Transcript Phase of Drug Substance Development

Good Clinical Practice (GCP)
in Clinical Research
Suchart Chongprasert, Ph.D.
Food And Drug Administration
ICH GCP for Clinical Research investigators, 16 December 2013, DMSC
Presentation Outline

Practice vs. Research
 clinical
research vs. clinical trial
 therapeutic vs. non-therapeutic research

GCP: Introduction and Principles

Basic GCP Applications for Investigators
 Ethical
Principles in Clinical Research
 Informed Consent Process: Introduction
Research vs. Practice

“Practice” refers to interventions that are
designed solely to enhance the well-being of
an individual patient or client, and that have a
reasonable expectation of success.
 standard
interventions scientifically proven and
accepted

The purpose of medical or behavioral practice
is to provide diagnosis, preventive treatment or
therapy to particular individual.
BELMONT REPORT
Research vs. Practice (2)

“Research” designates an activity
designed to test a hypothesis, permits
conclusions to be drawn, and thereby to
develop or contribute to generalizable
knowledge
 expressed
for example in theories, principles,
and statements or relationships) that can be
corroborated by scientific observation and
inference.
BELMONT REPORT
Research vs. Practice (3)

Research is usually described in a formal
protocol that sets forth an objective, and
a set of procedures designed to reach the
objective.
BELMONT REPORT
Research vs. Practice (4)

Research represents a systematic
investigation (formal), including research
development, testing, evaluation, that is
designed to develop or contribute
generalizable knowledge.
 methodology

Practice gains more flexibilities compared
with research
RESEARH vs. PRACTICE
GENERALIZABLE KNOWLEDGE
Question
Hypothesis
Established
Intervention
Objectives
RESEARCH
PRACTICE
Design
Similar
Conditions
Trial
Conclusion
UNMET MEDICAL NEEDS
[rationale and background]
Clinical Research

research that either directly involves a
particular person or group of people or uses
materials derived from humans such as
 behaviors
or samples of the tissues, that can be
linked to a particular living person (identifiable
tissue or bio-specimens)
Declaration of Helsinki 2013

ethical principles for medical research
involving humans subjects, including
research on identifiable human materials
and data
Clinical Research [2]:
categories
[1] Patient-oriented research: involves a
particular person or group of people or
uses of materials from humans
 studies
of mechanisms of human disease;
 studies of therapies or interventions for
diseases;
 clinical trials; and
 studies to develop new technology related to
diseases
Clinical Research [3] ]:
categories
[2] Epidemiological and behavior
studies:.. examining the distribution of
diseases, the factors that affect health, and
how people make health-related decisions
[3] Outcomes and health services
research: seeking to identify the most
effective and most efficient interventions,
treatments, and services
Clinical Trials

one type of clinical research that involves
a researcher or researchers who directly
observes a person or people, and/or who
collect data to answer a scientific or
medical question about the safety or
potential benefit of an intervention such
as medication, device, teaching concept,
training method or behavioral change
Clinical Trials[2]

a prospective biomedical or behavioral
research study of human subjects that is
designed to answer specific questions
about biomedical or behavioral
interventions (drugs, treatments, devices,
or new ways of using known drugs,
treatments, or devices) [US NIH]
Clinical Trials[3]

a controlled study involving human subjects that
is designed to prospectively evaluate the safety
and effectiveness of new drugs or devices or of
behavioral interventions [US DHHS, IRB
Handbook]

a systematic investigation, including research
development, testing, and evaluation that is
designed to develop or contribute to
generalizable knowledge [US CFR Title 46 Part
102]
Clinical trial [4]

any investigation in human subjects intended to
discover or verify the clinical, pharmacological,
and/or other pharmacodynamic effects of an
investigational product(s), and/or to identify
any adverse reactions to an investigational
product(s), and/or to study absorption,
distribution, metabolism, and excretion of an
investigational product(s) with the object of
ascertaining its safety and/or efficacy. The
terms clinical trial and clinical study are
deemed synonymous. [ICH GCP]
Clinical Trial
Clinical Research
Where generalizable knowledge
comes from
Data Quality vs. Data Integrity
Data Quality vs. Integrity


Quality: a measure of the ability of a product,
process, or service to satisfy stated or implied
needs
Data Quality: the essential characteristics of
each piece of data, in particular, quality data
should include:
 accurate;
 legible;
 complete and
contemporaneous (recorded at the time
activity occurs;
 original;
 attributable to the person who generated the data
Data Quality vs. Integrity

Data Integrity: the soundness of the body of
the data as a whole, in particular, the body of
data should be 1credible, 2internally
consistent, and 3verifiable

Both quality and integrity are essential for
data to be relied upon for regulatory decisionmaking
Good Clinical Practice (GCP)
in Clinical Research
Suchart Chongprasert, Ph.D.
Food and Drug Administration
ICH GCP for Investigators, 31 July 2013, Chaingmai
o
[1]
[2]
Special attentions paid on

Human subjects are protected
 Rights;
 Safety;
 Well being

Clinical trial data are credible
 for regulatory decision;
 for scientific use to
improve interventions
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)…
Source: WHO Handbook for GCP: Guidance for Implementation
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
product(s), and/or to identify any adverse reactions to
an investigational product(s), and/or to study
absorption, distribution, metabolism, and excretion of
an investigational product(s) with the object of
ascertaining its safety 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
phase or approved one
 the objective is to discover or verify
 clinical / pharmacological / pharmacodynamic
effects
 absorption/ distribution / metabolism / excretion

so as to ascertain the safety and efficacy of
investigational products
What is ICH GCP
…. international ethical and scientific quality
standard for the designing, conducting,
recording, performing, monitoring, auditing,
reporting a clinical trial that involves human
participation...
ICH GCP: Introduction
ICH GCP

quality system being used in a clinical trial
from the beginning to the end
 quality

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
are credible .
ICH GCP : Introduction
Importance is given to

Human subjects are protected
 Rights
 Safety,
 Well being

Clinical trial data are credible
 for regulatory decision
 for scientific use to
improve interventions
ICH GCP - Objective
…….to provide a unified standard for European
Union, United States, and Japan to facilitate
mutual acceptance clinical data by regulatory
authorities in the three jurisdictions
 no
repetition of quality clinical trials conducted
previously in any of these regions
 ensuring the quality for the protection of humans
as well as the quality and integrity of clinical data
ICH GCP - Development
...developed with the consideration of the current
GCP of the EU, Japan, US as well as Australia,
Canada, the Nordic Countries, and the WHO.
 combined
together principles and guidelines
implemented in advanced countries or
organization
 promoting global acceptance of clinical data
generated
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
a regulatory decision for
marketing authorization of
pharmaceutical products
ICH GCP: Introduction
other applicabilities
.. the principles established in this guideline
can also be used for other clinical
investigations that may affect safety and
well-being of trial subjects.
 can
be applied to broader than a clinical trial
considerations
..some principles of GCP may not apply to all
types of research on human subjects;
consideration of these principles is strongly
encouraged wherever applicable as a means of
ensuring the ethical, methodologically sound
and accurate conduct of human subject’s
research..
Source: WHO Handbook for GCP: Guidance for Implementation
Applications of GCP

studies of a physiological, biochemical, or
pathological process, or of a specific intervention

controlled studies of diagnostic, preventive or
therapeutic measures

studies designed to determine the consequence
for individuals and communities of specific
preventive or therapeutic measures
Source: WHO Handbook for GCP: Guidance for Implementation
Applications of GCP [2]

studies concerning human health-related
behavior in a variety of circumstances and
environments

studies that employ either observation or
physical, chemical, or psychological
intervention
 may
generate records or make use of existing
records containing biomedical or other information
about individuals who may or may not be identifiable
from the records or information
GCP Implementation:
Shared Responsibilities
ICH GCP: STRUCTURE & CONTENT
Glossary
Principles of ICH GCP
IRB/IEC
Investigator
Sponsor
Clinical Trial Protocol
Investigator’s Brochure (IB)
Essential Documents for the
conduct of Clinical Trials
Standard
arrangement
Personnel
Documents
Fundamental Concepts of ICH G CP
ICH GCP Principles
[1] ethical principles established in the
Declaration of Helsinki (updated 2013)
[2] favorable risk and benefits ratio at the
beginning and continuing of a clinical trial
[3] rights, safety, and well-being of trial
subjects most important consideration, and
precede the interests of science and society
[4] nonclinical and clinical data (if any) available
to support the proposed trial
ICH GCP Principles [2]
[5] trial scientifically sound and written in a clear
protocol
[6] protocol receives prior approval from IEC/IRB
[7] medial care and medical decision made be
responsible by qualified physicians or dentists
[8] investigator and staff qualified by education,
training, and experience
[9] freely informed consent obtained from
individual subject prior to his/her participation
ICH GCP Principles [3]
[10] clinical trial information be managed in a way
that allows accurate reporting, interpretation,
and verification
[11] confidentiality of trial subjects
[12] investigational product manufactured,
handles, and stored according to GMP
[13] QA system and procedures implemented
throughout the trial
Advantages of GCP
 importance
is given to (1) the protection of human
subjects and (2) the quality and integrity of clinical
data
 clear
assignment of key individuals involving in a
clinical trial i.e., investigator, EC, sponsor
 standardized
glossary of terms
 standardized
elements of informed consent
 standardized
IRB/IEC membership
 emphasize
on principles, de-emphasize on “how to”
Limitations of GCP

very high standards to be applied in for the Thai
context (in general);

subject to easy deviation;

require intensive resources to implement;

sponsor QA


may not be practical in a resource-poor setting;

require adequate resources and investment in a
regulatory authority
Ethics in Clinical Research and
Independent Ethics Committee
Suchart Chongprasert, Ph.D.
Food and Drug Administration
ICH GCP for Investigators, 16 December 2013, DMSC
Presentation Outline
Morality vs. Ethics
 Basic Ethical Principles in Clinical
Research

 RBJ
Principles
Practical Applications
 Independent Ethics Committee (IEC) /
Institutional Review board (IRB)

Clinical trials should be conducted in
accordance with the ethical principles that
have their origin in the Declaration of
Helsinki, and that are consistent with GCP
and the applicable regulatory requirements
ICH GCP Principle 1
Research involving humans should be
scientifically sound and conducted in
accordance with the basic ethical
principles, which have their origin in the
Declaration of Helsinki.
Three basic ethical principles of equal
importance, namely respect for person,
beneficence, and justice permeate all GCP
principles.
WHO GCP Principle 1
“… the two more important things needed for
ethical clinical research i.e., informed
consent and virtuous investigators.”
summarized from Dr. Henry Beecher’s Article
Basic Ethical Principles

Respect for person
 Autonomy

(independence)
Beneficence and [non-maleficence]
 maximizing
benefit; minimizing harms;
 do no harm

Justice
 distributive
justice
Respect for Person
Respect for person requires that subjects, to
the degree that they are capable, be given
opportunities to choose what shall or shall
not happen to them.
Belmont Report
Respect for Person

People should be treated as an
autonomous agent
 subject

autonomy
Subjects with diminished autonomy need
special protection
 vulnerable
subjects
Respect for Person

autonomous agent means individuals
who are able to make their own decision
regarding their goal and the process to
achieve such goals
 focus
paid on choice and opinion of each
autonomous individual upon one’s
determination
 right to self-determination
People with Diminished
Autonomy
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
People with Diminished
Autonomy (2)
Examples are members of a group with a
hierarchical structure such as medical,
pharmaceutical, and nursing students,
subordinate hospital and laboratory
personnel, employees of pharmaceutical
industry, members of the arm forces, and
persons kept in detention.
People with Diminished
Autonomy (3)
Other vulnerable subjects include patients
with incurable diseases, persons in
nursing home, unemployed or
impoverished persons, refugees, minors,
and those incapable of giving own consent
special safeguard measures

additional safeguards to protect the rights,
safety, and well-being of subjects with
diminished autonomy
 special
justification to the ethics committee
that research could not be carried out equally
well with less vulnerable subjects
 seeking permission of a legal guardian or
other legally authorized representatives
impartial witness
 monitoring the conduct of the study

Respect for Person
right for self-determination;
 human’s dignity;
 informed consent;
 vulnerable subjects;
 privacy and confidentiality

Beneficence
moral obligation to maximize the benefits
and to minimize harm
 requiring that

 risks
of research be reasonable in the light of
the expected benefits
 research design be sound
 instigators be competent both to conduct the
research and to safeguard the welfare of the
subjects
Before a trial is initiated, foreseeable risks
and inconveniences should be weighed
against the anticipated benefits for the
individual trial subject and society. A trial
should be initiated and continued only if
the anticipated benefits justify the risks
ICH GCP 2.2
Clinical trials should be scientifically sound
and described in clear detailed protocol
ICH GCP 2.5
The medical care given to, and medical
decision made on behalf of, subjects
should always be the responsibility of a
qualified physician or, when appropriate,
of a dentist
ICH GCP 2.7
Beneficence

in addition to maximizing benefits and
minimizing risks or harm

beneficence sometimes expressed as a
separate principle of non-maleficence
(do no harm)
“Risks and benefits of research may affect
the individual subjects… and society at
large (or special groups of subjects in
society).” “In balancing these different
elements, the risks and benefits affecting
the immediate research subjects will
normally carry special weight.”
Belmont Report
The rights, safety, and well-being of
the trial subjects are the most important
considerations, and should prevail over
the interests of science and society.
ICH GCP 2.3
Justice

“distributive” justice
 who
bears the burden/risk of research
 who takes benefits

giving rise to moral requirements that
there be fair procedures and outcomes in
the selection of trial subjects
Justice [2]

justice in the selection of research
subjects requires attention in two respects
 individual
 social

equity requires that no group or class of
persons should bear more than its fair
share of the burdens of participation in
research
Justice [3]

Subject should be drawn from qualifying
population in the general geographic area
of the trial without regard to race, ethnicity,
economic status, or gender unless there is
a sound scientific reason to do otherwise
CIOMS Guideline 12
Practical Applications

Informed consent [Respect for Person]
 informed

Risk/benefit assessment [Beneficence]
 favorable

decision making
ratio
Selection of trial subjects [Justice]
 fair
and equitable procedures and outcomes
Suitability of Informed Consent

sufficiency of information given;
 basic

minimum elements
understanding;
 understood

consent
voluntariness;
 freely
given without undue influence
Remember!

The three ethical principles are originally
derived from the Western culture

In applying these principles, please take
into account local norms, cultures, and
traditions as appropriate

Consult IEC, if needed
Ethics Committee
A trial should be conducted in compliance with
the protocol that has received prior
institutional review board (IRB) /independent
ethics committee (IEC) approval or/favorable
opinion.
ICH GCP Principle 2.5
A trial should be conducted in compliance with the
protocol that has received prior IRB/IEC
approval/favorable opinion.
ICH GCP Principle [2.6]
Institutional Review Board
An independent body constituted of medical,
scientific, and non-scientific members whose
responsibility is to ensure the protection of
rights [1], safety [2], and well-being [3] of human
subjects involved in a trial by, among other
things, reviewing, approving, and providing
continuing review of trial protocol and
amendment (s) and of the methods and
material to be used in obtaining and
documenting informed consent of the trial
subjects
ICH GCP [1.31]
Independent Ethics Committee
An independent body (a review board or a committee,
institutional, regional, national or supranational)
constituted of medical professionals and non-medical
members whose responsibility is to ensure the
protection of the rights [1], safety [2], and well-being [3]
of human subjects involved in a trial, and to provide
public assurance of that protection by, among other
things, reviewing and approving / providing favorable
opinion on, the trial protocol, the suitability of the
investigator(s), facilities, and the methods and
material to be used in obtaining informed consent of
the trial subjects
ICH GCP [1.27]
IRB/IEC
 Institutional
Review Board (IRB) used in the US
 Independent
Ethics Committee (IEC) used in
Europe
 deem
 in
synonymous
Thailand, both are used interchangeably
 ERC, REC
IRB/IEC
 independent
board / committee (free of any undue
influence to perform their task and make the
decision)
 exist
in several levels depending on situations e.g.,
institutional (CU, MU) , national (MOPH), regional
(EU), or supranational
 members
with medical and non-medical professions
 responsible
for protection of human subjects in a
trial (rights, safety, and well being)
84
IRB/IEC

assuring the public of their achieved
responsibilities by performing the following
tasks
reviewing and approving the trial protocol;
 suitability of the investigator and the team
(through most update CVs);
 adequate facilities to conduct the trial;
 methods and materials to be used in obtaining
informed consent
o etc.

85
IRB/IEC
86

interface between the investigator and the
subjects

possessing a formal authority for the approval
of the trial and/or suspending/terminating the
trial based upon the applicable laws and
regulations
Why IEC Review?

required independent review of a research
protocol
o one of the criteria for determining if the
conduct of a clinical trial is ethical

protection of subjects

ensure safety and well being of subjects
Declaration of Helsinki !!
87
Policy
88

IRB/IEC constituting and operating in
accordance with the ICH GCP

written approval received prior to initiating the
trial

if no constituted / appropriate IEC, use an
independent IEC such as MOPH IEC
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
If it is not scientifically valid, it is unethical
Preparation and Submission

90
investigator needs to

obtain confirmation of IEC members present
and occupation

inform IEC of any payments to subjects and
advertisements, if any

obtain a list of IEC members
Documents for Submission
Informed
Consent/Patient
Information Sheet
protocol and
amendments
Investigator’s
Brochure/drug
information
EC
submission
any
advertisements
Diary cards
payment
schedule
Roles of Investigator

interface between sponsor and ethics
committee

satisfies documentation requirements

updates ethics committee as required
 safety
progress;
 safety, SAEs;
 progress report, etc.
93
Roles of Investigator [2]
 Investigator
must
 not be involved in the approval process
 not
influence / apply pressure to committee
members
 communicate
with the IEC in an appropriate
manner (e.g., respect for their decision, appeal
the decision with supportive new scientific
evidence for the protocol etc.)
94
IRB/EC Decision
 unconditional
approval
 documented
in writing
 be
signed and dated by Chairman / Secretariat
 approval
letter bears full the protocol number and
title and/or version
Note: a trial must not be begun prior to receiving
the IEC approval letter !!
95
Summary
96

independent review is mandatory in biomedical
research, including a clinical trial

competent IRB/IEC fulfills the requirement of
the Declaration of Helsinki, ICH GCP, and
applicable regulations

investigator should ensure that the trial protocol
is reviewed and approved by a competent
ethics committee
Summary [2]

investigator should obtain an EC approval letter
before commencing the trial

investigator should ensure a regular contact with
the EC in case of new information, amendments,
progress report, or safety update etc.
Informed Consent Process
Suchart Chongprasert, Ph.D.
Food and Drug Administration
ICH GCP for Clinical Research investigators, 31July 2013, Chiangmai
Presentation Outline
What does it means?
 Basic Elements of Informed Consent
 Certain Important Aspect of Informed
Consent
 Exercise

Freely given informed consent should be
obtained from every subject prior to
clinical trial participation
ICH GCP Principle [2.9]
“… each potential subject must be adequately
informed of the aims, methods, anticipated
benefits and potentials hazards of the study
and the discomforts it may entail.”
“…the physician should obtain the subject’s
freely given informed consent, preferably in
writing.”
Declaration of Helsinki
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 subject’s
decision5 to participate. Informed consent
is documented by means of a written6
signed7 and dated8 informed consent
form.
ICH 1.28
Informed consent
..an ongoing
not a form
by which process,
a subject
for just signing
2
A process
voluntarily 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 subject’s 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
undue influence
voluntarily 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 subject’s 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
subject’s decision5 to participate.
Informed consent is thoroughly
documented
aboutby
means of a written6 signed
and
the trial7e.g.,
purpose,
benefits,
dated8 informed consent
form.
payment etc.
Informed consent
A process1 by which a subject voluntarily2
subject’s autonomy
confirms his or hertowillingness
to
make their own
participate in a particular
trial, after
judgment
having been informed3 of all aspects4 of
the trial that are relevant to the
subject’s 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
….acceptable
wayto
participate in a particular
trial,
after
under the ICH
GCP
3 of all aspects4 of
having been informedcontext
the trial that are relevant to the subject’s
decision5 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
not too technical
avoid a non-mother language
remember that the readers are not scientific
expert/ethics committee members
Methods for Documenting
Informed Consent

written informed consent
 In

accordance with ICH GCP
oral witnessed consents
 no
documented evidence
 beyond the scope of ICH GCP
Elements of IC (ICH GCP)
1. involve research;
2. research purpose;
3. choice of treatments, including
randomization;
4. trial procedures, including invasive ones;
5. subject’s responsibilities;
6. trial aspects that are experimental;
7. foreseeable risks/inconvenience
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 subject’s 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

consent must be informed;
 careful
about the uninformed informed consent
 ensure subjects’ understanding (understood consent)




subjects given ample time;
all questions answered to the subject's
satisfaction;
no undue pressure/influence;
language clearly understood by the subjects
 recommended
not higher than grade 8
Important Considerations [2]

no language causing the subjects or the
legally acceptable representatives to
waive their legal rights;
 IC


not a legal contract / agreement
ICF personally signed and dated by the
subject and the person obtaining the
ICF;
a copy of ICF given to subject prior to
participation;
Suitability Considerations for IC

informed and [ understood ] consent;
 respect
for subject’s right to self-determination
(autonomy)

disclose sufficient information;
 all

aspects about the trial
suitable for subject’s capacity (normal vs.
diminished);
 age;
 educational
status;
 sex;
 culture,
geosocial factors etc.
Suitability Considerations for IC [2]

voluntariness; and

practicality
 amount
of the given info. vs. time for
consideration in reality

short form??
 depending
on investigator’s explanation
Importantly!

In principle, obtaining informed consent in
a clinical research is a must

Waiving of informed consent is an
exception which should be well-justified
and received prior approval from IEC/IRB
before implementation
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
parent’s 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 committee’s 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
subject’s 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
Informed consent is a continuing process
to confirm subject's voluntary willingness to
participate in the trial.
o
Informed consent should be obtained from
each patient prior to enrolling the subject
into the trial.
o
Children’s assent form is required in most
clinical trials involving children (below
majority age) participation
Thank you for your attention