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Examining the Relationships that Exist during Clinical Development
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Examining the Relationships that Exist during Clinical Development
Clinical trials involve research for new medical drugs, therapies, or devices. Such research
involves human subjects being practically subjected to drugs, therapies, or devices. Clinical trials
may also be carried out to improve an already existing product. Since human subjects are involved
in the trials, their safety and rights must be guaranteed by developing a clinical trial protocol (Code
of Federal Regulations n.d.) The process involves several parties referred to as stakeholders. For
the clinical trial process to be successful, there is a need for optimized relationships between all
the stakeholders. This paper examines the relationships in a clinical trial process regarding
stakeholders, study processes, and the clinical trial protocol. The responsibilities of each party will
be determined and their relationships established.
Clinical Trial Stakeholders
Clinical trial stakeholders are individuals, organizations, and government agencies who
contribute to the success of the clinical research process. They include sponsor, contract research
coordinator, investigation site and clinical trial principal investigator, and subjects or Participants
(Chilkoti, 2019). The stakeholders are always bound by key responsibilities: administrative,
scientific, and ethical responsibilities.
Sponsor
A sponsor is one of the key stakeholders, an individual, an organization, a company, or a
government agency. In most cases, sponsors are academic institutions, biotechnology companies,
pharmaceutical companies, and other local and international health organizations. The sponsor
initiates, organizes, manages, and finances the clinical research and trial process. The sponsor's
responsibility is to ensure quality control and assurance under a written standard operating
procedure to comply with the protocol and the prevailing applicable regulations (Chilkoti, 2019).
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In addition, the sponsor is responsible for engaging the contract research organization (CRO),
designating qualified medical expertise, selecting the clinical trial investigator, and allocating them
responsibilities. Furthermore, while acting as a principal financier of the clinical trial, the sponsor
is responsible for the insurance and compensation of subjects, investigators, and other individuals
involved in the clinical research process.
Contractor Research Organization
A contract research organization (CRO) may be a private, commercial or academic
organization engaged by the sponsor to act and perform some duties in the process of clinical
research. A sponsor can delegate part or all sponsor-related duties and responsibilities to a contract
research organization in a written agreement (Ledesma, 2020). When all sponsor responsibilities
have been transferred to the CRO in writing, the CRO acts as the sponsor throughout the clinical
research process.
Investigation Site and Clinical Trial Principal Investigator
The principal investigator is supposed to possess Good Clinical Practice (GCP). In
addition, the investigator should comply with the regulatory requirements that apply to clinical
research. Furthermore, the investigator should provide valid documents and certifications to prove
academic or educational qualifications, professional certification and experience, and competency
in clinical practice to ensure that they are comprehensively familiar with the investigatory
procedure (Office of the Commissioner, 2019). Key responsibilities of the investigator include:
It is the principal investigator's responsibility to ensure that suitable subjects have been
recruited within the time limits of the clinical trial process. The investigator should also
ensure adequate qualified staff and sufficient facilities that guarantee the timely completion
of processes following the protocol.
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 Providing medical care for the subjects
The investigator should be or engage a qualified physician to care for the subjects’ health
issues. The physician should inform and respect the subject’s rights during the clinical trial
process.
 Carrying out in storage of investigatory products, documentation of investigatory
procedures, and obtaining informed consent of trial subjects in compliance with protocol
The investigator should carry out the trial following the protocol as agreed by the sponsor
and other stakeholders. In addition, the investigator should obtain and record the informed
consent of the trial subjects while adhering to ethical principles. Furthermore, the
investigator must ensure the safe-keeping of investigatory products and records of the trial
process and subjects in their original and accurate state, both written and electronic (Office
of the Commissioner, 2019). The investigator should ensure that serious adverse events are
reported as soon as possible to the sponsor as provided by the protocol. Finally, upon
completion of the trial process, the investigator should provide a final report of the outcome
of the trial process to the regulatory authority and other relevant parties. In case of
premature termination or suspension, the investigator should inform all parties according
to the protocol and prevailing regulations.
Key Clinical Trial Processes
There are various processes related to the conduct of clinical trials that have to be executed
to ensure that they adhere to the regulatory requirements that are in place for subject safety and
drug efficacy. Such processes are carried out to investigate and ensure ethics, safety, and protection
of human subjects and guarantee integrity in data and information records appertaining to the
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clinical trial process (Liu, 2010). The processes include the informed consent process and those
processes related to the clinical trial protocol.
Informed consent-Its Foundation and Elements
Informed Consent and its Foundation
Informed consent in clinical trials is a process that involves a physician, normally acting in
the position of an investigator and the human subject. The physician's responsibility is to obtain
an autonomous, freely given, and written consent of willingness of the human subject to participate
in the clinical trial (Office of the Commissioner, 2019). The participant consents to adhere to the
expectations of Good Clinical Practices (GCP). Therefore, the physician should sensitize the
potential human subject about the nature of the clinical research in a simple, non-technical
language that can be easily understood.
Informed consent is a human activity where the patient has to think about what the
physician explains and make an autonomous human decision. Therefore, the foundation of
informed consent lies in the human action of operation of human intellect through a process of
reason and will and execution of the power of free choice (Office of the Commissioner, 2019).
Written informed consent is essential for safeguarding the subject's autonomy regarding
willingness to participate in the clinical trial and, more importantly, building the trust that may
hinder the trial's success. If the patient or potential subject cannot give informed consent, it can be
obtained from a legally acceptable representative (LAR). Such situations arise when the potential
participant is a minor, unconscious, or suffering from mental disorders. The legally acceptable
representative can be an individual or an organization authorized by the prevailing laws of the
nation in which the trial is contacted to give consent on behalf of the subject to participate in the
clinical trial.
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Elements of Informed Consent
There are several elements of informed consent. However, these elements are critical:
information disclosure, voluntarism, and decision-making capacity.
Information disclosure
Information disclosure refers to the sensitization of information given to the potential
subject in a clinical trial to enable them to understand the nature of the trial before consenting to
participation. The information is necessary to ensure that subjects arrive at an informed decision
that is rational and logical. The decision made by a well-informed subject is bound to be influenced
by their social, cultural, and psychological beliefs. The information disclosed to the subject
includes the health disorder for which the trial is being conducted, the reason or purpose and nature
of the research, experimental treatment procedures, and potential risks and benefits linked to the
participation in the research (Liu, 2010). Additional information to be disclosed includes the
availability of alternative treatment, the risks and benefits of such alternatives, and the risk
involved in the failure to treat the illness. The subject should also be informed of their right to
withdraw at any stage and if any risks are involved in such withdrawal.
Voluntarism
A voluntary decision is made by an individual after thinking and reasoning on their own,
based on their prevailing situation and condition without being coerced or influenced. Autonomy
and voluntarism form the foundation of ethically obtained informed consent from a potential
subject (Office of the Commissioner, 2019). The voluntarism of the subject depends on intellectual
maturity, emotional stability, psychological conditions, and socio-cultural beliefs. Precaution
should be taken to eliminate factors that may compromise the voluntarism of the subject, like
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coercion, influence by force, or taking advantage of the subject’s inability to resist, such as
unconsciousness or mental disorder.
Decision-making capacity
Decision-making capacity refers to the subject's mental or intellectual ability to understand
the information delivered by the physician concerning the trial, think, reason, and arrive at a
rational, logical, and autonomous decision to consent or not to consent to participation in the trial.
Decision-making capacity depends on the subject's cognitive ability, voluntarism, and autonomy
(Office of the Commissioner, 2019). Four elements make decision-making capacity. They include
understanding the information disclosed to them, appreciating the situation, manipulating the
information rationally and logically, and finally communicating or making the final decision.
Clinical Trial Protocol
Among the foremost steps in the clinical trial process is the development of a clinical trial
protocol. It is a document describing how the clinical research will be carried clearly and concisely.
The protocol outlines the objectives of the trial, the design, methodology, statistical issues, and the
structure or organization of the trial (Clinical Trial Protocol Development, 2017). Furthermore,
the protocol is essential to ensure the safety rights of human subjects involved and uphold the
integrity of all data and information collected during the clinical trial.
Objectives and Study Rationale
This section of the protocol includes the purpose and reason why the clinical trial is being
conducted. The study rationale is stated as the problem or a question. The study rationale consists
of the description of the population, the disease, the current level of treatment, and its limitations
(Clinical Trial Protocol Development, 2017).
objectives of the study.
It also includes the primary and secondary
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Investigational Product
The investigational product may also be referred to as study intervention. This protocol
element includes the description of the investigation product, which may be a drug, biologic, or
device. Dosage and the routine are provided (Clinical Trial Protocol Development, 2017). For
devices, there is a need to provide principles of operation of each essential component of the
device.
Study Procedures
This element includes all study procedures to be done in the clinical trial. They are listed
following the objectives. The procedures should be discussed in the sequence of the events in the
trial (Peace, 2010). The section may describe physical examination, radiographic imaging,
collection of a biological specimen, laboratory examinations, special procedures required,
administration questionnaires, and procedures completed during the trial.
Major Relationships
Relationship between stakeholders in a clinical trial
Sponsors and contract research organizers relate closely to clinical trials since they share
responsibilities. However, the relationship is so intended that sometimes one cannot differentiate
between the two. In a written agreement, a sponsor delegates part or all sponsor-related duties and
responsibilities to a contract research organization (Ledesma, 2020). When all sponsor
responsibilities have been transferred to the CRO in writing, it becomes difficult to distinguish
between the two.
Relationship between the principal Investigator and other stakeholders
Investigators interact and relate with all other stakeholders in the trial. For instance, the
investigator interacts with the subjects or participants to obtain written informed consent. On the
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other hand, the investigator collaborates with the contract research organizers to ensure that the
trial is conducted following the clinical protocol while following issues of ethics and integrity
(Peace, 2010). Furthermore, the investigator communicates to all other stakeholders, updating
them on the trial's progress. In particular, it is the investigator's responsibility to write a completion
report to all other stakeholders or inform them of the premature suspension of the trial process.
Conclusion
The relationship in a clinical trial process is essential for its success. The roles played by
the stakeholders are not stand-alone cases, but they require that stakeholders interact and relate
closely. On the other hand, for the process to be harmonious there is a need for documented
guidelines and procedures in the form of a clinical trial protocol to be followed. The protocol
contains rules and regulations, and instructions that guide the trial process. Furthermore, the
protocol provides a foundation for protecting the safety and human rights, including acquiring
written informed consent.
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References
CFR - Code of Federal Regulations Title 21. (n.d.-b). Accessdata.Fda.Gov. Retrieved November 27,
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Ledesma, P. (2020, March 9). ¿What is a CRO?Sofpromed. https://www.sofpromed.com/whatis-a-cro
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Office of the Commissioner. (2019). Guide to Informed Consent. U.S. Food and Drug Administration.
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Peace, K. E., & Chen, D. (. (2010). Clinical trial methodology. CRC Press LLC.