The Fundamentals of Clinical Research. P. Michael Dubinsky

and selecting a CRO for data management).

      9.2.2.1 Before the Clinical Phase of the Trial Commences

       9.2.2.1.1 The Sponsor

       Implements a system to manage quality throughout all stages of the trial process (ICH E6(R2) 5.0 Quality Management). The sponsor will focus on those aspects of the trial to ensure human subject protection and the reliability of trial results when designing a protocol, preparing processes and procedures for data collection, processing, and reporting, and trial monitoring. The system will include:Risk‐based quality management methods to ensure that all aspects of the trial are operationally feasible and should avoid unnecessary complexity, procedures, and data collection. (Chapter 13 Risk Assessment and Quality Management)Protocols, case report forms, and other operational and procedural documents that are clear, concise, and consistent.The quality management system should be proportionate to the risks inherent in the trial and the importance of the information collected. (Chapter 31 Quality Responsibilities)In practice, the quality management system will require, for example, policies that require all those involved in activities related to a clinical trial to be compliant with guidelines, practices, SOPs, regulatory requirements, and any other policies and procedures of the firm. Additional requirements may include the establishment of a core scientific team for the review and approval of proposed protocol designs and changes, an operations core team for review and approval of proposed SOPS and changes to systems, and a safety core team for the review and assessment of reported adverse events.

       Creates and implements procedures to assure and control the quality of the trial (ICH E6(R2) 5.1 Quality Assurance and Quality Control; Part V Quality in Clinical Trials). The sponsor will establish, ensure training on, and implement SOPs for activities related to planning, initiating, management and control, and audit and inspections of a trial.

       Prepares a clinical trial protocol (ICH E6(R2) 5.4 Trial Design; Chapter 18 The Clinical Trial Protocol and Amendments). The protocol is the Investigational plan and must be scientifically sound.

       Prepares the investigational product according to good manufacturing practices (ICH E6(R2) 5.13 Manufacturing, Packaging, Labeling, and Coding Investigational Product(S); Chapter 17 The Investigational Product (Clinical Supplies)).

       Prepares the investigator's brochure that contains all information known to date about the test article, including nonclinical testing (ICH E6(R2) 5.12 Information on Investigational Product(S); Chapter 16 The Investigator's Brochure).

       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 15 Trial 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 11 Regulatory Authority Roles and Responsibilities.)

       Prepares plans, systems, and procedures for managing trial operations, collecting and processing trial data, and maintaining trial records (Chapter 29 Essential 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 20 Data Collection and Data Management)Regulatory compliant data collection systems (Chapter 20 Data Collection and Data Management)Informed Consent Template and other subject information and recruitment documents (Chapter 19 Informed Consent and Other Human Subject Protection)Monitoring Plan (Chapter 22 Monitoring Overview)Statistical Analysis Plan (Chapter 27 Study Design and Data Analysis)Safety Management Plan (Chapter 21 Safety Monitoring and Reporting)Audit Plan (Chapter 33 Quality Assurance Components)Trial Management Plan (Chapter 14 Trial Management; Start‐up, On‐Study, and Close‐Out)Risk Management Plan (Chapter 13 Risk Assessment and Quality Management)

       Selects qualified investigator(s) (ICH E6(R2) 5.6 Investigator Selection, 5.23 Multicenter Trials; Chapter 23 Investigator/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 20 Data 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 22 Monitoring 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 19 Informed 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 23 Investigator/Institution Selection).

       9.2.2.1.2 The Investigator

       Is qualified and agrees to specific stipulations prior to trial conduct (ICH E6(R2) 4.1 Investigator's Qualifications and Agreements; Chapter 24 Investigator/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