whether it could have led to an SAE (DD with SAE potential)
  • Report safety events as required by applicable laws (e.g. to EC/RA, and manufacturer if applicable)
  • If applicable, re-evaluate the risk-benefit of the study

More

For all AEs, Site-INV and SP-INV both assess intensity, seriousness, and causality. The SP-INV assesses expectedness based on previous occurrence of the same AE.

In the event the SP-INV and Site-INV disagree on the assessment, they should try to find a consensus. If not possible, the opinion of both the Site-INV and the SP-INV should be included in the safety report.

Where can I get help?

Your local CTU can support you with experienced staff regarding this topic

External Links

Swissmedic – see in particular information sheets

  • BW600_00_015e Clinical trials of medical devices
  • MU680_20_004e_MB Medical devices FAQs Patients

References

ISO 14155:2020 Medical device (access liable to cost) – see in particular sections and annex

  • 3.1 ADE definition
  • 3.2 AE definition
  • 3.19 DD definition
  • 3.33 Malfunction definition
  • 3.44 SADE definition
  • 3.45 SAE definition
  • 3.46 Serious health threat
  • 3.51 USADE definition
  • 3.52 Use error
  • 7.4 AE and DD
  • Annex F Adverse event categorization

MDCG 2020-10/1 – see in particular articles

  • 3.2 AE definition
  • 3.3 SAE definition
  • 3.4 DD definition
  • 9. Causality Assessment

MDR 2017-745 – see in particular articles

  • Art. 2 (57) AE definition
  • Art. 2 (58) SAE definition
  • Art. 2 (59) DD definition
  • Art. 80 (1) Recording and reporting of AE that occur during clinical investigations

Swiss Law

FEDLEX – law is available online under number

  • 810.306 ClinO-MD

ClinO-MD – see in particular articles

  • Art. 32 Documentation of AE
  • Art. 33 Reporting of SAE
  • Art. 34 Reporting of safety and protective measures
Abbreviations
  • ADE – Adverse Device Effect
  • AE – Adverse Event
  • CIP – Clinical Investigation Plan
  • ClinO-MD – Ordinance on Clinical Trials with Medical Devices
  • CTU – Clinical Trials Unit
  • EC/RA – Ethics Committee / Regulatory Authorities
  • DD – Device Deficiency
  • FAQ – Frequently Asked Questions
  • FEDLEX – Publication Platform for Federal Laws
  • IB – Investigator’s Brochure
  • ICH GCP – International Council for Harmonisation - Good Clinical Practice
  • IMD – Investigational Medicinal Device
  • ISO – International Organization for Standardization
  • MD – Medical Device
  • MDCG – Medical Device Coordination Group
  • MDR – Medical Device Regulation (EU)
  • RSI – Reference Safety Information
  • SA – Safety Assessment
  • SADE – Serious Adverse Device Effect
  • SAE – Serious Adverse Event
  • Site-INV – Site Investigator
  • SP-INV – Sponsor Investigator
  • USADE – Unanticipated Serious Adverse Device Effect
Conduct ↦ Safety ↦ Safety Assessment ↦ Medical Device
Study
Basic

Provides some background knowledge and basic definitions

Basic Protocol
Basic Statistics
Basic Monitoring
Basic Drug or Device
Basic Biobanking
Concept

Starts with a study idea

Ends after having assessed and evaluated study feasibility

Concept Protocol
Concept Statistics
Concept Drug or Device
Concept Biobanking
Development

Starts with confidence that the study is feasible

Ends after having received ethics and regulatory approval

Development Protocol
Development Statistics
Development Drug or Device
Development Biobanking
Set-Up

Starts with ethics and regulatory approval

Ends after successful study initiation

Set-Up Protocol
Set-Up Ethics and Laws
Set-Up Statistics
Set-Up Drug or Device
Set-Up Biobanking
Conduct

Starts with participant recruitment

Ends after the last participant has completed the last study visit

Conduct Protocol
Conduct Statistics
Conduct Drug or Device
Conduct Biobanking
Completion

Starts with last study visit completed

Ends after study publication and archiving

Completion Protocol
Completion Statistics
Completion Drug or Device
Completion Biobanking
Current Path (click to copy): Conduct ↦ Safety ↦ Safety Assessment ↦ Medical Device

Please note: the Easy-GCS tool is currently under construction.