Role of the Chief Investigator
According to the UK Clinical Trials Regulations 2 (1), the Chief Investigator means, “in relation to a clinical trial conducted at a single trial site, the investigator for that site”. Where a clinical trial is conducted across a number of trial sites, the Chief Investigator is the “authorised health professional” (a doctor, a dentist, a nurse, or a pharmacist), whether or not he is an investigator at any particular site, who takes primary responsibility for the conduct of the trial.” As Chief Investigator, you are also responsible for, and must ensure that, you have the necessary and suitable experience and expertise to design, conduct and report the study to the standards as set out in the Research Governance Framework (2nd edition).
According to the UK Clinical Trials Regulations 14, the Chief Investigator must obtain a favourable opinion from an appropriate ethics committee. The Chief Investigator cannot apply to any research ethics committee until the sponsor has signed the relevant documents agreeing to undertake sponsorship responsibilities. The Chief Investigator must also ensure that the study is registered with the University of Manchester Senate Committee on the Ethics on Human beings, and the necessary NHS R&D approvals have been obtained.
Authorisation from the UK Competent Authority (MHRA) and so must any subsequent amendments. The Chief Investigator, in liaison with the sponsor, will have to complete the Clinical Trial Authorisation (CTA) form which can be accessed via the IRAS portal. The Chief Investigator is not permitted to submit the CTA, as this is the responsibility of the sponsor.
The Chief Investigator as an employee of the University, must register with the University of Manchester any intention to submit a funding application for a CTIMP, whether or not the University of Manchester has been identified as a probable sponsor. The Chief Investigator must keep the University informed of the funding outcome, even in cases where the application is unsuccessful or where there will be a re-submission for funding. For successfully funded CTIMPs, the Chief Investigator must, at all stages, keep the University informed of any intended start dates.
The sponsor of any CTIMP will most likely delegate some of its responsibilities to the Chief Investigator. The delegation of any responsibilities is recorded in a delegation log. It is important, as the Chief Investigator that you are fully aware of the responsibilities and competently trained to fulfil the obligations that have been delegated to you. The sponsor remains ultimately responsible for all the responsibilities it may have delegated. Therefore it is important that the sponsor is kept informed of all developments throughout the CTIMP.
The Chief Investigator can delegate responsibilities to members of the trial team, but ultimately remains accountable and so must maintain close oversight of the trial. All delegated responsibilities must be written into a trial specific activities delegation log, and kept up-to-date. It is the responsibility of the Chief Investigator to ensure that the members of the trial team have the relevant experience and training to undertake the delegated responsibilities.
The purpose of the university Investigator Agreement is to make the obligations of the Chief Investigator clear. This Agreement must be signed by the Chief Investigator and will form a binding contract. Any deviation from the terms of this Agreement will be treated as research misconduct. In addition you must comply with the University of Manchester policies and SOPs, and the SOPs of any other sponsor(s). The contents of the Agreement are explained as part of the Chief Investigator’s Briefing.
The Regulations state that clinical trials will be conducted according to the principles of GCP, and Regulation 31A requires that a readily available Trial Master File (TMF) is kept, which contains the essential documents relating to that clinical trial. The filing of essential documents in an orderly, timely manner also assists the smooth running of the trial and any future audit or inspection. With the large volume of documentation required for each trial, a satisfactory filing system is necessary.
A CTIMP must be conducted within the parameters of good clinical practice (GCP). The definition from the EU Directive 2001/20/EC, article 1, clause 2 states that, “Good clinical practice is a set of internationally recognised ethical and scientific quality requirements which must be observed for designing, conducting, recording and reporting clinical trials that involve the participation of human subjects.”
Chief Investigators and members of their team working on a CTIMP must comply with principles of GCP, as this ensures that the rights, safety and well-being of trial subjects are protected, and that the results of the clinical trials are credible and accurate. Any researcher working on a CTIMP must have appropriate training in GCP. The University requires GCP training to be updated every two years.
The University provides free GCP training to all members of staff.
All adverse events which may occur in a study participant should be recorded and reported. The mechanism of recording and reporting should be detailed in the protocol. The responsibility for reporting of adverse events is usually delegated to the Chief Investigator. For detailed guidance on Adverse events and the definition of SUSARs, and reporting timelines please read the University SOP on Pharmacovigilence.
Annual safety reports have to be submitted to the MHRA and the main ethics committee. These reports list all the suspected serious adverse reactions which have occurred during that year. Please read the University SOP on Pharmacovigilence for detailed guidance.
The University retains a record of all CTIMPs conducted by its members of staff. Where the University is the sponsor of a CTIMP, it will monitor CTIMPs.
The University expects that the Chief Investigator to adhere to policies and SOPs. The University Code for Good Research Conduct should be followed including data security and management, archiving. The TMF must at all times be maintained in an inspection ready state and be made available for audit by the sponsor.
The University will also send out at regular intervals a CTIMP self-assessment questionnaire, including evaluation of on-going risk assessments, for all University sponsored CTIMPs.
The definition of the conclusion of any CTIMP should be provided in the study protocol. For most studies this point is the date on which the last participant was visited, or when any follow-up monitoring of participants and data collection has been completed.
According to the Regulations, the sponsor must notify both the MHRA and the main REC within 90 days of the conclusion of the trial. Where a CTIMP is terminated early, the sponsor must notify both the MHRA and the main REC within 15 days of the date of termination. For further guidance from the MHRA on closing CTIMPs, please visit the MHRA website: Managing your clinical trial authorisation: End of trial.
The relevant NHS Trust R&D offices must also be informed that the CTIMP has concluded.
Where the University is sponsor for a CTIMP, a close down visit will be scheduled with the Chief Investigator. The TMF must be complete, and this will be assessed by the Policy Research Officer for Clinical Trials.