The Fundamentals of Clinical Research. P. Michael Dubinsky

qualified staff who are allowed to perform significant trial‐related duties (i.e., record or change trial data).

       Has, supervises, and maintains adequate resources for trial conduct; i.e., subject recruitment, qualified and trained personnel and third parties, certified and adequate facilities, and time. Additionally, the investigator will implement procedures to ensure the integrity of trial activities and data that are generated (ICH E6(R2) 4.2 Adequate Resources; Chapter 22 Monitoring Overview; Chapter 25 Investigator/Institution Interim Monitoring)

       Obtains approval of trial protocol and subject information from a qualified IRB/IEC. IRB/IEC approval must be obtained before implementing a new or amended or revised study protocol or subject information document. (ICH E6(R2) 4.4 Communication with IRB/IEC; Chapter 8 IRB/IEC Roles and Responsibilities).

       9.2.2.1.3 The Sponsor

       Confirms qualification of investigator and site prior to initiation of the trial at the site (Chapter 24 Investigator/Institution Initiation).

       Confirms review and approval/favorable opinion of the trial by a qualified IRB/IEC. Obtains IRB/IEC name, address, composition, registration, copy of approval, and changes made to study documents by the IRB/IEC. (ICH E6(R2) 5.11 Confirmation of Review by IRB/IEC; Chapter 24 Investigator/Institution Initiation). Confirms approval/no objection from the regulatory authority(ies) to initiate the proposed investigational plan. (ICH E6(R2) 5.10 Notification/Submission to Regulatory Authority(Ies); Chapter 11 Regulatory Authority Roles and Responsibilities).

       Supplies investigational product and is responsible for the supply and handling of the product; i.e., the full chain of custody of the investigational product from shipment to the investigator to its return or destruction. (ICH E6(R2) 5.14 Supplying and Handling Investigational Product(S); Chapter 17 The Investigational Product (Clinical Supplies)).

      9.2.2.2 During the Clinical Conduct of the Trial

       9.2.2.2.1 The Investigator

       Ensures informed consent of trial subjects prior to the subject undergoing any study procedure at the start of and during the trial (ICH E6(R2) 4.8 Informed Consent of Trial Subjects) and provides adequate medical care to the subject for trial‐related adverse events during and following a subject's participation in the trial, and ensures confidentiality of subject information (ICH E6(R2) 4.3 Medical Care of Trial Subjects; Chapter 19 Informed Consent and Other Human Subject Protection)

       Complies with protocol procedures and records, reports, and corrects any deviations (ICH E6(R2) 4.5 Compliance with Protocol; Chapter 25 Investigator/Institution Interim Monitoring).

       Follows randomization procedures and procedures for any unblinding (ICH E6(R2) 4.7 Randomization Procedures and Unblinding; Chapter 25 Investigator/Institution Interim Monitoring).

       Stores, handles, and administer the test article according to the protocol and IB, and accounts for receipt, use, return, and destruction of test article (ICH E6(R2) 4.6 Investigational Product(s); Chapter 25 Investigator/Institution Interim Monitoring).

       Reports adverse events to the sponsor (ICH E6(R2) 4.11 Safety Reporting, Chapter 21 Safety Monitoring and Reporting).

       Maintains source documentation and complete case histories for each subject in accordance with good documentation practices and the applicable regulatory requirements. Source documentation includes all activities from informed consenting to study completion. (ICH E6(R2) 4.9 Records and Reports, Chapter 25 Investigator/Institution Interim Monitoring; Chapter 29 Essential Documents).

       Permits monitoring and auditing by the sponsor (ICH E6(R2) 4.1 Investigator’s Qualifications and Agreements; Chapter 22 Monitoring Overview).

       Communicates the study status and information per the IRB/IEC requirements and sponsor and regulatory requirements (ICH E6(R2) 4.10 Progress Reports; Chapter 29 Essential Documents; Chapter 25 Investigator/Institution Interim Monitoring; Chapter 8 IRB/IEC Roles and Responsibilities).

       9.2.2.2.2 The Sponsor

       Oversees and reviews the progress of the investigation to ensure protection of subject rights and safety, data integrity, and compliance with the protocol, SOPs, GCP, and regulatory requirements.

       Selects qualified monitors and implements procedures for on‐ and off‐site and centralized monitoring of the progress of the investigation using a risk‐based approach and methods as outlined in a Monitoring Plan for the trial (ICH E6(R2) 5.18 Monitoring; Chapter 22 Monitoring Overview)

       Collects, reviews, and assesses adverse events for ongoing risk‐benefit evaluation of the investigational product and to notify all concerned investigator(s) and the regulatory authority(ies) of findings that could adversely affect the safety of subjects, impact the conduct of the trial, or alter the IRB/IEC's approval/favorable opinion to continue the trial (ICH E6(R2) 5.16 Safety Information). These notifications may be as single reports, protocol amendments, and/or updates to the investigator's brochure (Chapter 21 Safety Monitoring and Reporting; Chapter 25 Investigator/Institution Interim Monitoring; Chapter 16 The Investigator's Brochure; Chapter 18 The Clinical Trial Protocol and Amendments)

       Reports adverse drug reactions that are both serious and unexpected as per ICH E2A Guideline for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting and applicable regulatory requirements [2] (ICH E6(R2) 5.17 Adverse Drug Reaction Reporting; Chapter 21 Safety Monitoring and Reporting)

       Assesses and manages risk for quality management (ICH E6(R2) 5.0; Chapter 13 Risk Assessment and Quality Management).

       Selects qualified independent auditors to conduct audits per the Audit Plan and/or for an unplanned cause (ICH E6(R2) 5.19 Audit, Chapter 33 Quality Assurance Components; Chapter 34 Regulatory Authority Inspections) and promptly secures compliance and implements corrective and preventive actions for deviations from the protocol, SOPs, GCP, and regulatory requirements that significantly