What is it? Why is it important?
Non-compliance addresses the non-adherence to given instruction(s).
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).
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
- 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
Basel, Clinical Trials Unit, CTU, dkf.unibas.ch
Bellinzona, Clinical Trials Unit, CTU-EOC, www.ctueoc.ch
Bern, Clinical Trials Unit, CTU, www.ctu.unibe.ch
Geneva, Clinical Research Center, CRC, crc.hug.ch
Lausanne, Clinical Research Center, CRC, www.chuv.ch
St. Gallen, Clinical Trials Unit, CTU, www.kssg.ch
Zürich, Clinical Trials Center, CTC, www.ctc.usz.ch
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)