An Urgent Safety Measure (USM) is a procedure which is not defined by the protocol that can be put in place with immediate effect without needing to gain 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.
USMs may be instigated by either the Sponsor or an Investigator; they apply when actions are taken regarding the whole study. The Chief Investigator will be required to sign to acknowledge that they have read and understood the relevant Noclor USM SOPs prior to study activation
All Investigators (as delegated through agreements - mNCAs) are responsible for implementing and reporting USMs to the sponsor. The clinical trial protocol should document the procedures for urgent safety measures, and Principal Investigators should be trained in regards to reporting requirements at site initiation.
- Taking the decision to implement an USM
The individual best able to take the appropriate immediate actions according to the protocol and Noclor USM SOPs will be the Chief Investigator and s/he should be the first point of contact for sponsor/Investigators to discuss the issue and proposed /implemented USMs (if time permits the Investigator should discuss such actions with the Chief Investigator prior to implementation).
The Chief Investigator, must notify the Noclor Sponsor Representative (sponsor) immediately (<24hours) to discuss the hazard and any actions taken or to be taken (if time permits prior to implementation). In consultation the Chief Investigator and sponsor will determine whether:
- An USM has been implemented/requires implementing and agree the subsequent course of action according to the protocol and Noclor USM SOPs. If this decision-making process includes one of the oversight committees (TSC or IDMC) this should be documented in the protocol and the relevant Committee Charter as appropriate.
- A temporary halt to the trial is the most appropriate course of action (depending on the issue and what action has already been taken/needs to be taken immediately)
- A serious breach or other event has occurred that requires further investigation
- Responsibilities for USMs
If the Chief Investigator and sponsor agree that an USM has been implemented or requires implementation for a clinical trial the following actions will need to be considered (in parallel):
- All Investigators who need to implement the same measures will need to be informed by the Chief Investigator
- The Chief Investigator (or sponsor representative as agreed) should make initial notifications by telephone to the REC and for CTIMPs the MHRA Clinical Trial Unit (to discuss the issue with a medical assessor). The details of all telephone calls should be documented in a file note (date, time who was spoken to and the outcome of discussions)
- Discussion over whether a temporary halt to trial is required – allowing time to assess the situation /safety data (notifying of the temporary halt as an action taken at the same time as notifying of the USM)
- Report event according to safety and incident reporting requirements - as required and depending on the reason for the USM
- Notify the Ethics Committee and MHRA (for CTIMPs) by substantial amendment within 3 days (further to the initial notification by telephone) of the measures being taken with a cover letter detailing what measures have been taken and the reason for the measures
- Record of all discussions, meetings, decisions and correspondence regarding the USM must be documented in the Study/Trial Master File (S/TMF)
- Examples of when an USM may be required
- Serious adverse reactions with an unexpected outcome (e.g. death)
- An increase in the frequency of a serious adverse reaction which is judged to be clinically important
- A serious adverse event associated with the study procedures which may be prevented by changing the procedures
- Lack of efficacy of an investigational medicinal product (IMP) used for the treatment of a life threatening illness
- A major safety issue identified from other studies (clinical or non-clinical) or from other usage of the IMP.