ICH GCP training – what are the expectations?
ICH E6 revision 3 has now been published. The Danish Medicines Agency anticipate questions regarding the need for training and retraining and therefore publish this Q&A.
Appropriate and adequate training on ICH GCP E6 R3 is essential because it helps maintain compliance with regulatory requirements, enhances the quality and reliability of clinical trial data, and ensures the protection of trial participants.
Investigator and persons or parties to whom the investigator has delegated trial-related activities
According to ICH E6 R3:
The investigator(s) should be qualified by education, training and experience to assume responsibility for the proper conduct of the trial (2.1.1) and should provide evidence of such qualifications and should be familiar with the appropriate use of the investigational product(s) as described in the protocol, in the current Investigator’s Brochure, in the product information and/or in other information sources provided by the sponsor (2.1.2).
The investigator should also have sufficient time, an adequate number of available and qualified staff, and adequate facilities for the foreseen duration of the trial to conduct the trial properly and safely (2.2.2).
Regarding other persons or parties to whom the investigator has delegated trial-related activities, the investigator should ensure that they are appropriately qualified and are adequately informed about relevant aspects of the protocol, the investigational product(s) and their assigned trial activities (including activities conducted by staff provided by other parties in accordance with local regulatory requirements). Trial-related training to persons assisting in the trial should correspond to what is necessary to enable them to fulfil their delegated trial activities that go beyond their usual training and experience (2.3.2).
The last sentence is key. E6 R3 focuses on the trial activities that go beyond their usual training and experience. Not all staff need ICH E6 training (or retraining), it depends on their role in the trial. For example, a laboratory technician drawing routine blood samples will hardly need any training at all whereas e.g. principal investigators will need to be thoroughly familiar with the guideline and sub-investigators will need to be trained in the trial activities they perform e.g. obtaining informed consent, registering and reporting adverse events etc. When involving a person or party in a clinical trial, it therefore needs to be considered what tasks the person or party will perform and what their current level of experience is in relation to the trial they will be involved in.
Regarding retraining, the same applies. In determining the need for retraining in general, it should be considered if performing clinical trials is a standard for that person or party (e.g. often the case in oncology and hematology departments) or the person or party only occasionally is involved in clinical trials, in which case training in relation to the individual trial is more appropriate. Retraining should specifically be considered whenever there are significant updates to the guidelines, such as the publication of a new revision like E6 R3.
More specifically to E6 R3, the Danish Medicines Agency is expecting that principal investigators are familiarised with/trained in E6 R3 as they are one of the two legally responsible parties of a trial (together with the sponsor). For the persons or parties to whom the investigator has delegated trial-related activities, the need for retraining will depend on their tasks. If a person performs tasks in areas where the guideline has not changed, retraining is not required; however, it is likely that for the major part of clinical trial staff they will need some degree of retraining, due to the substantial amount of changes in the guideline. It should be considered that some protocols and manuals already describe the tasks of delegated persons and parties to a degree that training and retraining may be reduced, depending on their tasks.
With regards to the amount, frequency and method of training, the Danish Medicines Agency does not have an expected standard. The responsible parties (the principal investigator and the sponsor) should ensure that training and qualifications are adequate for the tasks. As trials vary, this is consequently not a one size fits all approach.
As the sponsor is responsible for selecting the investigator(s)/institution(s) (3.7.1), the sponsor has co-responsibility to ensure that each investigator is qualified by education, training and experience.
Sponsor
According to ICH E6 R3:
The sponsor should utilise appropriately qualified individuals (and service providers) for the activities to which they are assigned (e.g., biostatisticians, clinical pharmacologists, physicians, data scientists/data managers, auditors and monitors) throughout the trial process (3.4, 3.11.2.1.(b), 3.11.4.2 (a), 3.16.1 (x) (ii), 4.3.2 and C.3.1.(l and m)).
When using service providers, the sponsor is responsible for assessing the suitability of and selecting the service provider to ensure that they can adequately undertake the activities transferred to them (3.6.7). This includes assessing the suitability of the training of the service provider’s staff.
The same thinking as described in the investigator section above applies here.
Gap analysis and inspections prior to the implementation
ICH E6 R3 will enter into force 6 months after publication at the website of the European Medicines Agency. In the period until then, the responsible parties (sponsors and investigators) should prepare themselves for the future implementation by performing a gap analysis or via other means identify new or revised training requirements for new or ongoing trials.
The GCP inspectors may evaluate this gap analysis during GCP inspections and assess whether the training requirements of ICH E6 R3 are adequately implemented and documented.