Good Clinical Practice Guidelines

Good clinical practice (GCP) guidelines are an internationally recognized standard for clinical trials that include ethical and quality requirements that must be adhered to for any clinical trial that involves people. It specifies good clinical practice guidelines for all aspects of a study, from trial documentation and protocol amendments to reporting lines for adverse events and medical care available for participants in trials testing pharmaceuticals for human use.

The good clinical practice guidelines provide detailed standards for all facets of clinical trials, including:

• Design
• Conduct
• Performance
• Monitoring
• Auditing
• Documentation
• Analysis 
• Reporting
• Termination

Compliance with good clinical practice guidelines provides assurances that the studies are scientifically and ethically sound. In addition, GCP ensures that trial subjects’ rights, integrity, and confidentiality are protected and that the clinical trial data are credible and accurate.

The Fundamental Tenets of Good Clinical Practice Guidelines

The rights, safety, and well-being of the trial subjects are the most important considerations and should prevail over interests of science and society.

Good Clinical Practice
Chapter 2, Section 3

GCP also provides unified, high-quality data to facilitate the mutual acceptance of clinical data by regulatory authorities of jurisdiction. As a result, comparable versions of food clinical practice guidelines, established by the World Health Organization, have been accepted by other countries.

A Brief History of Good Clinical Practice Guidelines

The history of good clinical practice guidelines begins with the Hippocratic Oath (460 BC) from ancient Greece, a guiding medical ethics code for millennia. The next major milestone in the history of good clinical practice is the Food and Drugs Act of 1906, which was passed to stop the sale of harmful and lethal drugs to consumers (e.g., Kopp’s Baby’s Friend Dr. King’s Consumption Cure that contained morphine). This was followed, in 1938, by the Federal Food, Drug, and Cosmetic Act, which required manufacturers to test drugs for safety and present the evidence to the FDA before taking products to market.

The atrocities carried out by Nazi physicians during World War II lead to the 1947 Nuremberg Code, which articulates the need for voluntary consent and protection for human subjects in research. The following year, the United Nations adopted the Universal Declaration of Human Rights that reiterated the rules set forth in the Nuremberg Code.

In 1962, tragic fetal limb deformities were linked to the use of thalidomide by pregnant women only after 10,000 affected infants were born in over 20 countries. This led to the Kefauver-Harris Amendments to the Food, Drug, and Cosmetic Act that give the Food and Drug Administration (FDA)  the authority to require proof of efficacy, in addition to safety, before approving a new drug.

In 1979, the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research issued the Belmont Report, which identifies basic ethical principles and guidelines that address ethical issues arising from research with human subjects. The three core principles also became foundational to the good clinical practice guidelines.

1. Respect for Persons
Individuals should be treated as autonomous agents, and second, that persons with diminished autonomy are entitled to protection

2. Beneficence
Individuals are treated in an ethical manner by respecting their decisions and protecting them from harm and making efforts to secure their well-being.

3. Justice
This principle requires equitable selection, recruitment, and fair treatment of human clinical research subjects.

In 1982, the World Health Organization (WHO) and the Council for International Organizations of Medical Sciences (CIOMS) released the International Guidelines for Biomedical Research Involving Human Subjects with the objective of helping developing countries apply the principles of the Declaration of Helsinki and the Nuremberg Code. Subsequently, organizations worldwide began to release their versions of these guidelines. 

The International Conference for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) issued the ICH Guidelines: Topic E6 Guideline for Good Clinical Practice (ICH-GCP E6) in 1996 to provide a global standard to replace the hodgepodge that had developed around the world. The developers of the good clinical practice guidelines were representatives of authorities and pharmaceutical companies from Australia, Canada, the European Union (EU), Japan, the Nordic countries, the United States, and the WHO.

The FDA adopted the ICH-GCP E6 (R2) Integrated Addendum as guidance in March 2018. FDA-regulated clinical trials must follow the aspects of good clinical practice guidelines that are aligned with the applicable FDA regulations. Parts of good clinical practice guidelines that are not included in FDA regulations are considered guidance.

What Is the ICH-GCP?

The ICH-GCP was borne out of an effort to create a single, international standard for good clinical practice guidelines. It was meant to replace the disparate guidelines that had been developed in countries around the world. The ICH-GCP is a harmonized standard that:

• Provides direction to protect the rights, safety, and welfare of human subjects in studies 
• Eliminates study subjects’ exposure to investigational products
• Improves the quality of data
• Accelerates time to market for new drugs

Many countries around the world have adopted the ICH-GCP. The FDA adopted it as a guideline to be used in conjunction with its regulations.

Core Principles of ICH-GCP

Good clinical practice guidelines include 13 principles that apply to all clinical research that can affect the safety and well-being of human participants. The thirteen good clinical practice guidelines can be considered in these categories:

• Ethics
• Protocols and science
• Responsibilities
• Informed consent
• Data quality and integrity

Ethics

1. Ethical conduct of clinical trials
Clinical trials should be conducted in accordance with good clinical practice guidelines and the applicable regulatory requirement(s).

2. Benefits justify risks
Before a trial is initiated, foreseeable risks and inconveniences should be weighed against the anticipated benefit for the individual trial subject and society at large.  

3. Rights, safety, and well-being of subjects prevail
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 science

4. Non-clinical and clinical information supports the trial
The available non-clinical and clinical information regarding the safety of an investigational product should be adequate to support proceeding with a proposed clinical trial.

5. Quality trials based on comprehensive protocols
Clinical trials should be scientifically sound and described in a clear, detailed protocol.

Responsibilities

6. IRB/IEC approval and compliance with the study protocol
A trial should be conducted in compliance with a study protocol that has received prior institutional review board (IRB)/independent ethics committee (IEC) approval.

7. Medical care and health-related decisions by a qualified physician
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, of a qualified dentist.

8. Trial staff has appropriate qualifications
Each individual involved in conducting a trial should be qualified by education, training,
and experience to perform their respective task(s).

Informed consent

9. Consent based on decision capacity, documentation of consent, disclosure, and competency
Freely given informed consent should be obtained from every subject prior to clinical trial participation.

Data Quality and integrity 

10. Accurate reporting, interpretation, and verification of clinical data
All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation, and verification.

11. Protection of personally identifiable information (PII) and other sensitive information  
The confidentiality of records that could identify subjects should be protected to adhere to privacy and confidentiality rules in accordance with good clinical practice guidelines.

12. Good Manufacturing Practice followed
Investigational products should be manufactured, handled, and stored in accordance with applicable good manufacturing practice guidelines. They should also only be used in accordance with the approved protocol.

13. Quality assurance embedded into study
Systems with procedures must be in place to assure the quality of every aspect of the trial.

What Is an IRB/IEC? (US)

Institutional review boards IRBs) and independent ethics committees (IECs) are independent bodies made up of medical professionals and non-medical members. An IRB/IEC evaluates risks and benefits throughout a study to ensure that clinical trial participants are exposed to minimal risk in relation to any benefits that might result from the research.

To adhere to good clinical practice guidelines, an  IRB/IEC  should consist of members who have the qualifications and experience to effectively review and evaluate the science, medical aspects, and ethics of the study. It is recommended that the IRB/IEC should include: 

• At least five members
• At least one member whose primary area of interest is in a nonscientific area
• At least one member who is independent of the study

The IRB/IEC reviews trials before they can begin and provides written and dated approval of the trial protocol. It also reviews and collects written informed consent forms, consent form updates, subject recruitment procedures (e.g., advertisements, notices, media), and any other written information that is provided to subjects.

Written records of activities and communications engaged in by IRBs/IECs and their members should be maintained for at least three years in order to adhere to good clinical practice guidelines. These include:

• Correspondence
• Lists of occupations, affiliations, and qualifications of members
• Membership lists
• Minutes of meetings
• Submitted documents
• Written procedures

According to good clinical practice guidelines, IRB/IECs are also required to monitor all aspects of clinical trials. The IRB/IEC tracks details about the study as reported to them by the study’s investigator, including:

• Deviations  from,  or  changes  to,  the  study protocol  
• Changes that increase the risk to subjects and/or significantly affect the conduct of the trial  
• All adverse drug reactions (ADRs) that are both serious and unexpected 
• Any new information that may adversely affect the safety of the subjects or the conduct of the trial

Why are Good Clinical Practice Guidelines Important?

Good clinical practice guidelines are important for research and studies because they:

• Address public and political concerns over the safety and ethical aspects of trials 
• Eliminate the frauds and accidents that participants previously encountered during trials
• Enhance the reliability, credibility, and accuracy of trial results 
• Ensure human subject protection
• Help better understand the trial concept
• Improve study methods and efficiency
• Increase ethical awareness for the involved participants
• Promote data integrity  
• Protect the rights, integrity, and confidentiality of study subjects 
• Support mutual recognition and analysis of the obtained data

Goals of Good Clinical Practice Guidelines

The goals of good clinical practice guidelines are to provide a unified standard to protect human subjects who participate in trials and to facilitate the mutual acceptance of clinical data by the regulatory authorities that adhere to the standards.

Among the goals for good clinical practice guidelines are the following.

• Protection for research subjects’ safety and rights, including:
  • Right to be informed
  • Right not to participate
  • Right to withdraw at any time
  • Right to protection of privacy
• Assurance of the high quality and integrity of research data by directing that it is:
  • Based on a scientifically sound protocol designed to meet its stated objectives 
  • Based on the quality conduct and oversight of the clinical study
• The existence and operation of quality systems

Who Is Responsible for Compliance with Good Clinical Practice Guidelines?

Good clinical practice guidelines describe the roles and responsibilities of those involved in studies. Ultimately, the sponsor is in charge of ensuring compliance with good clinical practice guidelines. Others who are required to abide by the rules enforced by the sponsor include: 

• Clinical investigators  
• Independent ethics committees (IECs)
• Institutional review boards (IRBs)
• Contract research organizations (CROs)
• Research nurses
• Medical monitors
• Clinical research coordinators 
• Clinical research associates  
• Data managers 
• Data entry personnel
• Statisticians
• Information technology staff

Good Clinical Practice Guidelines Provide Global Protections for Everyone

Good clinical practice guidelines ostensibly are focused on clinical trials. However, the standards set forth in good clinical practice guidelines, which have been accepted nearly all over the world, ultimately protect everyone. Good clinical practice guidelines ensure that participants in studies are taken care of and that everyone who is prescribed and takes medication is assured of its safety and efficacy.   

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Last Updated: 10th February, 2022