Documente Academic
Documente Profesional
Documente Cultură
in Clinical Research
Food And Drug Administration
Presentation Outline
accepted
BELMONT REPORT
Question
GENERALIZABLE KNOWLEDGE
Hypothesis
Established
Intervention
Objectives
RESEARCH
PRACTICE
Design
Similar
Conditions
Trial
Conclusion
UNMET MEDICAL NEEDS
Clinical Research
Clinical Trials
Clinical Trials[2]
Clinical Trials[3]
Clinical Trial
Clinical Research
[1]
[2]
GCP significance
..randomized controlled clinical trials form the
foundation for evidence-based medicine, but
such research can be relied upon only if it is
conducted according to principles and standards
collectively referred to as Good Clinical
Practice (GCP)
International Conference
on Harmonization GCP
Clinical trial
...any investigation in human subjects intended to
discover or verify the clinical, pharmacological, and/or
other pharmacodynamic effects of an investigational pr
oduct(s), and/or to identify any adverse reactions to an
investigational product(s), and/or to study absorption,
distribution, metabolism, and excretion of an investigat
ional product(s) with the object of ascertaining its safet
y and/or efficacy. The terms clinical trial and clinical
study are deemed synonymous.
ICH GCP [1.12]
Clinical Trial
investigation/research in humans
using pharmaceutical products
investigational
effects
absorption/ distribution / metabolism / excretion
ICH GCP
standard
encompassing both
[1]
scientific, and
[2] ethical aspects
Why GCP
. compliance with this guideline assures the
public that the rights, safety, and well-being of
trial subjects are protected, and that trial data ar
e credible .
Importance is given to
Applicability
When to apply the ICH GCP?
.should follow when generating clinical data
that are intended to be submitted to
regulatory authorities in the three regions.
support
other applicabilities
.. the principles established in this
considerations
..some principles of GCP may not apply to all
Applications of GCP
GCP Implementation:
Shared Responsibilities
Standard
arrangement
Personnel
Documents
Advantages of GCP
importance
clear
standardized
glossary of terms
standardized
standardized
IRB/IEC membership
emphasize
Limitations of GCP
sponsor QA
Ethics in Clinical
Research and
Independent Ethics
Committee
Suchart Chongprasert,
Ph.D.
Food and Drug
Administration
ICH GCP for
Investigators, 16 December 2013,
Presentation Outline
Morality vs. Ethics
Basic Ethical Principles in Clinical
Research
RBJ
Principles
Practical Applications
Independent Ethics Committee (IEC) /
Institutional Review board (IRB)
(independence)
Justice
distributive
justice
Belmont Report
autonomy
subjects
Beneficence
moral obligation to maximize the benefits
and to minimize harm
requiring that
risks
Beneficence
Justice
distributive justice
who
Justice [2]
Justice [3]
CIOMS Guideline 12
Practical Applications
decision making
ratio
minimum elements
understanding;
understood
consent
voluntariness;
freely
Remember!
Ethics Committee
IRB/IEC
Institutional
Independent
Europe
deem
in
synonymous
IRB/IEC
independent
exist
members
responsible
84
IRB/IEC
85
IRB/IEC
86
protection of subjects
Declaration of Helsinki !!
87
Policy
88
IEC Composition
3.2.1 consist of a reasonable number of
members, who collectively have the
qualifications and experiences to review
and evaluate the science[1], medical[2]
aspects, and ethics[3] of the proposed trial
89
90
investigator needs to
protocol and
amendments
Investigators
Brochure/drug
information
EC
submission
any
advertisements
Diary cards
payment
schedule
Roles of Investigator
progress;
safety, SAEs;
progress report, etc.
93
must
not be involved in the approval process
not
communicate
94
IRB/EC Decision
unconditional
approval
documented
in writing
be
approval
Summary
96
Summary [2]
Presentation Outline
What does it means?
Basic Elements of Informed Consent
Certain Important Aspect of Informed
Consent
Exercise
ICH 1.28
Informed consent
..an ongoing
a form
2
aprocess,
subjectnot
voluntarily
for just signing
A process by which
confirms his or her willingness to
participate in a particular trial, after
having been informed3 of all aspects4 of
the trial that are relevant to the subjects
decision5 to participate. Informed consent
is documented by means of a written6
signed7 and dated8 informed consent
form.
Informed consent
no coerce
or use
A process1 by which a subject
voluntarily
undue influence
confirms his or her willingness to
participate in a particular trial, after
having been informed3 of all aspects4 of
the trial that are relevant to the subjects
decision5 to participate. Informed consent
is documented by means of a written6
signed7 and dated8 informed consent
form.
Informed consent
A process1 by which a subject voluntarily2
confirms his or her willingness to
participate in a particular trial, after having
been informed3 of all aspects4 of the trial
that are relevant to the subjects
decision5 to participate. Informed consent
is documented by means of a written6
thoroughly about
7
8
signed and dated informed consent
the trial e.g.,
form.
purpose, benefits,
payment etc.
Informed consent
A process1 by which a subject voluntarily2
subjects autonomy
confirms his or her to
willingness
to
make their own
participate in a particular
trial, after having
judgment
been informed3 of all aspects4 of the trial
that are relevant to the subjects
decision5 to participate. Informed consent
is documented by means of a written6
signed7 and dated8 informed consent
form.
Informed consent
A process1 by which a subject voluntarily2
confirms his or her.acceptable
willingnessway
to
participate in a particular
after having
under thetrial,
ICH GCP
context 4 of the trial
been informed3 of all aspects
that are relevant to the subjects decision 5
to participate. Informed consent is
documented by means of a written6
signed7 and dated8 informed consent
form.
Informed consent
Desirable informed consent
o adequate information disclosed
o language suitable to the recipient
o
o
o
documented evidence
beyond the scope of ICH GCP
Elements of IC [2]
8. anticipated benefits, if not any, inform as well;
9. treatment alternative if not willing to
participate and related risks/benefit;
10. compensation/treatment in case of trialrelated injury;
11. prorated payment, if any;
12. expected expenses, if any, for participating;
Elements of IC [3]
13. voluntary statement;
14. statement for direct access by monitor,
auditor, IEC/IRB, authority upon signing the
consent form;
15. confidentiality of the subjects private info.
kept;
16. be informed timely available new
information affecting the willingness to
continue in the trial;
Elements of IC [4]
17. contact person for more information or
in case of injury;
18. circumstances for withdrawal/
termination;
19. expected duration;
20. approximate number of trial subjects
(local vs. global)
Important Considerations
status;
sex;
culture,
voluntariness; and
practicality
amount
short form??
depending
on investigators explanation
Importantly!
IC Exercise
Practical Considerations
Q: Who should obtain informed consent ?
A: In general, the investigator or authorized
person obtains the informed consent.
According to the Helsinki Declaration, the
physician who treats the potential subject
should not obtain the consent by
him/herself, instead other physician who
understands the protocol well does. Avoid
doctor/patient dependent relationship.
Practical Considerations
Q: Obtaining informed consent in children /
minor ?
A: For children with legal incompetence
(i.e., age <20 yrs), but able to give assent
to the research protocol, an assent form
should be obtained besides parents
informed consent
[assent: affirmative agreement to participate
in the trial]
Practical Considerations
Q: When to conduct the trial in relation to
the time to obtain the informed consent ?
A: The study cannot start prior to
receiving a written informed consent from
the subjects. Also, an unconditional
written ethics committees approval letter
must be obtained before beginning the
trial.
Practical Considerations
Q: Informed consent in a clinical
pharmacology trials (PK, phase I study)?
(i.e., non therapeutic trial)
A: Should be conducted in the subjects who
can give informed consent by themselves
by personally signing and dating on the
form.
Practical Considerations
Q: When should the informed consent be
amended ?
A: When new information that may affect
the safety and well being of the subject
becomes available, and it may affect the
subjects decision to continue
participating in the trial.
Practical Considerations
Q: How long should it take to obtain the
informed consent?
A: Depending on the situation. Remember that
informed consent is an ongoing process, not
finished upon the signature of the subject.
Specifically, how long it takes until the subject
signs and date on the form is what the
investigator needs to know. Exact time cannot
be established, but the investigator needs to
achieve efficient project management and
obligation under the GCP on obtaining informed
consent.
Summary
o