P. Michael Dubinsky - The Fundamentals of Clinical Research

In this chapter, we will present the responsibilities of sponsors and investigators in the context of the general trial process and provide the reader with references to book chapters that describe the responsibilities in greater detail. Plate 4 Individual Clinical Trial – Overview of Investigator and Sponsor Responsibilities displays the individual responsibilities in the context of the chapter content in the book and the reader may refer to the relevant sections of ICH E6(R2) for lists of the responsibilities by player.

The objectives of this chapter are to:

Define sponsor and investigator and various forms

Describe sponsor and investigator responsibilities in the context of the clinical trial process

Here are some important definitions for the sponsor and investigator players involved in conducting a clinical trial. A clinical trial will have,

1 The Sponsor:A sponsor who is “an individual, company, institution, or organization which takes responsibility for the initiation, management, and/or financing of a clinical trial” (ICH E6(R2) 1.53). The sponsor will be interested in collecting data from a series of clinical trials to prove the safety and efficacy of an investigational product so that they may apply to the governing regulatory authority(ies) for approval to market the product. The sponsor will seek out investigators who have access to the study population, i.e., healthy volunteers or the patients who have the indication being studied in the trial.The sponsor for a clinical trial may contract with a Contract Research Organization(s) (CRO), which is a person or an organization (commercial, academic, or other) contracted to perform one or more of a sponsor's trial‐related duties and functions (ICH E6(R2) 1.20). The CRO will bear the GCP and regulatory responsibilities for the contracted tasks ( Chapter 15Trial Resourcing and Outsourcing).

2 The Investigator:The investigator is “a person responsible for the conduct of the clinical trial at a trial site. If a trial is conducted by a team of individuals at a trial site, the investigator is the responsible leader of the team and may be called the principal investigator” (ICH E6(R2) 1.34). The investigator, or a qualified designee, will administer the investigational product to the study subjects.The investigator may subcontract or delegate tasks to others; however, unlike the sponsor, the investigator maintains full GCP and regulatory responsibilities for the delegated tasks.

3 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.

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).

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 13Risk 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 31Quality 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 18The 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 17The 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 16The Investigator's Brochure).