Ethical issues in global health research

1
Ethical issues in global health research

• Paul Komesaroff
• Director, Centre for Ethics in Medicine and
  Society
• Faculty of Medicine, Nursing and Health Sciences
• Monash University

2
Disclosures

• Clinician and researcher
• Professor of Medicine, Monash University
• Director of Ethics Centre
• Former member and Chair, Ethics Advisory
  Committee, The Endocrine Society
• Ethics Convener of the Royal Australasian College
  of Physicians
• Convener, Global Reconciliation Network
• Chair, Australian Health and Development Alliance
• Member or chair of various ethics committees
• Previous collaborative relationships in research
  projects with various pharmaceutical companies

3
Ethical issues in research

• Clinical and laboratory research are major
  contributors to advancements in health care in
  both developed and developing countries
• Since the Second World War there has been a
  growing awareness of the ethical complexity of
  research involving human subjects.
• This has led, since the 1960s, to the development
  of various systems of regulation involving both
  civil society and government processes.

4
The context of global health

• 87 of the A3 trillion spent on health care
  globally is spent on 16 of the world's
  population
• About A70b per year is spent worldwide on health
  research by both the public and private sectors.
• 10 of the global burden of disease attracts 90
  of global expenditure on health research.

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The role of the pharmaceutical industry

• Drugs account for a significant proportion of
  health expenditure in all countries.
• The U.S. drug market accounts for 40 of the
  industrys sales and 60 of its profits.
• Approximately 44 of global expenditure on health
  research is undertaken by industry in developing
  countries.
• Diseases such as malaria and tuberculosis attract
  little attention.
• Me too drugs, lifestyle drugs and drugs for
  prevention of diseases prevalent in developed
  societies predominate.

6
Ethics of research 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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Major issues in research ethics

• These include
• Consent
• Assessment of risk
• Scientific integrity
• Conflicts of interests
• Privacy and confidentiality
• Protection of vulnerable populations
• Issues of equity and fairness

8
Scientific aspects

• Scientific projects are driven by ethical goals
• Ethical issues are not merely supplemental to the
  science
• The social sources and outcomes of research must
  be taken into account when assessing its ethical
  content
• Ethics committees must consider the goals,
  scientific validity and conduct of a study,
  including methods of recruitment, data collection
  and analysis, dissemination results etc.

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Consent

• Ethical and legal requirements of consent
  include
• Information about the purpose, methods, demands,
  risks, and possible outcomes of the research
• Exercise of voluntary choice to participate.
• Participants with reduced capacity include
• Children and young people
• Persons with an intellectual or mental impairment
  
• Patients in emergency or intensive care
• Terminally ill people
• Persons in dependent or unequal relationships.

10
Risk

• May be difficult to assess and require
  specialised knowledge
• May 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.
• Often depends on assessment of existing evidence
• Including early studies of a drug and personal
  experiences
• Requires balancing of risks and benefits
• Often requiring imprecise and controversial
  judgments

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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
• E.g. responsibility to patients and to
  shareholders
• When a conflict exists the conflicting roles must
  be disengaged.

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Special issues in international research

• Social purposes and implications of research and
  research questions
• Processes and practices of research

13
Social purposes of research and research questions

• 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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Processes and practices of research

• Does the research take into account local
  cultural assumptions and practices with respect
  to consent and other issues?
• Is the standard of care adopted appropriate,
  especially for controls?
• Is it appropriate to include a placebo group?
• Is adequate access to care provided at the
  conclusion of the study?
• Is the project subject to adequate local
  monitoring and governance?
• Is it appropriate to accept different standards
  for research in different countries (with respect
  to consent, risk, privacy etc.)?

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Some recent controversies Consent issues

• Should individual or community consent be
  required?

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The case of research in Australian Aboriginal
communities

• A group of researchers wish to conduct research
  into kidney disease in indigenous people
  suffering from diabetes.
• They approach members of a community living in a
  remote community in the Western Desert.
• They are advised that permission must be obtained
  from the elders of the community rather than from
  individual community members.
• The researchers are then told that it has been
  decided that the community will participate in
  the research.
• Does this arrangement satisfy the requirements
  of recognition of the autonomy of individual
  subjects?

17
Cases raising consent issues in plenary and small
group discussions

• Case 1 A truly wonderful study
• Case 2 Preventing heart disease in children
• Case 3 International diabetes research
• Case 4 Health problems of Sudanese refugees in
  Australia
• Case 5 Development of a new agent for the
  reduction of HIV transmission
• Case 6 A study of Chinese medicines for the
  management of Polycystic Ovary Syndrome in young
  women
• Case 7 A trial of anti-psychotic medications

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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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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 study was terminated
  at the first interim analysis and 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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Cases raising issues relating to use of placebos
in plenary and small group discussions

• Case 1 A truly wonderful study
• Case 5 Development of a new agent for the
  reduction of HIV transmission
• Case 7 A trial of anti-psychotic medications

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Some recent controversies Access to care,
equity and justice

• At the conclusion of the study, every patient
  entered into the study should be assured of
  access to the best proven prophylactic,
  diagnostic and therapeutic methods identified by
  the study
• (Declaration of Helsinki, paragraph 30)

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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 and other markers, and improvements
  in life expectancy.
• Several of these studies were conducted in
  developing countries in which there is limited
  public investment in health care.
• Were the investigators obliged to provide an
  unlimited, ongoing supply of the drugs to all
  participants in these trials?

23
Cases raising issues relating to justice and
equity in plenary and small group discussions

• Case 1 A truly wonderful study
• Case 3 International diabetes research
• Case 4 Health problems of Sudanese refugees in
  Australia
• Case 5 Development of a new agent for the
  reduction of HIV transmission
• Case 7 A trial of anti-psychotic medications

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Conclusions

• Research involving human subjects raises a wide
  range of ethical issues, many of which are
  clearly established and have been widely
  discussed.
• Many countries have elaborate systems of research
  governance which define processes for assessing
  and monitoring research.
• There are nonetheless special issues which remain
  complex and are sometimes controversial.
• These issues relate to the consent process, use
  of placebos, continuing access to treatment,
  observance of local standards and other matters.
• The questions may be particularly difficult and
  important in the setting of research across
  international boundaries.
• Ethical research is not just about establishing
  standards and following guidelines. Ultimately,
  what is most important is open communication and
  dialogue that takes into account the crucial
  scientific, philosophical, ethical and cultural
  issues.