COURSE ON ETHICAL ISSUES IN INTERNATIONAL HEALTH RESEARCH, HOSTED BY THE UAE MINISTRY OF HEALTH Abu

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COURSE ON ETHICAL ISSUES IN INTERNATIONAL HEALTH
RESEARCH, HOSTED BY THE UAE MINISTRY OF
HEALTHAbu Dhabi, United Arab Emirates9-10
March 2002 Ethics of human subjects
research - Principles and historical
particularities

• Willem A. Landman CEO, Ethics
  Institute of South Africa (EthicSA)
  Extraordinary Professor of Philosophy,
  University of Stellenbosch, South Africa
• willem_at_ethicsa.com
  www.ethicsa.org
  

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OUTLINE OF PRESENTATION

• A. Unethical research Unethical practices in the
  history of human subjects research
  
•  
• B. Ethics documents Key ethics documents in
  response to ethical questions raised by human
  subjects research
  
•  
• C. Ethical principles Foundational ethical
  principles in human subjects research

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UNETHICAL RESEARCH
1. WARTIME RESEARCH BY THE USA

• World War II was a transforming event in the
  conduct of human subjects research in the USA
  
• Transition from benefiting subjects to benefiting
  others
  
• Research agenda dictated by military need (e.g.
  malaria after Pearl Harbor researchers infected
  residents of state hospitals and prisons)
  
• Use of vulnerable patients (mental patients,
  prisoners)
  
• Japanese use of Chinese residents and prisoners -
  Japanese given immunity from prosecution by the
  US in exchange for information about biological
  warfare

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A. UNETHICAL RESEARCH (Contd)
2. NAZI DOCTORS IN WORLD WAR II

• Types of experiments
• Hypothermia experiments subfreezing water
  immersion
  
• Oxygen deprivation to learn about endurance
• Deliberate injection by lethal organisms
• Efficient sexual sterilization
• Efficient death
• Research for the ends of war
• Third Reichs program for racial hygiene,
  purifying the German people by extermination and
  sterilization of groups
  
• Nuremberg War Crime Trials, and the Nuremberg
  Code (1946)
  

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A. UNETHICAL RESEARCH (Contd)

• African-American men from Tuskegee, Macon County,
  Alabama
  
• Observing the natural progression of secondary
  syphilis, for 40 years
  
• Was it a study in nature? Was it
  non-therapeutic research? If so, was it conducted
  ethically? If not, what was wrong with it?
  
• Ethical issues
• Not conscripted for World War II in case they
  might get treatment
  
• Not treated with penicillin after 1943
• Not informed about the availability of penicillin
  
  
• Nuremberg Code not seen as applicable to the USA,
  even 25 years later
  
• President Clintons apology in 1996

3. TUSKEGEE SYPHILIS STUDY (1932-1972)
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A. UNETHICAL RESEARCH (Contd)
4. WILLOWBROOK STATE SCHOOL (1954-1964?)

• Institution for mentally retarded children on
  Staten Island, New York
  
• Study of the origins and causes (etiology) of
  viral hepatitis
  
• Children intentionally infected with hepatitis
  and isolated in special unit
  
• Ethical questions regarding intentional infection
  (harm), alternative ways of controlling hepatitis
  in the institution (harm), and parental consent
  (autonomy)
• Ethical questions about 22 cases in the USA
  (including Willowbrook) by Henry Beecher of the
  Harvard Medical School in the New England Journal
  of Medicine (1966) unethical or questionable
  ethical procedures are not uncommon among
  researchers

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A. UNETHICAL RESEARCH (Contd)
5. PRESENT-DAY USA

• One of the most advanced regulatory systems for
  the protection of human research subjects, but
  unethical research continues
  
• Plastic surgeons in New York City (early 1990s)
  plastic surgery (face-lifts)
  
• 21 patients superficial and deep approach
  (two different procedures used for the two sides
  of the same individuals face)
  
• Comparing two different standard therapies on
  patients
  
• Ethical issue putting interest of science before
  those of patients
  
• Federal protection not for human subjects
  research supported only by private funds
  
• Animals better protected than humans?

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A. UNETHICAL RESEARCH (Contd)
6. DEVELOPING WORLD

• Research sponsored by the developed world in the
  developing world
  
• HIV/AIDS research
• Example - research in the Red Cross War Memorial
  Childrens Hospital in Cape Town, South Africa
  
• Most South Africans receive health care in the
  state or public sector
  
• Anti-retroviral treatment (ART) is unavailable
  for the majority of HIV-infected South Africans
  mainly because of government policies, and
  perhaps cost
• Several research protocols relate to the
  management of opportunistic infections and other
  HIV-related conditions

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A. UNETHICAL RESEARCH (Contd)
6. DEVELOPING WORLD (Contd)

• Are these studies in nature?
• If not, do researchers have an ethical obligation
  to influence the availability of ART for research
  subjects both as researchers, and as health
  professionals and citizens in a democracy?
• Is such research ethically justified because it
  serves the interests of HIV-infected people in
  poor countries where ART is not available?
  
• Whose interest is paramount that of the
  research subject, or that of science and
  society?
  

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B. ETHICS DOCUMENTS
1. CLAUDE BERNARD (1813-1978)

• Morals do not forbid making experiments on
  ones neighbor or ones self. The principle of
  medical and surgical morality consist in never
  performing on man an experiment which might be
  harmful to him to any extent, even though the
  result might be highly advantageous to science,
  i.e., to the health of others (1865).

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B. ETHICS DOCUMENTS (Contd)
2. NUREMBERG CODE (1946)

• The voluntary consent of the human subject is
  absolutely essential - research subjects should
  have legal capacity to consent, and the mentally
  disabled and children are not suitable subjects
• Research subjects should be so situated as to be
  able to exercise free power of choice which
  means the American practice of using prisoners is
  at least questionable
• Human subjects should have sufficient knowledge
  and comprehension of the elements of the subject
  matter involved as to make an understanding and
  enlightened decision ruling out the American
  practice of using the mentally disabled as
  subjects

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B. ETHICS DOCUMENTS (Contd)
3. DECLARATION OF HELSINKI (1964, several
subsequent revisions)

• World Medical Association (WMA)
• Modeled on Nuremberg Code
• Requires qualified investigators, and the consent
  of subjects
  
• Clinical research medical research combined with
  professional care - (t)he potential benefits,
  hazards and discomfort of a new method should be
  weighed against the advantages of the best
  current diagnostic and therapeutic methods
• Therapeutic versus non-therapeutic (non-clinical)
  research
  
• 1975 revision recommend review of research by an
  independent committee

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B. ETHICS DOCUMENTS (Contd)
4. BELMONT REPORT (1979)

• First US bioethics commission established
  National Commission for the Protection of Human
  Subjects of Biomedical and Behavioral Research,
  created in terms of the National Research Act
  (1974)
• Commission charged with identifying the basic
  ethical principles that should underlie the
  conduct of human subjects research
  
• Summarizes the basic ethical principles
  identified by the Commission in the course of
  its deliberations
  

• 5. CIOMS (1993)
• International Ethical Guidelines for
  Biomedical Research
  
• Involving Human Subjects Council for
  International
  
• Organizations of Medical Sciences (CIOMS) in
  collaboration with
  
• the World Health Organization (WHO)

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C. ETHICAL PRINCIPLES

• Three basic ethical principles in human subjects
  research
  
• 1. RESPECT FOR PERSONS informed consent by
  research subjects
  
• 2. BENEFICENCE (including NON-MALEFICENCE)
  evaluation of risks and benefits for research
  subjects and others
  
• 3. JUSTICE selection of research subjects, and
  outcomes in the distribution of the benefits of
  research
  

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C. ETHICAL PRINCIPLES (Contd)
1. RESPECT FOR PERSONS

• Respect for autonomy, being treated as autonomous
  agent, means
  
• Respect for personal self-determination
  (determining ones life plan in terms of ones
  own values and beliefs)
  
• Respect for privacy (access to a persons private
  sphere)
  
• Respect for confidentiality (not divulging such
  privileged knowledge)
  
• Protection for persons with diminished autonomy
  due to
  
• Ilness
• Mental disability
• Circumstances

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C. ETHICAL PRINCIPLES (Contd)
1. RESPECT FOR PERSONS (Contd)

• In a research setting, the ethical principle of
  respect for personal autonomy most notably finds
  expression in the moral requirement of informed
  consent.
• Aspects of informed consent (to being a research
  subject)
  
• Competence - capacity to give consent
• Information - being informed about relevant facts
  
  
• Voluntariness voluntarily or freely given
  consent
  

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C. ETHICAL PRINCIPLES (Contd)
1. RESPECT FOR PERSONS (Contd)

• INFORMED CONSENT 1 COMPETENCE
• Task-relative
• May change over time
• Competence is a process, rather than the (mere)
  ability to express a preference, or to give a
  certain answer (content)
  
• Three elements of competence
• Ability to communicate and understand relevant
  information about options
  
• Ability to reason and deliberate about
  alternative options
  
• Ability to evaluate options and their
  consequences by relating them to a stable set of
  values and goals

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C. ETHICAL PRINCIPLES (Contd)
1. RESPECT FOR PERSONS (Contd)

• INFORMED CONSENT 2 INFORMATION
• Broad kinds of information required to convey to
  research subjects (see US Federal Guidelines on
  Human Research)
  
• Purpose of research and expected duration
• Research procedure
• Reasonably foreseeable risks (of harm) or
  discomfort, and anticipated benefits
  
• Alternatives treatments or procedures
• Extent of confidentiality of records
• Compensation for injuries, and medical care if
  more than minimal risk
  
• Statement that participation is voluntary and
  that refusal or withdrawal will involve no
  penalty
  
• Opportunity to ask questions and to withdraw at
  any time
  

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C. ETHICAL PRINCIPLES (Contd)
1. RESPECT FOR PERSONS (Contd)

• INFORMED CONSENT 2 INFORMATION (Contd)
• Standards for determining the amount (how much?)
  of information required to convey to research
  subjects
  
• Professional standard
• Reasonable person standard
• Reasonable person plus what actual person wants
  
  
• Other considerations
• Opportunity to consider whether to participate
• Coercion and undue influence minimized
• Understandable language
• No waiver of legal rights

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C. ETHICAL PRINCIPLES (Contd)
1. RESPECT FOR PERSONS (Contd)

• INFORMED CONSENT 3 VOLUNTARINESS
• Coercion violates voluntariness
• Coerced treatment
• Coerced consent
• Manipulation violates voluntariness
• Outright deception information deliberately
  withheld
  
• More subtle manipulation manner and tone of
  voice, manner of presentation

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C. ETHICAL PRINCIPLES (Contd)
2. BENEFICENCE

• Essence of Hippocratic tradition first do no
  harm
  
• Concept of non-maleficence (passive)
• Refraining from deliberate infliction of harm on
  persons
  
• Concept of beneficence (active)
• Preventing harm
• Eliminating already existing harm
• Doing good, or promoting welfare
• Principle maximizing benefits and minimizing
  harms and wrongs
  

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C. ETHICAL PRINCIPLES (Contd)
2. BENEFICENCE (Contd)

• In a research setting, the principle of
  beneficence finds expression in a favorable
  risk/benefit assessment or ratio.
  
• Risks
• Risk of harm occurring to research subjects
• Kinds of harm physical pain or injury,
  psychological, social, economic, legal
  
• Two key aspects of risk assessment
• Probability that harm may occur
• Severity or magnitude of harm if it does occur
  
  
• Benefits
• Positive value related to health or welfare
• For research subject, and others

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C. ETHICAL PRINCIPLES (Contd)
2. BENEFICENCE (Contd)

• Weighing risks and benefits
• Balancing act
• Limitations of quantitative techniques
• Ideal of systematic, non-arbitrary analysis of
  risks and benefits
  
• CIOMS - norms requiring that the
• Risks of research be reasonable in the light of
  expected benefits
  
• Research design be sound
• Investigators be competent both to conduct the
  research and to safeguard the welfare of the
  research subjects
  

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C. ETHICAL PRINCIPLES (Contd)
2. BENEFICENCE (Contd)

• Other assessment considerations
• Treatments that are never justified
• Only risks necessary for results are justified
• Significant risks require the strongest
  justification
  
• With vulnerable populations the appropriateness
  of research should be demonstrated
  
• Risks and benefits integral to informed consent
  process
  

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C. ETHICAL PRINCIPLES (Contd)
3. JUSTICE

• Question of distributive justice (fairness in
  distribution equitable distribution) - Who
  ought to receive the benefits of research, and
  bear its burdens?
• Principle
• Treat equals equally, or treat like cases alike
• So, discriminate (i.e. distribute benefits and
  burdens differentially) only on the basis of
  relevant differences and not irrelevant ones
  
• Fairness in selection of human subjects
  research
  
• Certain considerations may ground justified
  discrimination (differential selection or
  treatment) such as age, or deprivation
  
• Vulnerable groups - welfare patients, persons
  confined to institutions, or racial or ethnic
  minorities - should not be systematically
  selected because they are easily available, in
  compromised positions, or can be manipulated
• Fairness in outcomes - public funds for research
  should not generate advantages only to those who
  can afford them

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C. ETHICAL PRINCIPLES (Contd)
3. JUSTICE (Contd)

• In a research setting, the principle of justice
  (fairness) most notably gives rise to moral
  requirements that there be fair procedures in the
  selection of research subjects and fair outcomes
  in the distribution of the benefits of research.
  
• Individual justice potentially beneficial
  research should be fair to individuals, by
  selecting impartially within the research design
  and not selecting against undesirable
  individuals

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C. ETHICAL PRINCIPLES (Contd)
3. JUSTICE (Contd)

• Social justice distinctions between different
  classes of subjects for selection purposes should
  be based on
  
• Ability of members of the class to bear burdens
• Appropriateness of placing further burdens on
  already burdened persons
  
• Adults preferred to children where appropriate
• Institutionalized mentally infirm and prisoners
  may be involved only on certain conditions

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C. ETHICAL PRINCIPLES (Contd)
3. JUSTICE (Contd)

• Injustice may occur even if individual
  investigators treat their individual research
  subjects fairly
  
• In any society - unjust social patterns in
  respect of social, racial, gender and cultural
  biases institutionalized in society
  
• New international injustice? Research sponsored
  by the developed world in the developing world
  what standards should prevail?