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Protocol Violations & Non-Compliance

Research sponsored by a Noclor partner should be managed and conducted in accordance with the approved protocol, Noclor procedures, GCP and the relevant regulations (as applicable).   Monitoring systems and quality control checks must be implemented within the study to identify any departures from the protocol /procedures.

Departures from the protocol and procedures can usually be categorised according to seriousness and type of departure into protocol deviations, minor or major violations and serious breaches. The mechanisms for recorded and reporting protocol deviations/protocol violations/non-compliances are outlined here. The ultimate assessment of the seriousness of a violation/non-compliance should be made by Noclor (in discussion with the Chief Investigator). 

The Chief Investigator is responsible for the overall management of deviations/non-compliances within their research study: escalating to sponsor (Noclor) according to Noclor procedures; ensuring that appropriate corrective and preventative actions (CAPA) are taken; circulating reports to the relevant parties involved in study oversight through agreed mechanisms; retaining all information pertaining to deviations/violations/non-compliances in the Study/Trial Master File and taking into account any non-compliances in the end of study report

Protocol Deviations

Clinical trials should be conducted in accordance with the approved protocol unless an Urgent Safety Measure must be taken.

Unintended (non-serious) departures from the approved protocol would be considered ‘protocol deviations’; they are usually identified retrospectively through monitoring and data validation of CRFs.  An example of a protocol deviation would be a study visit date being outside the window defined in the protocol.

Protocol deviations do not require reporting to the sponsor, they should be recorded on a protocol deviation log and retained at site in the Investigator Site File (ISF). The deviation log should be provided to the Chief Investigator/sponsor on request (for monitoring/audit purposes).

The Chief Investigator and study oversight groups should continually monitor protocol deviations to establish whether an amendment to the protocol or further training is required to prevent escalation into more serious violations or breaches. It is the responsibility of the Chief/ Principal Investigator to train the research team (as delegated) on the trial protocol to avoid repeat deviations.

Minor Protocol Violations / Non-Compliance

A protocol violation or non-compliance is any deviation from the protocol, study or sponsor procedures that is not approved by the sponsor/REC/MHRA prior to its implementation. 

A minor violation/non-compliance is one that does not impact on the subjects’ safety or compromise the integrity of study data. However if left unreported could lead to more major violations /non-compliance issues further down the line.   

An example of a minor violation would be: 

  • Missing original signed consent form (only photocopy present) 

Minor protocol violations /non-compliances for studies sponsored by a Noclor partner should be reported by the Principal Investigator (or Chief Investigator for study management non-compliances) using the Noclor Non-Compliance Report Form.  The form should be submitted to the sponsor (Noclor Sponsor Representative) and copied to the Chief Investigator within 24 hours of becoming aware of the violation so that the appropriate action and investigation can take place in a timely manner. 

Major Protocol Violations / Non-Compliance

A major violation/non-compliance is one that may impact on the participant safety or affects the integrity of the study data. 

Major protocol violations /non-compliances for studies sponsored by a Noclor partner should be reported by the Principal Investigator (or Chief Investigator for study management non-compliances) using the Noclor Non-Compliance Report Form.  The form should be submitted to the sponsor (Noclor Sponsor Representative) and copied to the Chief Investigator within 24 hours of becoming aware of the violation so that the appropriate action and investigation can take place in a timely manner. 

Reported major violations require prompt initial assessment by Noclor/Chief Investigator to confirm that the violation does not constitute: 

  • an Urgent Safety Measure -a measure has been implemented without prior authorisation by the REC (and MHRA where applicable) in order to protect clinical trial participants from any immediate hazard to their health and safety

OR

  • a serious breach which would require further investigation and escalated reporting. 

Examples of major violations are:

  • Failure to obtain informed consent (no evidence)
  • No evidence of  medical assessment of eligibility of participant in being enrolled in a CTIMPs
  • Subject does not meet the eligibility criteria for the study (protocol waivers are not acceptable)
  • Failure to report SAEs in line with the protocol and Noclor SOPs