present EC 190109

Role of EC/IRB

นพ.อน�นต์� มโนม�ยพ�บู ลย� พบู.,วทม (ระบูาดว�ทยาคล�น�ก).ว�ทยาล�ยแพทยศาสต์ร�กร�งเทพมหานครและวชิ�รพยาบูาล

Research process

Research processFormulate the problem

Review the literatures

Create hypothesis and objectives

Research design

Research methodology

-population, intervention, define variables, measurements

Data collection, analysis and interpretation

Communicate the result:

Presentation and publishing

History of Ethical Problems in Biomedical Research

History of informed consent

In 1900 , Dr. Albert Neisser, German physician, studied infected patients (mainl

y prostitutes) with syphilis without their co nsent.

Against by the academic community and public opinion

“A legally based, positivistic contract - theory of the patient doctor relationship" th

at was not adopted into German law

Nazism

Nazi Party (1920-1945)World War II

Nazi humanexperimentation A series of controversial medical

experiments on large numbers of prisoners during World War II .

Prisoners were coerced into participating: T hey did not willingly volunteer and there w

as never informed consent . Typically, the experiments resulted in death

, disfigurement or permanent disability.

Examples of Nazi Experiments Freezing Malaria Mustard Sulfonamide Sterilization Poison

Experiments with Poisons

The poisons were secretly administered to experimental subject

s in their food. The victims died as a result of the

poison or were killed immediately in order to permit autopsies .

Sterilization experiments

T o develop a method of sterilization w hich would be suitable for sterilizing

millions of people with a minimum of t ime and effort.

These experiments were conducted by means of -X ray , surgery

and various drugs . Thousands of victims were sterilized

compulsory .

Aftermath Many of the subjects died or were

murdered after the tests to study the effect post mortem

T he German doctors captured by Allied forces were put on trial which is

commonly known as the Doctors ' Trial

.

Japanese Experiments during WWII

T he results from Unit 731 were kept classified by the USA

T he majority of doctors involved were given pardons

The Nuremberg Doctors Trial of 1946

20 physicians. The judgment included a set of

standards knows as the Nuremberg Code.

Nuremberg Code

At the trial, several of the doctors arg ued in their defense that there was no

international law regarding medical experimentation.

T he development of the Nuremberg Code of medical ethics . 1947

Nuremberg Code

The Nuremberg code includes such principles as informed consent and absence of coercion; properly formulated scientific experimentation; and beneficence towards experiment participants.

Thalidomide

Thalidomide was approved as a sedative in Europe in the late 1950’s.

The FDA never approved the drug, but samples were sent to US doctors.

By 1961 thalidomide was shown to be very harmful to the fetus, interfering with the normal development of arms and legs.

Thalidomide

These events lead to the passage of the Drug Amendments of 1962 to the Food, Drug and Cosmetic Act.

This was the first US statues that required subjects be informed of a drugs experimental nature and to consent before starting the research study.

“Syphilis Victims in US Study Went Untreated for 40 Years”

US Public Health Service studies syphilis in Black men

Tuskegee Syphilis Study: 1932-1972

Tuskegee Syphilis Study: 1932-1972

When the study began in 1932, standard medical treatments for syphilis were toxic, dangerous, and of questionable effectiveness

By 1947 penicillin had become the standard treatment for syphilis. Prior to this discovery, syphilis frequently led to a chronic, painful, and fatal multisystem disease

The Belmont Report

is an important historical document in the field of medical ethics

The report was created on 1979 Prompted in part by problems arising from

the Tuskegee Syphilis Study (1932-1979) Department of Health, Education and

Welfare (HEW) revised and expanded its regulations for the protection of human subjects

The Three Fundamental Ethical Principles

respect for persons: protecting the autonomy of all people and treating them with courtesy and respect and allowing for informed consent;

beneficence: maximizing benefits for the research project while minimizing risks to the research subjects

justice: ensuring reasonable, and well-considered procedures are administered fairly (the fair distribution of costs and benefits.)

International Guidelines Nuremberg Code Declaration of Helsinki

Council for International Organizations of Medical Sciences (CIOMS)

International Conference on Harmonization “Guideline for Good Clinical Practice”(ICH/GCP)

WHO guidelines

The Declaration of Helsinki

The Declaration of Helsinki was developed by the World Medical Association (WMA), as a set of ethical principles for the medical in 1964 community regarding human experimentation.

It is widely regarded as the cornerstone document of human research ethics

Although it is not a legally binding instrument in international law

The Declaration of Helsinki

The Declaration developed the ten principles first stated in the Nuremberg Code.

The Declaration more specifically addressed clinical research.

A notable change from the Nuremberg Code was a relaxation of the conditions of consent, which was 'absolutely essential'

First revision (1975)

Introduction the concept of oversight by an 'independent committee‘ which became a system of Institutional Review Boards (IRB) in the US, and research ethics committees or ethical review boards in other countries.

In the United States regulations governing IRBs came into effect in 1981

Second to Sixth Revisions (1975-2008) In1994, WHO group concluded "Placebo-

controlled trials offer the best option for a rapid and scientifically valid assessment of alternative antiretroviral drug regimens to prevent transmission of HIV".

Direct conflict with CIOMS, which stated "The ethical standards applied should be no less exacting than they would be in the case of research carried out in country”

The Declaration of Helsinki

From 1982, the Declaration was not alone as a universal guide

CIOMS and the World Health Organization (WHO) had also developed their International Ethical Guidelines for Biomedical Research Involving Human Subjects.

Principles of the Declaration

The Declaration is morally binding on physicians

The obligation overrides any national or local laws or regulations, if the Declaration provides for a higher standard of protection of humans than the latter.

Investigators still have to abide by local legislation but will be held to the higher standard.

The CIOMS Guidelines

Created in 1993 by the Council for International Organizations of Medical Scie

nces (CIOMS) and updated in 2002 these 21 guidelines (15 in the original repor

t) address issues including informed conse nt, standards for external review, recruitme

nt of participants, and more. The Guidelines are general instructions and

principles of ethical biomedical research

Good Clinical Practice (GCP)

is an international quality standard It also provides assurance of the safety and

efficacy of the newly developed compounds.

GCP Guidelines include standards on how clinical trials should be conducted , define t

he roles and responsibilities of clinical trial sponsors, clinical research investigators, a

nd monitors.

ICH-GCP

The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH)

is a project that brings together the regulatory authorities of Europe, Japan and the United States and experts from the pharmaceutical industry in the three regions to discuss scientific and technical aspects of pharmaceutical product registration.

ICH GCP overview

Guidelines for the investigator Guidelines for the trial sponsor (industrial,

academic) Guidelines for the clinical trial protocol and

protocol amendments Guidelines for the Investigator's brochure

IRB and EC

I nstitutional R eview Board (IRB) also known as an independent ethics

committee (IEC) or ethical review board (E RB)

to approve, monitor, and review biomedical and behavioral research involving humans

to protect the rights and welfare of the rese arch subjects.

USA regulations, (FDA and Office for Human Research Protections, OHRP) have

empowered IRBs to approve, modifications or disapprove research.

Ethics Committee (EuropeanUnion)

The Ethics Committee , according to Directive 2001/20/EC, is an independ

ent body With the Clinical Trials Directive, the E

uropean Union (EU) envisioned a har monisation of research ethics commit

tees (RECs) across Europe,.

IRB or EC Approval Criteria

Risks to subjects minimized Risks to subjects reasonable in relation to

anticipated direct benefit knowledge to be gained

Selection of subjects equitable Informed consent sought and documented Appropriate provisions for monitoring safety Provisions for confidentiality Additional safeguards for vulnerable

populations

WHO guidelines

Operation guidelines for Ethical Committees that review biomedical research, WHO 2000

The basic principles of the ethical issues

Respect for persons Beneficence (beneficent) Justice (fairness)

Vulnerable population include some individuals who have limited

autonomy such that they cannot fully participate in the consent process.• Prisoners• Children• Subordinate Individuals• Decisionally Impaired.

Informed Consent Informed consent: right to know,

right to self determination The hallmark of consent are

informed understoodVoluntary - Oral, implied: to communicate

and idea without saying it directly , written consent

Research Ethics in Thailand

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กร�งเทพมหานคร ใชิ!ระยะเวลาประมาณ 2 - 3 เด/อน

Funding

Funding in BMA Medical College and Vajira Hospital

กองท�นว�จ�ยทางการแพทย� ม ลน�ธ�วชิ�รพยาบูาล ท�นละไม#เก�น 40 000, บูาท

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Communicate The Results

Knowledge

Index Medicus Pubmed Impact factor Citation International journal National journal

Index Medicus

is a bibliographic listing of references from biomedical journals worldwide

National Library of Medicine, National Institute of Health

Pubmed (www.nlm.nih.gov) included 4,844 journals till January 2005

N Eng J Med, JAMA, Lancet, Ann Intern Med, Annu Rev Med, Arch Intern Med, BMJ, Am J Med,

ICMJE: International Committee of Medical Journal Editors Informal meeting of medical journal

editors in 1978: Vancouver group Expanded and evolved to ICMJE Multiple editions of the Uniform

Requirements for Manuscripts Submitted to Biomedical Journals. (last revision 2001)

Clinical trial registration www.icmje.org

Journal impact factor (JIF)

Institute for Scientific Information (ISI) in USA

Journal citation report

Journal impact factor (JIF)

ISI was founded in 1961 AD. Tool for selecting the journal into the

database 3 databases

Databases of ISI

Science citation index 5876, journalsHigh JIF: N Eng J Med, JAMA, Lancet, Ann Intern Med, Annu Rev Med, Arch Intern Med, BMJ, Am J Med, Medicine,

Social science citation index 1700, journals

Arts and humanities citation index 1130 journals

3 indexes of Journal impact factor (JIF)

journal impact factor immediacy index cited half-life โดยเป5นท')ทราบูก�นโดยท�)วไปว#า วารสารใดม'ค#าด�ชิน'ด�งกล#าวส ง

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มาต์'พ�มพ�เผู้ยแพร#ได!มากข้*4น

JIF = number of citation in year (x) from articles in year (x-1) and

(x-2) of that journal / sum of articles published in year (x-1) and (x-2) of that journal

Technique of calculation

Thailand Citation Index (TCI)

Citation information of local journals Report Thai Journal Impact Factor

List of approved local journals ส.าน�กงานคณะกรรมการการอ�ดมศ*กษา

(สกอ.) โดยส.าน�กส#งเสร�มและพ�ฒนาสมรรถนะบู�คลากร

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ประกาศ ม�ถ�นายน 2550

List of approved international journals

Asian Pacific Journal of Allergy andImmunology

The Southeast Asian Journal of Tropical Medicine and Public Health

Journal of the Medical Association ofThailand

Siriraj Hospital Gazette (สั่�รุศ�รุ�รุ�ช) Chulalongkorn Medical Journal

(จั�ฬ�ลังกรุณ�เวิชสั่�รุ)

List of approved international journals ScienceAsia: Journal of the Science Society of

Thailand Songklanakarin Journal of Science and

Technology ECTI Transactions on Electrical Eng., Electronics,

and Communication Thai Journal of Agricultural Science Asian Journal of Energy and Environment Journal of Environmental Research Thai Forest Bulletin

List of approved national journals เป5นวารสารท')แนะน.าให!ใชิ!เพ/)อต์'พ�มพ�เผู้ยแพร#

ว�ทยาน�พนธ�ระด�บูปร�ญญาโท หร/อต์'พ�มพ�เผู้ยแพร#ว�ทยาน�พนธ�ระด�บูปร�ญญาเอกส.าหร�บูกล�#มมหาว�ทยาล�ยราชิภ�ฎ มหาว�ทยาล�ยเทคโนโลย'ราชิมงคล และกล�#มมหาว�ทยาล�ยต์�4งใหม# รวมถ*งผู้ลงานข้องน�กว�ชิาการ

ประกอบูด!วยวารสารจ.านวน 39 ฉบู�บู

List of approved national journals Thai Journal of Hematology and

Transfusion Medicine Vajira Medical Journal (วิช�รุเวิชสั่�รุ) Journal of the Nephrology Society of

Thailand Internal Medicine Journal of Thailand วิ�รุสั่�รุสั่�ขภ�พจั�ต้แห$งปรุะเทศไทย ศรุ�นคำรุ�นทรุ�เวิชสั่�รุ

Thank youfor

your attention