Ethical issues in global health research

Ethical issues in global health research

Paul KomesaroffDirector, Centre for Ethics in Medicine and Society

Faculty of Medicine, Nursing and Health Sciences

Monash University

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

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.

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.

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 industry’s 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.

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.

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

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.

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.

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

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.

Special issues in international research

• Social purposes and implications of research and research questions

• Processes and practices of research

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?

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.)?

Some recent controversies: Consent issues

Should individual or community consent be required?

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?

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”

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)

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?

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”

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)

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?

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”

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.