8.2 Investigator Responsibilities under GCP
Key Takeaways
- The Principal Investigator (PI) has ultimate responsibility for the conduct of the trial at the site, even when delegating specific tasks to the site team.
- The PI must ensure adequate resources, qualifications of staff, and proper medical care for trial subjects.
- Source data must meet ALCOA-C standards: Attributable, Legible, Contemporaneous, Original, Accurate, and Complete.
Investigator Responsibilities under GCP
The Principal Investigator (PI) is the leader of the clinical trial team at the research site. Under Good Clinical Practice (GCP), the PI holds the ultimate responsibility for the ethical and scientific conduct of the trial. While a Clinical Research Coordinator (CRC) performs many of the day-to-day operational tasks, they do so under the direct supervision and delegation of the PI. Understanding the PI's responsibilities is crucial for a CRC, as it dictates how tasks must be documented, overseen, and reported.
Ultimate Responsibility and Delegation
A fundamental tenet of GCP is that while the PI may delegate trial-related duties to appropriately qualified individuals, the PI cannot delegate responsibility.
The Delegation of Authority (DOA) Log
The DOA log is a critical regulatory document that formally assigns specific trial tasks to site personnel.
- Qualifications: The PI must ensure that any individual delegated a task is qualified by education, training, and experience. For example, delegating the administration of an intravenous investigational drug must go to a registered nurse or physician, not an unlicensed data entry clerk.
- Ongoing Oversight: The PI must maintain continuous oversight of all delegated tasks. This is typically demonstrated through regular team meetings, documented review of clinical data, and the PI's signature on key documents like lab reports and electronic Case Report Forms (eCRFs).
- Third-Party Vendors: If the PI retains a third party to perform trial-related duties (e.g., an external radiology facility), the PI must ensure they are qualified and maintain oversight of their work.
Adequate Resources and Medical Care
Before accepting a trial, the PI must ensure the site has the capacity to conduct it properly.
Demonstrating Adequate Resources
- Time and Staff: The PI must have sufficient time to properly conduct and complete the trial within the agreed period. The site must have an adequate number of qualified staff and adequate facilities.
- Patient Population: The PI must be able to demonstrate a potential for recruiting the required number of suitable subjects within the agreed recruitment period, often supported by a retrospective review of electronic health records.
Medical Care of Trial Subjects
- Qualified Physician: A qualified physician (who is the PI or a sub-investigator) must be responsible for all trial-related medical decisions.
- Primary Care Communication: With the subject's consent, the PI should inform the subject's primary physician about their participation in the trial.
- Adverse Events (AEs): The PI must ensure adequate medical care is provided for any AEs, including clinically significant laboratory abnormalities, related to the trial. The PI must also assess the causality (relationship to the investigational product) of all AEs.
Communication with the IRB/IEC
The PI serves as the primary liaison between the site and the Institutional Review Board (IRB) or Independent Ethics Committee (IEC).
- Initial Approval: The PI must obtain written and dated approval from the IRB for the protocol, informed consent form, subject recruitment procedures, and any other written information provided to subjects.
- Ongoing Reporting: The PI must promptly report to the IRB all protocol deviations, unanticipated problems involving risks to subjects, and new safety information (like Suspected Unexpected Serious Adverse Reactions - SUSARs).
- Continuing Review: The PI must submit written summaries of the trial status to the IRB annually, or more frequently if requested.
Source Documentation and ALCOA-C
A significant portion of PI responsibility revolves around data integrity. The PI must ensure the accuracy, completeness, legibility, and timeliness of the data reported to the sponsor. This is operationalized through the ALCOA-C principles for source documentation:
| Principle | Definition | Practical Application for the Site Team |
|---|---|---|
| Attributable | It must be clear who created or modified the record. | Staff must sign and date entries, or use secure electronic signatures. Never share passwords for EDC systems. |
| Legible | The record must be readable and decipherable. | Use clear handwriting. If an error is made, use a single line-through, initial, and date; never use correction fluid (white-out). |
| Contemporaneous | Data must be recorded at the time the observation or activity occurred. | Write down vital signs immediately when taken, not hours later at the end of the shift. |
| Original | The first capture of the data, whether on paper or electronic. | If a weight is jotted on a sticky note and then typed into an EMR, the sticky note is technically the original source. Sites should capture data directly into permanent records. |
| Accurate | The data must truthfully reflect the observation. | Calibrate equipment regularly (e.g., blood pressure cuffs, scales) to ensure measurements are correct. |
| Complete | All required data elements are present. | Ensure all blanks on a form are filled. Use "ND" (Not Done) or "NA" (Not Applicable) to explain empty fields. |
Investigational Product (IP) Management
The PI is responsible for IP accountability at the site. While often delegated to an investigational pharmacist or CRC, the PI must ensure:
- IP is stored as specified by the sponsor and regulatory requirements.
- IP is supplied only to subjects enrolled in the trial and strictly according to the protocol.
- Detailed records of IP delivery, inventory, use by subjects, and return or destruction are maintained.
According to GCP, how should a CRC correct an error made on a paper source document?
Who holds the ultimate responsibility for assessing whether an adverse event is related to the investigational product?
The principle that data must be recorded at the exact time the activity occurred corresponds to which letter in the ALCOA-C acronym?