Principal Investigator Training Course

This opening session provides a comprehensive survey of the regulatory authorities and guidelines that collectively define the principal investigator’s obligations in clinical research. Participants study FDA regulatory authority under 21 CFR Parts 11 (electronic records and electronic signatures), 50 (protection of human subjects and informed consent), 54 (financial disclosure by clinical investigators), 56 (institutional review boards), 312 (investigational new drug applications), and 812 (investigational device exemptions). The session explains not just what each regulation requires, but why it exists — tracing the historical events and patient safety failures that gave rise to each regulatory framework. Understanding the intent behind the regulations enables PIs to apply them with judgment rather than rote compliance.

ICH E6(R2) Good Clinical Practice requirements are covered in detail, with particular attention to the investigator-specific obligations outlined in Section 4 of the guideline. The session introduces the emerging ICH E6(R3) framework, highlighting the paradigm shifts toward risk-based quality management, proportionate approaches to clinical trial oversight, and technology-enabled trial designs that will reshape PI responsibilities in the coming years. Participants learn to distinguish between the principles that remain constant across regulatory revisions and the operational practices that are evolving, equipping them to adapt their oversight approaches as the regulatory landscape continues to develop.

Central to this session is the concept of the PI’s personal legal accountability. Unlike coordinators, sub-investigators, or other site staff, the PI bears individual responsibility for all aspects of trial conduct at the site. The session examines the spectrum of penalties for non-compliance: FDA Warning Letters, investigator disqualification proceedings under 21 CFR 312.70, debarment from future government-funded research, state medical board actions, and criminal prosecution under federal fraud statutes. Participants review actual FDA enforcement actions against principal investigators, analyzing what went wrong, how violations were detected through BIMO inspections and data integrity reviews, and what the professional and personal consequences were for the investigators involved. This grounding in real consequences ensures that participants approach subsequent sessions with the appropriate sense of gravity.

The Form FDA 1572 is the foundational document that establishes the contractual relationship between the investigator and the FDA. Many physicians sign this form without fully comprehending the breadth and depth of the commitments they are making — commitments that carry the force of federal law. This session conducts a line-by-line review of every section of the 1572, translating regulatory language into plain clinical terms and identifying the specific obligations that attach to the PI’s signature. Participants learn that the 1572 is not a formality but a binding agreement to conduct the trial in accordance with FDA regulations, to personally supervise all aspects of the investigation, to ensure informed consent is obtained in accordance with 21 CFR Part 50, and to report adverse experiences to the sponsor and IRB in compliance with applicable requirements.

Delegation of authority is a practical necessity for any PI who cannot personally perform every study-related task, which is to say every PI. This session provides detailed instruction on the proper construction, maintenance, and oversight of the delegation log — the formal document that records which study tasks have been delegated to which team members and serves as evidence of the PI’s organizational oversight. Participants learn the critical distinction between delegating a task and delegating responsibility: while a PI may delegate the performance of specific study procedures to qualified staff, the PI can never delegate the ultimate responsibility for trial conduct. The session covers common delegation log deficiencies identified during FDA inspections and sponsor audits, including tasks assigned to unqualified individuals, delegation logs not updated when staff change, tasks delegated without corresponding training documentation, and gaps between the delegation log and actual practice. Participants will construct a model delegation log and practice the decision-making involved in appropriate task delegation.

The session concludes with a practical framework for maintaining meaningful PI oversight across all delegated activities. This includes strategies for regular review of study operations, verification that delegated tasks are being performed correctly, documentation of oversight activities, and the systems and checkpoints that enable a PI to detect problems before they become compliance failures. Participants examine the balance between appropriate oversight and micromanagement, learning to build trust-based systems that ensure quality without creating operational bottlenecks. The 1572’s requirements for adequate facilities, adequate resources, and adequate patient access are also addressed, including how to assess these commitments realistically before agreeing to serve as PI on a new study.

Effective communication between the principal investigator and the Institutional Review Board or Ethics Committee is essential to maintaining regulatory compliance throughout the lifecycle of a clinical trial. This session covers the different models of ethics review that PIs may encounter — local institutional IRBs, central IRBs operating under the NIH single-IRB mandate, and commercial IRBs used by industry sponsors — examining the advantages, limitations, and operational differences of each arrangement. Participants learn the requirements for initial submission packages, including what the IRB expects to see in terms of protocol documentation, investigator qualifications, consent form drafts, recruitment materials, and conflict-of-interest disclosures. Common reasons for submission delays and rejections are reviewed, giving participants the knowledge to prepare complete submissions that move through the review process efficiently.

Continuing review obligations are covered in depth, including the timing and content requirements for annual progress reports, the process for reporting adverse events and protocol deviations to the IRB, and the submission workflow for protocol amendments. The session distinguishes between amendments that require full board review and those eligible for expedited review, and explains the PI’s obligation to ensure that no amendment-related changes are implemented before IRB approval unless necessary to eliminate an immediate hazard to participants. Reportable events — including unanticipated problems involving risks to subjects, non-compliance reports, and safety reports requiring IRB notification — are covered with practical templates and workflow examples.

The session addresses a critical but often overlooked scenario: what happens when IRB approval lapses. Conducting study activities without active IRB approval is a serious regulatory violation that can result in FDA enforcement action, participant safety concerns, and invalidation of collected data. Participants learn the steps required to reinstate lapsed approval, the documentation that must be maintained to demonstrate continuous compliance, and the communication obligations to sponsors and regulatory authorities when a lapse occurs. Institutional requirements beyond the IRB are also covered, including institutional biosafety committees, radiation safety committees, conflict-of-interest committees, and institutional agreements that may impose additional obligations on the PI. Practical exercises walk participants through the preparation of IRB submission packages for initial review, continuing review, amendment submissions, and reportable event notifications.

Enrollment is the lifeblood of any clinical trial, and chronic under-enrollment is the single most common reason for site termination by sponsors. The PI sets the tone for enrollment performance and must lead from the front. This session covers the development of comprehensive enrollment plans that go far beyond waiting for patients to appear in clinic. Participants learn to build proactive patient identification strategies, including systematic review of electronic medical records (EMR) to identify potentially eligible patients within the PI’s existing practice, collaboration with institutional disease registries and biobanks, and leveraging health system analytics to quantify the accessible patient population for specific therapeutic areas and indications before committing to enrollment targets.

Referral network development is covered as a critical long-term investment. Participants learn to establish and maintain referral relationships with community physicians, specialty clinics, and other healthcare providers who encounter potentially eligible patients. The session addresses common barriers to referral — including physician skepticism about clinical trials, lack of awareness of available studies, and logistical concerns about referring patients to another practice — and provides specific strategies for overcoming each barrier through education, relationship building, and systematic feedback to referring providers. Community engagement and direct-to-patient outreach strategies are covered, including the regulatory requirements for IRB-approved recruitment materials, social media use in patient recruitment, and the ethical considerations of recruitment advertising.

Enrollment diversity receives dedicated attention as both a scientific imperative and a regulatory requirement under evolving FDA Diversity Action Plan expectations. Participants learn to develop diversity-conscious enrollment strategies that broaden the demographics of clinical trial populations without compromising scientific rigor or protocol compliance. The session covers identifying underrepresented communities in the site’s catchment area, building trust with populations that have historical reasons for distrust of medical research, adapting recruitment approaches to different cultural contexts, and tracking diversity metrics throughout the enrollment period. Screen failure management is addressed as a critical operational metric — participants learn to analyze screen failure patterns, identify preventable failures caused by premature referrals or miscommunication, and implement feedback loops that improve the quality of pre-screening over time.

Informed consent is the most fundamental participant protection in clinical research, and consent-related deficiencies are the single most frequently cited category of findings in FDA BIMO inspections, accounting for approximately one-third of all observations. The PI bears ultimate responsibility for the informed consent process — not merely the presence of a signed form, but the genuine, voluntary, and informed decision by each participant to enroll. This session provides comprehensive training on the PI’s role in leading the consent process, starting with the eight required elements and six additional elements of informed consent under 21 CFR Part 50, and extending through the practical realities of conducting consent conversations with diverse patient populations.

Decision-making capacity assessment is covered in detail, as the PI must be able to determine whether a prospective participant has sufficient capacity to provide informed consent. The session covers formal capacity assessment tools, the clinical signs that may indicate diminished capacity, and the ethical and regulatory framework for proceeding when capacity is questionable. Legally Authorized Representative (LAR) consent is addressed for situations where the participant cannot provide direct consent, including state-specific legal definitions of LARs, the documentation requirements for LAR consent, and the PI’s ongoing obligation to monitor participants for changes in capacity that may affect the validity of consent. Pediatric assent requirements are covered, including age-appropriate assent processes, the relationship between parental consent and child assent, and the circumstances under which an IRB may waive assent requirements.

The session addresses consent process documentation from the auditor’s perspective — what evidence of a proper consent process must exist in the study records beyond the signed consent form itself. Participants learn to document the consent discussion, including who was present, what questions the participant asked, what additional information was provided, and the PI’s assessment that the participant demonstrated understanding. Re-consent requirements are covered for protocol amendments that introduce new risks, new safety information that emerges during the study, and changes in participant circumstances that warrant renewed discussion. Common consent errors encountered during monitoring visits and regulatory inspections are reviewed in detail: backdated signatures, missing pages, consent obtained by personnel not listed on the delegation log, use of outdated consent versions, failure to re-consent after protocol amendments, and inadequate documentation of the consent discussion. Each error is paired with the preventive practice and quality control checkpoint that eliminates it.

The PI is accountable for the actions of every individual listed on the delegation log, making team management not just an operational skill but a regulatory obligation. This session addresses the practical challenge of maintaining meaningful oversight without micromanaging experienced coordinators and sub-investigators. Participants learn how to build an effective study team, establish clear roles and expectations through the delegation log, assess and document staff competency for each delegated task, and maintain training records that satisfy both sponsor and regulatory requirements. The session covers the PI’s responsibility to ensure that staff are not only trained initially but maintain competency throughout the study, including processes for ongoing training when protocols are amended, new procedures are introduced, or performance issues are identified.

Managing sub-investigators is covered as a distinct skill set, including how to ensure sub-I clinical decisions align with the PI’s medical judgment and protocol requirements, how to establish clear communication channels for clinical decision-making during the PI’s absence, and how to document sub-I oversight in a manner that demonstrates the PI’s active engagement. Staff turnover is addressed as one of the highest-risk operational events for any clinical trial site — participants learn knowledge transfer protocols, documentation continuity procedures, delegation log update requirements within 24 hours of staff changes, and strategies for maintaining study quality during transition periods. The session emphasizes creating a culture of quality and compliance where staff feel empowered to raise concerns, report deviations without fear of blame, and maintain the standards the PI has established.

Monitor visit preparation and execution receive detailed coverage. Participants learn what monitors evaluate during routine monitoring visits, how to prepare the site and study documents for efficient review, the PI’s role during the visit (including the PI meeting with the monitor at the conclusion of each visit), and how to respond constructively to monitoring findings. Sponsor and CRO relationship management is addressed from the PI’s perspective: what sponsors expect from their investigators, how to communicate effectively with sponsor medical monitors, site qualification visits, investigator meeting participation, and the management of sometimes competing interests between patient care and protocol adherence. The session covers how to handle difficult sponsor interactions professionally, including requests for enrollment commitments the site cannot realistically meet, pressure to make eligibility determinations the PI disagrees with, and sponsor audit findings that require corrective action.