International Research Ethics

Jenell Coleman, M.D.

Clinical Fellow, Reproductive Infectious Diseases, UCSF

M.P.H. Candidate 2005, UCBMarch 1, 2005

My Experience

• Ethical sensitivity• Lack of adequate training in ethics• International research

– Unethical foundation

• Goal– Stimulate further ethical review of

your own projects

Definition

• Ethics: ways of examining the moral life– Normative: formulation and defense of a

system of fundamental moral principles and rules that determine which actions are right and which are wrong• What people ought to do

– Non-normative: factual investigation of moral behavior and beliefs • How people reason and act

Beauchamp and Childress. Principles of Biomedical Ethics. 1989

General Terms

Action

Rule

Principle

Theory

Ethical Principles• Autonomy

– Respect for persons; self-governance– Free choice without coercion; informed consent

• Justice– Equal distribution of risks and benefits– Persons from groups unlikely to be among the

beneficiaries of subsequent application should not be involved in research

• Beneficence– Minimize risks and maximize benefits

• Nonmaleficence– Do no harm

Ethical Theories

• Utilitarian– Greatest good for the greatest number– Some people may have to carry the

burden which will ultimately benefit society

– Social benefits of research for future pts.

• Deontological– Human rights based– Individual rights

Informed Consent

• Disclosure of information• Understanding of this information• Voluntariness• Competence• Consent

Incompetence• Inability to evidence a choice or preference

• Inability to understand one’s situation• Inability to understand disclosed

information

• Inability to give a reason• Inability to give a rational reason• Inability to give risk/benefit-related reasons• Inability to reach a reasonable decision

Appelbaum and Roth. Archives of General Psychiatry. 1982; Roth and Meisel. Emory Law Journal. 1982

Vulnerable populations

• People infected with HIV • Women• Children• People with drug addictions• Poor individuals• Elderly• Prisoners• Military recruits

Exploitation

Subjects participating in the research project are burdened with the risks of the project, yet are not recipients of the benefits– May even be doing harm– Violation of nonmaleficence principle

Ethical Guidelines

Post WWII– Nuremburg Code– Declaration of Helsinki– Belmont Report

Declaration of Helsinki

World Medical Association 1962

In any medical study, every patient-including those of the control group-should be assured the best proven diagnostic and therapeutic method

DHHS Ethical Guidelines

It is permissible to observe the standards of the host country, if it was determined that they “ afford protections that are at least equivalent to those provided in this policy”

International Ethical Guidelines 1993

...the ethical standards applied should be no less exacting than they would be for research in the sponsoring country itself

Placebo Trials

• 1994 ACTG 076 Results» $800-$1000

• 1994 WHO Recommendations• 1995 15 RCTs and 1

equivalency trial• 1997 Public Citizen letter to

DHHS• 1998 CDC funded trial results

Placebo Arguments

• Pro– beneficence– standard of care– scientific rigor– equipoise

• Anti– beneficence– autonomy– nonmaleficence– exploitation– violation of

international ethical guidelines

Colonialism

Cultural Relativism

Imperialism

-isms

Colonialism

• The state of developing countries is the byproduct of colonialism– Reason why substandard care is

provided– Reason for the widespread poverty– Reason for the dependence on 1st

world countries for financial assistance

Cultural Relativism

• Cannot apply our ethical standards and definitions to a different culture

• What are the ethical beliefs of the community?

Western Imperialism

• “These are Ugandan studies, conducted by Ugandan investigators, on Ugandans, for the good of their people”

• The extension or imposition of power, authority, or influence– Sweden RCT– South African viewpoint– Ethical Review Boards

Placebo Arguments

• Pro– beneficence– standard of care– scientific rigor– equipoise

• Anti– beneficence– autonomy– nonmaleficence– exploitation– violation of

international ethical guidelines

Discussion

• How do you define standard of care?

• Are placebo controlled trials in low income countries unethical?

• Are developing countries exploited?• What do researchers owe the

subjects, if anything?

Responsibility of researchers

• Disconnect between research and policy

• Passive role of many researchers• Lack of support for subjects after

study ends

RESEARCH FINDINGS

POLICY

Human Rights• Clarify the true purpose of the

research– Must matter to the subjects

• Evaluate likely effectiveness– Honest, rigorous investigation into the

potential effectiveness in that population

• Determine whether the research is well targeted– Disproportionately impacting certain

groups in society?

Human Rights• Examine the research for possible

human rights burdens– Balancing of potential benefits to the

health of the community with the human rights repercussions

• Determine whether the research is the least intrusive that can achieve the objective

• If a coercive measure is truly necessary to avert a significant risk, guarantee fair procedures to persons affected

Gostin and Mann

In sum,

Researchers– aim to strengthen the community– know the purpose of the research– formulate a plan to implement study

results

...a placebo-controlled trial may be ethically acceptable, even if proven therapy is available, under the following circumstances:

  - Where for compelling and scientifically sound methodological reasons its use is necessary to determine the efficacy or safety of a prophylactic, diagnostic or therapeutic method; or

  - Where a prophylactic, diagnostic or therapeutic method is being investigated for a minor condition and the patients who receive placebo will not be subject to any additional risk of serious or irreversible harm.

Declaration of HelsinkiRevision 2002

“The health of my patient will be my first consideration.”

-Declaration of Geneva of the World Medical Association