GCP Flashcards
GCP
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
Assure the quality, reliability and integrity of data collected, and that the clinical data are credible
To provide standards and guidelines for the conduct of clinical research
Good Clinical Practice = Ethics + Quality Data
Covers Phase I to IV clinical trials
GCP guidelines
Mainly focused on the protection of human rights in clinical trial.
Provide assurance of the safety of the newly developed compounds.
Provide standards on how clinical trials should be conducted.
Define the roles and responsibilities of clinical sponsors, clinical research investigators, clinical research associates, and monitors.
A clinical research associate (CRA), also called a clinical monitor or trial coordinator, is a health-care professional who performs many activities related to medical research,
particularly clinical trials.
US Food Drugs and Cosmetics Act 1938
Harmful drugs available over the counter(OTC)
Grandma’s Secret, Kopp’s Baby’s Friend, Dr King’s Consumption Cure, Dr Bull’s Cough Syrup
Enacted by US Food and Drug
Administration(FDA)
Manufacturers required t test drugs for safety, report evidence to FDA before marketing
Nuremberg Code 1947
Nuremberg Military Tribunal of German physicians who
experimented on World War II prisoners in Nazi camps
◦ Opened the eyes of the world for guidance on clinical testing on humans.
◦ The code did set ethical guidelines, but it lacked legislation to back it up
Need for scientific basis for research on human subjects
Voluntary consent and protection of human participants(the Nuremberg Code begins: “The voluntary consent of the human subject is absolutely essential.“)
Supported by the Universal Declaration of Human Rights
adopted by the United Nations
Declaration of Helsinki 1968
Developed by the World Medical Association
Fetal limb deformities from maternal thalidomide use.
Ethical principles to guide physicians and participants in medical research involving human subjects
Principles to conduct research requires careful consideration of i) informed consent, ii) risks benefit assessment, and iii)selection of subjects of research.
Well-being of subject takes precedence : Respect for persons
Protection of subjects health and rights – Special protection for vulnerable populations
These guidelines influenced national legislation, but there was no set standard between nations
Syphilis Trial
1932 and 1972 by the US public Health Service: studying the natural progression of untreated syphilis in rural African-American men in Alabama under the guise of receiving
free health care from the United States government.
Investigators enrolled in the study a total of 600 impoverished, African American.
399 had previously contracted syphilis before the study began, and 201 did not have the disease.
The men were given free medical care, meals, and free burial insurance for participating in the study. After funding for treatment was lost, the study was continued without
informing the men they would never be treated.
the men were told they were being treated for “bad blood”, a local term for various illnesses that include syphilis, anemia, and fatigue.
40 year study revelation
The 40-year study was controversial for reasons: ethics, justice, respect
Revelation in 1972 of study failures by a whistleblower led to major changes in U.S. law and regulation on the protection of participants in clinical studies.
Scientists prevented participants from accessing syphilis treatment programs available to other residents in the area.
The victims of the study, all African American, included numerous men who died of syphilis, 40 wives who contracted the disease, and 19 children born with congenital syphilis
Belmont Report, 1979
Issued by the National Commission for Protection of Human Subjects of Biomedical and Behavioural Research
Respect for persons – person’s dignity and freedom, autonomy; consent needed
Beneficence – researchers maximise benefits and minimise harm, reasonable risks vs expected benefits
Justice – equitable selection and recruitment and fair treatment of subjects
International Guidelines for biomedical researchinvolving human research, 1982
Issued by World Health Organisation (WHO) and Council for International Organisations of Medical Sciences(CIOMS)
To help developing countries apply the Nuremberg Code and Declaration of Helsinki
International conference on Harmonisation’s ‘ guideline for gcp’ 1996
Issued by ICH of Technical Requirements for Registration of Pharmaceuticals for Human Use.
To overcome inconsistencies in GCP internationally
European Union, United States, Japan; Australia, Canada, Nordic countries, WHO
Ethics
- 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
- 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
- The rights, safety, and well-being of the trial subjects are the most important considerations and should prevail over interests of science and society
Protocol and Responsibility
- The available non-clinical and clinical information on an investigational product should be adequate to support the proposed clinical trial
- Clinical trails should be scientifically sound, and described in a clear, detailed protocol
- A trial should be conducted in compliance with the protocol that has received prior MCRC and hospital EC approval
- 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
- Each individual involved in conducting a trial should be qualified by education, training, and experience to perform his or her respective tasks
Data and Investigation
- Freely given informed consent should be obtained from every subject prior to clinical trial participation
- All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation and verification
- The confidentiality of records that could identify subjects should be protected, respecting the privacy and confidentiality rules in accordance with the applicable regulatory requirements
- 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
- Systems with procedures that assure the quality of every aspect of the trial should be implemented
Clinical Trial Planning
The drug must be tested in living animals (pre-clinical) to ensure safety for human consumption (phase 1)
With this, drug companies make every effort to use as few animals as possible and ensure they are properly cared for
Then a protocol is created to map out what study procedures will be done, by whom, and why within a clinical trial.
Protocol
General information
Background information
Trial objective and purpose
Trial design
Selection and withdrawal of subjects
Treatment of subjects
Assessment of efficacy
Assessment of safety
Statistics
