Good Clinical Practice

(GCP)
UKTMN
6th June 2006
 What is GCP?
Good Clinical Practice (GCP) is defined as a
‘standard for the design, conduct, performance,
monitoring, auditing, recording, analyses and
reporting of clinical trials that provides
assurance that the data and reported results
are credible and accurate, and that the rights,
integrity and confidentiality of trial subjects are
protected’
(ICH GCP)
 GCP principles summary (1)
• Rights, safety & well being of subjects prevail
over interests of science and society
• Individuals involved in trial should be qualified
by education, training and experience to
perform his/her tasks
• Trials shall be scientifically sound and guided
by ethical principles in all their aspects
• Necessary procedures to secure the quality of
every aspect of the trial shall be complied with
 GCP principles summary (2)
• Available non-clinical and clinical information on an IMP
shall be adequate to support the trial
• Conducted according to Helsinki Declaration (1996)
• Protocol shall provide inclusion and exclusion criteria,
monitoring and publication policy
• Investigator/sponsor shall consider all relevant guidance
• Information recorded, handled and stored to allow accurate
reporting, interpretation and verification and confidentiality
of subjects’ records
 GCP compliance
• ICH GCP section 5.18.3 allows individual
researchers to assess the needs of their trial
and apply GCP appropriately
‘central monitoring in conjunction with
procedures such as investigators’ training
and meetings and extensive written guidance
can assure appropriate conduct of the trial in
accordance with GCP.’
• On-site monitoring not compulsory
Who must comply with GCP?
• All individuals involved in any aspect of
the trial must be suitably ‘qualified’ to be
able to comply with GCP.
• Sponsors/CIs are responsible for
ensuring that all staff are able to comply
with GCP.
 What counts as qualified?
According to GCP each individual involved in
conducting a trial ‘shall be qualified by
education, training, and experience to perform
his or her respective task(s)’ (GCP – principle 8)
• Education
• Training
• Experience
There is no GCP ‘qualification’
 Education
Individuals must be educated to be able
to competently perform their specific trial
task.
– Clinicians must be clinically qualified
– Statisticians must be qualified
– Managers must be appropriately educated
 Training
There are a variety of courses and seminars
currently available
– Employer induction courses
– Industry courses
– E-learning (Institute of Clinical Research)
– Private courses (usually run by freelance consultant)
– Host institution courses
– Trial specific workshops
– Investigators meetings
 Experience
On-the-job learning
– Discovering what is required
– Doing the job (sometimes wrongly)
– Cascading information and knowledge
through teams/units
– Talking to other trialists
 Rationale and documentation
As there is no formal qualification it is
essential to keep up to date records of
training.
• Describe the rationale for the methods of GCP ‘training’
used in the trial
• Document courses/seminars/meetings attended by staff
on a training file
• Keep it up to date
 Approvals and permissions
• Ethics committee approval
• Clinical Trials Authorisation (IMPs)
• R & D permission
• Sponsor approval
 Trial Master File
• Essential documents are defined as documents which individually and
collectively permit evaluation of the conduct of a trial and the quality of the
data produced and should be retained in the Trial Master File

• Documents to be contained in the Master File will vary according to the trial

• Trial Master File should be held at the principal site by the Chief
Investigator or at the Co-ordinating Centre

• Investigator’s Site Files are held by the Principle Investigators at sites and
contains copies of the essential documents, local approvals, signed
consent forms and completed data forms.
 Standard Operating Procedures
There should be a written description of all trial management
systems and conventions. This documentation forms the
operating procedures, often referred to as Standard Operating
Procedures (SOPs).
SOPS are usually generic to the Trials Unit or
Institution.

A trial specific operating procedure must be developed

for each trial. These may be called MOPs (Modified Operating
Procedures) or TSOPs (Trial Specific Operating Procedures).
 Trial monitoring
ICH-GCP Extent and Nature of Monitoring
The sponsor should ensure that the trials are adequately monitored. The
sponsor should determine the appropriate extent and nature of monitoring.
The determination of the extent and nature of monitoring should be based
on considerations such as the objective, purpose, design, complexity,
blinding, size,and endpoints of the trial. In general there is a need for on-
site monitoring, before, during, and after the trial; however, in exceptional
circumstances the sponsor may determine that central monitoring in
conjunction with procedures such as investigators’ training and meetings,
and extensive written guidance can assure appropriate conduct of the trial
in accordance with GCP. Statistically controlled sampling may be an
acceptable method for selecting the data to be verified.
5.18.3
 Informed consent
Informed consent – personal autonomy
‘…a competent individual should have the right to determine
those discretionary risks he/she is willing to accept for
whatever benefits he/she perceives may result .’

Weil WB. Informing and Consenting

In Silverman W. Where’s the evidence? OUP 1997

 Informed consent
• Following the second world war and the Nuremberg trials, the Nuremberg Code
and Declaration of Helsinki was agreed worldwide as a charter to protect
people/patients against human experimentation

• Up until 1995 USA, Japan and Europe worked to different standards in the conduct
of clinical trials

• 1995 ICH-GCP was implemented – a global standard

• 2001 EU Directive set out regulations for clinical trials of medicines conducted
within the EU

• 2004 (May) the UK implemented the Directive and the UK Regulations became law
 Consent
• Ethics committee must approve all information given to the
trial participant
• Statements to comply with Data Protection Act must also
be included in the PIL
• Consent forms and patient information leaflets must take
into account recent legislation
• SOPs required describing who is authorised to conduct
consent procedure
• Centre personnel who participate in the consent procedure
should be listed on the delegation log, provide CVs and be
trained!!
 Consent

Decision time: confusing

• ICH states ‘ample time to decide’

• The Directive does not state any time-frame
• ‘6-day rule’ in Ireland (being revised in 2006)
• UK has no time -frame
 Consent procedures
• Given freely
• Face to face
• Telephone
• Watch
• Listen
• Learn
• What works well?
• Share
 Safety reporting
• Adverse events (annual)
• Serious Adverse Events (SAEs)
(within 7 days)
• Serious Adverse Reactions (SARs)
(within 7 days)
• Suspected Unexpected Serious Adverse Reactions
(SUSARs)
(expedited)
 Expedited reporting

Fatal or life threatening SUSARS:

not later than 7 days after the person responsible for
pharmacovigilance received information that the case
fulfilled the criteria for a fatal or life threatening
SUSAR, and any follow up information within a
further 8 days.
All other SUSARs:
not later than 15 days after the sponsor for
pharmacovigilance had information that the case
fulfilled the criteria for a SUSAR.
 Archiving

• Essential documents NOT used in a regulatory

submission must be retained for at least FIVE years
after the end of the trial
• Destruction of essential documents and a record of
the destruction must also be retained for a further
FIVE years
• Local R&D offices may also impose a retention period
Good Clinical Practice in Practice
• Be pragmatic in your approach to GCP
• Use your Rick Assessment to justify your
approach
• Document the rationale behind the decisions
• Be brave