Penelitian Klinis dan Etika

Penelitian
Historical Background
NAZI human experimentation
•Experiments on twins
•Bone, muscle, and nerve transplantation
experiments
•Malaria experiment
•Freezing experiments
•Mustard gas experiments
•Sulfonamide experiments
•See water experiments
•Sterilization experiments
•….
 Historical Background
– Nuremburg Doctors Trials (1946)
• Atrocious trials done on Nazi’s camp.
• Typically never informed consent, ended with death,
dysfigurement, or permanent disabilities
•  Nuremburg Code, 1947
– Willowbrook Hepatitis Study (1958)
• School for mentally disabled children
• Dr. Saul Krugman, New York University School of Medicine
• Mental retarded children were deliberately fed a solution
including the feces of children with hepatitis
– Tuskegee Syphilis Trial
• 1932 -1972 study designed to look at the natural history of
untreated syphilis
• In 1951 penicillin was discovered, but African American
subjects continued to receive placebo
•  Declaration of Helsinki, 1964
 Some Ethics Guidelines
in Clinical Research
 1947 Nuremburg Code
 1964 Declaration of Helsinki
 1979 Belmont Report
 1993 CIOMS International Ethical Guidelines
for Biomedical Research (Updated 2002)
 1997 ICH-GCP
 Nuremburg Code (1947)
 Voluntary participation is absolutely essential
• Voluntary consent
• free to withdraw at any time
 Minimization of risk
• Avoiding unnecessary suffering
• Risk-benefit assessment
• Able to stop the study at any time
 Scientific quality
• Qualification of researcher
• Adequate facility and means to protect subject
 Belmont Report, 1979
• Basic Principles of Research Ethics
1. Respect for Persons
• Informed consent
• Protection of vulnerable populations
2. Beneficence
• Non-malfeasance
3. Justice
• Fairness
 Declaration of Helsinki, 1964
World Medical Association
The origin of Ethical Principles for Medical Research
Involving Human Subjects
 The International Conference on
Harmonisation (ICH-GCP)

• GCP is defined as a standard for the design,

conduct, performance, monitoring, auditing,
recording, analysis and reporting of clinical
trials or studies
 The Goals of GCP
• 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
• GCP  Quality data through ethical research.
 13 Principles of GCP
• Clinical trials are conducted aiming at obtaining
evidence regarding efficacy and safety of products
• The conduct of Clinical Trial should respect Ethical
principles which is based primarily on the
Declaration of Helsinki.
• Uji Klinik dilaksanakan untuk mendapatkan bukti efektivitas
dan keamanan suatu obat.
• Pelaksanaan Uji Klinik harus menghormati prinsip etik yang
bersumber dari Deklarasi Helsinki
 Principles of GCP
• Ethics
– 1. Decl. Helsinki
– 2. Risk-benefit assessment
– 3. Right and safety of subjects
– 9. Informed consent
– 11. Confidentiality
• Scientific soundness: 4,5
• IRB: 6
• Data integrity: 10
• Quality
– 7, 8. Research team
– 12. Product
– 13. System
 Principle 1
• 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 requirement(s).

• Uji Klinik hrus dilaksanakan sesuai dengan prinsip etik yang

bersumber dari Deklarasi Helsinki, dan sesuai dengan
peraturan yang berlaku.

– Tiga prinsip Etik Dasar: respect for persons, beneficence,

and justice.
 Principle 2
• Before a trial is initiated, foreseeable risks and
inconveniences should be weighed against the
anticipated benefit for the individual trial subject and
society.
• A trial should be initiated and continued only if the
anticipated benefits justify the risks
• Sebelum memulai suatu Uji Klinik, antisipasi risiko dan ketidak
nyamanan harus dilakukan/ditimbang terhadap manfaat bagi
subjek penelitian dan masyarakat.
• Uji Klinik hanya boleh dimulai dan dilanjutkan bila imbang
manfaat-risiko dapat dibenarkan.
 Principle 3
• The rights, safety, and well-being of the trial subjects
are the most important considerations and should
prevail over interests of science and society.

• Hak, keamanan, dan kesejahteraan subjek penelitian harus

menjadi pertimbangan terpenting, dan harus diutamakan di
atas kepentingan ilmu pengetahuan dan masyarakat.
– Contoh pelanggaran:
• Tuskegee syphilis trial
• Hepatitis study of Willowbrook Institue
 Principle 9
• Freely given informed consent should be obtained
from every subject prior to clinical trial
participation.
– When a subject is not capable of giving informed
consent, the permission of a legally authorized
representative should be obtained in accordance with
applicable law.
• Persetujuan secara sukarela (persetujuan setelah
penjelasan, PSP) harus diperoleh dari setiap subjek
sebelum yang bersangkutan ikut dalam Uji Klinik
– Bila subjek tidak bisa/tidak kompeten memberikan
persetujuan, maka harus dimintakan izin dari wali yang sah,
sesuai dengan hukum yang berlaku.
 Principle11
• The confidentiality of records that could identify
subjects should be protected, respecting the privacy
and confidentiality rules in accordance with the
applicable regulatory requirement(s).

• Kerahasiaan data dan privacy subjek harus dijaga dan

dihormati sesuai dengan kebiasaan dan peraturan yang
berlaku.
 Principle 5
• Clinical trials should be scientifically sound, and
described in a clear, detailed protocol.
– Clear scientific basis
– Logical background
– Clear methodology

• Uji Klinik harus punya nilai ilmiah dan dituangkan

dalam protokol yang jelas dan rinci:
– Dasar ilmiah yang kuat
– Latar belakang yang logis
– Metodologi yang jelas
 Principle 4
• The available nonclinical and clinical
information on an investigational product
should be adequate to support the proposed
clinical trial.
• Uji Klinik yang diajukan harus didukung oleh data klinik dan
non klinik yang memadai.

–  investigator’s brochure
 Principle 10
• All clinical trial information should be
recorded, handled, and stored in a way that
allows its accurate reporting, interpretation,
and verification.
• Semua informasi berkaitan dengan Uji Klinik harus dicatat,
ditata laksana, dan disimpan sedemikian rupa sehingga
memungkinkan pelaporan, interpretasi, dan verifikasi yang
akurat.
If it is not written, it had never happen
 Principle 6
• A trial should be conducted in compliance with the
protocol that has received prior institutional review
board IRB)/ independent ethics committee (IEC)
approval/favourable opinion.

• Uji Klinik Harus dilaksanakan sesuai dengan protokol yang

sudah disetujui Komisi Etik
 Principle 7
• The medical care given to, and medical
decisions made on behalf of subjects should
always be the responsibility of a qualified
physician or, when appropriate, of a qualified
dentist.
• Tindakan medik yang diberikan, dan keputusan medik untuk
subjek merupakan tanggung jawab dokter (dokter gigi) yang
kompeten
 Principle 8
• Each individual involved in conducting a trial
should be qualified by education, training, and
experience to perform his or her respective
task(s).

• Setiap orang yang terlibat dalam pelaksanaan UK haruslah

memiliki kualifikasi yang cukup berdasarkan pendidikan,
pelatihan, dan pengalaman, untuk melaksanakan tugasnya
masing-masing.
– Curriculum vitae
 Principle 12
• Investigational products should be manufactured,
handled, and stored in accordance with applicable
good manufacturing practice (GMP). They should be
used in accordance with the approved protocol.

• Bahan uji harus dibuat, ditangani, dan disimpan sesuai

dengan aturan good manufacturing practice (GMP) yang
berlaku. Dan harus digunakan sesuai dengan protokol yang
sudah disetujui.
 Principle 13
• Systems with procedures that assure the
quality of every aspect of the trial should be
implemented.

• Semua sistem dan prosedur yang menjamin kualitas

dan segala aspek uji klinik, harus diterapkan.