Your Easy Guide to Clinical Studies

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

• The Ethics Committee (EC), and if applicable Swissmedic, approved study protocol
• Applicable regulatory requirements (e.g. Swiss Law, FOPH, international)
• Applicable guidelines (ICH GCP, ISO 14155, Biobanking)
• Study quality processes / documents (e.g. SOPs. WIs)
• Ethical principles

 

Protocol non-compliance may threaten the Critical-to-Quality factors of the study, such as participant safety and rights, data quality, regulatory compliance, and the scientific validity of the study.

 

Protocol non-compliance are classified either as a:

• Deviation: Less serious, accidental or unintentional non-compliance that does not significantly affect the study (e.g. minor timing deviation, missing signatures on the study delegation-log)
• Violation: More serious non-compliance that may lead to the exclusion of participants from data analysis, the inability to reach study outcome / endpoint, and/or discontinuation of the study (e.g. enrolment of non-eligible participants, use of expired investigational product (IMP / IMD), deviation from correct consent procedures)

As a SP-INV,

• Document all protocol deviations, including reasons for the deviation in a Note-to-File or a deviation log. Date and sign documents and file documents in the study TMF/ISF
• Assess non-compliance and its potential impact on the study (e.g. study timeline, quality-process adaptations (e.g. SOP, WI), study analysis and reporting, protocol amendment, resources, budget)
• Participants non-compliant may significantly jeopardise data quality and study outcome (e.g. unreliable medication intake). Plan procedures that support participant compliance, and plan measure to assess participant compliance during study conduct
• In the event of persistent non-compliance at a particular study site, decide to close the site and report non-compliance to the EC, and if applicable Swissmedic

 

Define procedures on how to handle non-compliance such as to:

• Perform a root-cause analysis of the deviation
• Define appropriate Corrective and Preventative Actions (CAPA).
• Train study staff on defined risk control-measures
• Document CAPAs and plan risk reviews

References

ICH GCP E6(R3) – see in particular guidelines

• Glossary Definition: Compliance
• 3.12 Noncompliance

ICH E8(R1) – see in particular

• 3.2 Critical to Quality Factors

ISO 9001:2015 (access liable to costs) – see in particular section

• Quality Management Systems