Ethical Principles for Biomedical Research Involving Human Subjects: Overview of International...

Ethical Principles for Biomedical Research Involving Human Subjects:

Overview of International Guidelines

Ethical Principles for Biomedical Research Involving Human Subjects:

Overview of International Guidelines

Maria Fidelis C. Manalo, MD,

MSc Epidemiology

Department of Community & Family Medicine

Far Eastern University-

NRMF Medical Center

Philippines

Public Concern for Vulnerable SubjectsPublic Concern for Vulnerable 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 to study transplant rejection process

San Antonio Contraceptive Study-study of side effects of contraceptives on Mexican American women

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, such as, prisoners, soldiers, and students

Children, both healthy and ill

Mentally incompetent persons, whether adults or children

Unborn fetuses or still living aborted fetuses

Use of Vulnerable PersonsUse of Vulnerable Persons

Not forbidden by ethical codes or regulations

Need for justification for their inclusion Unsuitability of less vulnerable

populationsUse of mitigation to address

vulnerability

NUREMBERG CODE: INFORMED CONSENTNUREMBERG CODE: INFORMED CONSENT

The voluntary consent of the human subject is absolutely essential.

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

Should be . . . able to exercise free power of choice, without the intervention of any element of force, fraud, deceit, duress, . . . or coercion;

Should have sufficient knowledge and comprehension . . . .

NUREMBERG CODE: INFORMED CONSENTNUREMBERG CODE: INFORMED CONSENT

The duty and responsibility for ascertaining the quality of consent rests upon . . .each individual who initiates, directs, or engages in the experiment.

It is a personal duty that may not be delegated

ELEMENTS OF INFORMED CONSENTELEMENTS OF INFORMED CONSENT

(1) DISCLOSURE In general necessary items to disclose include:a) the patient’s current medical status including the likely course if no treatment is provided.b) the contemplated procedure or medicationc) alternative available procedures or medicationd) anticipated risks and benefits of bothe) a statement offering an opportunity to ask further questionsf) in case of research, his right to withdraw any timeg) a professional opinion about the alternatives


(2) COMPREHENSION 7th grade level (US Standard) Language understood by the subject Oral or written quizzes to assess

comprehension Use of educational intervention prior to getting

consent Allowed into research environment to

experience routine and procedures


(3) VOLUNTARINESS - The patient must of his own free will make a choice without being unduly pressured by anyone else. Being free in making a decision

means that the patient owns the decision, that the decision is the patient’s alone, that the patient has chosen the option based on the information disclosed to him/her.


(4) COMPETENCE - patient’s 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 one’s choice

(i.e, give reasons for one’s choice)

(c) one justifies one’s choice in a reasonable

manner

HUMAN SUBJECTS OVER SCIENCE AND SOCIETY

HUMAN SUBJECTS OVER SCIENCE AND SOCIETY

. . . considerations related to the well-being of the human subject should take precedence over the interests of science and society. (Helsinki Declaration, par. 5)

Protection of Special Populations Protection of Special Populations

Embryos And Human FetusesSince 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 norms valid for the child already born and for every human subject.

Pregnant Women, Embryos And Human FetusesResearch 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 the integrity of the expected child and the mother, and on the condition that the parents have given their consent.”


THERAPEUTIC CRITERIA ONLYTHERAPEUTIC CRITERIA ONLY

Experimentation is possible only for clearly therapeutic purposes, when no other possible remedy is available.

“No finality, even if itself noble, such as the foreseeing of a usefulness for science, for other human beings or for society, can in any way justify experimentation on live human embryos and fetuses, whether viable or not, in the maternal womb or outside of it.

Experimentation of embryos or fetuses has the risk, indeed in most cases the certain foreknowledge, of damaging their physical integrity or even causing their death.

To use a human embryo or the fetus as an object or instrument of experimentation is a crime against their dignity as human beings.


“The practice of keeping human embryos alive, actually or in vitro, for experimental or commercial reasons,” is especially and “altogether contrary to human dignity.”

The informed consent, normally required for clinical experimentation on an adult, cannot be given by the parents, who may not dispose of the physical integrity or the life of the expected child.

Protection of Special Populations

PROPORTIONALITY OF RISKS TO BENEFITSPROPORTIONALITY OF RISKS 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 the objective outweighs the inherent risks and burdens to the subject. (Helsinki, #18)

Right to refusal or withdrawal of treatment

Right to refusal or withdrawal of 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.”- Patient’s Bill of Rights

a patient may refuse or withdraw from medical treatment because their religious convictions prohibit them from doing so (e.g., a patient who is a member of a particular religious sect may refuse to undergo blood transfusions)

PLACEBO MAY BE USED:PLACEBO MAY BE USED: When there is no established effective

intervention; When withholding an established effective

intervention would expose subjects to, at most, temporary discomfort or delay in relief of symptoms;

When use of an established effective intervention as comparator would not yield scientifically reliable results and use of placebo would not add any risk of serious or irreversible harm to the subjects (CIOMS #11)

Are there ethical issues in social science or behavioral research?

Are there ethical issues in social science or behavioral research? Most common methodology used involves

interviewing people and asking questions“We would just like to ask some

questions…”“We would just like to observe…”“We would just like to share your life…”Focus Group discussion (FGDs), Survey

Does not involve invasive procedures

Ethical Issues in Social Science & Behavioral Research

Ethical Issues in Social Science & Behavioral Research

Privacy Confidentiality Linking behavior

with medical

procedure

DO NO HARMDO NO HARM Experiment should . . . avoid all

unnecessary physical and mental suffering and injury. (Nuremberg, #4)

Forms of Harm to Human Subjects in Behavioral Research

Forms of Harm to Human Subjects in Behavioral Research

Psychological harm – recalling a traumatic event

Social stigma – loss of reputation Cultural effects – going against existing

cultural norms Political effects – disturbing existing

power relationships Economic repercussions – loss of jobs

HOW TO AVOID HARMHOW TO AVOID HARM

The experiment should be conducted only by scientifically qualified persons. (Nuremberg #8)

. . . human subject should be at liberty to bring the experiment to an end . . . (#9)

. . . terminate the experiment at any stage, if . . . continuation of the experiment is likely to result in injury, disability, or death (#10)

HOW TO AVOID HARMHOW TO AVOID HARM

[Ensure that] risks involved have been adequately assessed and can be satisfactorily managed.

Cease . . . investigation if:1. the risks are found to outweigh the

potential benefits, or 2. there is conclusive proof of positive and

beneficial results (Helsinki #17)

Mitigating harm to human subjectsMitigating harm to human subjects

Research design- community inputs Adequate research preparation-

familiarization with local culture, sociopolitical structures, traditions and cultural norms

Good reason to conduct research in a particular community

Ethical Consideration Section in the protocol

NBAC GuidelineNBAC Guideline

“ Whenever possible, preceding the start of research, agreements should be negotiated by the relevant parties to make effective intervention or other research benefits available to the host country after the study is completed.”

Mitigating harm to human subjectsMitigating harm to human subjects

Research methodologies should avoid harmMechanisms for protection of privacy and

confidentialityAvoidance of social stigmatizationProcess of data storageAdequate infrastructure to protect privacy

Research methodologies should provide opportunities for empowerment-reflexivity

Technical review Risk-benefit analysis

Benefits should be defined in the protocol

Provisions for support mechanisms

Consent process should be as strict as requirements in clinical trials

Recruitment procedures

Full disclosure of information

Reconsenting mechanisms

Feedback to community

Mitigating harm to human subjects-Reviewing the protocol

Mitigating harm to human subjects- Reviewing the protocol

Mitigating harm to human subjects- 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

Informed consent: Community Context - CIOMS

Informed consent: Community Context - CIOMS“When it is not possible to request informed consent from every individual to be studied, the agreement of a representative of a community or group should be sought, but the representative should be chosen according to the nature, traditions and political philosophy of the community or group.”

Feedback to the CommunityFeedback to the Community

Reporting results to the communityA good means to highlight good practices: positive

reinforcementSuggestions for improvement should be presented

as constructive recommendationsPublic forum: a means to get public commitment

from public officialsOpportunities for researchers to connect community

to larger community

RELEVANCE & RESPONSIVENESS OF RESEARCH

RELEVANCE & RESPONSIVENESS OF RESEARCH

Medical research is only justified if there is a reasonable likelihood that the populations in which the research is carried out stand to benefit from the results of the research. (Helsinki #19)

CIOMS

RELEVANCE AND RESPONSIVENESSRELEVANCE AND RESPONSIVENESS

The sponsor and the investigator must make every effort to ensure that:

1. the research is responsive to the health needs and the priorities of the population . . . ; and

2. any intervention or product developed, or knowledge generated, will be made reasonably available for the benefit of that population. (CIOMS #10)

GENETIC RESEARCH: Privacy, Confidentiality and Integrity

GENETIC RESEARCH: Privacy, Confidentiality and Integrity

Respect the privacy of the subject,

the confidentiality of the patient's information and minimize the impact

of the study on the subject's physical and mental integrity (Helsinki #21)

MEDICAL RECORDS & BIOLOGICAL SPECIMENSMEDICAL RECORDS & BIOLOGICAL SPECIMENS

Exempted from individual consent requirement only if an ethical review committee has determined that:Research poses minimal riskRights or interests of the patients will not be

violatedprivacy and confidentiality or anonymity are

ensuredResearch is designed to answer an important

question Impracticable if the requirement for informed

consent were to be imposed (CIOMS)

HUMAN GENETIC DATAHUMAN GENETIC DATA

Clear, balanced, adequate and appropriate information shall be provided to the person whose prior, free, informed and express consent is sought.

Information shall . . . specify the purpose for which human genetic data . . . are being derived, . . . used and stored (International Declaration on Human Genetic DataAdopted by the UNESCO General Assembly on 16 October 2003)

WITHDRAWAL OF CONSENTWITHDRAWAL OF CONSENT

(a) . . . Consent may be withdrawn by the person concerned unless such data are irretrievably unlinked to an identifiable person.

(b) When a person withdraws consent, the person’s genetic data, proteomic data and biological samples should no longer be used unless they are irretrievably unlinked to the person concerned.

(c) If the person’s wishes cannot be determined or are not feasible or are unsafe, the data and biological samples should either be irretrievably unlinked or destroyed.

UNESCO Int’l Declaration, Art. 9

RIGHT TO BE, OR NOT TO BE INFORMED OF RESULTS

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


GENETIC COUNSELLINGGENETIC 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.


CLINICAL TRIAL REGISTRATION A Requirement for Publication

CLINICAL TRIAL REGISTRATION A Requirement for Publication Trials must register at or before the onset of patient enrollment.

Selective reporting . . . distorts the body of evidence available for clinical decision-making.

Trial results that place financial interests at risk are particularly likely to remain unpublished and hidden from public view.

Anyone should be able to learn of any trial's existence and its important characteristics.

BIBLIOGRAPHYBIBLIOGRAPHY1. Ethical Review of Research: Overview of International Guidelines and

Principles by Prof. Leonardo de Castro, Ph.D, Department of Philosophy, University of the Philippines, Diliman

2. Ethical Issues in Social Science Research: by Prof. Cristina E. Torres, Ph.D, College of Arts and Sciences, University of the Philippines, Manila & National Institute of Health

3. Protection of Vulnerable Subjects by Prof. Cristina E. Torres, Ph.D, College of Arts and Sciences, UP Manila & National Institute of Health

4. World Medical Association (WMA): Declaration of Helsinki, Tokyo, 2004

5. The Nuremberg Code 1947

BIBLIOGRAPHYBIBLIOGRAPHY6. The CIOMS Guidelines Nov 2000, International Ethical

Guidelines for Biomedical Research Involving Human Subjects

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

8. International Declaration on Human Genetic Data, UNESCO, October 16, 2003

9. The Belmont Report, 1979, Ethical Principles and Guidelines for the Protection of Human Subjects of Research

10. Fifth Global Forum for Health Research, Paris, 2004

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