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>> Alissa Mun: Hello.
My name is Alissa Mun,

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and I'm in the
Clinical Center,

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Office of Research
Support and Compliance,

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Clinical Research Quality
Management section.

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And today I'm going to introduce
good clinical practices

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that are known as
GCP or ICHE6(r2).

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The goals of today's session

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are understanding core
elements of GCP --

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I'll provide you a
historical background,

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and then the core
principles of ICHE6(r2).

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You'll be able to recognize
who is involved

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in good clinical practices,

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and finally, how
you implement GCP

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in your clinical
research study.

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There are three
critical principles

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that are universally
recognized

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when we think about good
clinical practices,

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and that is safety,
ethics, and quality.

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When we think about safety,

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it's to protect
the rights, safety,

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and welfare of human subjects
participating in research.

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And in ethics, it's to
provide ethical standards

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and guidelines for the
conduct of the research.

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And then finally, the quality of
data that is being collected,

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and this also helps in promoting
reproducibility of trial data.

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Now, we did not come up
with GCP on our own,

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and there were significant
historical events

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which were the foundation of
what is known today as GCP.

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In the 1940s, there was
the Nuremberg Code,

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which was a direct result
of the atrocities

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inflicted in the
concentration camps

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of unethical human
experimentations.

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The Nuremberg Code

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focuses on human rights
of research subjects,

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and those three elements
are voluntary participation,

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informed consent,
and minimization of risk.

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In the 1964, there was
the Declaration of Helsinki,

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and this with the main principle
to set ethical principles

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developed from the medical
community from the WMA

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that are known as the
World Medical Association.

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It is widely known as
the cornerstone document

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of human research and ethics.

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They focus on the
respective persons,

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the protection of subjects'
health and rights,

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and when we think about this,

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we also want to ensure
pre-clinical data.

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And this was a result of
the thalidomide trials

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where pregnant women were
provided thalidomide

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and resulted in severe
birth defects or deaths.

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There's also this
special protection

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now of the vulnerable
populations,

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the adults with the
incapacity to consent,

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or we think -- we think
about the minors.

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And this required a legally
authorized representative

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to consent for
these individuals.

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In 1979, there was
the Belmont Report,

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and there are three main
elements in the Belmont Report

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that talk about respective
persons with the informed

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consent and protection
of vulnerable populations,

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beneficence, which
means do no harm,

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better known in the
medical community,

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and then justice,

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which is the fairness in
selection of subjects.

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The Belmont Report was a result
of the Tuskegee trials,

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and I highly recommend that --

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considering reading
the Nuremberg trials,

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the thalidomide trial,

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and Tuskegee
trials to learn more on

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how clinical research
has evolved over time.

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From these documents,
a lot of countries

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then began to create
multiple different guidelines,

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and it became problematic
in the industry.

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And thus, the International
Conference of Harmonization

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was created to look
at standardization

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of good clinical practices.

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So today we have the ICHE6(r2),

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which is the International
Conference on Harmonization

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of Good Clinical Practices.
What this does -- what it was --

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it brought together
regulatory authorities

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and the pharmaceutical
industries to discuss scientific

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and technical aspects
of drug registration

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and how to formalize
the conduct of research.

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ICH has gradually
evolved over time,

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and by responding to the
increasing global development

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of drugs within the world,

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as well as the technological
advancements that we have today.

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ICHE6(r2) is focused
on the ethical

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and scientific quality
standards for designing,

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conducting, recording,

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and reporting of trials
that involve human subjects.

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So, who has
adopted ICHE6(r2)?

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Hundreds of countries
have adopted this,

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and it is widely
accepted and expected

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in all research
involving human subjects.

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But there are 13 core
principles of ICHE6(r2),

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and I'll go through
each one of them now.

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There's the ethical
conduct of research,

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ensuring that it
is in accordance

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with the Declaration
of Helsinki,

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as mentioned before,

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that the benefit justifies
the risk of the patients,

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and that the rights, safety,
and well-being of subjects

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prevails over all the
interest of science.

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And then when we think about
the protocol in and of itself,

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we want to ensure
that non-clinical

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and clinical information
support the trial

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that you will plan
on conducting

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and that it is in compliance
with scientifically sound data.

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And that should be, again,

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detailed in your
research protocol.

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There are major responsibilities
when it comes to GCP,

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and those are, of course,
within your IRB

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or your ethics committee,

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and there must be approval
from these committees

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prior to the initiation
of your research.

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You want to ensure
that the individuals

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that are providing
medical care or decisions

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are done by a qualified
physician or dentist

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and that any individual that is
involved in clinical research

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and are delegated to
perform specific tasks

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are qualified either
by education, training,

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and/or experience.

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And of course, you
have informed consent,

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that informed consent is
provided to all subjects

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and that they are
provided freely

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to make their own decision

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and there's no
coercion involved.

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You have your, of
course, your data,

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and they want to ensure

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that the data is accurately
recording, reporting,

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and handling verification
and storage of that data,

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and to ensure that there
are special protections

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involved for the confidentiality
of those records.

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In your research study,

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you will have your
investigational products,

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and you want to ensure that
they conform to the current good

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manufacturing practices that
are used in your protocol.

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And finally, quality control
and quality insurance.

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You want to ensure
that these are in place

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for the systems that
you have to ensure

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the quality of all
aspects of your trial.

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That includes electronic systems
as well as standards of SOPs

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or manuals of operations.

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So where does GCP apply?

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This really applies anywhere
that clinical trial data

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is being conducted,
collected, or assessed.

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That is your research
site, any laboratory,

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your pharmacy where
they are maintaining

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your investigational product,

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imaging centers, CROs,
the sponsors,

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and your other
oversight committees.

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So now that we know
where it applies,

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but who then is responsible
for good clinical practice?

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That is, of course,
the sponsors,

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and on a site level,

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the ultimate
responsibility is of --

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from the clinical investigators
or principal investigators.

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They are the ones that
are solely responsible

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for the conduct of research.

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You also have your
research staff,

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which could be research
nurses or data managers,

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your CRAs, or protocol monitors,
any medical monitor.

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The research subjects themselves
are also responsible for GCP,

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and then any
regulatory authority.

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So in summary,
protection of the rights

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and safety and welfare
of participants

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are extremely important,
and finally,

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to ensure the protection
of their confidentiality.

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This, again, follows
the three main things

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that I spoke of earlier,

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which is the safety,
ethics, and quality.

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You want to ensure that there
is informed consent process

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for all participants and that
the data is secured in a --

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in a secure location.

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What that means is if
there are paper records,

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they should be in a double
locked location,

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and if it is electronic,
that they are stored,

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password protected
with limited access.

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You want to ensure you follow
your approved protocol

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where you treat it
like a contract.

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This is your agreement not
only to yourself as the --

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as the principal investigator,

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but also to the IRB as well
as your research participants.

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You also want to
ensure research staff

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are appropriately
trained and qualified.

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How you do this is you maintain
a delegation of authority log

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which details each
individual's responsibilities

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and what they have
been delegated

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by the clinical investigator
or the principal investigator.

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You can also develop
manual of operations

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or standard of operations in
order to convey consistency.

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There's also the quality of data
that you want to ensure accurate

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source documentation
of your research data.

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This also means --
you will hear this

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consistently when people
talk about GCP --

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that if it's not documented,
it didn't happen.

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And lastly, the
investigational product

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should be manufactured
in accordance to GMP.

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So now that we've gone
through the presentation,

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just a few questions to get
a sense of your understanding.

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So, what are the
three core elements

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of good clinical practice?

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That is the safety,
ethics, and quality.

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What is considered
the cornerstone document

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of ethical human research?

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That's the Declaration
of Helsinki.

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And lastly, who is
ultimately responsible

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for good clinical
practice at a site?

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And that would be
your clinical investigator

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and principal investigator.

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I hope you were able to learn
some of the core elements

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of good clinical
practice, ICHE6(r2),

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and thank you so much
for listening.