P. Michael Dubinsky - The Fundamentals of Clinical Research

Identifies resources for all trial‐related duties and functions, including designating appropriately qualified medical personnel who will be readily available to advise on trial‐related medical questions or problems, other qualified internal personnel and the selection and qualification of any CROs to assume any responsibilities of the sponsor. (ICH E6(R2) 5.3 Medical Expertise, ICH E6(R2) 5.7 Allocation of Responsibilities, ICH E6(R2) 5.2 Contract Research Organization (CRO); Chapter 15Trial Resourcing and Outsourcing)

Prepares and submits an application/notification to initiate a clinical trial to the regulatory authority(ies) for their review of the proposed investigational plan. (ICH E6(R2) 5.10 Notification/Submission to Regulatory Authority(Ies); Chapter 11Regulatory Authority Roles and Responsibilities.)

Prepares plans, systems, and procedures for managing trial operations, collecting and processing trial data, and maintaining trial records ( Chapter 29Essential Documents). (ICH E6(R2) 5.5 Trial Management, Data Handling, and Record Keeping). The plans and systems will include, but not limited to:Case Report Forms ( Chapter 20Data Collection and Data Management)Regulatory compliant data collection systems ( Chapter 20Data Collection and Data Management)Informed Consent Template and other subject information and recruitment documents ( Chapter 19Informed Consent and Other Human Subject Protection)Monitoring Plan ( Chapter 22Monitoring Overview)Statistical Analysis Plan ( Chapter 27Study Design and Data Analysis)Safety Management Plan ( Chapter 21Safety Monitoring and Reporting)Audit Plan ( Chapter 33Quality Assurance Components)Trial Management Plan ( Chapter 14Trial Management; Start‐up, On‐Study, and Close‐Out)Risk Management Plan ( Chapter 13Risk Assessment and Quality Management)

Selects qualified investigator(s) (ICH E6(R2) 5.6 Investigator Selection, 5.23 Multicenter Trials; Chapter 23Investigator/Institution Selection):Assesses investigator and site qualifications for suitability to conduct the trial.Provides investigators with information they need to conduct the trial, including the protocol, the investigator's brochure and other investigational product information, for their review and assessment prior to agreeing to conduct the trial.Has signed written agreements with investigators to conduct the trial in compliance with GCP, the protocol, and applicable regulatory requirements. Ensures that the investigator knows of and agrees to regulatory and contractual obligations, including compliance requirements with GCP, the protocol, and the regulatory requirements, and permitting monitoring, auditing, and inspections, and retention of trial essential documents.For multicenter trials, identifies a coordinating investigator, provides uniform sets of standards for data collection and laboratory assessments, and facilitates communication between investigators ( Chapter 20Data Collection and Data Management).

Has written agreements with investigator for access to source data and source documents trial records for monitoring, auditing, and inspections, (ICH E6(R2) 5.15 Record Access; Chapter 22Monitoring Overview).

Ensures possession of trial insurance and provisions for compensating subjects for trial participation (as applicable) and trial‐related injury per applicable regulatory requirements. (ICH E6(R2) 5.8 Compensation to Subjects and Investigators; Chapter 19Informed Consent and Other Human Subject Protection).

Has agreements with the investigator/institution regarding financial arrangements for the trial (ICH E6(R2) 5.9 Financing; Chapter 23Investigator/Institution Selection).

Is qualified and agrees to specific stipulations prior to trial conduct (ICH E6(R2) 4.1 Investigator's Qualifications and Agreements; Chapter 24Investigator/Institution Initiation):Is qualified by education, training, and experience to assume responsibility for the proper conduct of the trial.Is thoroughly familiar with the appropriate use of the investigational product as described in the protocol and investigator's brochure.Is aware of and complies with GCP and applicable regulatory requirementsPermits monitoring, auditing, and inspectionsTrains site staff and maintains a list of appropriately 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 22Monitoring Overview; Chapter 25Investigator/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 8IRB/IEC Roles and Responsibilities).

Confirms qualification of investigator and site prior to initiation of the trial at the site ( Chapter 24Investigator/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 24Investigator/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 11Regulatory 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 17The Investigational Product (Clinical Supplies)).

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 19Informed 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 25Investigator/Institution Interim Monitoring).

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

Reports adverse events to the sponsor (ICH E6(R2) 4.11 Safety Reporting, Chapter 21Safety 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 25Investigator/Institution Interim Monitoring; Chapter 29Essential Documents).