Role of EC/IRB นพ . อนันต์ มโนมัยพิบูลย์ พบ ., วทม ( ระบาดวิทยาคลินิก ). วิทยาลัยแพทยศาสตร์กรุงเทพมหานครและวชิรพยาบาล
Research process Formulate 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 (mainly prostitutes) with syphilis without their consent.
Against by the academic community and public opinion
“ A legally based, positivistic contract theory of the patient-doctor relationship" that was not adopted into German law
Nazi Party ( 1920-1945 )
World War II
Nazi human experimentation
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 was never informed consent .
Typically, the experiments resulted in death, disfigurement or permanent disability.
Examples of Nazi Experiments
Experiments with P oison s
The poisons were secretly administered to experimental subjects in their food.
The victims died as a result of the poison or were killed immediately in order to permit autopsies .
T o develop a method of sterilization which would be suitable for sterilizing millions of people with a minimum of time and effort.
These experiments were conducted by means of X- ray , surgery and various drugs .
Thousands of victims were sterilized compulsory .
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
The judgment included a set of standards knows as the Nuremberg Code .
At the trial, several of the doctors argued in their defense that there was no international law regarding medical experimentation.
T he development of the Nuremberg Code of medical ethics . 1947
The Nuremberg code includes such principles as informed consent and absence of coercion ; properly formulated scientific experimentation; and beneficence towards experiment participants.
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.
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.)
Declaration of Helsinki
Council for International Organizations of Medical Sciences (CIOMS)
International Conference on Harmonization “Guideline for Good Clinical Practice” (ICH/GCP)
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 ".
D irect 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 Sciences (CIOMS) and updated in 2002
these 21 guidelines ( 15 in the original report) address issues including informed consent , standards for external review, recruitment 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 the roles and responsibilities of clinical trial sponsors, clinical research investigators, and monitors.
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 B oard (IRB )
also known as an independent ethics committee (IEC) or ethical review board (ERB)
to approve, monitor, and review biomedical and behavioral research involving humans
to protect the rights and welfare of the research subjects .
USA regulations, ( F DA and Office for Human Research Protections, OHRP ) have empowered IRBs to approve, modifications or disapprove research.
Ethics Committee (European Union)
The Ethics Committee , according to Directive 2001/20/ EC , is an independent body
With the Clinical Trials Directive , the European Union (EU) envisioned a harmonisation of research ethics committees (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
Operation guidelines for Ethical Committees that review biomedical research, WHO 2000
The basic principles of the ethical issues
Respect for persons
include some individuals who have limited autonomy such that they cannot fully participate in the consent process.
Informed consent: right to know, right to self determination
The hallmark of consent are
- Oral, implied: to communicate and idea without saying it directly , written consent