Good Clinical Practice + Ethics in clinical trials

Question 1

1. What is the definition of good clinical practice?

Answer 1

Good Clinical Practice (GCP) is defined as International ethical and scientific quality standard for designing, conducting and reporting clinical trials that involve human subjects.

Compliance of GCP assures the public that the rights, safety and well-being of trial subjects are protected, and that the clinical data are credible

Question 2

1. What is the history of Good clinical practices?

Answer 2

• 460BC Oath of Hippocrates: “first, do no harm” “never do harm”
• 1938 US Food Drugs and Cosmetic Act
• 1947 Nuremberg Code:
• Required is the voluntary, well-informed, understanding consent of the human subject in a full legal capacity.
• The experiment should aim at positive results for society that cannot be procured in some other way.
• It should be based on previous knowledge (like, an expectation derived from animal experiments) that justifies the experiment.
• The experiment should be set up in a way that avoids unnecessary physical and mental suffering and injuries.
• It should not be conducted when there is any reason to believe that it implies a risk of death or disabling injury.
• The risks of the experiment should be in proportion to (that is, not exceed) the expected humanitarian benefits.
• Preparations and facilities must be provided that adequately protect the subjects against the experiment’s risks.
• The staff who conduct or take part in the experiment must be fully trained and scientifically qualified.
• The human subjects must be free to immediately quit the experiment at any point when they feel physically or mentally unable to go on.
• Likewise, the medical staff must stop the experiment at any point when they observe that continuation would be dangerous.
• 1964 Declaration of Helsinki:

Ethical principles to guide physicians and participants in medical research involving human subjects

• 1979 Belmont Report:
• Respect for persons –person’s dignity and freedom (autonomy); consent needed
• Beneficence–researchers maximise benefits and minimise harm, reasonable risks vs expected benefits. Do no harm(Non-maleficence)
• Justice–equitable selection and recruitment and fair treatment of subjects
• 1982 International guidelines for biomedical research involving human research
• To help developing countries apply the Nuremberg code and declaration of Helsinki.
• 1996 International Conference on Harmonisation’s “Guideline for Good Clinical Practice” (ICH GCP):
• To overcome inconsistencies in GCP internationally

1. 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 requirements
2. Before a trial is initiated, forseeable risks and inconveniences should be weighed against the anticipated benefit for the individual trial subject and society. A trial should be initiated and continued only if the anticipated benefits justify the risks
3. The rights, safety, and well-being of the trial subjects are the most important considerations and should prevail over interests of science and society
4. The available non-clinical and clinical information on an investigational product should be adequate to support the proposed clinical trial
5. Clinical trails should be scientifically sound, and described in a clear, detailed protocol
6. A trial should be conducted in compliance with the protocol that has received prior MCRC and hospital EC approval
7. The medical care given to, and medical decisions made on behalf of, subjects should always be the responsibility of a qualified physician or, when appropriate, a qualified dentist
8. Each individual involved in conducting a trial should be qualified by education, training, and experience to perform his or her respective tasks
9. Freely given informed consent should be obtained from every subject prior to clinical trial participation
10. All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation and verification
11. The confidentiality of records that could identify subjects should be protected, respecting the privacy and confidentiality rules in accordance with the applicable regulatory requirements
12. Investigational products should be manufactured, handled, and stored in accordance with applicable good manufacturing practice(GMP). They should be used in accordance with the approved protocol
13. Systems with procedures that assure the quality of every aspect of the trial should be implemented

Question 3

1. What are the key players in GCP?

Answer 3

1. Investigational product (lead, GMP, pre clinical testing)
2. Regulator (ethical reviews and approval)
3. Investigator (ability to conduct clinical trial)
4. Participants (informed consent)
5. Sponsor (trial protocol)

Question 4

1. What should a trial protocol include?

Answer 4

1. General information
2. Background information
3. Trial objective and purpose
4. Trial design (eg. Whether giving tablet x 2 tablets 3 times a day for 2 weeks gives adverse effects/efficacy for a specific form of cancer (tumor size, biomarkers etc)
5. Selection and withdrawal of subjects
6. Treatment of subjects
7. Assessment of efficacy
8. Assessment of safety
9. Statistics

Question 5

1. What are the basic principles of ethics? How can these principles be applied in clinical trials?

Answer 5

1. Respect: Autonomy, free to decide
2. Beneficence: Do good, do no harm
3. Justice: uphold rights of subjects

Ethics and clinical trials:

• Protect the right and welfare of the subjects
• Maintain compliance with regulation, ethical codes and guideline
• Facilitate valuable research for the benefit of society
• Adherence to proper process

Question 6

What are the 2 key protections in clinical trials?

Answer 6

1. Ethical review by an independent committee
2. Informed consent by voluntary participants