The Fundamentals of Clinical Research. P. Michael Dubinsky

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 objectives of this chapter are:

      1 Define and describe the role of trial subject

      2 Describe the voluntary responsibilities of a trial subject regarding:Protection of rights, safety, and well‐beingIntegrity of trial dataTrial compliance

      3 Describe Quality by Design Considerations to facilitate subject compliance with the trial requirements

      10.2.1 The Definition and Role of Trial Subject

      A trial subject is an individual who participates in a clinical trial, either as a recipient of the investigational product(s) or as a control (ICH E6(R2) 1.57).

Trial subjects are needed for a clinical trial to receive the investigational product to obtain data to evaluate the safety and efficacy of the investigational product for eventual approval of the product to diagnose, treat, cure, prevent diseases. The trial subject will be administered the investigational product at the clinical research facility by the investigator or a qualified designee.

      10.2.2 Voluntary Responsibilities of a Trial Subject

      While there are no formal regulatory or GCP obligations prescribed to a trial subject, as there are for the sponsor, investigator, IRB/IEC, the subject will be asked to comply with requirements of the protocol and other operational procedures. A subject who has a thorough understanding of what to expect from their trial participation, who provides complete and truthful health and other information to trial staff, who follows study procedures as instructed, and who knows of their rights for trial participation will help to assure protection of their of rights, safety, and well‐being, integrity of trial data, and general trial compliance with SOPs, GCP, and applicable regulatory requirements.

      NOTE: If the trial subject is a minor or has a legally authorized representative (LAR), then the parent/guardian/LAR will assume the voluntary responsibilities on behalf of the research subject.

      We will describe examples of what subjects may do to facilitate their own protection and foster trial quality.

      10.2.2.1 Voluntary Responsibilities for Protection of Rights, Safety, and Well‐being

      A subject may help to ensure the protection of their rights, safety, and well‐being by following the study and operational requirements.

       10.2.2.1.1 Prior to Volunteering for a Clinical Trial

      Prior to volunteering for a clinical trial:

       A subject should understand what clinical research is and what to expect when they volunteer to take part in a clinical trial.

       The potential volunteer should know of their rights for participating in a clinical trial. The general GCP rights are:Fully informed consent and voluntarily participate in a trial without coercionConfidentiality of their identity and health informationCompensation for trial‐related injury and for the time, effort, and expenses for their involvement in the studyMedical care for study‐related injury or intercurrent illness(es)The ability to withdraw from the study at any timeRights may be outlined in the consent form and/or in a separate document. In addition to GCP rights, sometimes rights are specifically stipulated by the institution or regional regulatory authority(ies).

       The potential volunteer should ensure that they receive a copy of the consent form that has been approved by an IRB/IEC to take with them to review before they sign the consent form. The consent form and any other subject information documents will be in a language that the potential volunteer can understand. They may review the consent documents with their family and friends and ask as many questions as they need to from the research staff at the clinic site, the IRB/IEC, or other sources to help them