What is it? Why is it important?

Non-compliance addresses the non-adherence to given instruction(s).

In a study non-compliance are deviations from the EC/RA approved study protocol, GCP, study SOPs, and the applicable regulatory requirements.

Protocol non-compliance can affect participant rights and safety, and/or the quality and integrity of study data.

Participants can also be non-compliant jeopardising data integrity and study outcome (e.g. not follow medication intake procedures).

More

Protocol non-compliance is a divergence from the EC/RA approved protocol, and can be categorised as either a protocol:

  • Deviation: Less serious accidental or unintentional non-compliance that does not significantly affect the study
  • Violation: More serious non-compliance, that may lead to exclusion of participants from data analysis and/or discontinuation of the study

In the event of persistent non-compliance at a particular study site, the SP-INV should close the site and report non-compliance to the EC/RA, as applicable.

What do I need to do?

In the event of non-compliance:

  • Perform a root cause analysis and implement appropriate corrective and preventative measures
  • Document all protocol deviations including reasons for the deviation. Date and sign the deviation log
  • As applicable, include a note-to-file regarding the deviation in the TMF or ISF
  • Depending on the seriousness and persistence of non-compliance close the site and report to EC/RA

More

  • Substantial changes (amendments) in study conduct and its study protocol must initially be submitted to the EC/RA for approval prior to being implemented. An exception would be safety issues that require immediate adaptations to protocol procedures.
  • Include methods that measure or evaluate participant compliance in the study. Participant non-compliance can significantly affect study outcome. The ability to assess non-compliance and its potential impact will increasingly help to explain unexpected study results.
  • If possible, define any to be expected protocol deviations / violations during study conduct upfront in the study protocol.

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 guidelines

  • 5.18 Study monitoring
  • 5.19 Audit
  • 5.20 Non-compliance

ISO 9001:2015 – see in particular section

  • Quality Management Systems (access liable to costs)
Abbreviations
  • CTU – Clinical Trials Unit
  • EC/RA – Ethics Committee / Regulatory Authorities
  • GCP – Good Clinical Practice
  • ISF – Investigator Site File
  • SOP – Standard Operating Procedures
  • SP-INV – Sponsor-Investigator
  • TMF/ISF – Trial Master File / Investigator Site File
Development ↦ Quality and Risk ↦ Quality Control ↦ Non-Compliance
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): Development ↦ Quality and Risk ↦ Quality Control ↦ Non-Compliance

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