Essential GCP Training For Clinical Investigational Sites E6 July 2020 Attendee

Copyright ARCS Australia 4/23/2019
This course, all course content and course materials are copyright of ARCS Australia (unless
otherwise indicated) and are thus protected by International Copyright Laws. The course
materials may not be used or copied without the express permission of ARCS Australia.
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Training for Clinical
Investigational Sites ARCS Australia
E6 (R2) Jul 2020(5) arcsaustralia
ARCS Australia
ARCS Disclaimer
Reasonable care is taken to provide accurate information
at the date of creation of the course. This information is
not intended as a substitute for internal company
standard operating procedures, policies or guidelines.
Participants should refer to locally approved company
procedures or relevant regulatory bodies for further
information.
In participating in this workshop any materials or case

studies discussed whether verbal or written which refer
to a product (currently marketed or not) and /or
company are provided to enhance the learning
experience of the participant and are not intended to
bring discredit to an individual, group or company which
may be represented nor bring discredit to the
pharmaceutical industry.
©ARCS Australia
2
1
Copyright
This course, all course content and

course materials are copyright of ARCS
Australia (unless otherwise indicated)
and are thus protected by International
Copyright Laws. The course materials
© may not be used or copied without

express permission of ARCS Australia.
© ARCS Australia 3
Compliance statement
This ICH E6 GCP Investigator Site Training meets the Minimum Criteria for ICH
GCP Investigator Site Personnel Training identified by TransCelerate BioPharma as
necessary to enable mutual recognition of GCP training among trial sponsors.
© ARCS Australia
2
Who is ARCS?
• Previously the Association of
Regulatory and Clinical Scientists
• A professional development
association for people working in
the development of therapeutic goods
• ~ 1800 members
• Founded in 1984
• Tremendous expertise within the
association
© ARCS
What do we do?
3
What do we do?
ARCS enables the highest quality development and utilisation of
medicines and medical technology by facilitating the
professional development and connectivity of people involved
these areas through:
Educating for today and the future
Exchanging knowledge and information
Networking
Collaborating and engaging
Providing a forum for members’ perspectives
ARCS Membership
Professional development at 25-50% discount
CPD tracking
The opportunity to apply for annual scholarships and awards
Access to a presentation library and recordings in the Members Only Area on the ARCS website
Debate, share and collaborate on ideas with like-minded professionals at our monthly Interest Area e-meetings, and
through website discussion forums
Dedicated face-to-face networking time at all major functions
©ARCS Australia
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ARCS Membership
Representation on selected issues with state and federal governments
The weekly ARCS news service and jobs bulletin
Quarterly journal
Volunteering opportunities:
• Join our conference speaker pool

• Chair conference sessions
• Become an interest area convenor
• Sit on the National Conference advisory panel and contribute to the direction of ARCS education
• Contribute content to the quarterly journal or become an editorial committee member
• Become a board member
©ARCS Australia
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Roadmap
Research Practices
and principles What is the purpose of ICH GCP
Fundamental principles of ICH-GCP
• Overview of research Roles and responsibilities under ICH-GCP
standards
Applying ICH –
GCP to workplace
examples
© ARCS Australia 10
10
5
Reg.
Discovery Non-clinical Clinical Post Marketing
Review
Phase I
Marketing Approval
Phase III
20-100 Volunteers
5-10,000 Volunteers
10,000 1
250 Compounds 5 Compounds Approved
Compounds Compound
Phase II
500 Volunteers
2-3 years 2-3 years 5-8 years 1-2 years Ongoing
© ARCS Australia
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Research practices and principles

Session 1
12
6
Greater risk demands greater

Clinical Research protections for the participant
 Potential impact on future medical

practice demands integrity of methods
Medical Practice and data
© ARCS Australia
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© ARCS Australia
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Who am I?
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Events which have shaped our ethical guidance

1020: 1906: 1964: 2011 2013: 2016:
Avicenna’s US Food Declaration ISO14155 FDA Title 21,
Canon of and Drugs of Helsinki Guidance on CFR part 11
International
Medicine Act Risk-based

Monitoring
1947: 1962: 1996:

1747: Nuremburg Thalidomide ICH-GCP 2006: 2016:
First Code and the E6 (R1)
2003 TeGenero / ICH-GCP
randomised Kefauver
ISO14155 TGN1412 E6 (R2)
trial Amendments
1937: 1966: 1999: 2007: 2016: 2018: Code of for

Therapeutic Statement on National Code of Safety responsible
Goods Human Statement Conduct for monitoring & conduct of
Legislation Experimentation Research research
Australian
reporting
2018:
Serious
1989-90: 2007: Breaches
2003: Therapeutic National
Pan Goods Act & Statement
Pharmaceutical Regs
© ARCS Australia
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Australian Clinical Trial

Handbook – Guidance on
Australian Code for the National Statement on
conducting clinical trials in
Responsible Conduct of Ethical Conduct in Human
Australia using an
Research Research
unapproved therapeutic
goods
WHAT
STANDARDS DO Other National and State
ISO 14155 – Clinical
WE FOLLOW? based legislation (research

dependent)
Good Clinical Practice (ICH-
GCP)
investigations of medical
devices for human subjects
– good clinical practice
Belmont Report Declaration of Helsinki Nuremburg Code
Ethical conduct in in
research with Aboriginal and Keeping research on track: a
Safety monitoring and
Torres Strait Islander guide for Aboriginal and
reporting in clinical trials
Peoples and communities: Torres Strait Islander people
involving therapeutic goods
Guidelines for researchers about health research ethics
and stakeholders
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The Australian Scope Sections

• 8 Principles
Code for • Research... is original
investigation undertaken to • 29 Responsibilities
Responsible gain knowledge,
Research understanding and insight
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The National Scope

• Any researcher conducting
Sections
• Values and principles of
Statement research with human subjects ethical conduct
• Any members of an ethical • Themes in research
review body reviewing that ethics: risk and benefit,
research consent
• Those involved in governance • Ethical considerations in
the design,
development, review
and conduct of research
• Ethical considerations
specific to participants
Following the ‘National • Processes of research
Statement’ is a condition for governance and ethical
conducting human research in review
Australia
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© ARCS Australia
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‘National Statement’ is intended for:

• Any researcher conducting research
with human subjects
• Any members of an ethical review
body reviewing that research
• Those involved in governance and
• Potential research participants
© ARCS Australia
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Following the ‘National

Statement’ is a
condition for
conducting human
research in Australia
© ARCS Australia
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The Sections
• Clinical trials involving
Australian therapeutic goods
Clinical Trial • Australian regulatory
environment
Handbook • CTN/CTX scheme
• Clinical trial phases and
stages
• Advertising ‘unapproved’
therapeutic goods
• Manufacturing
• Importing and exporting
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NATURE OF HUMAN RESEARCH

Human research is conducted with or
about people, or their data or tissue.....
Research Non-research
Non-clinical Clinical
Non-interventional Interventional
• Epidemiological • Drug and non-drug

• Case-controlled studies • CTs – registration
• Cohort or longitudinal studies • CTs – non-registration
• Cross-sectional studies
• Observational
• Systematic review of existing data (e.g.
meta-analysis
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© ARCS Australia
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How do we get access to unregistered products?

Mechanism to access unapproved/unlisted therapeutic
goods - exemptions to the Therapeutic Good Acts, 1989.
Sets up the following exemptions to the Act
Use in clinical
trials Personal Authorised
SAS
importation Prescriber
CTN CTX
Australian clinical trial handbook – Guidance on conducting clinical trials in Australia using
an unapproved therapeutic goods – (2018)
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An overview
CLINICAL TRIAL EXEMPTION (CTX) CLINICAL TRIAL NOTIFICATION (CTN)

• TGA evaluate summary information about • No review by TGA. HREC initial and on-going
the product including relevant, but limited, safety review
scientific data (which may be preclinical and • Any product not entered on the ARTG,
early clinical data) prior to the start of a trial including any new formulation or any new
• The HREC is responsible for considering the route of administration, or new technology,
scientific and ethical issues of the proposed new material or a new treatment modality;
trial protocol. • Use of a product beyond the conditions of its
• The sponsor must notify us of each trial marketing approval, including new indications,
new population group, extension of doses or
conducted using the unapproved therapeutic duration of treatments.
good/s approved in the CTX application
• TGA may request Investigators brochure and
protocol for FTIH trials or because of a degree
of concern
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OTHER
REGULATIONS
Privacy and Health Guardianship and Dangerous Goods
Records Acts Children Acts Handling
Embryos and cloning acts Human tissue act
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Good Clinical Practice (GCP)

Session 2
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Good Clinical A standard for the design, conduct, performance,

monitoring, auditing, recording, analyses and reporting
Practice of clinical trials that provides assurance that the data and
reported results are credible and accurate, and that the
(GCP) rights, integrity, and confidentiality of trial participants
ICH GCP 1.24 are protected.
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Good Clinical Practice

Closure &
Set up Recruitment Maintenance
Completion
Chapter 1 – Glossary Chapter 5 – Sponsor
Review
Chapter
Chapter 2 – General Principles Chapter 6 – Protocol
2
Chapter 3 – IEC (‘National Chapter 7 – Investigator’s

Statement’) Brochure
Chapter 8 – Essential
Chapter 4 – Investigator
Documents
© ARCS Australia
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What is the purpose of ICH –GCP?

Session 3
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ICH - GCP
Sponsor
Ethics Committee Investigator
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Appropriate Oversight
Laws (Federal/State),
GCP 4.1, 4.2, 4.3 & 4.4 regulations, Role of the
HRECs expectations
guidelines and Investigator
standards
Appropriate
Approvals Essential documents
delegation
Protocol, pharmacy
Professional codes
manual, laboratory HREC
of conduct
manual etc
© ARCS Australia
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Participant's rights and safety

GCP 4.3, 4.4, 4.6, 4.7, 4.8 & 4.11
Subject
Consent Subjects kept
appropriately
processes informed
cared for
Dosed correctly
Per protocol
Eligible Drug stored
assessments
correctly
S/AEs
© ARCS Australia
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Can the study be reconstructed?

GCP 4.5, 4.6, 4.7 & 4.9 Patients CRFs vs
Protocol
verified to be source
followed
real documents
Eligibility Appropriate
Lab Samples
Criteria Monitoring
Essential
Deviations
Documents
© ARCS Australia
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Data support the conclusion?

GCP 4.1, 4.2, 4.6 Accurate data
Subject Appropriate
Source Data
Documentation equipment or
procedures
Appropriately
AEs & Con Meds
Corrections Qualified &
recorded
Trained Staff
Study Medication Appropriate QC
© ARCS Australia
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A process by which a subject voluntarily

confirms his or her willingness to
participate in a particular trial, after having
Informed been informed of all aspects of the trial
that are relevant to the subject's decision
Consent to participate. Informed consent is
documented by means of a written, signed
ICH GCP 1.28 and dated informed consent form.
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Individuals whose willingness to volunteer in a

clinical trial may be unduly influenced by the
expectation, whether justified or not, of
benefits associated with participation, or of a
retaliatory response from senior members of a
hierarchy in case of refusal to participate.
Examples are members of a group with a
hierarchical structure, such as medical,
Vulnerable pharmacy, dental, and nursing students,
subordinate hospital and laboratory personnel,
Participant employees of the pharmaceutical industry,
members of the armed forces, and persons
ICH GCP 1.61 kept in detention. Other vulnerable subjects
include patients with incurable diseases,
persons in nursing homes, unemployed or
impoverished persons, patients in emergency
situations, ethnic minority groups, homeless
persons, nomads, refugees, minors, and those
incapable of giving consent.
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ALCOA+ Principles
Contempora-
Attributable (A) Legible (L) Original (O) Accurate (A) Plus (+)
neous (C)
• Clearly • It must be • Data must • Data must be • Data must • Complete
indicates who possible to be recorded persevered in correctly • Consistent
recorded the read or at the time it its unaltered reflect the • Enduring
data or interpret the was state action /
• Available
performed the data after it is generated • If not, why not observation
activity recorded • Close • Certified made
• Signed / dated • Permanent proximity to Copies • Data checked
• Who wrote it • No occurrence where
/ when unexpected necessary
hieroglyphics • Modifications
• Properly explained if
corrected if not self-
necessary evident
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Roles and Responsibiltes

Session 3
39
1. Must have appropriate education, training and experience

2. Is responsible for the medical care of trial participants and all trial
related medical decisions
3. Provides training and oversight of their research team
INVESTIGATOR 4. Is an advocate for protocol compliance, regulatory and GCP
RESPONSIBILITIES compliance
5. Protects and safeguards the rights of trial participants
6. Ensures the safety of trial participants
7. Maintains oversight of the investigational product being tested
8. Has adequate resources (staff, equipment etc.) to conduct the trial
9. Has a sufficient (and suitable) patient pool for recruitment
10. Is responsible for maintaining adequate documentation and
archives
11. Must allow monitoring and auditing
12. Complies with HREC requirements & reporting
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1. Designs an ethical and scientific protocol

2. Selects, trains and log suitable study personnel, including monitors.
3. Selects appropriately qualified investigators with adequate
resources to work on the trial
SPONSOR 4. Provides ongoing safety assessment of the investigational product
RESPONSIBILITIES 5. Supplies and ensures appropriate handling of the investigational

product
6. Manages data collected during the trial
7. Makes available the Investigators Brochure
8. Verifies ethics approval and ensuring regulatory authority
notification
9. Maintains appropriate trial files and archives
10. ‘Adequately monitors’ the clinical trial
11. Implements a QA/QC system for the trial
12. Report the trial results
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Where do CRA’s fit in?

A CRA is a professional who, irrespective of
job title, supervises, monitors, and supports
the administration and progress of a clinical
trial on behalf of a sponsor. The sponsor,
whose intent is the research of
pharmaceuticals, biologics or devices may
employ these individuals directly or
indirectly. The CRA MUST be independent
of the investigative staff conducting the
research at the site or institution and
should not be employed or supervised by
the investigative site or institution.
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What is the role of the CRA?
© ARCS Australia
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1. Reviews all human research (including clinical trials) to ensure the

research has merit and is ethical
2. Are composed to ensure appropriate review of human research
3. Assess human research against the standards outlined in the
‘National Statement’
HREC 4. Assess human research against the standards outlined in other
RESPONSIBILITIES relevant regulations and policies.
5. Review relevant clinical trial documentation
6. Meet regularly
7. Provide a final opinion (favourable or non favourable) on the
research reviewed
8. Specify conditions of approval (including reporting requirements)
9. Can withdraw approval for the continued conduct of the trial
10. Facilitate communication
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During a site visit, the monitor discovers that the

consent process for a trial was being conducted by
Case study 1 the Trial Coordinator.
Protects and The Investigator’s involvement was limited to a

short interview that primarily involved obtaining the
safeguards the signatures from the participant
rights of trial
participants
Copyright ARCS Australia 45
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While reviewing source documents at a trial site, the

monitor discovers that the eligibility of patients is being
Case study 2 assessed using photocopies of the patients medical
records from another hospital (as the other hospital would
Maintain not allow direct access to these documents).
Furthermore, the trial coordinator jotted down notes in
adequate her personal work diary to record patient conversations
before transcribing them into the patient medical records.
documentation These entries into the patient’s medical record were
signed, dated and accurately copied from the personal
and archiving diary entries.
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Over the course of an oncology clinical trial, 5 of the 7

active participants have experienced SAEs.
These SAE reports to the sponsor (both initial and follow
up) where completed and signed by the study coordinator
Case study 3 (who was an oncology RN). There was no evidence that
any of the SAE reports have been reviewed by the
investigator.
Ensures safety of On further investigation, it was found that the causality
assessment on the AE forms in the CRF and the SAE
trial participants reports sometimes differed.
When a meeting was conducted with the investigator to
discuss these findings, the investigator confirmed that
although he was aware of the SAEs and had instructed the
study coordinator on follow up actions, he did not read the
SAE forms or documented any of his instructions to the
coordinator. He indicated he is confident that the study
coordinator is able to complete the SAE form on his behalf.
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• A trial coordinator is screening potential patients for a

trial and discovers that a patient meets all the eligibility
Case study 4 criteria except that a CT scan was performed 1 week
outside the timeframe stated in the protocol. In
Advocate for standard clinical practice the CT scan would not be
repeated.
protocol,
regulatory and
GCP compliance
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A patient participating in a trial is based in regional NSW.

The trial involved a short treatment phase and a long term
survival follow up phase. The follow up visits requires a
Case study 5 trial specific investigation (i.e. not part of standard clinical
practice). After the completion of his treatment he returns
Medical care of to his home town and continues follow-up performed by
his local GP, only occasionally coming to see the
participants and Investigator as part of follow up.
After 12 months, it is discovered that the patient has
all trial related relapsed. The GP notifies the Principal Investigator at the
institution where the patient was treated that he has
medical decisions relapsed via a letter. The Investigator then completes the
CRF using this information
49
Join the
discussion!
Thank you!
To learn more about future events and ARCS Australia
to register, visit www.arcs.com.au
arcsaustralia
ARCS Australia
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Copyright ARCS Australia 4/23/2019

In participating in this workshop any materials or case

This course, all course content and

© may not be used or copied without

The opportunity to apply for annual scholarships and awards

Dedicated face-to-face networking time at all major functions

The weekly ARCS news service and jobs bulletin

• Join our conference speaker pool

• Overview of research Roles and responsibilities under ICH-GCP

2-3 years 2-3 years 5-8 years 1-2 years Ongoing

Research practices and principles

Greater risk demands greater

 Potential impact on future medical

Events which have shaped our ethical guidance

Medicine Act Risk-based

1947: 1962: 1996:

1937: 1966: 1999: 2007: 2016: 2018: Code of for

Australian Clinical Trial

WE FOLLOW? based legislation (research

Belmont Report Declaration of Helsinki Nuremburg Code

The Australian Scope Sections

The National Scope

‘National Statement’ is intended for:

Following the ‘National

NATURE OF HUMAN RESEARCH

• Epidemiological • Drug and non-drug

How do we get access to unregistered products?

Sets up the following exemptions to the Act

CLINICAL TRIAL EXEMPTION (CTX) CLINICAL TRIAL NOTIFICATION (CTN)

Embryos and cloning acts Human tissue act

Good Clinical Practice (GCP)

Good Clinical A standard for the design, conduct, performance,

Good Clinical Practice

Chapter 1 – Glossary Chapter 5 – Sponsor

Chapter 3 – IEC (‘National Chapter 7 – Investigator’s

What is the purpose of ICH –GCP?

Ethics Committee Investigator

Participant's rights and safety

Can the study be reconstructed?

Data support the conclusion?

Study Medication Appropriate QC

A process by which a subject voluntarily

Individuals whose willingness to volunteer in a

Copyright ARCS Australia

Roles and Responsibiltes

1. Must have appropriate education, training and experience

1. Designs an ethical and scientific protocol

RESPONSIBILITIES 5. Supplies and ensures appropriate handling of the investigational

Where do CRA’s fit in?

What is the role of the CRA?

1. Reviews all human research (including clinical trials) to ensure the

During a site visit, the monitor discovers that the

Protects and The Investigator’s involvement was limited to a

Copyright ARCS Australia 45

While reviewing source documents at a trial site, the

Copyright ARCS Australia 46

Over the course of an oncology clinical trial, 5 of the 7

Copyright ARCS Australia 47

• A trial coordinator is screening potential patients for a

Copyright ARCS Australia 48

A patient participating in a trial is based in regional NSW.

Copyright ARCS Australia 49

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