TM-6 Ethical Principles for Biomedical Research Involving Human Subjects

8/10/2019 TM-6 Ethical Principles for Biomedical Research Involving Human Subjects

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Ethical Principles for

Biomedical ResearchInvolving Human Subjects:

Overview of International Guidelines

http://www.pitt.edu/~super7/21011-22001/21071.ppt


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Public Concern forVulnerable Subjects

Nazi Experiments and the Nuremberg Trials Tuskegee Syphilis Study-involvement of black

males

Willowbrook Study-hepatitis study among

children in New York State institution for

mentally defective persons

Jewish Chronic Disease Hospital Study-

injection of live cancer cells into patients tostudy transplant rejection process

San Antonio Contraceptive Study-study of side

effects of contraceptives on Mexican American

women


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In research using human subjects, several

categories of persons maybe involved:

Normal healthy adults, including the investigator,and elderly persons

Sick adults, including the acutely and terminally ill

People living in highly controlled situations, suchas, prisoners, soldiers, and students

Children, both healthy and ill Mentally incompetent persons, whether adults or

children

Unborn fetuses or still living aborted fetuses


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Use of Vulnerable Persons

Not forbidden by ethical codes or

regulations

Need for justification for their inclusion

Unsuitability of less vulnerable

populations

Use of mitigation to address

vulnerability


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NUREMBERG CODE:INFORMED CONSENT

The voluntary consent of the human subjectis absolutely essential.

This means that the person involved shouldhave legal capacity to give consent;

Should be . . . able to exercise free power ofchoice, without the intervention of any

element of force, fraud, deceit, duress, . . . orcoercion;

Should have sufficient knowledge andcomprehension . . . .


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NUREMBERG CODE:

INFORMED CONSENT

The duty and responsibility for

ascertaining the quality of consentrests upon . . .each individual who

initiates, directs, or engages in the

experiment. It is a personal duty that may not be

delegated


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ELEMENTS OF INFORMEDCONSENT

(1) DISCLOSUREIn general necessary items to disclose include:

a) the patients current medical status includingthe likely course if no treatment is provided.

b) the contemplated procedure or medicationc) alternative available procedures or medication

d) anticipated risks and benefits of both

e) a statement offering an opportunity to askfurther questions

f) in case of research, his right to withdraw anytime

g) a professional opinion about the alternatives


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ELEMENTS OF INFORMED

CONSENT(2) COMPREHENSION

7thgrade level (US Standard)

Language understood by the subject Oral or written quizzes to assess

comprehension

Use of educational intervention prior to gettingconsent

Allowed into research environment toexperience routine and procedures


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CONSENT

(3) VOLUNTARINESS - The patient must of his

own free will make a choice without beingunduly pressured by anyone else.

Being free in making a decision means

that the patient ownsthe decision, that

the decision is the patients alone, thatthe patient has chosen the option based

on the information disclosed to him/her.


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CONSENT(4) COMPETENCE - patients capacity for

decision making. One is considered competent

when(a) one has made a decision (i .e. one can

choose between alternatives)

(b) one has the capacity to justify ones choice

(i.e, give reasons for ones choice)

(c) one justifies ones choice in a reasonable

manner


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HUMAN SUBJECTS

OVER SCIENCE AND SOCIETY

. . . considerations related to

the well-being of the humansubject should take

precedence over the interests

of science and society.(Helsinki Declaration, par. 5)


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Protection of Special

Populations Embryos And Human Fetuses

Since the human individual, in the

prenatal stage, must be given the dignity

of a human person, research and

experimentation on human embryos and

fetuses is subject to the ethical normsvalid for the child already born and for

every human subject.


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Pregnant Women, Embryos And Human

Fetuses

Research in particular, that is the

observation of a given phenomenon

during pregnancy, can be allowed only

when there is moral certainty that there

will be no harm either to the life or theintegrity of the expected child and the

mother, and on the condition that the

parents have given their consent.

Protection of SpecialPopulations


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THERAPEUTIC CRITERIAONLY

Experimentation is possible only forclearly therapeutic purposes, when noother possible remedy is available.

No finality, even if itself noble, such asthe foreseeing of a usefulness forscience, for other human beings or forsociety, can in any way justifyexperimentation on live human embryosand fetuses, whether viable or not, in the

maternal womb or outside of it.


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Experimentation of embryos orfetuses has the risk, indeed in most

cases the certain foreknowledge, ofdamaging their physical integrity oreven causing their death.

To use a human embryo or the fetusas an object or instrument ofexperimentation is a crime against

their dignity as human beings.

Protection of Special

Populations


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The practice of keeping humanembryos alive, actually or in vitro, forexperimental or commercial reasons,is especially and altogether contrary

to human dignity.

The informed consent, normally

required for clinical experimentationon an adult, cannot be given by theparents, who may not dispose of thephysical integrity or the life of the

expected child.

Protection of Special Populations


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PROPORTIONALITY OFRISKS TO BENEFITS

Degree of risk to be taken should never

exceed . . . humanitarian importance of

the problem to be solved . . . .(Nuremberg, #6)

Medical research . . . should only be

conducted if the importance of theobjective outweighs the inherent risks

and burdens to the subject. (Helsinki,

#18)


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Right to refusal or withdrawalof treatment

the patient has the right to refuse or withdraw

from treatment to the extent permitted by law

and to be informed of the medical

consequences of his action.- Patients Bill of

Rights

a patient may refuse or withdraw from medical

treatment because their religious convictionsprohibit them from doing so (e.g., a patient

who is a member of a particular religious sect

may refuse to undergo blood transfusions)


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PLACEBO MAY BE USED:

When there is no established effectiveintervention;

When withholding an established effectiveintervention would expose subjects to, atmost, temporary discomfort or delay inrelief of symptoms;

When use of an established effectiveintervention as comparator would notyield scientifically reliable results and useof placebo would not add any risk ofserious or irreversible harm to thesubjects (CIOMS #11)


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Are there ethical issues in socialscience or behavioral research?

Most common methodology used

involves interviewing people and asking

questionsWe would just like to ask some

questions

We would just like to observeWe would just like to share your life

Focus Group discussion (FGDs), Survey

Does not involve invasive procedures


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Ethical Issues in Social Science

& Behavioral Research Privacy

Confidentiality Linking behavior

with medical

procedure


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DO NO HARM

Experiment should . . . avoid all

unnecessary physical and mental

suffering and injury. (Nuremberg, #4)


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Forms of Harm to Human

Subjects in Behavioral Research Psychological harmrecalling a

traumatic event

Social stigmaloss of reputation Cultural effectsgoing against existing

cultural norms

Political effectsdisturbing existingpower relationships

Economic repercussionsloss of jobs


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HOW TO AVOID HARM

The experiment should beconducted only by scientificallyqualified persons. (Nuremberg #8)

. . . human subject should be atliberty to bring the experiment to anend . . . (#9)

. . . terminate the experiment at anystage, if . . . continuation of theexperiment is likely to result ininjury, disability, or death (#10)


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HOW TO AVOID HARM

[Ensure that] risks involved have beenadequately assessed and can be

satisfactorily managed. Cease . . . investigation if:

1. the risks are found to outweigh the

potential benefits, or2. there is conclusive proof of positive and

beneficial results (Helsinki #17)


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Mitigating harm to human

subjects Research design- community inputs

Adequate research preparation-

familiarization with local culture,sociopolitical structures, traditions andcultural norms

Good reason to conduct research in aparticular community

Ethical Consideration Section in theprotocol


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NBAC Guideline

Whenever possible, preceding the start

of research, agreements should be

negotiated by the relevant parties tomake effective intervention or other

research benefits available to the host

country after the study is completed.


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Mitigating harm to humansubjects

Research methodologies should avoid

harm

Mechanisms for protection of privacy and

confidentiality

Avoidance of social stigmatization

Process of data storage

Adequate infrastructure to protect privacy

Research methodologies should provide

opportunities for empowerment-reflexivity

Mitigating harm to human


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Technical review

Risk-benefit analysis

Benefits should be defined in the protocol

Provisions for support mechanismsConsent process should be as strict asrequirements in clinical trials

Recruitment procedures Full disclosure of information

Reconsenting mechanisms

Feedback to community

Mitigating harm to humansubjects-Reviewing the protocol

Mi i i h h


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Mitigating harm to humansubjects- Reviewing the protocol

Culturally competent consent form Individual consent

Family consent-secondary subjects

Community consent

Mechanisms for protection of privacy and

confidentiality defined in the consent form of

information sheet

Provision of support/coping mechanism

Need to take precaution to protect identity

of host community


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Informed consent:

Community Context - CIOMSWhen it is not possible to requestinformed consent from every

individual to be studied, theagreement of a representative of acommunity or group should besought, but the representative shouldbe chosen according to the nature,traditions and political philosophy ofthe community or group.


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Feedback to the Community

Reporting results to the community

A good means to highlight good practices:

positive reinforcement

Suggestions for improvement should bepresented as constructive recommendations

Public forum: a means to get public

commitment from public officialsOpportunities for researchers to connect

community to larger community


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RELEVANCE &RESPONSIVENESS OF RESEARCH

Medical research is only justified

if there is a reasonable likelihoodthat the populations in which the

research is carried out stand to

benefit from the results of theresearch. (Helsinki #19)

CIOMS


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RELEVANCE AND

RESPONSIVENESS The sponsor and the investigator must

make every effort to ensure that:

1. the research is responsive to the healthneeds and the priorities of thepopulation . . . ; and

2. any intervention orproduct developed,or knowledge generated, will be madereasonably available for the benefit ofthat population. (CIOMS #10)


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GENETIC RESEARCH:Privacy, Confidentiality and

Integrity

Respect the privacy of the subject,

the confidentiality of the patient'sinformation and minimize the

impact

of the study on the subject'sphysical and mental integrity

(Helsinki #21)


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MEDICAL RECORDS &BIOLOGICAL SPECIMENS

Exemp ted from indiv idual consent requirementonly if an ethical review committee hasdetermined that:

Research poses minimal risk

Rights or interests of the patients will notbe violated

privacy and confidentiality or anonymity areensured

Research is designed to answer animportant question

Impracticable if the requirement forinformed consent were to be imposed

(CIOMS)


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HUMAN GENETIC DATA

Clear, balanced, adequate andappropriate information shall be

provided to the person whose prior, free,informed and express consent is sought.

Information shall . . . specify the purposefor which human genetic data . . . are

being derived, . . . used and stored(International Declaration on Human GeneticDataAdopted by the UNESCO General Assembly on 16 October2003)


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WITHDRAWAL OF CONSENT

(a) . . . Consent may be withdrawn by theperson concerned unless such data areirretrievably unlinked to an identifiable person.

(b) When a person withdraws consent, the

persons genetic data, proteomic data andbiological samples should no longer be usedunless they are irretrievably unlinked to theperson concerned.

(c) If the persons wishes cannot be determinedor are not feasible or are unsafe, the data andbiological samples should either beirretrievably unlinked or destroyed.

UNESCO Intl Declaration, Art. 9


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RIGHT TO BE, OR NOT TO

BE INFORMED OF RESULTS

The person concerned

has the right to decide

whether or not to be

informed of the results



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GENETIC COUNSELLING

. . . When genetic testing . . . is being

considered, genetic counselling should

be made available . . . .

Genetic counselling should be non-

directive, culturally adapted and

consistent with the best interest of the

person concerned.



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CLINICAL TRIAL REGISTRATIONA Requirement for Publication Trials must register at or before the

onset of patient enrollment.

Selective reporting . . . distorts the

body of evidence available forclinical decision-making.

Trial results that place financialinterests at risk are particularly likely

to remain unpublished and hiddenfrom public view.

Anyone should be able to learn ofany trial's existence and its

important characteristics.

BIBLIOGRAPHY


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BIBLIOGRAPHY1. Ethical Review o f Research : Overview o f

Internat ional Guidel ines and Princip lesby Prof.

Leonardo de Castro, Ph.D, Department ofPhilosophy, University of the Philippines, Diliman

2. Ethical Issues in Soc ial Science Research: by Prof.Cristina E. Torres, Ph.D, College of Arts and

Sciences, University of the Philippines, Manila &National Institute of Health

3. Protect ion of Vu lnerable Subjectsby Prof. Cristina E.Torres, Ph.D, College of Arts and Sciences, UP

Manila & National Institute of Health

4. Wor ld Medical Associat ion (WMA): Declarat ion ofHelsinki, Tokyo, 2004

5. The Nuremberg Code 1947

BIBLIOGRAPHY


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BIBLIOGRAPHY6. The CIOMS Gu idelinesNov 2000, International

Ethical Guidelines for Biomedical Research InvolvingHuman Subjects

7. The NBAC Report Aug 2001, Ethical and PolicyIssues in Research Involving Human Participants

8. Internat ional Declarat ion on Human Genetic Data,UNESCO, October 16, 2003

9. The Belmon t Repo rt, 1979, Ethical Principles andGuidelines for the Protection of Human Subjects ofResearch

Documents

TM-6 Ethical Principles for Biomedical Research Involving Human Subjects