The Fundamentals of Clinical Research. P. Michael Dubinsky

product to determine its pharmacological properties, safety, and/or effectiveness in humans. By definition, the sponsor is:

      An individual, company, institution, or organization that takes responsibility for the initiation, management, and/or financing of a clinical trial. (ICH E6(R2) 1.53)

      A Sponsor can be, for example, a pharmaceutical or biotechnology company, a nongovernmental organization (NGO), a governmental agency, an academic institution, a single individual or any entity that wants to take responsibility for the initiation, management, and/or financing of a clinical trial.

The Sponsor often is the financial owner and/or the developer of the product being investigated; however, the Sponsor may simply have access to the investigational product through an agreement with the financial owner or developer. In all instances, the Sponsor does not actually conduct the investigation (i.e., administer the investigational product to research subjects and record data from the study assessments), but will be legally responsible for all handling and use of the investigational product in the trial, the integrity of the trial data collected, and the submission of the trial findings to the Regulatory Authority. A Sponsor will usually be ultimately interested in getting approval for marketing their product or for publishing new information about the product.

      7.2.1.2 The Investigator

      The Clinical Investigator is the qualified doctor (or dentist) who administers the investigational product to the research subjects. By definition, an 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) 1.57).

      A clinical Investigator is the physician who has access to and gives medical care to the research participant who is being administered the investigational product, or the control product, in the clinic. The clinic where the research participant is seen by the physician and undergoes trial procedures is known as the trial site. The Investigator can be practicing alone, be part of a clinical group practice or clinical research management organization, or a member in a hospital or other institution. Any of the different types of practices can be private or public.

      In all situations, the Investigator will have responsibility for the medical care of the research participant and all activities of the trial at the trial site, regardless of who actually conducts those activities. If there are other individuals, such as a nurse, laboratory technician or other physicians, who conduct the trial procedures, the Investigator leading the team is typically called the Principal Investigator, and is legally responsible for the work of all those individuals and all trial conduct at the trial site.

      7.2.1.3 The Subject/Trial Subject

      The Subject/Trial Subject is a human who volunteers to participate in the clinical trial to receive the investigational product or control product. By definition, the Subject/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)

The human research subject or Trial Subject, also known as clinical research subject, participant, or volunteer, is the individual who volunteers to participate in the clinical trial to receive the investigational product or to act as a control in the trial. The volunteer will be an individual from the population being studied in the trial; therefore, research participants can be healthy volunteers or someone who has the disease under study, and can be of any age, race, or gender. For all Trial Subjects, participation in a clinical trial is voluntary. The term Subject or Trial Subject is generally used to describe the person once they consent to being in a trial, although some prefer “patients” to refer to individuals who have the disease. Others also prefer the neutral term “volunteer” or participant' to refer to all types of trial participants.

      7.2.1.4 The IRB/IEC

      The ethics committee, which is formally known as Independent Ethics Committee (IEC) or IRB, is a body of individuals that ensures the protection of human research subjects (the term “IRB” is used in the United States regulations). By definition, an Independent Ethics Committee (IEC) is:

      An independent body (a review board or a committee, institutional, regional, national, or supranational), constituted of medical/scientific professionals and nonmedical/nonscientific members, whose responsibility it is to ensure the protection of the rights, safety, and well‐being of human subjects involved in a trial and to provide public assurance of that protection, by, among other things, reviewing and approving/providing favorable opinion on the trial protocol, the suitability of the investigator(s), facilities, and the methods and material to be used in obtaining and documenting informed consent of the trial subject. (ICH E6(R2) 1.27)

      An IRB is:

      An independent body constituted of medical, scientific, and nonscientific members, whose responsibility it is to ensure the protection of the rights, safety, and well‐being of human subjects involved in a trial by, among other things, reviewing, approving, and providing continuing review of trials, of protocols and amendments, and of the methods and material to be used in obtaining and documenting informed consent of the trial subjects. (ICH E6(R2) 1.57)

An ethics committee that is responsible for the physical and psychological protection of human research subjects is known as an IRB or IEC, or ethical review board, depending on the geographical region or country, or institution. An institution where a trial is taking place, for example a hospital or academic center, may have a department dedicated to performing IRB activities for all clinical research studies that are executed at that institution. There are also IRBs that review a given trial for all the clinical sites participating in the given study and these IRBs are known as central IRBs. Additionally, a particular ethics committee may review research protocols for all studies conducted within its geographic region.

      For all types of IRBs/IECs, the composition and functions remain the same per GCP (ICH E6(R2) 3). An IRB/IEC’s review is independent of the influence of the investigator, sponsor or their representatives; however, for a given trial, some IRB/IECs may take into consideration the opinions of other IRB/IECs that are reviewing the same trial at other participating sites.

      7.2.1.5 The Regulatory Authority

      The regulatory authority is a public authority or government agency charged with overseeing clinical investigations that involve unapproved medicinal products. By definition, the Regulatory Authority is:

      A body having the power to regulate. In the ICH GCP guidance the expression “Regulatory Authorities” includes the authorities that review submitted clinical data and those that conduct inspections. These bodies are sometimes referred to as competent authorities. (ICH E6(R2) 1.49)

      A regulatory authority is a public authority or government agency. There may be an agency named specifically to oversee the safety, effectiveness, quality, and security of medicinal products, such as the Food and Drug Administration (FDA) in the United States of America and the Medicines and Healthcare Products Regulatory Agency (MHRA) in the United Kingdom, or the function may fall under the general authority of, for example, a country’s Ministry of Health.

      The authority or authorities make rules to govern the activities for drug development, that is, manufacturing of the medicinal product, animal testing, and clinical testing. For clinical testing specifically, there are rules that govern the activities of the Sponsor, Clinical Investigator, and the IRB. Each of the clinical testing players has rules to follow and these rules are typically called “responsibilities.” The Sponsor submits the data from clinical trials as part of an application for approval for marketing the test product. The Regulatory Authority reviews the application to assess a product’s safety and efficacy, will conduct inspections to ensure that trials were conducted according to GCP and the applicable regulatory requirements, and will consider other factors prior to granting approval.