Ethical Clinical Research

Ethical Clinical Research
Urmila Thatte
Seth GS Medical College
urmilathatte@gmail.com
ETHICS
Moral code of conduct defining the right and

wrong behavior in a civil society and comes from
within.
It is different from Law which regulates external

behavior.
2 UG Certificate Course 11/14/2010

What is Clinical Research?
A systematic investigation in human beings

designed to produce generalisable knowledge

Practice vs. Research
Interventions that Activity designed

Practice:
Research:
are designed solely to test an
to enhance the hypothesis, permit
well-being of an conclusions to be
individual patient drawn; and
that has a thereby develop or
reasonable contribute to
expectation of generalizable
success knowledge
Patients vs. Participant
Therapeutic misconception
Vulnerability of the patient
Doctor-patient vs. Investigator-participant

relationship and heirarchy
Ethics in Biomedical Research
• the nature of research,

Right of the
human • risks & benefits
participant involved
to
understand • to agree or not agree
to participate.

14th May 1796
Jenner approached a farmer called Phipps
• Asked if he could inoculate his son James against smallpox
• Explained that if his theory was correct, James would never contract smallpox.
• Surprisingly, the farmer agreed.
Jenner made two small cuts on James's left arm. He then poured the liquid from a
milkmaid’s cowpox sores into the open wounds
James went down with cowpox but was not very ill.
Six weeks later when James had recovered, Jenner vaccinated him again, this time with
the smallpox virus.
To Jenner's relief James did not catch smallpox. His experiment had worked.

1900
United States Army Yellow Fever Commission: how does
yellow fever get transmitted (Walter Reed) conducted in
experimental stations just outside Havana
Paid $100 in US gold to participants to allow themselves

to be bitten by infected mosquitoes (yellow fever)
Additional $100 if they consequently contracted the viral

disease
Payable to family in case of death

“Regulations on New Therapy and Human
Experimentation” from the Reich Minister of the
Interior, Feb 1931
 Medical science must advance, but individual physician has special
duty and major responsibility for life and health of patient-subject
 Risks proportionate to anticipated benefits
 Tested in advance on animals
 Unambiguous consent
 Special caution if minors
 Exploitation of social hardship is unethical
 Academic training should stress special obligations when conducting

research or publishing

End point of experiments - DEATH

Defendants and Defense Counsel
15 of 23 guilty, 7 hanged, 5 life sentences

Nuremberg Code 1949: 10 points
voluntary (informed) consent must be obtained:

investigator’s responsibility

Clinical Trial Ethics: Nuremberg Code
The code
specifies that:
volunteers have the

right to withdraw
at any time
experiments must
provide benefits
for society
avoid unnecessary
injury
Thalidomide Trial
Thalidomide was approved as a sedative
No danger to mother but extremely damaging

to the foetus
Harris-Kefauver Amendment to Food,
Drug given
Drugs and to cure morning
Cosmetics Act,sickness
1962
Subjects were not informed of experimental
drugs
Subjects were not asked to give their consent

Declaration of Helsinki: 1964
Adopted by the 18th World Medical Assembly
Revised 6 times
Latest version 2008, Seoul, South Korea
Para 13: protocols must be submitted to an Ethics Committee for

review, which must be independent of the investigator, the sponsor
or any other kind of undue influence.

Tuskegee Syphilis Study
 American medical research

project conducted by the
U.S. Public Health Service
from 1932 to 1972,
Taliaferro Clark,
 Examined the natural course Head of the
Public Health
of untreated syphilis in black Service at the
beginning of the
American men. Tuskegee
Experiment

Tuskegee Syphilis
Study
Results:
28 deaths,
100 cases of disability,
19 cases of congenital
Lacksyphilis
of informed consent, putting subjects and their
U families to risk, exploitation of vulnerable population,
G
C deception, withholding information, no benefit to subjects
e
rt
if
ic 17 11/14/2010
at
e
Tuskegee 1997

8
The Belmont Report
Ethical Principles and Guidelines for the Protection of

Human Subjects of Research
The National Commission for the Protection of Human Subjects of Biomedical

and Behavioral Research
April 18, 1979

The Belmont Report: 3 principles
Respect for
Beneficence Justice
Persons-
subjects should be
autonomy of maximize the
selected fairly to
individuals possible benefits
ensure that the
benefits and
Special protection burdens of medical
minimize possible research are
for those with
evenly distributed
diminished harm
autonomy

ICH - International Conference on
Harmonization, 1996
Three observers:
• WHO
Joint initiative by regulators and
industry from three regions - US, EU & • Canada
Japan • IFPMA (International Federation of
Pharmaceutical Manufacturers
Association)

GCP = Good Clinical Research Practice
A standard for the

• design,
• conduct,
• monitoring,
• recording,
• auditing,
• reporting
of clinical trials
Good Clinical Practice
DESIGN
International
Scientific &
Ethical quality
Standard
COLLECT
Patient Safety Credibility of Data

India
2001 Indian GCP
2005 Schedule Y of Drugs and

Cosmetics Act Amendment:
pertinent to clinical trials
ICMR Guidelines
U
G
C
e
rt
if
ic 25 11/14/2010
at
e
An erosion of
public trust...

Twin pillars of human
protection
Independent Review Informed Consent

Informed consent
A process by which a participant voluntarily confirms his or her

willingness to participate in a particular trial, after having been
informed of all aspects of the trial that are relevant to the participant’s
decision to participate.
Informed consent is documented by means of a written, signed and

dated informed consent form.
ICH- GCP 1.28

Informed Consent Document
Both integrated in to
Part I : Participant
one document called
Information Sheet Part II : Consent form
the Informed Consent
(PIS)
Document (ICD)
Provides information
Consent documented
about the study.

Informed consent
 Consent given by a competent individual who
 Has received the necessary information
 Has understood the information
 And having understood the information has arrived
at a decision without having been under any

coercion, undue influence or inducement or
intimidation

Informed consent
 Written informed consent
 Voluntary
 from every subject
 before any study related procedure
 and documented on EC approved form
 Signed copy given to participant

Who gives the consent?
if subject unable to give

Participant consent (minor, dementia
etc.) then -
Legally subject should be informed

acceptable to the extent compatible
with his/her
representative understanding and consent
sought and documented.
(LAR)

How should the consent be documented?
Signed and
dated by
Subject / subject’s Person conducting

If illiterate, an
legally acceptable the informed
impartial witness
representative consent discussion

Informed Consent: Non-English speaking
Summary
and Thumb Document
Written
consent in impressions Witness method in
translation
the allowed source
vernacular

Informed Consent: Children
Approval of older children:

understand the concepts: assent
Consent from parents/legally

acceptable representative
Informed Consent . . .
. . . is not a piece of paper.
. . . is not a signature.
It is a PROCESS by which we . . .
. . . ENSURE that our subject’s right to be informed, and right to consent to
research, is protected.
. . . DOCUMENT our efforts to protect the subject’s rights to the satisfaction of

independent observers.

Twin pillars of human
protection
Independent Informed Consent

Review
Ethics Committee
Any board,
committee • review,
or other • approve the initiation of
group and
formally • conduct periodic review
designated of biomedical research
by an involving human subjects.
institution to
All proposals on
biomedical research
involving human
subjects must be
cleared by an
Ethics Committee

Ethics Committees: Why?
An objective
by a group of most likely to
review of research promote ethically
diverse protect human
activities involving sound research
individuals is subjects and
human subjects

Composition of the EC
collectively have to review and

the evaluate
• the science,
• medical aspects
and
A reasonable
qualifications and • ethics of the
number of
experience proposed trial
members who

What does an EC do for Clinical Research?
Before the During the After the
study begins: study: study:
Review and Review of

approval of amendments Study report,
research proposal (Protocol, ICD)
Review of
Decision making Post trial
Serious Adverse
process management
Events
Protocol
Record keeping Publishing
deviations
Monitoring
progress Record keeping
(reports, on-site)
Record keeping
Criteria For Approval
Suitability of
Investigator, Equitable
Protocol and Selection Of
informed consent Subjects
processes
Confidentiality of
Time Provision
subjects and data

EC : Approval
No study can be started without EC approval
No changes made without prior written EC

approval
EC may revoke any prior approval depending

on ongoing review

Challenges
If studies are
NOT submitted
for review, then
the safeguard of
ECs is
meaningless!

Ethics is not definable, is not
implementable, because it is not
conscious; it involves not only our
thinking, but also our feeling.
… Valdemar W. Setzer

The Road Not Taken
Robert Frost
Two roads diverged in a yellow wood,
… I could not travel both
…. long I stood
I shall be telling this with a sigh

Somewhere ages and ages hence:
Two roads diverged in a wood, and I,
I took the one less traveled,
And that has made all the difference.
4 Pharmatech 2008 14 November 2010

8

Ethical Clinical Research

Încărcat de

Informații document

Descriere originală:

Drepturi de autor

Formate disponibile

Partajați acest document

Partajați sau inserați document

Opțiuni de partajare

Vi se pare util acest document?

Este necorespunzător acest conținut?

Drepturi de autor:

Formate disponibile

Ethical Clinical Research

Încărcat de

Drepturi de autor:

Formate disponibile

Ethical Clinical Research

Moral code of conduct defining the right and

It is different from Law which regulates external

2 UG Certificate Course 11/14/2010

A systematic investigation in human beings

3 UG Certificate Course 11/14/2010

Interventions that Activity designed

Vulnerability of the patient

Doctor-patient vs. Investigator-participant

• the nature of research,

6 UG Certificate Course 11/14/2010

7 UG Certificate Course 11/14/2010

Paid $100 in US gold to participants to allow themselves

Additional $100 if they consequently contracted the viral

Payable to family in case of death

8 UG Certificate Course 11/14/2010

 Tested in advance on animals

 Special caution if minors

 Exploitation of social hardship is unethical

 Academic training should stress special obligations when conducting

9 UG Certificate Course 11/14/2010

10 UG Certificate Course 11/14/2010

11 UG Certificate Course 11/14/2010

voluntary (informed) consent must be obtained:

12 UG Certificate Course 11/14/2010

volunteers have the

No danger to mother but extremely damaging

Subjects were not asked to give their consent

14 UG Certificate Course 11/14/2010

Adopted by the 18th World Medical Assembly

Latest version 2008, Seoul, South Korea

Para 13: protocols must be submitted to an Ethics Committee for

15 UG Certificate Course 11/14/2010

 American medical research

16 UG Certificate Course 11/14/2010

1 UG Certificate Course 11/14/2010

Ethical Principles and Guidelines for the Protection of

The National Commission for the Protection of Human Subjects of Biomedical

19 UG Certificate Course 11/14/2010

20 UG Certificate Course 11/14/2010

21 UG Certificate Course 11/14/2010

A standard for the

Patient Safety Credibility of Data

2001 Indian GCP

2005 Schedule Y of Drugs and

26 UG Certificate Course 11/14/2010

Independent Review Informed Consent

A process by which a participant voluntarily confirms his or her

Informed consent is documented by means of a written, signed and

ICH- GCP 1.28

28 UG Certificate Course 11/14/2010

29 UG Certificate Course 11/14/2010

 Consent given by a competent individual who

 Has received the necessary information

 Has understood the information

 And having understood the information has arrived

at a decision without having been under any

30 UG Certificate Course 11/14/2010

 Written informed consent

 from every subject

 before any study related procedure

 and documented on EC approved form

 Signed copy given to participant