sponsor and investigator are two key players in the clinical trial process. 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). 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 sponsor and investigator must comply with the GCP guidelines and regulatory requirements that clearly describe their respective trial‐related duties and responsibilities. The sponsor may transfer any or all of their study‐related duties to a CRO and the regulatory obligations that are associated with the transferred task; however, the sponsor retains regulatory responsibility for the oversight of the CRO and the overall safety of trial subjects and integrity of the trial data. The investigator may also delegate trial‐related duties to staff or subcontractors; however, the investigator retains all regulatory obligations associated with delegated or subcontracted tasks.
Knowledge Check Questions
1 What is the role of the sponsor?
2 What other individuals or parties may assist the sponsor with trial‐related duties, and under what conditions?
3 What is the role of the investigator?
4 What other individuals or parties may assist the investigator with trial‐related duties, and under what conditions?
5 What are the sponsor's responsibilities before the trial commences, during the conduct of the trial, and after completion or termination of a trial?
6 What are the investigator's responsibilities before the trial commences, during the conduct of the trial, and after completion or termination of a trial?
7 Overheard:“We should have ethics committee approval of the protocol tomorrow so we will enroll the patient the following day. We can then submit to the study to the regulatory authority.”Physician at a clinic who received donated study drug from a manufacturer to conduct their own clinical trial. This physician will otherwise wholly finance and resource the study.Comment and discuss:What are the GCP and regulatory responsibilities of this “investigator”?Is the investigator violating any GCP requirement? If yes, which?
References
1 1 International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), Integrated Addendum to ICH E6(R2):Guideline for Good Clinical Practice, E6(R2) (2016). Current Step 4 version dated 9 November 2016. https://www.ich.org/page/efficacy‐guidelines
2 2 International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), Guideline for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting E2A (1994) Current Step 4 version dated 27 October 1994. https://www.ich.org/page/efficacy‐guidelines
3 3 International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), Guideline for Structure and Content of Clinical Study Reports E3 (1995). Current Step 4 version dated 30 November 1995. https://www.ich.org/page/efficacy‐guidelines
4 4 International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), Implementation Working Group ICH E3 Guideline: Structure and Content of Clinical Study Reports Questions & Answers (R1) Current version dated 6 July 2012. https://www.ich.org/page/efficacy‐guidelines
10 The Research Volunteer
Karen A. Henry
GCP Key Point
The rights, safety, and well‐being of the trial subjects are the most important considerations and should prevail over interests of science and society. (Source: ICH E6(R2) 2.3 [1])
10.1 Introduction
The goal of clinical research is to determine the safety and effectiveness of investigational products to diagnose, treat, cure, or prevent a disease or relieve the symptoms of a disease in humans. Given the risks of new products for which the safety and efficacy are unknown, it is unethical to expose more numbers of people than are necessary to obtain sufficient information to evaluate the benefits versus the risks of the investigational product. Fortunately, we are able to use the scientific method of testing the product on a representative subset of individuals from the entire population and infer the findings to the larger population.
An individual who participates in a clinical trial, either as a recipient of the investigational product(s) or as a control is known as the subject or trial/study subject (ICH E6(R2) 1.57). In practice, alternative terminology are used to refer to the trial/study subject, such as participant, subject, volunteer, patient (for trial subjects who have the disease that is being studied), healthy volunteers (for trial subjects who are generally healthy and without the disease being studied; e.g., typically phase 1 pharmacokinetic studies).
The trial subject will be recruited by the investigator and will be administered the investigational product by the investigator. Today, anyone participating as a research subject in a clinical trial has certain rights (Chapter 19 Informed Consent and Other Human Subject Protection):
1 Fully informed consent and voluntarily participate in a trial without coercion
2 Confidentiality of their identity and health information
3 Compensation for trial‐related injury and for the time, effort, and expenses for their involvement in the study
4 Medical care for study‐related injury or intercurrent illness(es)
5 The ability to withdraw from the study at any time
In addition to the sponsor and investigator, trial subjects also have a role to facilitate ensuring protection of their rights, safety, and well‐being, the integrity of trial data, and trial compliance. Trial subjects do not have any formal GCP or regulatory obligations; however, they are asked to fulfill certain responsibilities during the consenting process for their participation in the trial. We must always keep in mind that that humans volunteering in a clinical trial are not required to and should not be coerced into doing anything. The investigator and sponsor do have the obligation to discontinue study treatment to a subject or withdraw the subject from the trial at any time if they determine that the subject's participation (or lack of participation and compliance with the protocol) puts the subject at risk for harm in the trial. It is also helpful if the trial protocol and trial operations are designed to facilitate the subject's compliance.
In this chapter, we will review the role and voluntary responsibilities of the trial subject, and quality by design concepts to facilitate the subject's compliance with trial requirements for their protection.
10.2 Objectives
The
