Roles and Responsibilities of the Principal Investigator

1. Purpose

This SOP sets out the duties of the Principal Investigator (PI) at [SITE NAME] for FDA-regulated clinical investigations, how the PI documents acceptance of those duties, how the PI oversees the people and parties to whom tasks are delegated, and how investigator coverage is maintained when the PI is absent.

2. Scope

This SOP applies to every PI and Sub-Investigator (Sub-I) at all [SITE NAME] locations, for drug and biologic studies under 21 CFR 312, device studies under 21 CFR 812, and studies that are exempt from an IND or IDE but still subject to 21 CFR 50 and 56. It also applies to all staff who support the PI.

This SOP states the PI's duties and points to the SOPs that hold the detailed procedures. It does not cover sponsor duties held by a PI who also holds the IND or IDE; see SOP-800 Sponsor-Investigator Responsibilities (IND/IDE Holder).

Follow the protocol, sponsor or IRB requirement where it is stricter than this SOP.

3. Responsibilities

4. Definitions

5. Procedure

5.1 Before accepting a study

• the PI is qualified by education, training and experience for the study population and procedures, and holds a current license in [STATE]
• the PI has enough time for the study for its full duration, taking into account current active studies, clinical practice and other commitments
• the site can show a realistic potential to recruit the agreed number of eligible participants in the recruitment period, based on records or current data
• qualified staff, facilities, equipment and any needed service providers are available or can be arranged

5.2 Investigator commitments: 1572, investigator agreement and protocol signature

• Section 3 lists every location where the PI's team sees participants or conducts study procedures, including other [SITE NAME] locations
• Section 4 lists each clinical laboratory or testing facility that directly contributes to or supports the study, including the sponsor's central laboratory and any local laboratory, imaging center or other testing facility the site uses for protocol tests (FDA 1572 FAQs)
• Section 5 names the reviewing IRB ([CENTRAL IRB NAME] unless otherwise approved)
• Section 6 lists each Sub-I who will make a direct and significant contribution to the data
• the commitments in Section 9 are understood: conduct per the current protocol, personally conduct or supervise, inform participants and obtain consent, report adverse experiences, read the IB, inform all staff of their obligations, keep records, and use an IRB that complies with 21 CFR 56

5.3 IRB approval and communication

5.4 Personal conduct and supervision of the study

• reviews and signs eligibility for each participant before randomization, treatment-assigning IRT registration or first dose, whichever comes first (SOP-303, 5.4.3; F-303-02 Eligibility Verification Checklist)
• reviews and assesses each AE for seriousness, severity, expectedness where required, and causality (F-500-01 Adverse Event Assessment Worksheet)
• reviews, signs and dates laboratory, ECG, imaging and other test results, with clinical significance noted, within the timeframe the protocol sets or, where the protocol is silent, safety-relevant results within [DEFAULT: 2 business days] of receipt (same day for critical values) and other results within [DEFAULT: 5 business days] of receipt or before the participant's next visit, whichever is first. This is the site's single rule for result review; SOP-306 and SOP-500 point to it
• reviews data from external sources that can affect eligibility, treatment or safety (central laboratory, central imaging reads, other providers' records, ePRO alerts) when the sponsor makes it available
• reviews protocol deviations and decides which are important (SOP-308 Protocol Deviations and Noncompliance)
• reviews monitoring visit findings and follow-up actions (F-600-02 Monitoring Follow-Up Action Tracker)

5.5 Oversight of service providers

5.6 Protocol compliance

5.7 Informed consent

5.8 Medical care and safety reporting

• each SAE immediately, whether or not considered related to the IP and including SAEs listed in the protocol or IB, with an assessment of whether there is a reasonable possibility the IP caused the event. SAEs that the protocol defines as study endpoints are reported as the protocol specifies, unless there is evidence of a causal relationship to the IP, in which case they are reported immediately (21 CFR 312.64(b); ICH E6(R3) Annex 1, 2.7.2(b))
• other AEs and abnormal test results as the protocol requires
• for device studies, each UADE to the sponsor and the IRB as soon as possible and no later than 10 working days after the PI first learns of it (21 CFR 812.150(a)(1))

Detailed procedures are in SOP-500 Adverse Event Identification, Assessment and Recording, SOP-501 Serious Adverse Event and Expedited Safety Reporting, and SOP-502 Unanticipated Problems and Reportable New Information.

5.9 Investigational product control

5.10 Records and data

5.11 Reports to the sponsor and IRB

5.12 Monitoring, audits and inspections

5.13 PI availability and coverage when absent

• notify the sponsor and IRB promptly in writing
• obtain sponsor and IRB approval of a replacement PI, with a new 1572 or investigator agreement
• arrange for the outgoing PI to complete outstanding signatures, AE assessments and data endorsements before leaving where possible
• tell the sponsor the name of the person responsible for keeping the essential records (ICH E6(R3) Annex 1, 2.12.13)
• update the delegation log and remove system access (SOP-102 Site Organization, Roles and Staff Responsibilities)

5.14 Financial disclosure and conflicts of interest

6. Related Forms and SOPs

• F-200-01 Study Feasibility Assessment
• F-302-01 Delegation of Authority Log
• F-303-02 Eligibility Verification Checklist
• F-306-01 Note to File
• F-500-01 Adverse Event Assessment Worksheet
• F-600-02 Monitoring Follow-Up Action Tracker
• F-904-01 Shared Staff Assignment and Credentialing Log (Model N only)
• Appendix B Central and Site Responsibility Matrix (Model N only)
• SOP-102 Site Organization, Roles and Staff Responsibilities
• SOP-103 Staff Qualification, Training and Training Records
• SOP-104 Conflict of Interest and Financial Disclosure
• SOP-105 Oversight of Service Providers and Vendors
• SOP-200 Study Feasibility and Selection
• SOP-203 IRB Submissions, Approval and Continuing Oversight
• SOP-204 Essential Documents and the Investigator Site File
• SOP-301 Informed Consent Process and Documentation
• SOP-302 Delegation of Authority
• SOP-304 Investigational Product Management
• SOP-306 Source Documentation and Data Integrity (ALCOA+)
• SOP-307 Case Report Forms, EDC Entry and Query Resolution
• SOP-308 Protocol Deviations and Noncompliance
• SOP-400 Participant Privacy and HIPAA in Research
• SOP-402 Record Retention, Archiving and Destruction
• SOP-500 Adverse Event Identification, Assessment and Recording
• SOP-501 Serious Adverse Event and Expedited Safety Reporting
• SOP-502 Unanticipated Problems and Reportable New Information
• SOP-600 Sponsor Monitoring Visits
• SOP-701 Sponsor and IRB Audits
• SOP-702 FDA Inspections and Remote Regulatory Assessments
• SOP-703 Corrective and Preventive Action (CAPA)
• SOP-705 Business Continuity and Emergency Preparedness
• SOP-800 Sponsor-Investigator Responsibilities (IND/IDE Holder)
• SOP-902 Network Study Feasibility, Allocation and Central Contracting (Model N only)
• SOP-904 Shared Staff, Cross-Site Coverage and Central Services (Model N only)

7. References