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Introduction

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What is the right thing to do?

How should we do our research in a

responsible way towards the

participants ?

How do we avoid, minimize or balance

any kind of risk/harm to the study

subject as the result of the research?

What makes an effective councelor?

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Definitions and concepts

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What is ethics?

Principles of Biomedical Ethics

Regulations in Research Ethics

Research Ethics Committee

Ethical review in Ethiopia

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Ethics: Greek word ethos - custom or

culture

A branch of philosophy that deals with

moral principles

Right way of doing; based on basic

human values; respect for human

dignity.

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Ethics

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It is a set of principles that tells as whether we do right or wrong.

Ethics provide guidelines for acceptable behavior.

Gives a philosophical account of justified behavior and belief.

Systematic study of morality Influenced by various factors

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Morality: It is beliefs and standards of good and bad, right and wrong, that people actually do and should follow in a society.what people do and believe.A science concerned with the

distinction between right and wrong.

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Medical Research: “research involving

intervention in the integrity of a person,

human embryo or human fetus for the

purpose of increasing knowledge of the causes,

symptoms, diagnosis, treatment and prevention

of diseases or the nature of disease in general”

Medical research act, Helsinki, April 1999.

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Bioethics: "the application of theories,

principles, and general ethical rules to

the particular problems of therapeutic

practice and of biomedical and biological

research.“

Biomedical Ethics: the systematic study of

value questions that arise in health care

delivery and in biomedicine.

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“Specific bioethical issues attention

needed:-

Euthanasia, new reproductive technologies,

cloning, human experimentation, genetic

engineering, abortion, informed consent, AIDS,

organ donation and transplantation, and

managed care and other concerns in the

allocation of health care resources.”

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Historical Back Ground

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There have been historical cases of unethical

research that have been contributed to how we

work with participants today.

These studies led to the creation of the Belmont

Report and the Institutional Review Board (IRB)

which were formed to protect human subjects

involved in research.

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Some example

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The unethical Nazi experiment (WWII)

The Tuskegee Syphilis study (1932-1972)

The Willow brook study (1963-1966): New york

The Jewish Chronic Disease Hospital Study 1963:NY

The Stanley Milgram's experiment (after WWII)

The Laud Humphrey's "Tearoom Sex“ study (1960s)

Humphrey’s PhD.

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NAZI Experiments

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The history of research ethics begins with the

tragic history of research abuse by Nazi

doctors during World War II.

A total of 16 German physicians practiced

unethical medical experiments on Jews,

gypsies, and political prisoners.

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NAZI Experiments

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In 1947, out of this horror, came the Nuremberg Code and other international codes of ethics written to protect research participants.

Under this code, the physicians were convicted for crimes against humanity. This also led to standards in research requiring that subjects participate voluntarily and are informed of the risks of the research.

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Nazi experiments

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The Nazi experiments fell into three basic categories

1. Medico-Military Research;

2. Miscellaneous, Ad Hoc

Experiments; and,

3. Racially Motivated Experiments

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1. Medico-Military Research

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Includes the following;a. Freezing Experimentsb. High Altitude Experimentsc. Sea Water Experimentsd. Sulfanilamide Experimentse. Tuberculosis Experiments:

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1 Medico-Military Research

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A. High Altitude Experiments: To determine the best means of rescuing pilots from the risks of high altitude when they abandoned craft (with or without oxygen equipment) and were subjected to low atmospheric pressures. Used a decompression chamber to simulate high altitude conditions. Dissect several of the victims' brains, while they were still alive, to demonstrate that high altitude sickness was a result of the formation of tiny air bubbles in the blood vessels of the subarachnoid part of the brain.

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B. Freezing Experiments: Prisoners were immersed into tanks of ice water for hours at a time, often shivering to death, to discover how long German pilots downed by enemy fire could survive the frozen waters of the North Sea. 300 prisoners were victimsC. Sea Water Experiments: Tests on the potability of sea water were conducted at Dachau on 90 Gypsy prisoners. The subjects were given unaltered sea water and sea water whose taste was camouflaged as their sole source of fluid.

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Medico-Military …..

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D. Sulfanilamide(C6H8N2O2S) Experiments

Wartime wounds were recreated and inflicted on

healthy Jews designated to be treated by the new

drug.

Wounds deliberately inflicted on the experimental

subjects were infected with bacteria such as

streptococcus, gas gangrene and tetanus.

Circulation of blood was interrupted by tying off

blood vessels at both ends of the wound to create a

condition similar to that of a battlefield wound.

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Medico-Military …..

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E. Tuberculosis Experiments: To determine whether there were any natural immunities to Tuberculosis (TB) and to develop a vaccination serum against TB. To disprove the popular belief that TB was an infectious disease. "inferior organism of the Jews.” Injected live tubercle bacilli into the subjects' lungs to immunize against TB. And also removed the lymph glands from the arms of twenty Jewish children.

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2. Miscellaneous, Ad Hoc Experiments

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Conducted unspeakable varieties of

torture that carried no pretense of

scientific inquiry. E.g

a. Poison Experiments: IV injection of

phenol gasoline and cyanide on

Russian prisoners.

To see how fast the subjects die.

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Miscellaneous…..

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b. Wound Experiments: the cause of death

of most soldiers on the battlefield was

hemorrhage, to develop a blood coagulant to

be administered to the German troops before

they went off to war.

Tested coagulant by observing the rate of

blood drops that would ooze from freshly cut

amputation stumps of living and conscious

prisoners at the Dachau crematorium.Shoot

Russian prisoners in the spleen whenever to

take extra blood to test.

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3.Racially Motivated Experiments

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Towards Jewisha. Artificial Insemination

Experiments:b. Sterilization Experiments:

c. Twin Experimentsd. Jewish Skeleton Collection:

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A. Artificial Insemination Experiments

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Racially …..

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B. Sterilization Experiments:

Thousands of prisoners had their genitals

mutilated.

Injections of caustic substances into their

cervix or uterus, producing horrible pain,

inflamed ovaries, bursting spasms in the

stomach, and bleeding.Young men had their testicles subjected to

large doses of radiation and were subsequently castrated to ascertain the pathological change in their testes.

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C. Twin Experiments: Jewish twins kept alive to be used in Josef Mengele's medical experiments. These children from Auschwitz were liberated by the Red Army in January, 1945.

D. Jewish Skeleton Collection: wished to acquire a large collection of Jewish skulls and skeletons to form a museum dedicated to the extinct Jewish race.

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Tuskegee Syphilis Study(Bad Blood) (1932)

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Syphilis is a venereal disease spread during sexual intercourse.

It can also be passed from mother to child during pregnancy. It is caused Treponema Pallidum.

It has three clinical stages 1. primary 2. Secondary 3. Tertiary

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Tuskegee Syphilis Study(Bad Blood) (1932)

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A 40-year project administered by the US PHS in Macon County, Tuskegee, Alabama

Purpose: Evaluate the natural history of untreated Syphilis, in humans Population.

The American Government promised 400Afro-American men free treatment for “bad blood” which had become an epidemic in the county.

The study sample was made up of poor, African American men who were told that they had "bad blood".

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The treatment was never given to the men and was in fact withheld.

These men did not receive standard treatment for syphilis even when penicillin was available later during the study.

Were not informed of the research design and it's risks to them.

The investigators were government physicians, respected men of science, who published their reports of the study in medical journals.

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The government doctors who participated in this study failed to obtain informed consent from the subjects.

Invasive procedures like lumbar puncture was used to get data on alive subjects.

The information for the experiment was to be collected from autopsies of the men, and they were deliberately left to degenerate under the ravages of tertiary syphilis.

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Tuskegee ….

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The study's unethical features did not come to light until 1972 when Jean Heller who broke the story.

By this time, over one hundred of the infected men died and others suffered from serious syphilis related conditions.

www.tuskegee.edu/bioethics

04/15/202334Bil Clinton...Apologize the remaining victims- 1997

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Willowbrook Hepatitis Study 1963‐1966

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Would YOU like to be injected with Hepatitis?

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Willowbrook Hepatitis Study 1963‐1966

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New YorkMentally defective children deliberately

infected by hepatitis virus .”Designed to : Gain an understanding of

the natural history of infectious hepatitis.

– Test the effects of gamma globulin to prevent or

ameliorate the disease.During the study the school closed door to all

sections except the “hepatitis section”

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The Jewish Chronic Disease Hospital Study 1963 -New York

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To develop information on the nature of the human transplant rejection process.

These studies involved the injection of live cancer cells into patients who were hospitalized with various chronic debilitating diseases.

Researchers said that consent had been given orally, but was not documented.

Patients were not told that they would receive cancer cells.

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Individual Assignment1 (10%)

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1. The Stanley Milgram's experiment

(after WWII)

2. The Laud Humphrey's "Tearoom Sex“

study (1960s) Humphrey’s Phd

Font size 12pt,Times new roman, 1.5 Line spacing, Max 1 page

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Research Ethics:

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Why Research Ethics?Research is itself ‘ethical’However: Tuskegee, Nazi experiment

etc.More generally: patients are vulnerable –Sick –Care or science? –Dependency and pressure / seduction

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Research Ethics

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Research ethics: involves the application of fundamental ethical principles to a variety of topics involving scientific research. These include the design and implementation of research involving human experimentation, animal experimentation, various aspects of academic scandal, including scientific misconduct (such as fraud, fabrication of data and plagiarism)

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Principles of Biomedical Ethics

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Principles Biomedical ethics

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The basic ethical principles: are those general judgments that serve as a basic justification for ethical evaluations of human actions.

They are considered universal regardless of geographic, economic, legal and political boundaries.

Researchers are obliged to assure that these principles are followed while conducting research involving human participants.

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Principles….

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Ethical guidelines assist both investigators and ethical review committees in acting responsibly.

Epidemiological studies in the past were widely regarded as not raising any significant ethical issues and were commonly carried out without approval of an ethical review committee.

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Ethical Principles

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Four basic ethical principles

1. Respect for persons

2. Beneficence: the act of doing good

3. Non-maleficence: not doing harm

4. Justice: fairness or moral rightness

(Based on Belmont Report, 1979)

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1. Respect for person’s:

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Respect for persons; autonomy, informed choice and confidentiality. i. Autonomy: right of self determinationAn autonomous person is one who is

capable of deliberation about personal goals and of acting under the direction of such deliberation.

To respect autonomy is, therefore, to give weight to the considered opinions and choices of the individual, while refraining from obstructing his/her actions.

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Respect for person’s ….

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Respect for persons demands the voluntary participation of the research participant with adequate information

It refers to the investigator to respect each participant as a person capable of making an informed decision regarding participation in the research study.

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Respect for person’s ….

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ii. Informed consent : Voluntary participationInformed: everything should be revealed to

the study subject or the surrogate; No fact should be concealed

They should be told about the purpose of the research, procedures and interventions like randomization, placebo, prior animal research, possible therapeutic benefits, potential risks etc. Who pays for undesired outcomes? Researchers? Insurance? Subjects?

Do not give more hope than is justified.The possibility to withdraw from the

experiment/interview at any time.

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Informed consent

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Respect for persons…..

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Non disclosure for scientific Reason:Deception is unacceptable! Even if

disclosure might result in refusal of consent

But it is not always necessary to reveal every detail if there is a risk of invalidating the research. General rather than particular disclosure is sufficient and ethical. E.g. randomization to experimental and control groups)

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Respect of …

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Surrogacy:In case of competent individual, decisions

should be made by the person. When the person is not competent (minors, mentally handicapped), decisions are made by a surrogate (legally authorized representative for the subjects)

Such a study is justified only if mentally competent adults are not suitable subjects. (E.g. pediatric drugs, psychiatric medications)

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Respect for ..

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Surrogates may use one of the following 3 principles to arrive to a decision

1. Substitute judgment principle: if the surrogate knows what the subject wants or would want in the situation2. Best interest principle: possible ‘best interest’ of the person; works in the absence of risk. 3. Rational choice principle: consideration of the good and evil consequences for the others as well as the subjects

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Elements of Written Consent

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PurposeProceduresVoluntary ParticipationHow the information will be usedHow to opt out at any pointHow to contact the researcherSignatures

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Respect…

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iii. Confidentiality: The use of information for any purpose other than that to which participants consented is unethical to the participants.The privacy of individual participant

needs to be kept through out the investigation by the researcher(s).

To protect participants from possible harm at the revelation of information

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2. Beneficence and Non-maleficence

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Do not harmMaximize possible benefits and

minimize possible harms.Direct benefit to subjectOverall benefits to society “do no harm” : The Hippocratic oath: a

fundamental principle of medical ethics

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B. Beneficence and Nonmaleficence

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Risks:The following need to be noted with regard to risks:To Whom

Research participant: Is the risk limited only to the research participant?

Community: Does the risk extend to the community?

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Beneficence and Nonmaleficence

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Types Physical: any damage to any of the organs, e.g., handicapped

Social: offence by the society, e.g., stigma

Psychological: a feeling of discomfort, e.g., stress

Economic: loss of earning capacity, e.g., loosing job because of getting involved in a research which the employer does not like.

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Beneficence and Nonmaleficence

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Magnitude: The degree of severity of the risk, i.e., mild, moderate or severe

Duration : How long the risk lasts, i.e., the risk may be (For the period of the study only or Extended further after the study is complete)

Population exposed: are vulnerable groups, such as Children, pregnant women, prisoners, mentally handicapped, elderly enrolled to participate ?

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Beneficence and Nonmaleficence

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Benefits:Beneficiaries Research participants, Community, Country

Forms of benefits Monetary, i.e., financial Health care Capacity building: research facility

and manpower development

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Beneficence and Nonmaleficence

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Magnitude of benefitsCompensation, i.e., to compensate

the time participants spent for the study, the expenses they covered for the meal and transport

Undue Inducements, i.e., to provide benefits for participation more than they earn and more than they deserve. This might coerce !

Duration of benefits Short term, i.e., only for the study period

Long term. i.e., extends beyond the study period

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C. Justice

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The underlying principle of justice is to treat

each person in accordance with what is

morally right and proper, i.e., fairness in

distribution: distributive justice

There must be equitable distribution of both

the burdens and benefits of participation in

research.

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Justice…

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Fair distribution of benefits– Equal shares– Equal individual need– Equal individual effort– Equal societal contribution– Equal merit

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Individual vs community interest has to be considered in the principle of justice. The research might compromise the interest of the individual, while benefiting the community or vice versa. This might create an ethical dilemma.

In this case, it is up to the Ethics Committee to pass a fair decision considering the cons and pros of the research both on the individual research participant and the community.

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Components of justice

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Local participation right from the inception to preparation of the proposalInvolvement of the community in the planning and implementation of the studyFair research participant selectionJustified use of placebo and randomization

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Components of justice…

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Standard care for research participantsCompensation of research participantsClear procedures for results disseminationMemorandum of understanding pertaining to authorship, intellectual property rightPost trial responsibilitiesPermission for sample transport

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Balance between the principles

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Any risk needs to be justified by humanitarian goods to be obtained from the research that directly promote the welfare and dignity of the person.

It is humanitarian goods and not scientific knowledge that supply justification for the risks.

In human research knowledge is not self justifying. Nothing can justify research that disregards the dignity of human subjects.

The decision on the ethical correctedness of a given piece of research cannot always be delineated with absolute clarity.

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Balanced emphasis is given to the

following points;

Protecting the subject from harm:

“when in doubt do what is safest for the

subject”

Social concerns: humanitarian good

for the society and community who are

not in the research study

Freedom of choice: subjects have the

right to choose what is most

convenient, provided with enough

information, even if it involves risk.

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Regulations in Research Ethics

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International The Nuremberg Code of human rights

(1947)The Helsinki Declaration(since 1964 till now)

By WMA Council for international organization of

Medical Sciences (CIOMS) 2001International guidelines for Biomedical

Research involving human subject 1982The WHO and ICH (International Conference

on Harmonization) 1995Guidelines for good clinical practice-by WHO-For trials and pharmatical products The

Belmont Report(1979)..others

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Nuremberg Code:1947

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Ten (10) principles1. Informed consent.

2. Experiment should be useful and

necessary.

3. Human experiments should be based

on previous animal experiments.

4. Physical and mental suffering should

be avoided.

5. Death and disability should not be

the expected outcomes.

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Nuremberg Code…

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6. Degree of risk should not exceed the humanitarian importance of solving a problem.7. Human subjects :‐protected against even remote possibilities of harm.8. Human subjects are free to end an experiment at any time.9. Only qualified scientists should conduct medical research.10.Must be prepared to end experiment at any stage.

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Declaration of Helsinki-1964

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(revised 75,83,89,96,2000,2002,2004,2008)HighlightsWell being of the subject takes

precedence over science and society.Respect for persons & protection of

subjects health & rights.Vulnerable populations require special

protection.Procedures must be detailed in a

protocol & submitted to an ethical review committee, including the monitoring of information

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Declaration of Helsinki-1964

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Assessment of risks and benefits to the subjects or others before conducting the research.

– Informed consent is a must.– Informed consent must be Documented.In 2000 – art.16 , Every medical research project involving human subjects should be preceded by careful assessment of predictable risks and burdens in comparison with foreseeable benefits to the subject or to others. This does not preclude the participation of healthy volunteers in medical research.

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Belmont report: 1979

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US response, 1979

Belmont Report…

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The basic ethical principles were addressed

Protect humans from exploitationSpecial protection for most

vulnerable (children, pregnant women, prisoners)

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National Regulations

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The Constitution of the Federal Republic of Ethiopia,

Relevant laws (Civil Code and Penal Code)

ESTC Health department, National Health Research Ethics Review Guidelines,

Relevant International conventions to which Ethiopia is a party

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National regulations….

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All health researches involving human participants must be subjected to independent ethics review and thus must be conducted by a health research ethics review committee.

In Ethiopia Health research ethics review committee (HRERC) are established at three levels :

National (NERC)Regional(RERC) Institutional (IERC)

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Research Ethics Committee

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Evaluates Research Proposals Based on Criteria

Approves or disapproves the research Objectives:1. Safeguard the study participants from

any harm related research 2. Assure that individual benefit and civil

rights are being respected.

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Research Ethics Committee

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Specific objectives which include the following:To safe guard research participants from any risk,

To evaluate ongoing and post research implications on the participants and the community at large, and

To make sure that research participants are participating in the study with written informed consent.

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IRB (Institutional Review Board)

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Definition : An independent body constituted of medical ,scientific , and non scientific members whose responsibility is to ensure the protection of the rights, safety and well being of human subjects by; reviewing, approving, and providing continuing review of protocols, amendments of the methods ,material to be used in obtaining and documenting informed consent of the human subject.

Contains at least 5 members of varying background.

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IRB…

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Law requires hospitals, educational and research institutions have an institutional review board (IRB).

The IRB reviews and approves or disapproves of the proposed research in its institutions in terms of risk benefit analysis.

The boards are not infallible but provide ethical safeguards in research.

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IRB..

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This goals is accomplished by having the IRB assure that the following requirements are satisfied:

1. Risk to subjects are minimized2. Risk to subjects are reasonable in

relation to anticipated benefits,3. Selection of subjects is equitable, i.e.

fair4. Informed consent is sought form each

subject or his/her legally authorized representative,

5. Informed consent is appropriately documented,

6. When appropriate, the research plan makes provisions for monitoring data collection,

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IRB

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7. Privacy and confidentiality of research

subjects is appropriately protected, and

8. When some or all of the subjects are

likely to be vulnerable to coercion or

undue influence, additional safeguards

have been included.The IRB has to approve that these requirements are followed before they approve a research study and must review these documents on, at the least, an annual basis.

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Ethical review in Ethiopia

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Applications first submitted to the

appropriate Regional or Institutional

Ethical Review Committee.

RERC/IERC reviews, gives comments and

where necessary forwards to the

National Ethical Review Committee.

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Ethical review in Ethiopia

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National Ethical Review Committee reviews –

• All clinical trials• Research on very sensitive issues• Multi-centre collaborative research• Research financed/carried out by

external donors• Research to be carried out by a

national agency with bilateral or multilateral collaboration

• Research to be conducted in more than one region

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Thank you!

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