“Good Clinical Practice” (GCP) is a worldwide ethical and scientific quality standard for clinical trial design, conduct, performance, monitoring, auditing, recording, analysis, and reporting. It also helps to protect the privacy, honor, and rights of test participants. Understanding the history of the ICH-GCP principles is important since it offers reason for their use. In this article, we will look at the historical backdrop and events that led to the formation of these proposals. Today, the fundamental purpose of implementing ICH-GCP principles in clinical trials is to protect and preserve human rights.
“Good Clinical Practice” (GCP) is a worldwide ethical and scientific quality standard for clinical trial design, conduct, performance, monitoring, auditing, recording, analysis, and reporting. GCP provides confidence that the rights, integrity, and confidentiality of trial participants are preserved and maintained, and that the data and reported conclusions are trustworthy and accurate . Despite the fact that it was finished in 1996 and put into effect in 1997, no law was in place to implement it at the time. The European Union (EU) Directive on ICH Good Clinical Practice and the Medicines for Human Use (Clinical Trials) Regulations 2004 changed the global perspective, and GCP compliance is now mandatory in the UK and Europe for all studies including medicinal products research .
Understanding the history of the ICH-GCP standards is important because it demonstrates the motives and need for doing so ((Table 1)). The Hippocratic Oath (460 BC) demonstrates that the concept of a “good doctor” has been around since antiquity. The Food and Drugs Act of 1906 established drug regulation in the United States. This was caused by harmful and lethal pharmaceuticals that could be acquired over-the-counter like any other consumer commodity. Grandma’s Secret, Kopp’s Baby’s Friend, Dr. King’s Consumption Cure, and Dr. Bull’s Cough Syrup are just a few instances of items containing large amounts of morphine as well as morphine and chloroform . In 1938, the Food and Drug Administration (FDA) approved the Federal Food, Drug, and Cosmetic Act, which for the first time required manufacturers to test their goods for safety before releasing them to the public .
Historical background of GCP
|460BC||Oath of Hippocrates|
|1930’s||U.S. Food, Drugs and Cosmetic Act|
|Dec. 10th 1948||Declaration of Human Rights|
|Dec. 10th 1948||Declaration of Human Rights|
|1964, revised 2000||Declaration of Helsinki|
|1979||The Belmont Report|
|1982||International Guidelines for Biomedical Research Involving Human Subjects|
|1996||ICH-GCP guidelines issued|
|1997||ICH-GCP guidelines becomes law in some countries|
German physicians who performed unethical and terrible experiments in Nazi concentration camps during WWII were eventually convicted and punished before the Nuremberg Military Tribunal, which resulted in the Nuremberg Code being created in 1947. This regulation specifies the requirement for a scientific basis for human subjects research, as well as participant protection and free consent [4,5]. Following the tragedies of WWII, the United Nations also ratified and proclaimed the Universal Declaration of Human Rights (December 10th, 1948), which reinforced the human aspect in medical research.
In 1964, the World Medical Association issued the Helsinki Declaration, which served as the basis for the ethical principles that support the present ICH-GCP guidelines. The introduction of this proclamation makes it clear that the safeguarding of human rights is its primary priority :
The World Medical Association produced the statement of Helsinki, a statement of ethical norms, to serve as guidance for physicians and other participants in human-centered medical research. The role of the physician is to promote and defend the public’s health. The doctor’s expertise and conscience are dedicated to completing this duty.
In 1962, the world was astonished by severe limb malformations in fetuses caused by maternal thalidomide use. In fact, 10,000 infants were born in over 20 countries before this pharmaceutical interaction was discovered. In response, the Kefauver-Harris Amendments were passed, which required the FDA to evaluate all new drugs for safety and efficacy .
The National Commission for the Protection of Human Subjects of Biomedical and Behavioural Research’s Belmont Report, issued in April 1979, was another key turning point in the establishment of the ICH-GCP standards . The report’s guiding concepts are as follows:
- Respect for Individuals: This principle appreciates each individual’s intrinsic worth and independence. It requires the informed consent of research participants (or their officially chosen representatives).
- Beneficence: This concept holds that researchers must maximize the good consequences of their work while limiting the bad ones. Risks associated with research must be reasonable in light of the expected gains.
- According to this concept, study subjects must be treated properly and be chosen and recruited in an equal way.
The World Health Organization (WHO) and the Council for International Organizations of Medical Sciences (CIOMS) published ‘International Guidelines for Biomedical Research Involving Human Subjects’ in 1982. This guidance was created to help developing countries apply the Nuremberg Code and the Helsinki Declaration . Several organizations and committees throughout the globe issued papers and recommendations on the same subject. All of these recommendations were determined to be combined into a single, globally applicable standard.
The ICH Recommendations: The International Conference for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) issued Topic E6 GCP Guidelines in an effort to overcome national disparities in GCP. On July 17, 1996, this suggestion was adopted, and it became effective for clinical investigations on January 17, 1997. Participants in the preparation of these suggestions included officials and representatives from the EU, Japan, the United States, Australia, Canada, the Nordic countries, and WHO. .
Go to ICH-GCP
The ICH-GCP is a unified standard that protects human subjects’ rights, safety, and welfare, limits the amount of time people are exposed to investigational items, improves data quality, expedites the marketing of novel pharmaceuticals, and reduces costs for sponsors and the general public. By adhering to this criteria, the public may be guaranteed that the rights, safety, and welfare of trial participants are protected in accordance with the precepts of the Declaration of Helsinki, and that clinical trial data is credible . Table 2 offers a historical context for the goals and importance of GCP.
Reasons for GCP
|Increased Ethical Awareness|
|Improved Trial Methods|
|Clinical Trial Concept Better Understood|
|Public/Political Concern over Safety Aspects|
|Frauds and Accidents during Trials|
|Growing Research and Development Costs|
|Mutual Recognition of Data|
|New Market Structure|
The following are the 13 guiding principles of the ICH-GCP:
- Clinical trials should be conducted in accordance with the Helsinki Declaration’s ethical principles, as well as any applicable regulatory restrictions.
- Potential risks and downsides should be weighed against the predicted benefit for each trial participant and society as a whole before beginning a study. A research should be initiated and continued only if the benefits exceed the risks.
- The rights, safety, and general well-being of trial participants are paramount and must take priority over social and scientific concerns.
- Existing non-clinical and clinical data on a product under investigation should be adequate to support the intended clinical trial.
- Clinical investigations should be defined by clear, complete guidelines based on sound evidence.
- A research should be conducted in line with a protocol that has previously received approval or a positive decision from an independent ethics commission (IEC) or institutional review board (IRB).
- A competent doctor or, if required, a skilled dentist should always be in control of subjects’ medical care and medical decisions made on their behalf.
- Based on education, training, and experience, each participant in a research should be competent to carry out his or her specialized task(s).
- Before taking part in a clinical investigation, each subject should provide their free and informed consent.
- It is critical to collect, analyze, and store all clinical trial data in a way that allows for accurate reporting, interpretation, and verification.
- To protect the confidentiality of documents that might be used to identify people, privacy and confidentiality standards must be observed in line with the applicable regulatory requirement(s).
- Research items must be prepared, handled, and stored in accordance with Good Manufacturing Practices (GMP). They must be used in accordance with the stated protocol.
- Systems and processes that ensure the quality of each component of the trial should be implemented.
All clinical studies should adhere to ethical norms, rely on solid scientific data, and follow clear, rigorous protocols. These are self-explanatory notions. If the benefits outweigh the risks, trials should be done. Informed consent and anonymity are critical for protecting trial participants’ rights, safety, and general well-being. Care must be delivered by appropriately skilled and experienced individuals. Records must be readily accessible and retrievable to guarantee proper reporting, verification, and interpretation. When making experimental goods, Good Manufacturing Practices should be observed (8).
The GCP participants in clinical studies, as well as their respective responsibilities, must be indicated. A overview of them is provided in (Table 3).
|Regulatory Authorities||Review submitted clinical data and conduct inspections|
|The sponsor||Company or institution/organization which takes responsibility for initiation, management and financing of clinical trial|
|The project monitor||Usually appointed by sponsor|
|The investigator||Responsible for conduct of clinical trial at the trial site. Team leader.|
|The pharmacist at trial location||Responsible for maintenance, storage and dispensing of investigational products eg. Drugs in clinical trials|
|Ethical review board or Committee for protection of subjects||Appointed by Institution or if not available then the Authoritative Health Body in that Country will be responsible|
|Committee to monitor large trials||Overseas Sponsors eg. Drug Companies|
GCP for the Asia-Pacific Region
Since the development of the ICH-GCP guidelines, other countries in the Asia-Pacific region have realized the need to develop their own recommendations based on the original standards’ framework . This is evident in (Table 4), which details the adoption of GCP throughout our country and its neighbors.
Table 4 GCP Adoption in the Asia Pacific Region
|Original ICH-GCP Guidelines||1996|
|Malaysian GCP||1999, revised 2004|
As a consequence of rising demand from the pharmaceutical industry to perform clinical trials in Malaysia, similar laws were adopted. The Malaysian Guidelines for ICH Good Clinical Practice were initially published in October 1999, with the second edition following in January 2004. The essential concepts of the International Committee on Harmonization of Good Clinical Practice (ICH-GCP) are embraced by the guideline, with specific adaptations made to match local situations [1,7].
The “why” and “how” of GCP research are critical to comprehending their importance. The historical backdrop that inspired the development of GCP standards in the United States and Europe, as well as the ICH, is where we must go for an answer to this topic. The circumstances that led to the ICH Good Clinical Practice guidelines increased public awareness of the need of monitoring and managing clinical trials involving drugs and humans. Since human rights violations were a crucial issue, the Helsinki Declaration and the Nuremberg Code continue to serve as the cornerstone of present rules. As a result, the ICH-GCP guidelines are considered the “bible” of clinical trials and have been transformed into a global regulation that protects contemporary humanity.
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