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Serious Breaches

A ‘serious breach’ is defined as a breach likely to effect to a significant degree:

  • the safety or physical or mental integrity of the subjects of the trial; or
  • the scientific value of the trial

For clinical trials, the requirements for reporting serious breaches should be documented in the protocol and investigator sites should be made aware of their role in reporting (and how to report) at site initiation. The Chief Investigator will also be required to sign to acknowledge that they have read and understood the Noclor Serious Breach SOP prior to study activation

Making a judgment on whether a potential breach or non-compliance (or persistent non-compliance) is ‘serious’ and requires reporting is the responsibility of the Noclor (where Noclor is acting on sponsor behalf).  

If Noclor fails to discharge the sponsor’s responsibilities for CTIMPs in reporting serious breaches within the regulatory timeframes it is a criminal offence.

Noclor and the other regulatory bodies may take the information regarding reported serious breaches into account when assessing future applications for sponsorship, favourable ethics and Clinical Trial Authorisation (CTA).

Identifying a Serious Breach

The identification of potential serious breaches may come from various sources:

  • through complaints or reported incidents
  • flagged by monitoring (review of monitor reports) or sponsor oversight activities
  • flagged at audit notified by external personnel (for example by host site R&D or members of the public)
  • through TSC /IDMC
  • via central review of meeting minutes and email correspondence
  • analysis of samples/data
  • on further investigation of a reported non-compliance/protocol violation.

If the Noclor Sponsor Representative is not the person to have identified the potential serious breach then they should be the first person that is notified at Noclor.

All research/Trust staff have a responsibility to report adverse events and incidents and violations/non-compliances according to the protocol, Noclor procedures and local policies.

Reporting Serious Breaches

When Noclor has received notification (from whatever source) that a potential serious breach may have occurred the clock starts (Day 1 = day made first aware of potential serious breach).

Making a judgment on whether a potential breach or non-compliance (or persistent non-compliances) is ‘serious’ and requires reporting is the responsibility of the Noclor (where Noclor is acting on sponsor behalf).  

If the evidence is clear that a serious breach has occurred Noclor will notify the REC and MHRA (for CTIMPs) within the 7 calendar days, and investigate and take action simultaneously (or after notification) in accordance with the Noclor Serious Breach SOP.

In situations where a potential serious breach has occurred but the evidence is not clear, a degree of immediate initial investigation may be required by Noclor prior to notification (notification still needs to be within the 7 calendar days timeframe) to confirm that a reportable breach has occurred.  Updates after the initial report are acceptable (using the same report template form which will be clearly identified as a follow-up report and will include the unique GCP identifier).

Noclor may seek clarification from the MHRA on a potential serious breach by contacting the GCP inspectorate directly.

Noclor will report serious breaches (for CTIMPs and non-CTIMPs) using the MHRA Template Serious Breach Notification Form, detailing the nature of the event, the impact of the event and any corrective and preventative actions taken (or planned).

After a Serious Breach has been identified

Noclor and the Chief Investigator should ensure that all corrective and preventative actions have been taken (and the breach is closed).

It is important that a complete audit trail of information and decision-making is documented in regards to a serious breach (including any telephone conversations). The Chief Investigator is responsible for retaining copies of serious breach reports and all correspondence relating to a serious breach in the Study/Trial Master File (S/TMF).

Be prepared - for CTIMPs, a reported serious breach may trigger an inspection from the Competent Authority (MHRA).

The Chief Investigator should notify the relevant study oversight committees and investigator sites of reported serious breaches and provide instruction on any corrective and/or preventative action that has/should be implemented.

Noclor will retain a central record of all non-compliances and serious breaches across all sponsored research.

Noclor and the other regulatory bodies may take the information regarding reported serious breaches into account when assessing future applications for sponsorship, favourable ethics and Clinical Trial Authorisation.