Good Clinical Practices

Overview: Good Clinical Practice

Good Clinical Practice (GCP) is defined as being an “internationally accepted standard for the designing, conducting, recording and reporting of clinical trials.” It provides the framework for a participants’ safety and wellbeing, and ensures that all the data collected during a clinical trial is credible.

Good Clinical Practice (GCP) originated during the World Medical Association’s Declaration of Helsinki in 1964 with a statement known as the “Declaration of Helsinki”, listing ethical principles and specific guidelines to ensure that a human participants’ rights, safety and wellbeing will always be a higher priority than any other aspect of a clinical trial.

The Therapeutic Goods Administration (TGA) has adopted the European Union version of these guidelines in regards to Good Clinical Practice and clinical trial conduct in general. Australia’s National Statement on Ethical Conduct in Research Involving Humans by the National Health and Medical Research Council (NHMRC) works in accordance with GCP. This is particularly important in Australia as the ethics committee have a primary role in assessing and approving clinical trial proposals, as well as making sure clinical trial conduct complies with GCP standards. The use of GCP guidelines and the NHMRC National Statement provide the framework for a standardised approach to clinical research in Australia. This results in a high standard of research that international regulatory bodies can trust.

 

Good Clinical Practice Principles

There are 13 Good Clinical Practice principles which were established in the World Medical Association’s Declaration of Helsinki. These principles include:

Principle 1: Ethical Conduct

All research involving humans should be carried out in accordance with three basic ethical principles including respect, beneficence and justice. Each individual participating in clinical research has a responsibility for ensuring research is ethically and scientifically conducted according to the highest standards.

Principle 1 is applied through:

• The design of the clinical trial.
• Informed consent.
• Ethical review.
•  A favourable risk/benefit assessment.
• Compliance with national and international laws, regulations and standards.

Principle 2: Protocol

All research involving human participants should be scientifically justified and described in a detailed manner.

Principle 2 is applied through:

• The development of a clear, detailed, scientifically justified and ethically sound protocol that adheres to the laws and regulations put in place by regulatory authorities and ethical committees.
• Protocol undergoes a thorough scientific and ethical review before implementation.

Principle 3: Risk Identification

Identifies any potential risks or benefits before clinical research begins. Research of investigational products and procedures should be supported by both non-clinical and clinical information.

Principle 3 is applied through:

• Conducting a thorough search of available information about the investigational product and procedures.
• Producing the investigator’s brochure, the study protocol, and the informed consent document which accurately and objectively reflect the available scientific information about the potential risks and benefits.

Principle 4: Benefit-Risk Assessment

The clinical trial can go ahead only if the benefits outweigh the risks. Although the benefits should be taken into account, the most important considerations are the rights, safety and well being of the participants.

Principle 4 is applied through:

• Appropriate study design and thorough ethical, scientific and regulatory review of the study protocol before the clinical trial begins.

Principle 5: Review by IEC (Institutional Ethics Committee) and IRB (Institutional Review Board)

Clinical research involving human participants should receive an independent ethics committee and institutional review board approval before a clinical trial begins.

Principle 5 is applied through:

• Protocol review by an IEC and IRB which operates in accordance with GCP guidelines and national laws and regulations.

Principle 6: Protocol Compliance

Research in humans should be conducted in compliance with the approved protocol.

Principle 6 is applied through:

• Investigator compliance with the protocol requirements.
• Submission of any protocol changes to the sponsor and the IEC/IRB with approval before a clinical trial begins.
• Effective and ongoing monitoring of the clinical trial by the sponsor.

Principle 7: Informed Consent

Freely given informed consent needs to be obtained by every participant before they take part in clinical research, in accordance with the national culture and requirements. When a participant can’t give informed consent, the permission of a legally authorised representative should be given in accordance with the relevant laws and regulations.

Principle 7 is applied through:

• The process of informing and ensuring comprehension by participants or their legally authorised representatives about the clinical trial, and obtaining their consent (including written consent).

Phase 8: Continuing Review/Ongoing Benefit-Risk Assessment

The clinical trial should go ahead only if the benefit-risk assessment remains favourable.

Principle 8 is applied through:

• The development and implementation of processes for evaluating risks and benefits as additional information becomes available as the trial continues.
• The monitoring of the clinical trial by the investigators and sponsor.
• The reporting of serious adverse effects.
• The review by the IEC/IRB of any unexpected risks.
• Reviewing the protocol, investigator's brochure, and the informed consent document as needed.
• Suspending the clinical trial if necessary to protect the rights and safety of the participants.

Principle 9: Investigator Qualifications

Qualified and licensed medical professionals should be responsible for the medical care of participants and any medical decisions made for them.

Principle 9 is applied through:

• The responsibilities of the clinical trial investigator to the participant and through the sponsor’s selection of qualified investigators.

Principle 10: Staff Qualifications

Every individual involved in the clinical trial should be qualified by education, training and experience to perform their respective jobs and should also be licensed to do so.

Principle 10 is applied through:

• The clinical investigator’s selection of qualified and experienced staff to assist with the conduct of the study.

Principle 11: Records

All information collected throughout the clinical trial should be recorded, handled and stored so that accurate reporting, interpretation and verification can be carried out.

Principle 11 is applied through:

• The understanding and application of the basic principles of data quality and integrity.
• Adherence to the study protocol and written procedures for collecting, recording, reporting, maintaining and analysing data.
• The preparation of all required documents during the clinical trial.

Principle 12: Confidentiality/Privacy

The confidentiality of all records that could identify the participants should be protected. Respecting the privacy and confidentiality laws in accordance with the applicable regulatory requirements.

Principle 12 is applied through:

• Appropriate procedures put in place to protect the privacy of the participant.
• By document and data control which protects the personal information of every participant.
• The informed consent process which requires certain explanations be provided to the subject about the confidentiality of the participant’s records and about access to those records by monitors, auditors, the IEC/IRB and the regulatory authorities.

Principle 13: Good Manufacturing Practice

Investigational medications or medical devices should be manufactured, handled and stored in accordance with applicable Good Manufacturing Practice (GMP) and should be used with adherence to the approved protocols.

Principle 13 is applied through:

• Appropriately characterizing the investigational drug/medical device and placebo (if applicable).
• Adhering to applicable Good Manufacturing Practice (GMP) standards during the manufacturing, handling and storage of the investigational product.
• Using the product according to the approved study protocol.

 

Roles of Regulatory Authorities and Staff in Accordance with Good Clinical Practice (GCP).

Human Research Ethical Committees

• Responsible under GCP for reviewing the trial design, protocol, investigator’s brochure, informed consent forms, confidential information, participant recruitment processes, and any compensation initiatives.

Investigators

• Must provide medical care to participants who experience adverse effects during the clinical trial.
• Must ensure that all related trial documents are subject to HREC review.
• Must be able to recruit participants in an effective manner.
• Ensure that participants are fully informed of any potential risks, and have given their written consent to take part in the clinical trial.

Sponsors

• Ensure Quality Assurance and Quality Control systems are implemented to ensure trials are conducted, data is gathered and reported in compliance with GCP, the trial protocol and TGA requirements.
• The selection of experienced investigators and appropriate clinical trial sites according to GCP standards.
• Data handling and trial management.
• Ensuring medical care is on hand for participants' care.
• Complying with monitoring and inspection requirements.
• Completion of Clinical Study Report.