Training requirements for the new version of Good Clinical Practice (ICH E6 R3)
The EMA-approved version of ICH E6 R3 was published on January 23, 2025, and will come into effect on July 23, 2025. Before it comes into effect, responsible parties (sponsors and investigators) must identify new and updated training requirements for new or ongoing clinical drug trials.
Training from the Investigator's perspective
According to ICH E6 R3:
The investigator should be qualified by education, training and experience to assume responsibility for the proper conduct of the trial (Annex 1, 2.1.1). The investigator must be able to provide evidence of his/her qualifications and be familiar with the proper use of the investigational product as described in the information sources provided by the sponsor (Annex 1, 2.1.2). The investigator must also have sufficient time, qualified staff, and suitable facilities for the duration of the trial to ensure it is conducted properly and safely (Annex 1, 2.2.2). If the investigator delegates trial-related tasks to others, he/she must ensure that these individuals have sufficient knowledge of the trial protocol, investigational product, and their assigned trial tasks. The training of individuals performing trial-related tasks must correspond to the requirements of their delegated tasks, especially when the tasks exceed their usual training and experience: "Trial-related training to persons assisting in the trial should correspond to what is necessary to enable them to fulfill their delegated trial activities that go beyond their usual training and experience" (Annex 1, 2.3.2).
This highlighted sentence is important: E6 R3 emphasizes trial tasks that exceed individuals' usual training and experience. Not all staff necessarily need ICH E6 training (or retraining); it depends on their role in the trial. For example, a laboratory technician who routinely takes blood samples needs very little training, but the lead investigator must be thoroughly familiar with the guideline. Assistant investigators must be trained in their specific trial tasks, such as the consent process and adverse event reporting. When a new individual or entity is assigned trial-related tasks, it is important to consider their current level of experience in relation to these trial tasks.
The same applies to retraining. When determining the general need for retraining, it is important to consider whether conducting clinical drug trials is routine for the individual or entity (e.g., often in oncology and hematology departments) or if the individual or party only occasionally participates in clinical trials in human medicines. In the latter case, training for a specific trial is more appropriate. Retraining should be considered whenever there are significant updates to trial guidelines, such as the publication of the new E6 R3 version.
Especially regarding ICH E6, Fimea expects lead investigators to familiarize themselves with/train in its R3 version, as they are one of the two legally responsible parties for the trial (along with the sponsor). Individuals or parties to whom the investigator has delegated trial-related tasks need retraining depending on their tasks. If an individual performs tasks for which the guidelines have not changed, retraining is not necessary. However, it is likely that most clinical trial staff will need some retraining due to significant changes in the guidelines. If the trial protocol and other trial manuals already comprehensively describe the tasks of delegated individuals or parties, the need for retraining may be less.
The appropriate amount, frequency, and methods of training are case-specific. Responsible parties (investigator and sponsor) must ensure that training and qualifications are sufficient for the tasks. Since trials vary, there is no one-size-fits-all solution.
Since the sponsor is responsible for selecting the investigator/organization (Annex 1, 3.7.1), the sponsor has a shared responsibility to ensure that each investigator is qualified based on training, orientation, and experience.
Training from the Sponsor's perspective
According to ICH E6 R3:
The sponsor must utilize appropriately qualified individuals and service providers (e.g., biostatisticians, clinical pharmacologists, physicians, data analysts/data managers, auditors, and monitors) throughout the trial (Annex 1, 3.4, 3.11.2.1.(b), 3.11.4.2 (a), 3.16.1 (x) (ii), 4.3.2 and Appendix C.3.1.(l and m)).
When the sponsor uses service providers, it is their responsibility to assess the suitability of the service provider. The sponsor must ensure that the selected service provider can properly perform the tasks assigned to them (Annex 1, 3.6.7). Therefore, the sponsor must assess whether the service provider's staff training is sufficient.
The same training principles apply to sponsors as described in the previous section for investigators.
ICH E6 R3 training
Responsible parties must prepare for the future by comparing guideline versions using methods such as gap analysis or other means to identify new or updated training requirements for new or ongoing clinical trials.
GCP inspectors may request this comparison or equivalent documentation during GCP inspections and use it to assess whether the ICH E6 R3 training requirements have been properly implemented.