What is it? Why is it important?

Safety assessments (SAs) of Other Clinical Trials (OCT) are standardised procedures used to evaluate adverse events (AEs), and other reportable events, during study conduct.

In OCT studies, SA of AEs is based on 3 main criteria:

  • Severity: grades the intensity of an AE, such as:
    • CTCAE, criteria mainly used in oncology
    • Other grading systems. Such as to distinguish between mild, moderate, and severe AEs (ICH E2A)
  • Seriousness: grades the effective harm of an AE to study participants. The grading is based on clear regulatory definitions (e.g. serious / non-serious)
  • Causality: assesses the suspected relationship between study intervention and AE occurrence

More

Severity

Suggested ratings:

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

Seriousness

For OCT, serious is defined as any event which:

  • Requires inpatient treatment not envisaged in the protocol or extends a current hospital stay
  • Results in permanent or significant incapacity or disability
  • Is life-threatening or results in death; or
  • Causes a congenital anomaly or birth defect
  • Is a congenital anomaly/birth defect

Causality

Suggested assessment (according to Art. 63 ClinO):

  • It can be excluded that the SAE is attributable to the intervention under investigation
  • It cannot be excluded that the SAE is attributable to the intervention under investigation

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 if there is a relationship between study intervention and AE occurrence

As a SP-INV:

  • Re-assess each AE reported by the Site-INV(s) on severity, seriousness, and relationship
  • Report safety events as required by applicable laws (e.g. to EC)
  • If applicable, re-evaluate the risk-benefit of the study
  • Inform the Site-INV

For all AEs, Site-INV and SP-INV both assess severity (intensity), seriousness, and causality.

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 Site-INV and SP-INV should be included in the report.

Where can I get help?

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

References

ICH GCP E6(R2) – see in particular guideline

  • 6.8 Assessment of Safety

Swiss Law

FEDLEX – law is available online under number

  • 810.305 ClinO

ClinO – see in particular article

  • Art. 63 Documentation and notification of SAE
Abbreviations
  • AE – Adverse Event
  • ClinO – Clinical Trials Ordinance
  • CTCAE – Common Terminology Criteria for Adverse Events
  • CTU – Clinical Trials Unit
  • EC – Ethics Committee
  • FEDLEX – Publication Platform for Federal Laws
  • ICH – International Council for Harmonisation
  • ICH GCP – International Council for Harmonisation - Good Clinical Practice
  • OCT – Other Clinical Trial
  • SA – Safety Assessment
  • SAE – Serious Adverse Event
  • Site-INV – Site Investigator
  • SP-INV – Sponsor Investigator
Conduct ↦ Safety ↦ Safety Assessment ↦ Other Clinical Trials
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 ↦ Other Clinical Trials

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