The Sponsor‐Investigator:An individual may decide to take responsibility for the supply of the investigational product and to test the investigational product on research volunteers as well. In this scenario, the individual or organization assumes the GCP and regulatory responsibilities as both sponsor and investigator. This sponsor‐investigator is therefore an individual who both initiates and conducts, alone or with others, a clinical trial, and under whose immediate direction the investigational product is administered to, dispensed to, or used by a subject. The term does not include any person other than an individual (e.g., it does not include a corporation or an agency). The obligations of a sponsor–investigator include both those of a sponsor and those of an investigator (ICH E6(R2) 1.54). For example, an investigator at an academic medical research institution may be interested in testing an approved or investigational product for a new indication that the original sponsor may not pursue. The investigator will then procure the product, create the clinical trial protocol and conduct the trial as the sponsor as well as enroll the patients and administer the product to the patients.An example of an Investigator–CRO combination is that of what is known as a phase 1 facility, where typically first‐in‐human testing is performed to obtain pharmacokinetic information of an investigational product. The sponsor may select such a facility because these facilities are equipped with on‐site housing and hospital services and the phase 1 study is testing the investigational product on few individuals who must be constantly monitored for safety and pharmacokinetic results. This facility may not only perform investigator responsibilities, in that they will enroll and administer the product to the study subjects, but may also perform the pharmacokinetic testing and data analyses, and prepare the clinical study report for the sponsor. The facility has then also assumed sponsor responsibilities in that they are contracted as a central laboratory to perform the pharmacokinetic testing and as the writer of the clinical study report.
9.2.2 Sponsor and Investigator Responsibilities in the Context of the Clinical Trial Process
This chapter describes the responsibilities of sponsors and investigators in the context of the general clinical trial process (Plate 4 Individual Clinical Trial – Overview of Investigator and Sponsor Responsibilities). While some activities are necessarily sequential (e.g., IRB/IEC approval/favorable opinion of a protocol prior to consenting a human research subject), some activities may occur concurrently for efficiency (e.g., selecting investigators 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,
