The Fundamentals of Clinical Research. P. Michael Dubinsky

       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 impact or have the potential to significantly impact subject safety and data integrity. If monitoring or audit observations reflect serious or persistent noncompliance on the part of an investigator/institution then the sponsor should terminate the investigator's/institution's participation in the investigation and promptly notify the regulatory authority(ies). (ICH E6(R2) 5.20 Noncompliance, Chapter 25 Investigator/Institution Interim Monitoring, Chapter 33 Quality Assurance Components, Chapter 34 Regulatory Authority Inspections, Chapter 31 Quality Responsibilities).

       Submits reports of final trial status and outcome to IRB/IEC and regulatory authority(ies) as required (ICH E6(R2) 4.13 Final Report(s) by Investigator; Chapter 29 Essential Documents; Chapter 26 Investigator/Institution Close‐out; Chapter 8 IRB/IEC Roles and Responsibilities).

       In the event of premature termination or suspension of a trial, promptly informs the trial subject, arranges for appropriate medical care follow‐up for the subject, and informs the sponsor, IRB/IEC, and/or regulatory authority(ies) as applicable, (ICH E6(R2) 4.12 Premature Termination or Suspension of a Trial; Chapter 29 Essential Documents; Chapter 26 Investigator/Institution Close‐out; Chapter 8 IRB/IEC Roles and Responsibilities).

       Permits audits/inspections by Sponsor, IRB, and Regulatory Authority(ies) at ANY time! (ICH E6(R2) 4.1 Investigator's Qualifications and Agreements; Chapter 24 Investigator/Institution Initiation)

       In the event of premature termination or suspension of a trial, promptly informs the investigator(s), the regulatory authority(ies), and IRB/IEC as applicable, of the termination or suspension and the reason(s) for termination or suspension (ICH E6(R2) 5.21 Premature Termination or Suspension of a Trial; Chapter 18 Clinical Trial Protocol and Amendments; Chapter 26 Investigator/Institution Close‐out; Chapter 8 IRB/IEC Roles and Responsibilities).

       Closes trial sites upon study completion (Chapter 26 Investigator/Institution Close‐out).

       Prepares and submits clinical trial/study reports of trial results to the regulatory authority(ies) whether the trial is completed or prematurely terminated as required by the regulatory requirements. The clinical trial reports in marketing applications will meet the standards of the ICH E3 Guideline for Structure and Content of Clinical Study Reports [3,4]. (ICH E6(R2) 5.22 Clinical Trial/Study Reports; Chapter 28).

       Permits audits/inspections by Regulatory Authority(ies) at ANY time! (ICH E6(R2) 5.1 Quality Assurance and Quality Control; Chapter 31 Quality Responsibilities).