What is it? Why is it important?
Non-compliance addresses the non-adherence to given instruction(s).
Protocol non-compliance is either a protocol:
- Deviation: Less serious accidental or unintentional non-compliance that does not significantly affect the study (e.g. participant safety, data quality)
- Violation: More serious non-compliance, that may lead to exclusion of participants from data analysis and/or discontinuation of the study
Protocol non-compliance can affect participant safety and rights, 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).
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?
As a SP-INV, in the event of non-compliance:
- Perform a root cause analysis and implement appropriate corrective and preventative actions (CAPA)
- Document all protocol deviations including reasons for the deviation in a Note-to-File or a deviation log. Date and sign the Note-to-File and keep track of deviations in an deviation applicable log. The ability to assess non-compliance and its potential impact on the study will increasingly help to explain unexpected study results
- File both the Note-to-File and the deviation log in the TMF and/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, prior to implementation, be submitted to the EC/RA for approval. An exception would be safety issues that require immediate adaptations to protocol procedures. If possible, define any to be expected protocol deviations during study conduct upfront in the study protocol.
Participant non-compliance can significantly affect study outcome. Thus, include methods that measure or evaluate participant compliance during study conduct.
Where can I get help?
Your local CTU↧ can support you with experienced staff regarding this topic
Basel, Departement Klinische Forschung, CTU, dkf.unibas.ch
Lugano, 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.usz.ch
ICH GCP E6(R2) – see in particular guidelines
- 5.18 Study monitoring
- 5.19 Audit
- 5.20 Non-compliance
ISO 9001:2015 (access liable to costs) – see in particular section
- Quality Management Systems