Ethical Issues

in
Public Health
International Health Regulations (IHR)

“As we have seen recently with SARS and

H5N1 avian influenza, diseases respect no
boundaries. In today’s world, a threat
anywhere means danger everywhere.”

December 13, 2006

HHS Secretary Michael O. Leavitt, on the occasion of the
official United States acceptance of revised IHR
Salient Features of IHR (2005)
 International legal instrument enforced on 15th June 2007.
 Replace IHR (1969) – only included cholera, plague & yellow
fever.
 World Health Assembly empowered to adopt binding
regulations concerning sanitary and quarantine requirements
and other procedures designed to prevent international spread
of disease.
 Focuses on serious public health threats with potential to
spread beyond a country’s borders, to other parts of the world.
Such events are defined as a “Public Health Emergency of
International Concern (PHEIC)”.
Assessing Threat Under IHR (2005)

 Always Notifiable:
Smallpox
Poliomyelitis, wild-type
Human Influenza new subtypes H5N1, H1N1
SARS

 Other Events Potentially Notifiable:

Examples: Cholera, Pneumonic Plague, Yellow
Fever, Viral Hemorrhagic Fever and West Nile
Fever.
Other Biological, radiological or chemical
events may fit the decision algorithm and be
reportable.
IHR in Practice Reporting Timeline

48-hour Time Requirement

 After a U.S. Governmental Agency (USGA) learns
of a potential PHEIC in a U.S. state or territory, it
must assess the event within 48 hours.

24-hour Time Requirement

 The USGA has 24 hours to notify WHO after it
believes that a potential PHEIC may exist.
Health Measures - Recommendations

 Review travel history and proof of medical

examination, lab analysis, vaccination or
other prophylaxis.

 Require medical examination, vaccination or

other prophylaxis.

 Public health observation, quarantine,

isolation and contact tracing.
1. Health Measures - Recommendations

 Examples of health measures for baggage, cargo, containers,

conveyances, goods and postal parcels
- Review manifest, Proof of measures taken on departure or in
transit, Routing and implement inspections
- Implement treatment to remove infection and contamination,
vectors and reservoirs.
- Isolation and quarantine, seizure and destruction
- Refuse departure or entry.
2. Protections for Travellers

Sanitation and hygiene of transport

- Travel advice, entry and exit screening at points of entry
(ports, airports, ground crossings)
3. Health Measures - General application
 GENERIC
◦ Arrival and departure
 Information about travellers
itinerary, destination, non-
invasive medical examination
 Inspection of baggage, cargo,
containers, conveyances, goods,
postal parcels and human
remains
 SPECIFIC
◦ Yellow fever vaccination

◦ Vector control - Disinfection of

conveyances
4. Affected Conveyances and Imported Cases

Affected or diverted
conveyances and
emergencies
Imported cases
 Ethical Issues
in
Health Research
Ethical Issues in Health Research

Clinical and laboratory research are major

contributors to advancements in health care
in both developed and developing countries.
Since the World War-II a growing awareness
of the ethical complexity of research on
human subjects.
Since 1960s, development of various systems
of regulation involving both civil society and
government processes.

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Role of Pharmaceutical Industries

 DRUGS and Vaccines significant proportion of health

expenditure in all countries.

 The U.S. drug market accounts for 40% of the

industry’s sales and 60% of its profits.

 Approximately 44% of global expenditure on health

research is undertaken by pharmaceutical industry in
developing countries.

 Diseases such as MALARIA and TUBERCULOSIS

attract little attention.
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The Context of Public Health

 10% of the global burden of disease attracts

90% of global expenditure on health
research.

 90 percent of $US is spent on the illnesses in

the wealthiest countries.

 Only about 10 % of money is spent for the

care for 84 % of the global population.

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Social Purposes of Research

 Does the research address the health

problems and reflect the priorities of the
society in which it is being conducted?

 Does it contribute to local capacity and

knowledge?

 Will it lead to practical changes at the level of

individuals and local communities?

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Importance of Ethical Issues

To AVOID UNETHICAL PRACTICES.

Summarize potential benefits and risks.
Benefits of research should outweigh the
risks posed to the human subjects.
Privacy and confidentiality should be
maintained & informed consent taken.

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Major Issues about Ethics in
Biomedical Research

 Written Informed Consent

 Conflicts of interests
 Assessment of risk
 Scientific integrity
 Privacy and confidentiality
 Protection of vulnerable
populations
 Issues of equity and fairness
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 Research Ethics Milestones

TRIGGER EVENTS ETHICS MILESTONES

Tuskegee, Syphilis
Study Begins

Nazi Experiments Nuremberg Code 1947

Declaration of Helsinki 1964

Human Radiation
Experiments
Belmont Report 1979

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History of Protection of
Human Subjects
 Nuremberg Code (1947)
 Declaration of Helsinki (1964,’75,’83,’89,2000)
 Beecher “Ethics and Clinical Research” (1966)
[NEJM 274 (1966) 1354-60]
 Willowbrook (195601965)
 Jewish Chronic Disease (1963)
 USPHS Syphilis Study (aka Tuskegee Study) (1932-72)
 Radiation experiments (1940s - 60s)
 Modern day scandals….
 Response to Research
Abuses

National Research Act 1974

May 1974 – 45 CFR 46
June 1974- National Commission
April 1979 – Belmont Report
1981 – 45 CFR 46 revised
Research Ethics and
Regulatory Frameworks

 The Nuremberg Code (1946), the

Declaration of Helsinki (1964) and the
Belmont Report (1988).

 In most developed countries there are now

rigorous regulatory regimes, often linked to
national ethical codes.

 Development of ethics committees and

research governance processes.

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Nuremberg Code

Voluntary Consent
Build on Previous Knowledge
Benefit to Society
Qualified Investigators
Justification of Risks

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Declaration of Helsinki
 Statement of ethical principles developed by the
WMA to provide guidance to physicians and others
conducting medical research involving human
subjects.

 Researchers should be aware of the ethical, legal and

regulatory requirements for research on human
subjects in their own countries as well as applicable
international requirements.
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Declaration of Helsinki
 Consistent with the Declaration of Geneva regarding
the obligation of a physician (“health of my patient
will be my first consideration”).

 Well-being of human subject takes precedence over

the interests of science and society.

 Medical research is subject to ethical standards that

promote respect for all human beings and protect
their health and rights.

 A medical researcher must protect the life, health,

privacy and dignity of human participants.

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The Belmont Report

The National Commission for the

Protection of Human Subjects of
Biomedical and Behavioral
Research
April 18, 1979
Belmont Report

 Was in response to Tuskegee.

 Respect for Persons

 Beneficence
 Justice
 The Belmont Report
Application:

Principles have:

Equal moral force

and ,
Ethical conflict expected
Belmont Principles:
Are general prescriptive judgments;
(Other principles may also be
relevant)
they cannot always be applied so as to
resolve beyond dispute particular
ethical problems;
their objective is to provide an
analytical framework that will guide
the resolution of ethical problems
arising from research involving human
subjects.
The Belmont Report

Basic Ethical Principles:

 Respect for Persons
◦ Individual autonomy
◦ Protection of individuals with reduced
autonomy
 Beneficence
◦ Maximize benefits and minimize harms
 Justice
◦ Equitable distribution of research costs and
benefits
 The Belmont Report

 All principles are essential to sound

ethical research (regulatory
compliance)
 Principles carry equal moral weight
 Cannot approve research that violates
or diminishes principles
 Some IRBs consider “beneficence” first
in deliberations
Unethical Study:
Nazi Human Experimentation

 A series of medical
experiments on large numbers of prisoners by the
German Nazi regime in its concentration camps
during World War II.
 Prisoners were forced to participate: They did not
willingly volunteer. There was never any informed
consent obtained from them.
 Typically, the experiments resulted in death,
disfigurement or permanent disability.
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Unethical Study:
Tuskegee Study of Syphilis (TSS)

Federally-funded study of natural history of

syphilis (TSS).
In 1932 – No effective treatment for Syphilis.
A total of 412 infected, indigent blacks
enrolled (vulnerable population).
1951 – Penicillin Standard Treatment: TSS
subjects were excluded from penicillin
administration.
1972-74 – A public disclosure followed by
hearings and financial settlement.

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Unethical Treatment of Human Subject:
Gene Transfer Trial

 Jesse Gelsinger, an 18 yr. old with mild

ornithine transcarbamylase deficiency.
 Symptoms controlled with drugs & diet.
 Gene-therapy study to determine safety, not
efficacy; consent incomplete.
 Injection of the virus that had killed animals.
 Parents inadequately advised about risks.
 Personal conflict of interest
 Four days after therapy, patient had brain-
death on 17 Sep 99.

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 Hexamethonium Challenge Study

 Normal volunteers inhaled

Hexamethonium as a pulmonary
vasodilator.

 Large literature on toxicity (in

older publications).

 Volunteer #1 with “flu” not

officially reported to IRB.

 Shortly after the inhalation, Ellen Roche

volunteer #3, 24 years old died of Volunteer #3
respiratory failure 2nd June 2001.
Some recent controversies:
The Use of Placebos

 The benefits, risks, burdens and effectiveness of a

new method should be tested against those of the
best current prophylactic, diagnostic, and
therapeutic methods.

 This does not exclude the use of placebo or no

treatment, in studies where no proven prophylactic,
diagnostic or therapeutic method exists.

(Declaration of Helsinki, paragraph 29)

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Unethical Studies – HIV Transmission

 Zidovudine
reduces HIV transmission
from mother to child by 2/3 (1994):
◦ Complex & costly treatment regimen
◦ Simpler regimen suspected effective

 Placebo-controlled trials:
◦ 15 of 16 in developing countries
◦ 9 of these U.S. funded (1997)
◦ Stimulated debate on placebo treatment

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The Case of AZT
 The AIDS Clinical Trials Group Study 076 tested zidovudine
given orally in HIV-positive pregnant women in the United
States and France and intravenously during labour, and
subsequently administered to the newborn infants.
 The drug was found to reduce the incidence of infection by two
thirds. the regimen was recommended for HIV-positive pregnant
women.
 In developing countries the drug remained prohibitively
expensive.
 The World Health Organization supported placebo-controlled
trials of alternative antiretroviral drug regimens to prevent
perinatal transmission of HIV.
 Was the use of placebo controls in such studies unethical?
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The Case of Protease Inhibitors

 International trials of protease inhibitors

conducted on patients infected with HIV
demonstrated reductions in viral load,
increases in CD4 counts improvements in life
expectancy.
 Several of these studies were conducted in
developing countries in which there is limited
public investment in health care.
 Investigators did not obliged to provide an
unlimited, ongoing supply of the drugs to all
participants in these trials.
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Aspects of Scientific Research

 Scientific projects should be driven by ethical

goals.

 The social implications and outcomes of research

must be taken into account while assessing its
ethical content.

 Ethics committees must consider these goals:

- Scientific validity and methodology of a study.
- Methods of recruitment, data collection and analysis,
dissemination results etc.

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Informed Consent

 Document

◦ A form through which people are offered the

opportunity to participate in research
◦ Legal document that protects institutions

 Process

◦ Dialogue between prospective participant and

members of research team
◦ Continuing
◦ Embodiment of Respect for Persons

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Informed Consent

 Items included in informed consent form include:

◦the nature of the research procedures and their
purposes
◦risks and anticipated benefits
◦alternative procedures
◦Statement that participation is voluntary and option to
withdraw anytime from the study
◦opportunity to ask questions and who to contact for
answers
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Informed Consent

 For long and/or complicated studies,

investigators should stress to subjects the
importance of keeping a copy of the consent
form for their reference.

 The original consent form, which is kept in the

investigator’s records, needs to be signed
BEFORE ANY RESEARCH TAKES PLACE
and dated by the subject.
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Vulnerable Populations
Vulnerable populations include
individuals who have limited autonomy
such that they cannot fully participate
in the consent process.
• Prisoners
• Children
• Mentally challenged
 Patients in emergency or intensive care
 Terminally ill people
 Persons in dependent

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RISK

 Risks can be physical, psychological or social:

- Including dangers from drugs or invasive procedures,
costs, inconvenience, exposure to legal or social
consequences, revival of traumatic memories etc.

 Requires “balancing” of risks and benefits:

- Often requiring imprecise and controversial
judgments.

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Assessment of Risk and Benefit

Assess risks and benefits with relevant data

Examine whether the proposed research is
properly designed
Determine whether risks presented to
subjects are justified
Examine whether there are alternatives to
the research

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Dualities and Conflicts of Interests

 Dualities may include:

- Relationships with industry, roles as clinicians and
researchers, direct or indirect payments, potential non-
pecuniary benefits from research.

 Conflicts of interest occur when duties associated with two

social roles are contradictory:
- Responsibility to patients and to shareholders

 When a conflict exists the conflicting roles must be

disengaged.

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Investigator Fraud: Dr. Robert Fiddes
 Conducted >200 studies for 47 sponsors at Southern
California Research Institute.

 Usedfalse study subjects, laboratory results, urine

samples, medical records, radiographs.

 Passedall audits, but turned in by a “whistle

blowing” former employee.
 Sentenced to 15 months in prison, fined $800,000, lost
medical license (1997).
 FDA debars Dr. Fiddes and 3 nurse coordinators
from all clinical research activities (2002).

Ref: www.thompson.com/libraries/fooddrug/clin/index.html
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Investigator Conflicts of Interest

 Professional gain: publications / promotion.

 Financial gain:
◦ Patient finder’s fee to collaborators
◦ Recruitment bonuses
◦ Affiliation with / funding from sponsor for
future studies and consultant relationships
 Other incentives (e.g., travel, presentations).
 Per patient payment system presents conflicts of
interest inherent in capitalist society.

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Governing Research

Peer review
Internal / External auditing
Training and Education
Monitoring committees
Governmental review organization

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Institutional Review Board (IRB)

 IRB panels oversee and approve research on human

subjects.

 IRB reviews:

◦ Beneficence (risks are minimized)

◦ Justice (equitable selection of subjects)

◦ Respect for Persons (informed consent)

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Conclusion

Before doing research, investigators must ask:

◦ Is it right to conduct this research?
◦ Do the benefits outweigh the risks?
◦ Is there a genuine state of uncertainty?
◦ Is the study design well conceived?
◦ Are the rights of the participants protected?

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