Good Clinical Practice

What is Good Clinical Practice (GCP)?

• Good Clinical Practice (GCP) is an international ethical and scientific
quality standard for designing, conducting, recording and reporting
trials that involve the participation of human subjects. Compliance
with this standard provides public assurance that the rights, safety
and well-being of trial subjects are protected, consistent with the
principles that have their origin in the Declaration of Helsinki, and
that the clinical trial data are credible.
• The guideline was developed with consideration of the current good
clinical practices of the European Union, Japan, and the United States,
as well as those of Australia, Canada, the Nordic countries and the
World Health Organization (WHO).
What is Good Clinical Practice (GCP)?
• Good Clinical Practice is a set of guidelines that must be followed when
conducting clinical trials to ensure that the rights and well-being of the trial
participants are protected and that the data generated in the trial is valid.
Good Clinical Practice is an international ethical and scientific quality
standard for designing, conducting, recording and reporting trials that involve
human participants. The guidelines were developed in order to provide clinical
trials with a unified standard across the European Union, Japan and the
United States and were labelled ICH-GCP at the International Conference on
Harmonisation, 1996.
Why was GCP introduced?
• Concern for the regulation of trials emerged in response to medical
tragedies such as the discovery of the effects of thalidomide in
pregnancy in the 1960’s which highlighted the world-wide need for
central records of trials that are occurring. In addition problems have
arisen with obtaining marketing authorisations for drugs across
different countries where different versions of GCP are being adhered
to. With a common piece of legislation this should be avoided.
What is the purpose of GCP?

There are two main purposes of GCP:-

1) To protect participants involved in trials
2) To ensure the credibility of the data generated in the trial.
Potential participants should also be made aware of the expected
benefits or if they are no intended clinical benefits, this should also be
explained.
Records and reports

The investigator should ensure the accuracy, completeness, legibility

and timeliness of the data reported to the sponsor in the Case Report
Form (CRF). Any changes made to the CRF should be dated, initialed
and explained. The investigator should maintain trial documents as
specified and these documents should be retained for at least 2 years
following the last marketing authorisation where applicable and longer
if agreed by the sponsor.
Progress reports

• The investigator should submit written summaries of the trial status

to the ethics committee and the sponsor where applicable.
Safety reporting (for further details see pharmcovigilance leaflet)

• All serious adverse events (SAE’s) should be reported immediately to

the sponsor except for those SAE’s stated in the protocol or in the
Investigator’s Brochure. The immediate reports should be followed
promptly by detailed, written reports.
Premature termination or suspension of a trial

• If the trial is prematurely terminated or suspended for any reason, the

investigator should inform the trial participants and assure
appropriate alternative therapy is provided (where possible). The
MHRA and ethics committee should also be informed.
Final report
• Upon completion of the trial, the investigator should inform the ethics
committee and the MHRA and provide a final report.
Investigators brochure

• The investigators brochure (IB) is a compilation of the clinical and non

clinical data on the investigational product(s) that are relevant to the
study.
• The purpose of the IB is to provide key information about the product
such as the dose/frequency, methods of administration and the key
features of the protocol. An IB should be compiled for each trial
(where appropriate).
Informed consent

• Investigators should ensure that they obtain approval for the written
consent form to be used in the study from the ethics committee prior
to the trial starting. Consent forms and information sheets should be
revised when important new information becomes available that may
be relevant to participant’s consent. Revised consent forms should
first be approved by the ethics committee before being used.
• Neither the investigator nor the trial staff should coerce or unduly
influence an individual to participate or to continue in a trial.
• The investigator or the person designated by the investigator should
fully inform the participant or the participants’s legal representative of
all the pertinent aspects of the trial including the written information
provided to participants.
• The language used in the oral and written information about the trial
should be non-technical as practical and should be understandable to
the participants and the participant’s legal representative (where
applicable).
• Before consent is obtained, the investigator should provide participants
with ample time and opportunity to inquire about details of the trial
and decide whether or not to participate.
• Prior to participant’s recruitment to the trial, the written informed
consent form should be signed and dated by the participant or by the
participant’s legal representative.
• If a participant is unable to read, or the representative unable to read,
an impartial witness should be present during the entire consent
discussion and oral consent may be given. The witness confirms that
the study information was understood and that informed consent was
given freely.
• Both the informed consent discussion and the written information
sheet should include explanations about what the trial involves, the
purpose of the trial, the trial treatment and whether randomization
occurs as well as details of foreseeable risks or inconveniences.
• The ICH-GCP guidelines outline the core principles of GCP and
describe the responsibilities of individuals and organisations involved
or associated with carrying out a clinical trial.
Principles of ICH Good Clinical Practice.

Ethics.
Clinical trials should be conducted in accordance with the ethical
principles stated in the Declaration of Helsinki, and that are consistent
with GCP and the Medicines and Healthcare products Regulatory
Agency (MHRA) standards.
Trials risk vs trial benefit.
Before a trial commences, the foreseeable risks and inconveniences
should be weighed against the anticipated benefit for the individual
trial participants and society. A trial should be initiated and continued
only if the anticipated benefit/s justify the risks.
Principles of ICH Good Clinical Practice.

Trial participants
The rights, safety, and well-being of the trial participants are the most
important consideration and should prevail over the interests of
science and society.
Information on the medicinal product
The available non-clinical and clinical information on an investigational
medicinal product should be adequate to support the proposed clinical
trial.
Principles of ICH Good Clinical Practice.

Good quality trials

Clinical trials should be scientifically sound, and be described in a clear,
detailed protocol.
Compliance with the study protocol
A trial should be conducted in compliance with the protocol that has
received ethics committee and MHRA approval.
Principles of ICH Good Clinical Practice.

Medical decisions
The medical care given to, and medical decisions made on behalf of
trial participants should always be the responsibility of a qualified
physician or, when appropriate, of a qualified dentist/
Trial staff
Each individual involved in conducting a trial should be qualified by
education, training and experience to perform his or her respective
task(s).
Principles of ICH Good Clinical Practice

Informed consent
Freely given informed consent should be obtained from every participant prior
to recruitment to a clinical trial.
Clinical trial data
All clinical trial information should be recorded, handled and stored in a way
that allows accurate reporting, interpretation and verification.
Confidentiality
The confidentiality of records that could identify trial participants should be
protected, respecting the privacy and confidentiality rules in accordance
MHRA requirements.
Principles of ICH Good Clinical Practice.

Good Manufacturing Practice

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.
Quality assurance
Trial sponsors should have systems and procedures in place that assure
the quality of every aspect of the trial is maintained.
Responsibilities
The ICH-GCP guidelines describe the responsibilities of all parties
involved in clinical trials such as ethics committees, sponsors and
clinical trial investigators.
Investigator responsibilities

The investigator is the person responsible for the conduct of the clinical trial
at the trial site. ICH-GCP outlines the investigators’ responsibilities;
Investigator qualifications
The investigator should be qualified by education, training and experience to
assume responsibility for the proper conduct of the trial. Investigators should
provide an up to date curriculum vitae.
Investigators should be familiar with the medicinal products to be used and
should be aware of, and should comply with GCP.
Investigators should permit monitoring and auditing by the sponsor and
inspection by the MHRA.
Adequate resources
• The investigator should be able to demonstrate a potential for
recruiting the required number of trial participants.
• The investigator should have sufficient time to properly conduct and
complete the trial.
Medical care of trial participants and Compliance with the trial
protocol

• Medical care of trial participants

• A qualified physician should be responsible for trial related medical
decisions and that adequate medical care is provided to trial
participants should adverse events or reactions arise.
• Compliance with the trial protocol
• The investigator should conduct the trial in compliance with the
protocol agreed by the ethics committee and the MHRA. If any major
protocol changes are made they must be agreed by the ethics
committee, sponsor and MHRA. Any protocol changes should be
clearly documented.
Investigational product
• Responsibility for the investigational medicinal product (IMP) at the
trial site rests with the investigator although some of these
responsibilities can be delegated to a pharmacist or another
appropriate person. The IMP should be stored in accordance with
MHRA requirements and should only be used in accordance with the
approved protocol. The investigator should explain the correct use of
the IMP to the trial participant and check at intervals that they are
following the instructions properly.
Randomisation procedures & unblinding
• The investigator should follow the trial’s randomisation procedures. If
the trial is blinded, the investigator should discuss any unblinding
incidents (either accidental or due to a serious adverse event) with
the spo
• Where the investigational product is being used under license the
summary of product characteristics can be used. nsor.
Sponsor responsibilities ICH-GCP
• guidelines also outline the responsibilities of trial sponsors. Trial
sponsors are the organisation/s taking overall responsibility for the
trial. The sponsor is responsible for implementing and maintaining,
quality assurance and quality control systems and the production of
written standard operating procedures to ensure that trials are
conducted and are data generated, recorded and reported in
compliance with the protocol, GCP and MHRA requirements. In
academic led studies these duties are often delegated to the Chief
Investigator who is responsible for the study. For more information
about sponsorship, please contact the R&D Office at the address
below.
References
ICH Harmonised Tripartite Guideline for GCP, Institute of Clinical
Research, 1996
Medicines & Healthcare products Agency (MHRA)
www.mhra.gov.uk
Clinical Trials Toolkit www.ct-toolkit.ac.uk
GCP, King’s College of London, University of London, 2010
Integrated Addendum to ICH E6 (R1), Guideline for GCP, E6 (R2), Nov 9,
2016