Research Ethics

Ethics in Clinical
Research
Dr. Meita Dwi Utami, MSc

Whats past is prologue

(William Shakespeare, The Tempest)

Research
Research is the repeated
search to the unknown
Hypothesis (causeeffect) Thesis
Cause Independent
variable Effect
Dependent variable

Science and Scientific method

Mathematical logic

DEDUCTION
SCIENCE

RATIONAL WORLD
EMPIRICAL WORLD
INDUCTION
FACTS

STATISTIC

HYPOTHESIS

TESTS

RESEARCH METHOD

Scientific Methods
Characteristics of Scientific Method
1.
2.
3.
4.
5.
6.

Based on facts
Free from prejudice
Using analytical principles
Objective measurements
Has hypothesis
Quantitative techniques

Characteristic of
Research
1.
2.
3.
4.
5.
6.
7.
8.

Problem oriented
Curiosity
Originality
Phenomena: Law and Order
Goal Generalization
Cause and Effect Study
Accurate measurement
Sound and known methods and
techniques

RESEARCH
PROCEDURES

MEMILIH MASALAH PENELITIAN

TEORI, HUKUM, DALIL

Studi
Pendahuluan

MERUMUSKAN MASALAH DAN TUJUAN

MERUMUSKAN HIPOTESIS

Merumuskan TOPIK
Atau JUDUL

MEMILIH PENDEKATAN
(METODE PENELITIAN)
MENENTUKAN VARIABEL

MENENTUKAN SUMBER DATA

MENENTUKAN DAN MENYUSUN INSTRUMEN

MENGUMPULKAN DAN ANALISIS DATA

MEMBUAT
KESIMPULAN dan LAPORAN
fkk umj

Relation of Problems, Goals and

Conclusions
in a Research

Problems:
Question

Goals:
Answer

Conclusions:
A defined answer

Research components
Who
What

When

Research
Where

Whom
How

Overview to Research Studies

Why Do Research Studies?
To collect data
To test hypotheses formulated from
observations and/or intuition
To understand better

The Ten Commandments for Picking a

Research Project
(C. Ronald Kahn, M.D, NEJM, 330: 1530, 1994)

I. Pick an Area on the Basis of the Interest of the

Outcome.
II. Look for an Underoccupied Niche that has Potential.
III. Go to Talks and Read Papers outside Your Area of
Interest.
VI. Build on a Theme.
VI. Find a Balance Between Low-Risk and High- Risk
Projects, but Always Include a High-Risk, High
Interest Project in Your Portfolio.
VII. Be Prepared to Pursue a Project to any Depth
Necessary.
VIII. Differentiate Yourself from Your Mentor.
IX. Do Not Assume that Outstanding, or Even Good

 Various types of research study

design!!!
Epidemiology study:
The study of the distribution of a
disease or condition in a
population and the factors that
influence the distribution.

Classifications of Research Studies:

Three Main Types
1. Observational Studies:
Groups are studied & contrasts made between groups
Analyzing the observed data
2. Analytic (Experimental) Studies :
Study the impact of a certain therapy/treatment
3. Clinical Trial:
Gold Standard of clinical research

Study designs
Cohort
Case
control

Case
Reports

Survey

Meta
analysis
RCT

Case series

Historical minutes of clinical trials

Formal record of clinical trials dates
back to the time of the Trialists:
Dr. Van Helmonts proposal for a
therapeutic trial of bloodletting for fevers
[1628]
Dr. Linds, a ship surgeon, trial of oranges
& limes for scurvy [1747]

Historical Highlights of Drug Trials

1909: Paul Ehrlich - Arsphenamine
1929: Alexander Fleming - Penicillin
1935: Gerhard Domagk - Sulfonamide
1944: Schatz/Bugie/Waksman Streptomycin
By 1950, the British Medical Res. Council
developed a systematic methodology for
studying & evaluating therapeutic
interventions

Another selective history of clinical

research
Who

When

What

Ibnu Sina

900 C.E.

Water borne transmission

Hippocrates

Hippocratic method: Observation in a

disease

Frederich II

1200 C.E.

Effect of exercise on digestion

Wren

1656

First IV line for first blood transfusion

Anthonj van Leeuwenhoek

1674

Microscopy bacteria, yeast,

protozoa,

Core Components of Clinical Trials

1.
2.
3.
4.
5.
6.

Involve human subjects

Move forward in time
Most have a comparison CONTROL group
Must have method to measure intervention
Focus on unknowns: effect of medication
Must be done before medication is part of
standard of care
7. Conducted early in the development of
therapies

Core Components of Clinical Trials

8. Must review existing scientific data &
build on that knowledge
9. Test a certain hypothesis
10.Study protocol must be built on sound &
ethical science
11. Control for any potential biases
12.Most study medications, procedures,
and/or other interventions

Phases of Clinical Trials

Most trials that involve new drugs go
through a series of steps:
#1: Experiments in the laboratory
#2: Once deemed safe, go through 14 phases

Phases of Clinical Trials

Phase I: Small group [20-80] for 1st time
to evaluate safety, determine safe dosage
range & identify SE
Phase II: Rx/tx given to larger group
[100-300] to confirm effectiveness,
monitor SE, & further evaluate safety

Phases of Clinical Trials (cont.)

Phase III: Rx/tx given to even larger group
[1,000-3,000] to fulfill all of Phase II
objectives & compare it to other commonly
used txs & collect data that will allow it to
be used safely
Phase IV: Done after rx/tx has been
marketed - studies continue to test rx/tx to
collect data about effects in various
populations & SE from long term use.

History of Medical Research Ethics

Year

Documents

1948

Nuremberg Code: International Code of Ethic

1954

NIH CC Medical Board: call for informed consent and protocol

review

1963

FDA requires informed consent

1964,
2000(rev)

Declaration of Helsinki

1993, 2002 International ethical guidelines for Biomedical Research Involving

(rev)
Human Subject

Case
Dr. R, a general practitioner in a small rural town, is
approached by a contract research organization
(C.R.O.) to participate in a clinical trial of a new
non-steroidal antiinflammatory drug (NSAID) for
osteoarthritis. He is offered a sum of money for
each patient that he enrols in the trial.
The C.R.O. representative assures him that the trial
has received all the necessary approvals,
including one from an ethics review committee.
Dr. R has never participated in a trial before and is
pleased to have this opportunity, especially with
the extra money.

Some principles from DoH:

Paragraph 15 of DoH:
...every proposal for medical research on
human subjects must be reviewed and
approved by an independent ethics
committee before it can proceed.
Ethics Review Committee Approval

Some principles from DoH:

Paragraph 12 of DoH:
...medical research involving human
subjects must be justifiable on scientific
grounds.
Scientific Merit

Some principles from DoH:

Paragraph 17 and 21 of DoH:
...social value has emerged as an important
criterion for judging whether a project
should be funded.
Social Value

Some principles from DoH:

Paragraph 20 of DoH:
If the risk is entirely unknown, then the
researcher should not proceed with the
project until some reliable data are
available
Risks and Benefits

Some principles from DoH:

Paragraph 24, 26, 27 and 29 of DoH:
(Nuremberg code)
The voluntary consent of the human subject
is absolutely essential.
Informed Consent

Some principles from DoH:

Paragraph 31 of DoH:
...the physicians role in the physician patient
relationship is different from the
researchers role in the researcher-research
subject relationship
Conflict of roles

Some principles from DoH:

...research subjects have a right to privacy
with regard to their personal health
information
Confidentiality

Some principles from DoH:

...there have been numerous recent
accounts of dishonest practices in the
publication of research results

Honest reporting of the results

Integrity
investigators should be qualified and
competent to conduct the study by virtue
of their education and experience
.plus Honesty

 UI Komite Kaji Etik FKUI

Unhas Komisi Etik FKUH
UGM Pusat Kajian Bioetik dan
Humaniora Kedokteran
Setiap RS biasanya memiliki
Komite Etik

Komnas Etik Penelitian Kesehatan

Komisi Etik membahas usulan-usulan penelitin
biomedis yang menggunakan manusia sebagai
subyek penelitian, baik untuk kegiatan penelitian
yang dilakukan oleh unit-unit penelitian di
lingkungan Badan Litbangkes, ataupun kegiatan
penelitian yang dimonitor oleh Badan
Litbangkes.

Sekretariat Bersama Komisi Etik Penelitian

dan Komisi Ilmiah

Gedung Sekretariat Badan Litbangkes

Jl. Percetakan Negara, No. 29
Jakarta Pusat, 10560
Telp. 021 4261088 ext. 114 / 127
http://www.litbang.depkes.go.id

Dr. R should not have accepted so quickly. He

should first find out more about the project and
ensure that it meets all the requirements for
ethical research.
In particular, he should ask to see the protocol that
was submitted to the ethics review committee
and any comments or conditions that the
committee put on the project. He should only
participate in projects in his area of practice, and
he should satisfy himself about the scientific
merit and social value of the project. If he is not
confident in his ability to evaluate the project, he
should seek the advice of colleagues in larger
centres.

He should ensure that he acts in the best interests

of his patients and only enrols those who will not
be harmed by changing their current treatment to
the experimental one or to a placebo.
He must be able to explain the alternatives to his
patients so they can give fully informed consent
to participate or not to participate.

He should not agree to enrol a fixed number of

patients as subjects since this could lead her to
pressure patients to agree, perhaps against their
best interests. She should carefully monitor the
patients in the study for unexpected adverse
events and be prepared to adopt rapid corrective
action.
Finally, He should communicate to his patients the
results of the research as they become available.

Conclusion
The history of clinical research can be
traced to all cultures.
The future requires information
exchange to maximize progress in
health care.
Ethical clearance is strongly advised in
medical research with human being as
the subject.

Whats past is prologue

(William Shakespeare, The Tempest)

Wassalamu alaikum Wr.Wb

References
World Medical Association, Medical Ethics Manual:
Chapter 5, 2005.
59th World Medical Association General Assembly.
Declaration of Helsinki: ethical principles for medical
research involving human subjects. 2008.
NIH, History of Clinical Research and Choosing a
Research Question, 2008.
Fadel, Ethics of Clinical Research: An Islamic
Perspective, JIMA vol. 42, 2010.