mmmc - ethics in public health

8/7/2019 MMMC - Ethics in Public Health

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Ethical IssuesEthical Issues

inin

Public HealthPublic Health


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As we have seen recently with SARS and

H5N1 avian influenza, diseases respect

no boundaries. In todays 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

International Health Regulations (IHR)International Health Regulations (IHR)


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Salient Features of IHRSalient Features of IHR (2005(2005))

y International legal instrument enforced on 15th June 2007.

y Replace IHR (1969) only included cholera, plague &

yellow fever.

y

World Health Assembly empowered to adopt bindingregulations concerning sanitary and quarantine

requirements and other procedures designed to prevent

international spread of disease.

y Focuses on serious public health threats with potential to

spread beyond a countrys borders, to other parts of the

world. Such events are defined as a Public Health

Emergency of International Concern (PHEIC).


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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.

Assessing Threat Under IHR (2005)Assessing Threat Under IHR (2005)


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IHR in Practice Reporting TimelineIHR in Practice Reporting Timeline

48-hourTime RequirementAfter a U.S. Governmental Agency (USGA)

learns of a potential PHEIC in a U.S

. state orterritory, it must assess the event within 48

hours.

24-hourTime RequirementThe USGA has 24 hours to notify WHO after it

believes that a potential PHEIC may exist.


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HealthHealth MeasuresMeasures -- RecommendationsRecommendations

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.


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1. Health Measures1. Health Measures -- RecommendationsRecommendations

Examples of health measures for baggage, cargo,containers,conveyances,goods and postal parcels

- Review manifest, Proof of measures taken on departureor in transit,Routing and implement inspections

- Implement treatment to remove infection andcontamination,vectors and reservoirs.

- Isolation and quarantine, seizure and destruction

- Refuse departure or entry.


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2. Protections for2. Protections for TravellersTravellers

y Sanitation and hygiene of transport- Travel advice, entry and exit screening at points of

entry (ports, airports, ground crossings)


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3. Health Measures3. Health Measures -- General applicationGeneral application

y

GENERIC Arrival and departure

x Information about travellersitinerary, destination, non-invasive medical examination

x Inspection of baggage, cargo,containers, conveyances,goods, postal parcels andhuman remains

y SPECIFIC Yellow fever vaccination

Vector control - Disinfection ofconveyances


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4.4. Affected ConveyancesAffected Conveyances andand Imported CasesImported Cases

y Affected or diverted

conveyances and

emergencies

y Imported cases


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Ethical IssuesEthical Issues

ininHealth ResearchHealth Research


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Ethical Issues in Health ResearchEthical Issues in Health Research

y Clinical and laboratory research aremajor contributors to advancements inhealth care in both developed anddeveloping countries.

y Since the World War-II a growing

awareness of the ethical complexity ofresearch on human subjects.

y Since 1960s, development of varioussystems of regulation involving both civilsociety and government processes.

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Role of Pharmaceutical IndustriesRole of Pharmaceutical Industries

y DRUGS and Vaccines significant proportion of

health expenditure in all countries.

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

industrys sales and 60% of its profits.

y Approximately 44% of global expenditure on

health research is undertaken by pharmaceutical

industry in developing countries.

y Diseases such as MALARIA and TUBERCULOSIS

attract little attention.

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The Context of Public HealthThe Context of Public Health

10% of the global burden of diseaseattracts 90% of global expenditure onhealth research.

90 percent of $US is spent on the

illnesses in the wealthiest countries.

Only about 10 % of money is spent forthe care for 84 % of the global

population.

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Social Purposes of ResearchSocial 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 IssuesImportance of Ethical Issues

y To AVOID UNETHICAL PRACTICES.

y Summarize potential benefits and

risks.

y Benefits of research should outweigh

the risks posed to the human subjects.

y Privacy and confidentiality should be

maintained & informed consent taken.

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Major Issues about Ethics inMajor Issues about Ethics in

Biomedical ResearchBiomedical Research

Written Informed Consent

Conflicts of interests

Assessment of risk Scientific integrity

Privacy and confidentiality

Protection of vulnerablepopulations

Issues of equity and fairness

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Research Ethics MilestonesResearch Ethics Milestones

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TRIGGER EVENTS ETHICS MILESTONES

Tuskegee, Syphilis

Study Begins

Nazi Experiments Nuremberg Code 1947

Declaration of Helsinki 1964

Human Radiation

ExperimentsBelmont Report 1979


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History of Protection ofHistory of Protection of

Human SubjectsHuman Subjectsy Nuremberg Code (1947)y Declaration of Helsinki (1964,75,83,89,2000)

y Beecher Ethics and Clinical Research (1966)

[NEJM 274 (1966)1354-60]

y Willowbrook (195601965)

y Jewish Chronic Disease (1963)

y USPHS Syphilis Study (aka Tuskegee Study) (1932-72)

y

Radiation experiments (1940s - 60s)y Modern day scandals.


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Response to ResearchResponse to Research

AbusesAbuses

y National Research Act 1974

y May 1974 45 CFR 46

y June 1974- National Commission

y April 1979 Belmont Report

y 1981 45 CFR 46 revised


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Research Ethics andResearch Ethics and

Regulatory FrameworksRegulatory Frameworks

The Nuremberg Code (1946), theDeclaration of Helsinki (1964) and theBelmont Report (1988).

In most developed countries there arenow rigorous regulatory regimes, oftenlinked to national ethical codes.

Development of ethics committees andresearch governance processes.

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Nuremberg CodeNuremberg Code

y Voluntary Consent

y Build on Previous Knowledge

y Benefit to Society

y Qualified Investigators

y Justification of Risks

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Declaration of HelsinkiDeclaration 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 HelsinkiDeclaration of Helsinki

Consistent with the Declaration of Genevaregarding 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 theProtection of Human Subjects of

Biomedical and BehavioralResearch

April 18, 1979


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Belmont ReportBelmont Report

Was in response to Tuskegee.

y Respect for Persons

y Beneficence

y Justice


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The Belmont ReportThe Belmont ReportApplication:Application:

Equal moral forceand ,

Ethical conflict expected

Principles have:


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Belmont Principles:Belmont Principles:

y Are general prescriptive judgments;

(Other principles may also berelevant)

y

they cannot always be applied so asto resolve beyond dispute particularethical problems;

y their objective is to provide ananalytical framework that will guidethe resolution of ethical problemsarising from research involving humansubjects.


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The Belmont ReportThe Belmont Report

Basic Ethical Principles:

y Respect for Persons

Individual autonomy Protection of individuals with reducedautonomy

y Beneficence

Maximize benefits and minimize harms

y Justice

Equitable distribution of research costs andbenefits


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The Belmont ReportThe Belmont Report

y All principles are essential to soundethical research (regulatorycompliance)

y Principles carry equal moral weight

y Cannot approve research that violatesor diminishes principles

y Some IRBs consider beneficence firstin deliberations


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Unethical Study:Unethical Study:

Nazi Human ExperimentationNazi 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:Unethical Study:

Tuskegee Study of Syphilis (TSS)Tuskegee Study of Syphilis (TSS)

y Federally-funded study of natural historyof syphilis (TSS).

y In 1932 No effective treatment forS

yphilis.y A total of 412 infected, indigent blacks

enrolled (vulnerable population).

y 1951 Penicillin Standard Treatment:TSS

subjects were excluded from penicillinadministration.

y 1972-74 A public disclosure followed byhearings and financial settlement.

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Unethical Treatment of Human Subject:Unethical Treatment of Human Subject:

GeneTransferTrialGeneTransferTrial

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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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HexamethoniumHexamethonium Challenge StudyChallenge Study

Normal volunteers inhaledHexamethonium as a

pulmonary vasodilator.

Large literature on toxicity (in

older publications).

Volunteer #1 with flu not

officially reported to IRB.

Shortly after the inhalation,

volunteer #3, 24 years old died

of respiratory failure 2nd June

2001.

Ellen Roche

Volunteer #3


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Some recent controversies:Some recent controversies:

The Use of PlacebosThe 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 methodexists.

(Declaration of Helsinki,paragraph 29)

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Unethical StudiesUnethical Studies HIV TransmissionHIV Transmission

Zidovudine reduces HIV transmissionfrom 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 AZTThe Case of AZT

y The AIDS Clinical Trials Group Study 076 tested zidovudinegiven orally in HIV-positive pregnant women in the United

States and France and intravenously during labour, and

subsequently administered to the newborn infants.

y The drug was found to reduce the incidence of infection by

two thirds. the regimen was recommended for HIV-positive

pregnant women.

y In developing countries the drug remained prohibitively

expensive.

y The World Health Organization supported placebo-

controlled trials of alternative antiretroviral drug regimens

to prevent perinatal transmission of HIV.

y Was the use of placebo controls in such studies unethical?

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The Case of Protease InhibitorsThe Case of Protease Inhibitors

International trials of protease inhibitorsconducted on patients infected with HIVdemonstrated reductions in viral load,increases in CD4 counts improvements in

life expectancy.

Several of these studies were conductedin developing countries in which there islimited public investment in health care.

Investigators did not obliged to provide anunlimited, ongoing supply of the drugs toall participants in these trials.

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Aspects ofScientific ResearchAspects ofScientific Research

y Scientific projects should be driven by ethical

goals.

y The social implications and outcomes of

research must be taken into account whileassessing its ethical content.

y 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 ConsentInformed Consent

y Document

A form through which people are offeredthe opportunity to participate in research

Legal document that protects institutions

y Process

Dialogue between prospective participant

and members of research team

Continuing

Embodiment of Respect for Persons

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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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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 investigators records, needs to be

signed BEFORE ANY RESEARCH TAKES

PLACE and dated by the subject.

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Vulnerable PopulationsVulnerable Populations

y Vulnerable populations includeindividuals who have limitedautonomy such that they cannotfully participate in the consentprocess. Prisoners

Children

Mentally challengedx Patients in emergency or intensive

carex Terminally ill peoplex Persons in dependent

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RISKRISK

y 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.

y Requiresbalancing of risks and benefits:

- Often requiring imprecise and controversial

judgments.

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Assessment of Risk and BenefitAssessment of Risk and Benefit

y Assess risks and benefits with relevant

data

y

Examine whether the proposed researchis properly designed

y Determine whether risks presented to

subjects are justified

y Examine whether there are alternatives

to the research

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Dualities and Conflicts of InterestsDualities 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:Investigator Fraud: Dr. RobertDr. Robert FiddesFiddes

y Conducted >200 studies for 47 sponsors atSouthern California Research Institute.

y Used false study subjects, laboratory results,urine samples, medical records, radiographs.

y Passed all audits, but turned in by a whistleblowing former employee.

y Sentenced to 15 months in prison, fined$800,000, lost medical license (1997).

y FDA debars Dr. Fiddes and 3 nurse coordinatorsfrom all clinical research activities (2002).

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Ref: www.thompson.com/libraries/fooddrug/clin/index.html


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Investigator Conflicts of InterestInvestigator Conflicts of Interest

y Professional gain:publications / promotion.

y Financial gain:

Patient finders fee to collaborators

Recruitment bonuses Affiliation with / funding from sponsor for

future studies and consultant relationships

y Other incentives (e.g., travel, presentations).

y Per patient payment system presentsconflicts of interest inherent in capitalistsociety.

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Governing ResearchGoverning Research

y Peer review

y Internal / External auditing

y Training and Education

y Monitoring committees

y Governmental review organization

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Institutional Review Board (IRB)Institutional Review Board (IRB)

y IRB panels oversee and approve research on

human subjects.

y IRB reviews:

Beneficence (risks are minimized)

Justice (equitable selection of subjects)

Respect for Persons (informed consent)

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ConclusionConclusion

y 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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