Ethics and Research in Resource-Poor Countries

Selected resources from The Hastings Center.

Table of Contents

Bioethics Briefings:

Research in Resource-Poor Countries

As health problems and disease threats cross borders on a global scale, wealthy countries are increasingly funding and conducting research in low- and middle-income countries. Sponsors and researchers choose to conduct research in lower-income countries for various reasons, including disease prevalence and access to a large number of research subjects under fewer financial and regulatory constraints. Read our briefing to consider: what are the ethical issues to research sponsored by wealthy countries and conducted in relatively poor countries? What efforts are necessary to forge sustainable research partnerships?

From Hastings Bioethics Forum:

  • Oncology, Bioethics, and War
    Like many other Ukrainians, I woke up on February 24 from the sounds of explosions. I had some difficult decisions to make. I treat cancer patients.
  • Responding to Ebola: Fostering Transparency and Inclusivity
    Media reports indicate that seven individuals have received ZMapp to date, two of whom have died. The first recipients were two American health care workers from Liberia who were treated and airlifted to Atlanta last month. This is commendable – an outstanding example of the duty of rescue owed by the United States to two…
  • How Bioethicists Can Help Reduce Global Health Inequities
    The state of global health is a major concern. Despite advances in medicine and medical care and massive growth of the global economy, health in the world is characterized by widening disparities within and between countries; lack of access to even basic health care for billions of people; the emergence of multidrug-resistant tuberculosis, HIV, and…
  • The Ethical Imperialism of Moral Science
    In December, the Presidential Commission for the Study of Bioethical Issues released a 200-page report, Moral Science: Protecting Participants in Human Subjects in Research. Continuing a decades-old tradition, the report treats medical experimentation as the model for all research with human beings, ignoring the rights and responsibilities of researchers in other fields. By doing so, it…

From the Hastings Center Report:

Incidental Findings in Low-Resource Settings

First published: 26 May 2018

Abstract

Much new global genetic research employs whole genome sequencing, which provides researchers with large amounts of data. The quantity of data has led to the generation and discovery of more incidental or secondary findings and to vigorous theoretical discussions about the ethical obligations that follow from these incidental findings. After a decade of debate in the genetic research community, there is a growing consensus that researchers should, at the very least, offer to return incidental findings that provide high-impact, medically relevant information, when it is not unduly burdensome to the research enterprise to do so.

Much as genetic research has been limited to U.S. and European settings, the incidental findings debate has primarily focused on research conducted in high-income countries. In a 2015 paper, Alberto Ortiz-Osorno, Linda Ehler, and Judith Brooks note salient differences between the circumstances of research participants in low- and high-resource settings that alter the analysis of when and why incidental findings should be offered to research participants. In this article, we expand on their analysis and present a framework for thinking about how investigators’ obligations to return genomic data might change in low-resource settings, particularly in settings where participants do not have access to the medical care needed to treat, assess, or monitor incidental findings that are actionable in settings with plentiful resources.

Standards of Care in Global Health: Identifying the Right Question

First published: 20 September 2017

Abstract

Govind Persad and Ezekiel Emanuel’s article “The Case for Resource Sensitivity: Why It Is Ethical to Provide Cheaper, Less Effective Treatments in Global Health,” in this issue of the Hastings Center Report, is a reminder of the debates around resources for health care that raged during the years immediately preceding and following the fifth revision of the Declaration of Helsinki, in 2000. In global health, it is a common expectation for rich countries to assist poor countries in resolving health challenges, yet global health involves not only the governments of rich and poor nations but also nongovernmental organizations, pharmaceutical companies, the World Health Organization, philanthropic organizations, and other parties—all of whom take roles in ensuring that health interventions become available to poor countries, including deciding which types of interventions to make available. The question whether it is ethical to provide cheaper, less effective interventions to poor countries is perhaps relevant only in wealthy nations, where there really is a choice to be made.

Toward an Ethically Sensitive Implementation of Noninvasive Prenatal Screening in the Global Context

First published: 16 March 2017

Abstract

Noninvasive prenatal screening using cell-free DNA, which analyzes placental DNA circulating in maternal blood to provide information about fetal chromosomal disorders early in pregnancy and without risk to the fetus, has been hailed as a potential “paradigm shift” in prenatal genetic screening. Commercial provision of cell-free DNA screening has contributed to a rapid expansion of the tests included in the screening panels. The tests can include screening for sex chromosome anomalies, rare subchromosomal microdeletions and aneuploidies, and most recently, the entire fetal genome.

The benefits of this screening tool are generally framed, by both providers and commercial laboratories, as enhancing reproductive autonomy and choice by providing an earlier, simpler, and more accurate screening while potentially reducing the need for invasive follow-up testing. The majority of the literature has explored these issues empirically or conceptually from a European or North American vantage point, one that assumes normative priorities such as individual reproductive autonomy and the clinical availability of maternal health care or prenatal screening programs within which cell-free DNA screening is offered. While its implementation has raised both challenges and opportunities, very little is known about real-world experiences and the implications of the rapid introduction of cell-free DNA screening outside of North America and Europe, especially in low- and middle-income countries. To begin addressing this gap in knowledge, we organized a four-day international workshop to explore the ethical, legal, social, economic, clinical, and practical implications of the global expansion of cell-free DNA screening. We describe eight key insights that arose from the workshop.

The FDA and Helsinki

First published: May 2009

Abstract

To gain entry to the lucrative American market, newly developed drugs must be licensed by the U.S. Food and Drug Administration. Since 1975, the FDA has required applications for licensure from research studies conducted outside the United States to comply with the Declaration of Helsinki, one of the most influential international codes of research ethics. But last October, the FDA announced that it will now use Good Clinical Practice (GCP) regulations, an international quality standard written by the International Conference on Harmonisation, to ensure that foreign-based studies have been conducted ethically. What is the motivation behind the FDA’s change of regulatory requirements, and what is the larger ethical significance of this move as ever more clinical trials are outsourced to resource-poor, developing countries?

Should the Gold Rule? Assessing “Equivalent Protections” for Research Participants across International Borders

First published: September 2005

Abstract

There are compelling moral and practical reasons for conducting research across international borders, yet such research can involve particularly difficult ethical issues. Consider the urgent need to develop and evaluate new ways of preventing the transmission of HIV. There is terrible morbidity and mortality associated with the HIV pandemic in certain regions of the world, especially in poverty-stricken parts of sub-Saharan Africa and Southeast Asia. People in wealthier parts of the world arguably have a moral obligation to help, including by engaging in research to find effective ways to lower transmission rates. Yet as those knowledgeable about preventive modalities make clear, new interventions must be tested in the environment where they will be used to ensure that they are culturally acceptable, safe, and effective. 

Justice and the Human Development Approach to International Research

First published: January 2005

Abstract

The debate over when medical research may be performed in developing countries has steered clear of the broad issues of social justice in favor of what seem more tractable, practical issues. A better approach will reframe the question of justice in international research in a way that makes explicit the links between medical research, the social determinants of health, and global justice.

Moral Standards for Research in Developing Countries From “Reasonable Availability” to “Fair Benefits”

First published: May 2004

Abstract

Commentators have argued that when research conducted in a developing country shows an intervention to be effective, the intervention must be made “reasonably available” to the host population after the trial. But this standard is sometimes too stringent, and sometimes too lenient. It offers a benefit, but not necessarily a fair benefit.

AIDS Care and Treatment in Sub-Saharan Africa: Implementation Ethics

First published: May 2006

Abstract

With the advent of new AIDS treatment initiatives such as the World Health Organization’s “3 by 5” program and the United States’ “President’s Emergency Plan for AIDS Relief,” the ethical questions about AIDS care in the developing world have changed. No longer are they fundamentally about the conduct of research; now, we must turn our attention to developing treatment programs. In particular, we must think about how to spread limited treatment resources among the vast reservoir of people who need them.


From Hastings Center Bioethics Timeline:

1946: Guatemala Syphilis Studies 

The Syphilis Study Section of the National Institutes of Health-approved grants for Public Health Service researchers to study intentional infection with syphilis, gonorrhea, and chancroid, followed by treatment with newly available penicillin. The studies, involving more than 1,300 Guatemalan soldiers, prisoners, and mental patients, began in 1946 and ended in 1948. The studies remained buried in the archives until 2010. See timeline 2011.

1962: Publication of Maurice Pappworth’s Human Guinea Pigs: A Warning

British physician Maurice Pappworth publishes an article in the literary magazine Twentieth Century on human experimentation. He raised similar issues about lack of informed consent that would later be raised by Henry Beecher in the United States. The two “whistleblowers” corresponded with and supported each other’s efforts; both referenced violations of the informed voluntary consent requirement of the Nuremberg Code in their critiques of current research ethics violations.

1964: The Declaration of Helsinki

The World Medical Association issues the Declaration of Helsinki, its recommendations guiding doctors performing clinical research. The Declaration supplemented the Nuremberg Code’s landmark defense of research subjects’ rights, which, by mandating the informed voluntary consent of research subjects, inadvertently precluded research on children and others incapable of consenting. The Declaration clarified these issues for researchers permitting surrogate consent and similar accommodations to the realities of clinical research.

1974: National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research

The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, the first public national body to shape bioethics policy in the United States, was created as Title II of the National Research Act, which was signed into law by President Richard Nixon. The Commission, which was formed in the aftermath of the Tuskegee Syphilis Study, was charged with identifying ethical principles to be followed when conducting biomedical and behavioral research on humans and with establishing guidelines for the conduct of such research.

https://bioethicsarchive.georgetown.edu/pcsbi/history.html

1983: Proposed International Guidelines for Biomedical Research Involving Human Subjects

Issued by the Council of International Organizations of Medical Science (CIOMS) and the World Health Organization (WHO), the CIOMS guidelines modified the World Medical Association’s 1964 Declaration of Helsinki to address the outbreak of HIV/AIDs and to address the biopharmaceutical industry’s multinational field trials on human subjects, focusing on those conducted in the developing world.

http://www.frqs.gouv.qc.ca/documents/10191/186011/CIOMS+ethics+guidelines.pdf/3a3307e9-65f7-4fb1-b7d8-b69c977df155

1997: Publication of Peter Lurie and Sidney Wolfe’s “Unethical Trials of Interventions to Reduce Neonatal Transmission of Human Immunodeficiency Virus in Developing Countries

Peter Lurie and Sidney Wolfe report that after research demonstrates reduced HIV transmission to newborn infants, the standard of care for HIV-positive pregnant women becomes the regimen used in the AIDS Clinical Trials Group (ACTG) Study 076. However, in developing countries, the potential cost of the ACTG regimen prevents access. Follow-up research studies in developing countries often do not provide patients with antiretroviral drugs or use placebos in the control groups. The article highlights that researchers often ask the wrong question by not assessing the effectiveness of less expensive interventions, do not appreciate the ethically challenged use of placebos, and fail to appreciate the implications of using a standard of care that does not conform to the standard of care in the sponsoring country.

P. Lurie and S. Wolfe, “Unethical Trials of Interventions to Reduce Neonatal Transmission of Human Immunodeficiency Virus in Developing Countries,”New England Journal of Medicine337, no. 12 (1997): 853-56. https://www.researchgate.net/profile/Peter_Lurie/publication/13926523_Unethical_Trials_of_Interventions_to_Reduce_Perinatal_Transmission_of_the_Human_Immunodeficiency_Virus_in_Developing_Countries/links/575339bb08ae17e65ec678be/Unethical-Trials-of-Interventions-to-Reduce-Perinatal-Transmission-of-the-Human-Immunodeficiency-Virus-in-Developing-Countries.pdf/

2004: Publication of Ruth Macklin’s Double Standards in Medical Research in Developing Countries

Macklin provides a policy-based argument that research populations in the developing world must, whenever possible, receive treatment and benefits equal to those enjoyed by their counterparts in the developed world. The book takes ethical guidelines that inform policy to focus on the practical application for the conduct of research. 

R. Macklin, Double Standards in Medical Research in Developing Countries (New York: Cambridge University Press, 2004). https://www.amazon.com/Standards-Research-Developing-Countries-Cambridge-ebook/dp/B001S2PMP2

2008: Publication of Jennifer S. Hawkins and Ezekiel J. Emanuel’s Exploitation and Developing Countries: The Ethics of Clinical Research

In this edited volume, philosophers and bioethicists reflect on the meaning of exploitation and consider whether it is inherently morally troubling. They examine whether and when clinical research in developing countries counts as exploitative and consider what can be done to minimize the possibility of exploitation in such circumstances.

J. S. Hawkins and E. J. Emanuel, Exploitation and Developing Countries: The Ethics of Clinical Research (Princeton: Princeton University Press, 2008).

2010: Uncovering the Guatemala Sexually Transmitted Disease Studies

Susan Reverby, a professor at Wellesley College, finds documents concerning unethical research experiments conducted by the U.S. government in Guatemala from 1946-48. The experiments involved intentionally infecting over 1,300 subjects with venereal disease to assess the effectiveness of penicillin. Her detective work led to an apology by President Obama.

http://academics.wellesley.edu/WomenSt/fac_reverby.html