The Fundamentals of Clinical Research. P. Michael Dubinsky

such a deficiency if you were part of an IRB/IEC.

References

      1 1 FDA (2002). Code of Federal Regulations Title 21 CFR 56.115 (b). https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=56.115 (accessed 6 April 2020).

      2 2 EU Regulation (2014). REGULATION (EU) No 536/2014 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 16 April 2014 on clinical trials on medicinal products for human use, and repealing Directive 2001/20/ECEU Regulation 536, Article 58 ‐ Archiving of the clinical trial master file. https://ec.europa.eu/health/sites/health/files/files/eudralex/vol‐1/reg_2014_536/reg_2014_536_en.pdf (accessed 6 April 2020)

      3 3 FDA Bioresearch Monitoring (BIMO)(2021). Inspection Metrics. https://www.fda.gov/science‐research/clinical‐trials‐and‐human‐subject‐protection/bimo‐inspection‐metrics (accessed 6 April 2020)

9 Investigator and Sponsor Roles and Responsibilities

       Karen A. Henry

      GCP Key Point

       Clinical trials should be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with GCP and the applicable regulatory requirement(s). Source: ICH [1]

9.1 Introduction

      The ICH GCP guidance (E6(R2)), as it is today, reflects the attempt to prevent harmful consequences of experimentation on humans over centuries (Chapter 1 History). In societies, there have always been someone seeking to sell the next “wonder drug” and a “scientist” who is curious about how human bodies work and how they would respond to new or modified vaccines, treatments, or potential cures. Per ICH E6(R2), the sponsor 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) and the investigator is “a person responsible for the conduct of the clinical trial at a trial site” (ICH E6(R2) 1.34). ICH has provided guidance on the responsibilities of the sponsor (ICH E6(R2) 5) and of the investigator (ICH E6(R2) 4). Although the sponsor and investigator essentially collaborate to create and execute a clinical trial with an aim to discover new or improved vaccines, treatments, or potential cures new treatments, the sponsor and investigator have specific and independent responsibilities that are stipulated by ICH (E6(R2)) and perhaps regional or local regulatory requirements.

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.

9.2 Objectives

      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

      9.2.1 Definitions

      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 15 Trial 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.

      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