Ethics in Research

An Overview

Nurul  Aida  Fathya.,dr.,SpF  

Introduksi (lanjutan…)

§  Penelitian kesehatan (= biomedical research)

ü  Umum:
Farmasetika, Alkes, radio-imaging, prosedur bedah,
rekam medik, sampel biologik, epidemiologi, ilmu
sosial & perilaku, teknologi kloning dan stem cells

ü  Menghasilkan konsep : → pergeseran paradigma

 New  
Biomedical    
Sciences  

New
Technology

Methods of Medical Methods of Medical

Sciences Techniques

Drugs
Divices
Physical Setting

Scholar Medical
Physicians Technology
Economics of
Medical Care

Ethical
Issues

Fig. 3 Biomolecular Technology and issues of medical-health ethics

Landasan Hukum
•  Etik : menghargai martabat manusia dan
hak azasi nya sebagai sesama
ciptaan

•  Hak azasi manusia:

–  Sebagai pribadi
–  Sumber informasi
–  Persetujuan secara sadar & bebas
–  Ada outside reviewer
 What are the foundations for
the ethical conduct of clinical
research?
•  The  Nuremberg  Code  (1947)    
•  The  DeclaraAon  of  Helsinki  (1964  -­‐  2013)    
•  The  Belmont  Report  (1979)    
•  CIOMS  (1982,  1993,  2002,  2008,  2012)  
 LOGO

The Doctor Trials

The Nuremberg
Code
LOGO

From the Doctor’s Trial, came up

The Nurmberg Code
Declaration of Helsinki

1964
 www.themegallery.com

Declaration of Helsinki

§  The Declaration was originally adopted on

June 1964 in Helsinki, Finland, and has
since undergone seven revisions (the
most recent at the General Assembly in
October 2013)
§  The Declaration is an important document
in the history of research ethics as it is the
first significant effort of the medical
community to regulate research itself, and
forms the basis of most subsequent
documents. Company Logo
 www.themegallery.com

Declaration of Helsinki

v Helsinki becomes “the most widely accepted

guidance worldwide on medical research involving
human subjects.
§  Its purpose was to provide guidance to physicians
engaged in clinical research and its main focus was
the responsibilities of researchers for the protection
of research subjects.
v The Declaration of Helsinki was first adopted at the
1964 WMA General Assembly in Helsinki.

Company Logo
 Declaration of Helsinki

§  Declaration of Helsinki undergoes many

revision. The last revision was in 64th
WMA General Assembly in Fortalezza,
Brasil 2013
§  The basic of the declaration: “The health
of my patient will be my first
consideration,” and the International Code
of Medical Ethics declares that, “A
physician shall act in the patient's best
interest when providing medical care.”
Company Logo
 LOGO

Belmont Report
Tuskegee syphilis experiment
1932 - 1972
R   §  Involving  600  men  
–  299  experimen  
group  
–  Control  group  
•  Untreated  shypilis,  
although  there  
was  pinicilin  to  
cure  the  shypilis  
LOGO
R

From Tuskegee syphilis experiment

Came up

Belmont Report
 www.themegallery.com

CIOMS
Council for International
Organizations of Medical Sciences
1964

Company Logo
LOGO
What is CIOMS?

§  An NGO: international, non-governmental, non-

profit organization
§  Forum to consider and prepare advice on
contentious issues in research ethics and safety of
pharmaceuticals...
§  ... for WHO, public health authorities, academia,
pharmaceutical industry and others.
§  Established 1949 by WHO and UNESCO
§  Offices located in Geneva c/o WHO, Switzerland
LOGO
CIOMS’ main fields of interest

v 1. Drug safety and drug development

v 2. Bioethics:
§  1970s: newly independent WHO members set
up health care systems
§  Ethics was too sensitive for WHO
§  CIOMS was asked to indicate how the Helsinki
declaration (revised in 1975) could be applied,
particularly in developing countries
§  1982: guidelines on biomedical research
published
§  Revision: 1993, 2002, 2008, 2013
LOGO
Purpose:

v Purpose: indicate how fundamental ethical

principles and Declaration of Helsinki can be
applied effectively in medical research world-
wide in different:
§  cultures, religions, traditions,
socioeconomic circumstances;
§  with special attention for developing
countries.
 Contens 2008
1.Ethical justification and scientific validity of
epidemiological research involving human subjects
2.Ethical review committees
3.Ethical review of externally sponsored research
4.Individual informed consent
5.Obtaining informed consent : essential information
for prospective research subjects
6.Obtaining informed consent :obligations of
investigators and sponsors
 Contens 2008
7. Compensation for participation
8.Benefits, harms and and risks of study participation
9.Special limitations on risk when research involves
individuals who are not capable of giving informed
consent
10.Research in populations and communities with
limited resources
11.Choice of controls in clinical trials
12.Equitable distribution of burdens and benefits in
the selection of subjects in research
 Contens 2008
13.Research involving vulnerable persons
14.Research involving children
15.Research involving individuals who by
reason of mental or behavioural disorders
are not capable of giving adequately
informed consent
16.Women as research participants
17.Pregnant women as research participants
18.Safeguarding confidentiality
 Contens 2008
19.Right of injured subjects to treatment and
compensation
20.Strenghtening capacity for ethical and scientific
review and biomedical research
21.Ethical obligation of external sponsors to provide
health-care services
22.Disclosure and review of potential conflicts of
interest
23.Use of the Internet in epidemiological studies
24.Use of stored biological samples and related data
ETHICAL CLEARANCE
Mengapa ETHICAL CLEARANCE
diperlukan?

§  Bagi subjek

Untuk kepastian perlindungan hak
§  Bagi peneliti
1.  Menghindari pelanggran HAM
2.  Publikasi ilmiah di jurnal internasional
3.  Pencairan dana penelitian
Penelitian yang membutuhkan
ETHICAL CLEARANCE
§  Semua penelitian yang menggunakan manusia
sebagai subjek penelitian, juga hewan serta
bahan biologik tersimpan(BBT)
§  Penelitian
ü  Farmasetik ü  Prosedur diagnosa
ü  Radiofarmasi ü  Sampel biologik
ü  Tanaman obat ü  Epidemiologik
ü  Alat kesehatan ü  Rekamm medis
ü  Radiasi medik ü  Perilaku sosial & psikososial
 Etika Penelitian (pada manusia)
3 prinsip etika umum :
§  Menghormati harkat martabat manusia (= respect for persons)
ü Self determination
ü Kelompok dependent & vulnerable harus dilindungi terhadap harm &
abuse
§  Berbuat baik (=Beneficence) & tdk merugikan (=nonmaleficence)
ü  Reasonable (risk)
ü  Scientific (design study)
ü  Mampu meneliti & menjaga kesejahteraan subjek
ü  Non – maleficence (= tidak merugikan)
§  Keadilan (=justice)
ü  Distributive justice dalam hal risk / benefit
ü  Equitable (usia, gender, etnik, sosek)
Vulnerable group
v Wanita hamil / menyusui / anak2 (kecuali
jenis terapi memang khusus untuk mereka)

v Penderita kelainan jiwa

v Narapidana ( kebebasan dicabut secara

hukum)

v Mahasiswa, tentara (dependent)

Prinsip tambahan
§  Utamakan kepentingan subjek / masyarakat
§  Menghormati integritas subjek
§  Menghentikan pelitian bila bahaya >> manfaat
§  Publikasi akurat
Informed Consent
Aspek tercantum dalam persetujuan
setelah penjelasan (PSP) / Informed
Consent
1. Informasi
Kalimat / kata-kata yg mudah dimengerti orang awam

2. Informasi berisi
ü  Latar belakang penelitian
ü  Berapa lama dan berapa subjek penelitian diperlukan
ü  Perlakuan terhadap subjek
ü  Tujuan penelitian
ü  Prosedur penelitian
Aspek tercantum dalam persetujuan
setelah penjelasan (PSP) / Informed
Consent

ü  Ketidaknyamanan / risiko yang ada dan mungkin akan

terjadi
ü  Keuntungan yang diharapkan
ü  Tindakan pengganti (alternatif)
ü  Penjelasan kompensasi atau asuransi
ü  Penjelasan terjaminnya rahasia subjek
ü  Nama jelas & alamat penanggung jawab medis
ü  Partisipasi harus bersifat sukarela
Etika Penelitian pada Hewan
•  Penderitaan hewan coba untuk kebaikan
manusia perlu dijamin kesejahteraan &
diperlakukan secara manusiawi

•  Prinsip 3R (reduction, refinement,

replacement) harus menjadi dasar
penggunaan hewan coba
Reduction : jumlah hewan coba <<
Refinement : Pilih metode yang mengurangi nyeri,
penderitaan
Replacement : In vitro (relatif), Tidak gunakan
hewan (absolut)
 Phase Of Clinical Development
Phase Main  aims  /  means  of  invesAgaAon subjects

Preclinical •  Pharmacology   •  In  vitro  

•  Toxicology •  In  laboratory  animals
Phase  1 •  Clinical  pharmacology  and  toxicology   •  Healthy  individuals  and/or  
•  Drug  metabolism  and  bioavailability   paAents    (20-­‐80)
•  First  administraAon  to  men
Phase  2 •  IniAal  treatment,  uncontrolled  studies   •  Small  numbers  of  paAents  
•  Evaluate  relaAve  safety  and  efficacy  Dose-­‐ (100-­‐200)
ranging  studies
Phase  3 •  Large  randomized  controlled  trials   •  Large  numbers  of  paAents  
•  Comparing  new  to  old  treatments   (1000-­‐3000)
•  Evaluate  safety  and  efficacy  in  specific  
indicaAon
Phase  4 •  Post-­‐markeAng  surveillance   •  All  paAents  prescribed  the  drug  
•  Long-­‐term  efficacy,  safety  and  rare  events   (N/A)
•  Yellow  card  scheme
 Prinsip cara uji klinik yang baik
1.  Sesuai prinsip etik deklarasi Helsinki

2.  Pertimbangan resiko / ketidaknyamanan dan manfaat (manfaat >> resiko)

3.  Hak, keamanan, kesejahteraan >> kepentingan ilmu pengetahuan / masyarakat

4.  Informasi non-klinik memadai

5.  Berlandaskan ilmiah yang kuat dan diuraikan dalam protokol dengan rinci / jelas

6.  Sesuai dengan protokol yang telah mendapat ethical cleareance

7.  Pelayanan medik
Tanggung jawab dokter / dokter gigi
8.  Peneliti memenuhi syarat
ü  Pendidikan
ü  Pelatihan
ü  Pengalaman
9.  Ethical clearence
Bebas dari tekanan
Prinsip cara uji klinik yang baik

1.  Informasi direkam, ditangani dan disimpan

dilaporkan ⎯ diinterpretasi, diverifikasi
secara akurat
2.  Lindungi kerahasiaan subjek
3.  Produk yang diteliti dibuat, ditangani,
disimpan sesuai protokol yang disetujui
4.  Sistem penjaminan mutu
Fungsi Komite Etik Penelitian
Kesehatan (KEPK)
1.  Mengkaji, memberikan penilaian serta pertimbangan dari
segi ilmiah, aspek medis dan etik uji klinik / penelitian
2.  Kajian awal dan berkelanjutan atas usulan penelitian
3.  Menilai manfaat dan penerapan keilmuan
4.  Menyatakan
ü  Tidak ada subjek yg boleh dimasukkan ke dalam penelitian sebelum
ada ethical clearance
ü  Tidak ada penyimpangan
ü  Peneliti melaporkan secara berkala

5.  Memberitahu peneliti bila:

ü  Keputusan mengenai usulan penelitian
ü  Alasan dari keputusan tersebut

6.  Dokumentasi
 The goal of the Research
ethic
on Human Subbject:
•  To protect the rights, safety and welfare
of humans participating in research
•  To assure the quality, reliability and
integrity of data collected
•  To provide standards and guidelines for
the conduct of clinical research
•  Good Clinical Practice = Ethics + Quality
Data