Investigator Responsibilities and Oversight
Part of Good Clinical Practice (GCP) — ICH E6(R3): Roles and Responsibilities in Clinical Trials.
About 7 minutes. Free, in your language, no account needed.
Why this matters
Many site inspection findings are oversight findings, not knowledge findings. A competent person did a task nobody had delegated to them. ICH E6(R3) is explicit: the investigator may delegate the activity, but the investigator keeps the responsibility.
The six terms you must be able to define
These are the core definitions from the ICH E6(R3) Glossary.
| Term | E6(R3) definition, in short |
|---|---|
| Good Clinical Practice (GCP) | A standard for the planning, initiating, performing, recording, oversight, evaluation, analysis and reporting of clinical trials. It gives assurance that results are reliable and that participants' rights, safety and well-being are protected. |
| Investigator | A person responsible for the conduct of the clinical trial, including the participants for whom that person has responsibility. If a team conducts the trial, the investigator is the responsible leader, and may be called the principal investigator. |
| Investigator site | "The location(s) where trial-related activities are conducted and/or coordinated under the investigator's/institution's oversight." |
| Sub-investigator | Any individual member of the trial team designated and under the oversight of the investigator to perform significant trial-related procedures or make important trial-related decisions. Examples: associates, residents, research fellows. |
| Sponsor | An individual, company, institution or organization that takes responsibility for the initiation, management and arrangement of the financing of a clinical trial. A trial may have several sponsors. |
| Service provider | "A person or organization (commercial, academic or other) providing a service used by either the sponsor or the investigator to fulfill trial-related activities." |
Note the change from the previous revision. E6(R2) treated the contract research organization (CRO) separately. In E6(R3), the Glossary entry for CRO says only "See Service Provider". A CRO is now one kind of service provider, and so is a central laboratory or an electronic data capture supplier.
Qualifications and training
E6(R3) section 2.1 requires the investigator to be "qualified by education, training and experience to assume responsibility for the proper conduct of the trial" and to "provide evidence of such qualifications". Evidence means a current curriculum vitae, training records and licenses where they apply. The investigator must also be familiar with the appropriate use of the investigational product, as described in the protocol, the current Investigator's Brochure or other sources the sponsor supplies.
Resources
Section 2.2 sets two requirements sites often treat as optional.
- Recruitment feasibility — the investigator "should be able to demonstrate (e.g., based on retrospective or currently available data) a potential for recruiting the proposed number of eligible participants within the recruitment period as agreed with the sponsor."
- Time, staff and facilities — sufficient time, an adequate number of available and qualified staff, and adequate facilities for the foreseen duration of the trial.
An honest feasibility answer protects participants. An optimistic one produces rushed visits.
Responsibilities, delegation and the delegation record
Section 2.3 is the core of this lesson. Three rules follow.
Delegation does not move responsibility. The investigator "retains the ultimate responsibility and should maintain appropriate oversight of the persons or parties undertaking the activities delegated". Oversight "should depend on the nature of the delegated activities and be proportionate to the importance of the data being collected and the risks to trial participant safety and data reliability."
Training is targeted, not blanket. Trial-related training for people 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." A qualified phlebotomist does not need training in venepuncture. That person may still need training on the protocol-specific tube order.
The delegation record is proportionate. The investigator should ensure a record is maintained of the persons and parties to whom activities were delegated. Documentation of delegation "should be proportionate to the significance of the trial-related activities." E6(R3) then adds a genuinely new allowance: "In situations where the activities are performed as part of clinical practice, delegation documentation may not be required."
Section 2.3 adds two points. Agreements the investigator or institution makes with service providers should be documented. The investigator or institution must permit monitoring and auditing by the sponsor, inspection by regulatory authorities, and IRB/IEC review where applicable.
Communication with the IRB/IEC
Section 2.4 places these duties on the investigator or institution, or in some regions the sponsor.
- Hold documented and dated approval or favorable opinion from the Institutional Review Board or Independent Ethics Committee (IRB/IEC) before initiating the trial. This covers the protocol, the informed consent materials, recruitment procedures such as advertisements, and other participant-facing information.
- Provide the current Investigator's Brochure, or basic product information brochure, and any updates.
- Provide updates to participant information as the trial progresses.
- Submit documented summaries of trial status as local requirements demand or on request.
- Promptly communicate any change that significantly affects trial conduct or increases risk.
Compliance with the protocol
Section 2.5 requires the investigator or institution to sign the protocol, or an alternative contract, to confirm agreement with the sponsor. The investigator complies with the protocol, GCP and applicable regulatory requirements.
E6(R3) states two obligations on deviations. The investigator "should document all protocol deviations". For those deemed important, the investigator explains the deviation and implements measures to prevent recurrence where applicable. The investigator should deviate "only where necessary to eliminate an immediate hazard(s) to trial participants", and must then inform the sponsor promptly and report to the IRB/IEC and, where applicable, regulatory authorities.
In practice
At Dr. Sarah's hypertension site, a new nurse, Rafael, begins performing 12-lead electrocardiograms (ECGs) for trial visits. He does ECGs daily in the clinic. He is not on the delegation record.
Ana, the coordinator, asks two questions. Is the ECG a trial activity or part of usual clinical practice? Here the protocol requires it at set time points and it supports a safety endpoint, so it is a trial activity. Is it significant? Yes.
So delegation must be documented, and Rafael needs protocol-specific ECG training, not general ECG training. Ana adds him to the delegation record with the correct start date, files his curriculum vitae and training record, and asks Dr. Sarah to sign. The ECGs already performed are documented as a deviation and reported to the sponsor.
Responsibility cannot be delegated.
Key takeaways
- The investigator may delegate activities but retains ultimate responsibility, and oversight must be proportionate to the risk and to the importance of the data.
- E6(R3) requires training only for delegated activities that go beyond a person's usual training and experience, not blanket retraining of every skill.
- The delegation record must be proportionate to the significance of the activity, and delegation documentation may not be required where an activity is performed as part of clinical practice.
- IRB/IEC approval or favorable opinion must be documented and dated before the trial is initiated, covering consent and recruitment materials.
- All protocol deviations must be documented, and deviation is permitted only where necessary to eliminate an immediate hazard to participants.
- In E6(R3) a CRO is a service provider, which is any person or organization providing a service used by the sponsor or investigator to fulfill trial-related activities.