ETHICS IN MEDICAL RESEARCH

Teguh Wahju Sardjono Ethics Committee for Medical Research Faculty of Medicine University of Brawijaya

August 2010

Objectives

To explain the role of moral and ethics in health research To identify ethic problems in health research To determine ethical choices in conducting health researches and ethical dilemmas in medical practice

ETHICS
Ethics is the branch of philosophy that deals with distinctions between right and wrong with the moral consequences of human action (Coughlin & Beauchamp, 1996)

ETHICS
Consists of three meanings : 1. Moral values or norms that used to be a guidelines of individuals or groups in their activities 2. A moral philosophy that deals with distinctions between right and wrong 3. Collection of moral rules ethical codes (K. Bertens, 2004)

Defining Research with Human Subjects

What is Research?
o A systematic investigation which designed to prove the

hypothesis and produce new concepts or information and contribute to generalizable knowledge.
o Look forward how the knowledge will be used and its

usefulness in practice.
o Developing new concepts knowledge based

development
o Developing new system and application in Health

service Knowledge based health systems

knowledge vs KNOWLEDGE

knowledge: is used for internal purposes only, to improve a curriculum, see if students are graduating on time, to measure substance abuse on campus - but no publication or public presentations will be made then it is not research designed to contribute to generalizable knowledge. KNOWLEDGE: when it is published (thesis and grant reports count), presented at a conference, sent to another organization so that others may build upon it, then it is furthering science, or advancing a field and it is generalizable knowledge.

Research Involving humans = Biomedical Researches (WHO)

o o o o o o o o o Pharmaceutical Researches Research Using Medical Equipments Medical Radiations Radio-Imaging Procedures Surgical Procedures Medical Records Biological samples (waste or extra materials) Epidemiological studies Social and psychological studies

What and who are Human Subjects?

Any living individual about whom an investigator (professional or student) conducting research, through data obtained from intervention or interaction with the individual, or identifiable private information Health research and development can also be performed on human or corpse, family, community, animals, plants, microorganisms or environment [PP No. 39/1995:5(1)]

How are the Human Subjects involved?

Human Subjects are involved if: The person is alive (or death), and Data pertaining to the person will be obtained through intervention (e.g., blood sample, biopsy) interaction (e.g., interview) a private confidential source (e.g., medical records) necropsy

Researches involving humans (biomedical researches)

Has ethical, law and social implications (ELSI) Should be some mechanisms which regulate and guarantee that medical research will always : respect and protect the life, health, privacy and dignity of volunteers who are willing to be the research subjects Follow the rule of kindly handling experimental animals (humane) Declaration of Helsinki point 11 and 12

Direct vs Indirect Interactions

Research may involve direct interactions or interventions such as obtaining data by interview, taking blood samples or treating patients in part to gain generalizable knowledge. Indirect interaction by analyzing specimens or data that already exist or participation of subjects in an indirect activity, particularly if results will be published, constitutes human subjects research.

Researches require IRB Approval

o IRB (Institutional Review Board) Ethics

Committee o the local/institutional panel that reviews human subject protocols. o reviews and approves human subjects research protocol o ALL Biomedical Researches require IRB Approval Ethical Clearance (EC) o Mainly : Protection of Human Subjects from Research Risks

Why does Health Research needs IRB Review?

Protection of Researcher from Ethical, Law and

Social Implications (ELSI) Protection of Human Subjects from Research Risks Requirement for funding (sponsored research) Requirement for publication

ALL Research includes:

Research conducted at another institution Research in foreign countries Research conducted in courses Faculty-supervised student research Research at a pilot or feasibility stage Research involving secondary use of data Research using waste or extra material

The Three Belmont Principles

Respect for persons/humane Beneficence do no harm Justice equal

What are the IRB Reviewed?

The IRB will review the involvements of Human Subjects in the research. Is it safe? (Beneficence) Is the data confidential? (Respect) Is the participation informed and voluntary? (Respect) Are the recruitment, selection, and treatment of subjects fair? (Justice)

Why Should We Protect the Human Subjects?

The Unethical Biomedical Researches
1946 - Nuremberg Trial :
developing a vaccine for typhus by exposing prisoners Nuremberg Code -1947

Tuskegee Syphilis Study: 1930s-1972 400 black males - death rate twice as high as control Jewish Chronic Disease Hospital Study - 1963 Injection of live cancer cells into chronically ill patients to develop information on the nature of the human transplant rejection process Willowbrook Study - 1963-1966 : Study natural history of infectious hepatitis. Subjects were all children who were deliberately infected.

History (1)
1947 1964 1966 1979 Nuremberg Code Declaration of Helsinki (renewed year 2000 in

Edinburgh)
Beecher Publication (questionable practices) Belmont Report (USA)

1982
1990

Proposed International Guidelines CIOMS

International Guidelines for Ethical Review of Epidemiological Studies CIOMS

1993
1996

International Ethical Guidelines for Biomedical Research Involving Human Subjects CIOMS
ICH Good Clinical practice Guidelines
(CIOMS = Council for International Organization of Medical Sciences)

History (2)
2000 - Operational Guidelines for Ethics Committees that review biomedical research (WHO-TRD) - Ethical Considerations in HIV preventive vaccine research (UNAIDS) - Development of FERCAP in Bangkok - Ethical Guidelines for Biomedical Research on Human Subject (India) - Revision of Declaration of Helsinki, Edinburgh - Surveying and Evaluating Ethical Review Practices (WHO-TRD) - CIOMS International Guidelines

2002

Ethics in Medical Research in Indonesia

1982 1984 1986 FKUI Publication : Etik Penelitian Kedokteran Ethical Committee on Medical Research FKUI Workshop FKUI: Indonesian Ethical Guidelines for Medical Research (Pedoman Etik Penelitian Kedokteran Indonesia) National Committee of Medical Research Ethics Balitbangkes

1989

1992 UU No.23/1992 about Health punishment 1995 PP No.39/1995 about Litbangkes informed consent

Ethics in Medical Research in Indonesia

2000 - 1st Congress of BioEthics and Humaniora -Yogyakarta

2001 -

1st Workshop on Ethical Research - Bogor Research Ethic Course - Bogor Mapping Study of Ethics Commission in Indonesia Decision of Head of POM No. 2002 about Procedures for Clinical Trials - Guidelines for Good Clinical Trial Procedure in Indonesia

2002 - 2nd Workshop on Ethical Research - Reg.Min.Hlth No. 1333/2002 about Approval of Research involving humans - RegMinHlth No. 1334/2002 about National Ethical Committee on Medical Research

National Commission for the Protection of Human Subjects

1974 - Established by a Congressional Mandate 1979 - Belmont Report - ethical principles that guide all research today 1981- Code of Federal Regulations Title 45 CFR Part 46, Protection of Human Subjects minimum ethical and legal obligations 1994 - National Bioethics Advisory Commission. 1998 - Freedom of Information Act Amendment

PERATURAN PEMERINTAH RI tentang Penelitian dan Pengembangan Kesehatan

Barang siapa yang menyelenggarakan litbang pada manusia tanpa persetujuan tertulis dan tanpa informasi terlebih dahulu, dapat dipidana denda maksimum Rp.10 juta (psl 20 PP No. 39 tahun 1995), Barang siapa yang menyelenggarakan litbang pada manusia tanpa memperhatikan kesehatan dan keselamatan yang bersangkutan serta norma yang berlaku dalam masyarakat, dihukum dengan pidana penjara maksimum 7 tahun dan/atau denda maksimum Rp.140 juta (Psl 81 ay.2 UU Keshtn, 1992)

The Three Belmont Principles

Respect for persons acknowledges dignity and freedom of every person requires informed, voluntary consent Beneficence maximize benefit, minimize harm risk must be reasonable Justice equitable recruitment and selection and fair treatment of research subjects

Respect for persons

Informed consent

why do we have to know?

Learning objectives

Informed Consent
Consent given by a competent individual who has received the necessary information, who has adequately understood the information, who after considering the information has arrived at a decision without having been subjected to coercion, undue influence or inducement, or intimidation ( CIOMS)
(CIOMS = Council for International Organization of Medical Sciences)

Researcher should understand

That the primary aim of informed consent is based on respect for person, adequate understanding and voluntary consent, not a signature on a piece of paper That informed consent is at most a necessary condition of ethically acceptable research Issues related to readability of informed consent forms Issues related to informed consent with minors and vulnerable populations Exceptions to informed consent requirements Cross cultural issues related to informed consent

The Informed Consent Process

More important : the consent process !

Communication between the researcher & the prospective subject, not just a single event or a form to be signed ! Exchange of information - Listening, Explaining, Answering questions, Repeating, Assuring understanding Begins with initial contact Continues throughout the course of the study

General Requirements

Informed consent must be prospectively obtained from the subject or legally authorized representative of the subject Information must be conveyed in understandable language. Subjects must be given sufficient opportunity to consider whether they want to participate or not. Consent must be given without coercion or undue influence. Subjects must not be made to give up legal rights or be given the impression that they are being asked to do so

Information Needed for Informed Consent

Research Purpose Research Procedures Risks Benefits Alternatives Level of Confidentiality Disclosure of Conflict of Interest Research Related Injury Contact Information Withdrawal

Informed Consent

Not just about signing a form only It is about understanding and willingness to participate. Time to consider decision. Understanding of risks and benefits Understanding the procedures Understanding that they do not to have to be volunteer Understanding that they can withdraw at any time without penalty

Informed Consent Form

Follow Whitworths sample form. Washington state law requires written consent prior to taping conversations. Default to the more stringent criteria. Keep separate from data and locked. Signed prospectively/before participation occurs.

Recruitment/Selecting Participants
Non-biased Non-power

based such

as:
Therapist-Client

Student Employees Proxy (parents or other relatives)

Teacher-

Special Consideration !!!

Children and minors Elderly Prisoners Cognitively Impaired Persons Fetus and Human IVF Women Traumatized and Comatose Terminally Ill Minorities Students and Employees

Children

Under the age of 18 - parental consent is required. Child must give assent - affirmative agreement on part of the child to participate. Remember: Not all your students are over 18.

Subjects unable to give consent

- Whenever the minor child is in fact able to give consent, the minors consent must be obtained in addition to the consent of the minors legal guardian ( Declaration of Helsinki ) - Incompetent adults : developmentally disabled, cognitive impaired elderly, unconscious patient or inebriated (OHRP)

Liability

The IRB process protects you and the college. If you follow the procedures and research is approved, you are protected under the colleges risk management program. If you do not seek IRB approval or go ahead with something not approved, you are not protected.

Unsur-unsur Informed Consent (PerMenKes tentang informasi yg harus diberikan kpd masing-2 subyek)
Identitas peneliti Penjelasan menyeluruh tentang penelitian, terutama tujuan dari penelitian tersebut, prosedur eksperimental dan perkiraan lama partisipasi Deskripsi resiko atau ke-tidak-nyaman-an subyek yang dapat diperkirakan; Deskripsi keuntungan yang diharapkan, jika ada Pemberitahuan tentang prosedur alternatif terhadap keikutsertaannya jika tersedia, jika ada; Pernyataan yang menjelaskan sejauh mana kerahasiaan pribadi akan dilakukan

Unsur-unsur Informed Consent (lanjutan)

7. penjelasan harus diberikan mengenai semua kompensasi atau pelayanan medik, jika ada, yang tersedia untuk subyek jika terjadi luka 8. siapa yang harus dihubungi jika ada pertanyaan mengenai penelitian serta hak subyek penelitian; 9. siapa yang harus dihubungi jika subyek mengalami luka yang terkait dengan penelitian;

10. penjelasan bahwa partisipasi tersebut adalah sukarela.

Contoh Penjelasan untuk mengikuti Penelitian

Kami adalah . staf peneliti dari ..., dengan ini meminta anda untuk berpartisipasi dengan sukarela dalam dalam penelitian yang berjudul .. Tujuan dari penelitian ini adalah . sehingga hasil penelitian ini dapat memberi manfaat berupa.. .. . Penelitian ini akan berlangsung selama . .. dengan sampel berupa .. Prosedur pengambilan sampel adalah . Cara ini mungkin akan menyebabkan , tetapi anda tidak perlu khawatir karena . Keuntungan yang anda peroleh dengan keikut sertaan anda adalah

Seandainya anda tidak menyetujui cara ini, maka anda dapat memilih cara lain yaitu...., atau anda boleh tidak mengikuti penelitian ini samasekali. Untuk itu anda tidak akan dikenai sanksi apapun Nama dan jatidiri anda akan tetap dirahasiakan

Contoh Pernyataan Persetujuan untuk Berpartisipasi dalam Penelitian

Saya yang bertanda tangan di bawah ini menyatakan bahwa 1. Saya telah mengerti tentang apa yang tercantum dalam lembar persetujuan di atas dan yang telah dijelaskan oleh tim peneliti 2. Dengan ini saya nyatakan bahwa secara sukarela saya bersedia untuk ikut serta menjadi salah satu subyek dalam penelitian yang berjudul : .. Malang. .. Saksi ( ) Subyek (.)

Conclusion
Medical Research Unlike non medical research Living organisms or human subjects Direct or indirect interaction Three important aspects: Ethics, Law, and Social Implications (ELSI) Needs ethical clearance (EC)

The Three Belmont Principals : Beneficence Respect for persons Justice Informed consent

Conclusion
IRB approval (Ethical clearance = EC) Doesnt mean that it inhibits the process of research and researcher The IRB process (EC and IC) protects you and the college from ELSI Requirement for funding and publication