Good Clinical Practice GCP

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Good Clinical Practice(GCP)

• UKTMN
• 6th June 2006

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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)

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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

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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

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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

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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.

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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

8
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

9
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

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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

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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

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Approvals and permissions

• Ethics committee approval
• Clinical Trials Authorisation (IMPs)
• R D permission
• Sponsor approval

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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
• Investigators 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.

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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).

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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

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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. Wheres the evidence? OUP 1997

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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

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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!!

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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

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Consent procedures

• Given freely
• Face to face
• Telephone
• Watch
• Listen
• Learn
• What works well?
• Share

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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)

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Expedited reporting

• Fatal or life threatening SUSARSnot 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 SUSARsnot later than 15 days after
  the sponsor for pharmacovigilance had information
  that the case fulfilled the criteria for a SUSAR.

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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 RD offices may also impose a retention
  period

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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