Good Clinical Practice and

Monitoring Governance

Clinical Operations Unit

Housekeeping

Questions Audio Video Survey

Your facilitator
o Clinical Operations Unit at the Swiss TPH
o Over 15 years of Global clinical research expertise
o Pediatric experience
o FDA & Sponsor inspection/audit experience
o Facilitates clinical research capacity building for the WHO
Session objectives

 To understand what clinical research is

 Introduction to different types of clinical trials

 To understand the evolution of research ethics and clinical research

regulations

 To understand the 13 key principles of GCP

 To understand the concept of monitoring

 To understand your responsibilities

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What is Clinical Research?

“Research in which people, or data or samples of tissue from people, are

studied to understand health and disease.

Clinical research helps to find new and better ways to detect, diagnose,
treat, and prevent diseases.” 1

1. Cancer. GOV Available at : https://www.cancer.gov/publications/dictionaries/cancer-terms/def/clinical-research

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Why performing clinical research?
The goal:
To prevent, to treat, to diagnose or to relieve (symptoms of) a disease

To test a new treatment

or

improve (line extension) of an existing treatment

What is being tested?

Medical devices (protheses, stents, pacemakers)

Medicinal product :

a pharmaceutical product (medicine/drug)

an immunological product (vaccine)

a metabolic product (lipid/protein infusion)

a biological compound (gene or tissue therapy)

a diagnostic product (medical swab)

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Different types of clinical research:
Explanatory trials
• Can the intervention work under optimal
and controlled conditions? If and how
• Different phases
Ideal circumstances
Controlled setting
Placebo/best treatment
Fixed protocol
Regulatory & ethical approval
Pragmatic trials
• Is the intervention working in real-life
routine practice conditions?
Real world circumstances
Usual clinical practice
Standard of care
Minimally restrictive
Protocol flexible
Ethical approval only
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Research ethics and regulations
Research ethics and regulations

Good laws have their origin

in bad morals
Ambrosius Theodosius Macrobius (395-423)

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Research ethics and regulations
What is ethical research?

Doing a scientific study with people implies to:

1. Being “ethical”: protect participating subjects

2. Obtaining data which are reliable = true and complete

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Guidelines for Clinical Trials
History context: the Nuremberg trials
Nazi War Crimes
(1939-1945)
Which European Country had
an ethical code of conduct in
research in 1939?
Nuremberg Code for Clinical Trials (1947)
1. Voluntary consent
2. Experiment necessary
3. Anticipated results justify the experiment
4. No unnecessary physical & mental suffering
5. No anticipated chance of death/disability
6. Minimal risks to subjects
7. Appropriate preparation & facilities
8. Conduct only by qualified persons
9. Subject is free to stop participation
10. Stop in case of safety concerns
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Guidelines for Clinical Trials
Harvard Radiation Tests (1946-1956) AZT trials Zimbabwe- 1994-1998
•AZT trials in HIV positive African women- > 17000 women
•19 school boys, participating in a
•Trial looked at women-to-child transmission of HIV
science club, were fed radioactive milk
by researchers who wanted to learn about •Researchers said that consent has been given, but was not well
documented
the digestive system
•Participants did not fully understand the methods and study and
•Researchers from Harvard University and MIT fed radioactive forms of placebo effect.
iron and calcium to the boys, sometimes in their breakfast milk to study • An est. 1000 babies contracted HIV/AIDS although a proven
the boy’s ability to digest minerals life-saving regimen already existed

Willowbrook Study (1963-1966) Tuskegee Syphilis Study (1932-1972)

•Research at an institution of retarded children
•Children were intentionally infected with Hepatitis virus, parents were not
fully informed what the study involved
•Institution would only take in those
accepting to participate in the study; underprivileged
people had no other institutional option
U.S. Public Health Service conducted a study of the natural
progression of “untreated” syphilis in rural African-American
men in Alabama, under the guise of receiving free health care
from the United States government.
Guidelines for Clinical Trials
Evolution of clinical trials
Sulfanilamide 1937 Trigger events

WW II Nazi experiments 1939-1945

Contergan tragedy 1962
The syphilis study 1932-1972
1930 1940 1950 1960 1970 1980 1990 2000 2010

EU Clinical Trial Directive 2001

ICH-GCP 1996
CIOMS guidelines 1993, 2002
Natl Research Act 1974 Belmont report 1979

Declaration of Helsinki 1964

Food, Drug & Cosmetic Act – Efficacy 1962

Responses
Nuremberg code 1947

Food, Drug & Cosmetic Act – Safety 1938

Pure Food and Drug Act – Safety 1906

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Guidelines for Clinical Trials
Evolution of clinical trials
Trigger events

1930 1940 1950 1960 1970 1980 1990 2000 2010

ICH-GCP 1996

•Protecting life, health, privacy and dignity

Declaration of Helsinki 1964 •Well-being considerations must take
precedence
•Maintain accuracy of results
•Publish positive and negative results

Responses
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Guidelines for Clinical Trials
From Guidelines to Legislation

1947 Nuremberg Declaration

1960s-70s National regulatory systems

1964 Declaration of Helsinki (DOH) (first edition)

1990 International Council for Harmonisation (ICH) begins

Joint initiative of regulators, industry and organisations developing

unified guidelines for research to facilitate mutual acceptance of
clinical data by regulatory authorities

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Good Clinical Practice
Definition
Good Clinical Practice (GCP) is defined as an international, ethical and
scientific quality 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’

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Good Clinical Practice
Principle elements

GCP

Protection of Study Credibility and reliability

Subjects of study data

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GCP Principles - 1
Clinical trials must be conducted in accordance with:

The ethical principles that have their origins in the Declaration of Helsinki
and are consistent with Good Clinical Practice and local regulations.

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GCP Principles - 2

RISKS

BENEFITS

Any test can only be initiated and started,

whether the expected benefits justify the risks

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GCP Principles - 3
Rights, welfare and security of the participants are most important
and prevail the interests of society and science

Mircosoft.com

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GCP Principles - 4
There must be sufficient prior data (pre-clinical and clinical) to support the
proposed protocol

Mircosoft.com

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GCP Principles - 5
The clinical trial must be scientifically sound and described in a clear and
detailed protocol.

CE
S
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GCP Principles - 6
A clinical trial must be conducted in accordance with an approved protocol or
with the advice of an Institutional Review Board (IRB) or an Independent Ethics
Committee (IEC).

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GCP Principles - 7
Only qualified physicians or dentists can provide care or make medical
decisions for study subjects.

Microsoft.com

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GCP Principles - 8
All study personnel, regardless of their role, must be qualified by
• Training
• Education
• Experience

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GCP Principles - 9
Informed consent must be freely given by each clinical trial participant prior to
the commencement of their participation.

Microsoft.com

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GCP Principles - 10

Case
Repor
t
Form
s

All clinical data must be recorded, manipulated and

stored in a manner that allows for accurate
reporting, interpretation and verification.

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GCP Principles - 11
Confidentiality of data must be maintained and the integrity and privacy of
subjects must be protected.

Microsoft.com

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GCP Principles - 12
The investigational product should be manufactured and handled according to
GMP (Good Manufacturing Practice) rules.

Microsoft.com

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GCP Principles - 13
A quality assurance and control process must be in place to cover every
aspect of a clinical study.

Source: enterprisecioforum.com

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Ask me a question
GCP in pragmatic trials
THE TIMCI study
Good Clinical Practice
Clinical trial of medical device/drug
• Must have a Sponsor
• Requires ethical approval
• Must have a study master file
• Must receive consent from participant
• Must collect accurate data
• Must have a clear audit trail
• Must be aware of safety reporting requirements
• Must follow GCP standards
• Must demonstrate financial transparency
• Must be adequately funded
• Are governed by law and come under the jurisdiction of the
competent authority
• Must receive a clinical trial authorization
• Must register on the relevant clinical trial database
• Are subject to mandatory inspections
• Must follow Good manufacturing practice
Clinical trial with no medical device/drug
• Must have a Sponsor
• Requires ethical approval
• Must have a study master file
• Must receive consent from participant
• Must collect accurate data
• Must have a clear audit trail
• Must be aware of safety reporting requirements
• Must follow GCP standards
• Must demonstrate financial transparency
• Must be adequately funded

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Applying Good Clinical practice in TIMCI
Monitoring- GCP Principle 13

 Keep patient safe

 Ensure participants are consented properly

Monitoring Plan
 Ensure protocol is followed

 Ensure GCP is respected

 Ensure data is credible and reliable

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Applying Good Clinical practice in TIMCI
Monitoring Governance

 Verify key data

 Verify participants are consented properly

 Keep track of serious events

 Can trigger an on-site visit

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What are your responsibilities?
 Applying Good Clinical practice in TIMCI
How?
By respecting the 13 Principles of GCP through:

Principle 1 Principle 2 & 3 Principle 5 & 6

 Respect the patient  Ensure the patient  Respect and follow the
 Be ethical safety approved protocol

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 Applying Good Clinical practice in TIMCI
How?
By respecting the 13 Principles of GCP through:

Principle 7 & 8 Principle 10

Principle 9  Only doctors can make a  Obtain accurate data

medical decision  Check data is true and
 Obtain  All staff should be correct
informed
trained on the study  Transfer the data in a timely
 All staff working on the manner
consent
study must be delegated  Notify the study coordinator
to do so is you have problems

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In conclusion

• Following GCP is essential

• Collecting good data is essential- what is not written does not exist!

• If you are unsure talk to us or the project lead

• Notify us of serious events

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Thank you for your attention