Note: The links below are to articles and reports that identify and address current ethical issues in international research with human participants. 
General frameworks or approaches to conducting medical research in developed and in resource-limited countries are listed first. The articles and reports that come next address more specific issues such as community involvement; ways to communicate; informed consent; equivalent protections; standard of care and infrastructure development. Work on these specific issues may also be found in the general articles.

General articles

Emanuel E J, Wendler D, Grady C. What Makes Clinical Research Ethical? JAMA. 2000;283:2701-2711 (2000) – This link is to an article by Emanuel, Wendler and Grady, all from the NIH Department of Bioethics. Drawing on the basic philosophies underlying major codes, declarations, and other documents relevant to research with human subjects, the authors propose seven requirements that  elucidate a coherent framework for evaluating the ethics of clinical research studies. Although not specifically directed toward international research, the requirements are universal. However, they must be adapted to the health, economic, cultural, and technological conditions in which clinical research is conducted (adapted from abstract).

What Makes Clinical Research in Developing Countries Ethical: the Benchmarks of Ethical Research (2004) – This paper by Emanuel, Wendler, Killen and Grady, all NIH investigators, applies the framework that they developed for research in developed countries to developing countries. Benchmarks are proposed to guide research ethics committees in assessing how well the ethical requirements for research have been fulfilled. (J. Infectious Diseases)

The Ethics of Research Related to Healthcare in Developing Countries (revised 2005) – This site links to a report published by the Nuffield Council of Bioethics. The report identifies both the need for externally supported research in developing countries and the need for ethical safeguards to protect the participants in that research from exploitation. An ethical framework for the conduct of health research in developing countries is proposed. The report emphasizes the need for externally supported research organizations to help developing countries build capacity and infrastructure for conducting and reviewing research. It identifies the main areas of controversy that the working group grappled with. 

Research Involving People Living in Developing Countries (2005) – This position paper from the Wellcome Trust provides guidance for researchers who conduct Trust supported research with people in developing countries. The paper identifies and takes a position on ethical issues germane to such research. They include meeting healthcare needs for the developing world, selecting research participants, consent, ethical review, collateral benefits, standards of care for control groups, post-trial access to treatments demonstrated to be effective, compensation for injury, post-research monitoring, confidentiality and data management, and the roles and responsibilities of the Wellcome Trust, principal investigators and their employing institutions.
Ethical Issues in the Design and Conduct of Clinical Trials in Developing Countries (2001) – This article by Shapiro and Meslin, chair and executive director of the National Bioethics Advisory Commission when they wrote it, addresses the controversies surrounding clinical trials in developing countries, particularly the need for additional ethical standards to avoid exploitation. They address issues of research design, ethics committee review, the consent process, and health benefits and health care needs. (N. Engl. J. Med.)

International Clinical Research (2006) – Stanley G. Korenman produced this on-line material on ethical issues in clinical research in resource poor countries. The text consists of bulleted points and points out situations when ethical principles may conflict. This link is to Chapter 6. A bibliography at the end of the chapter has useful references, most of which are on-line. (International Clinical Research).

Multinational Research and Capacity Building – This site from the NIH Department of Clinical Bioethics includes descriptions of conceptual and empirical research on issues related to the ethics of multinational clinical research. The topics include empirical studies on the quality of informed consent, on attitudes toward consent to collection of tissue samples for research, research participants’ perceptions of personal and community risks and benefits, and motivation of research participants to remain in a clinical trial. Conceptual topics include an analysis of the “standard of care” controversy, a proposal for a new model for understanding researchers’ “ancillary care responsibilities” in the context of multinational research, a proposal for a new model of benefit arrangements for multinational collaborative research, an analysis of exploitation in the context of multinational collaborative research, globalization and health policy (such as options for physician migration from developing countries). A bibliography of publications resulting from these research projects is included.

Towards Progress in Resolving Dilemmas in International Research Ethics (2004, J. Law, Med. and Ethics); Reflections and Recommendations on Research Ethics in Developing Countries (2002 Soc. Sci. and Med.); and Ethical Issues in Research in Low-Income Countries (2007, abstract plus on web, Int. J. Tuberc. Lung Dis.) - These articles by Benatar et al from the University of Cape Town discuss practical and philosophical concerns underlying disagreements about ethical requirements for international research in developing countries. Some of the articles reference areas of agreement and disagreement described by Macklin in her paper, After Helsinki: Unresolved Issues in International Research (2001).  (Abstract only available on the web. The full text is not. Kennedy Inst. of Ethics J.)

UK Clinical Ethics Network – The Network’s main mission is to provide information and support to UK clinical ethics committees. It links to many resources relevant to ethical issues in general and to international research. The site includes clinical case studies, a link to ethical issues, a practical guide to clinical ethics support and educational resources

Specific issues

Standard of care

Ethics of Clinical Research in the Developing World (2002) – This article authored by Killen, Grady, Folkers & Fauci, all NIH scientists, considers whether all participants in clinical research must receive a uniform level of care for the research to be ethical.  The authors argue that clinical trials in developing countries must focus on the countries’ health problems and priorities and methodologies that address them and the views of the local affected population.  A framework for ethical research in developing countries is proposed.  The site links to other resources related to HIV/AIDs research and to the conduct of research in developing countries. (Nature Reviews: Immunology)

The Standard of Care Debate: Can Research in Developing Countries Be Both Ethical and Responsive to Those Countries’ Health Needs? (2004) – This paper by staff of the NIH Department of Bioethics, Emanuel, Wendler and Lie, addresses the dilemma of the appropriate standard of care in international research. The authors propose a framework for the conditions under which it is acceptable to provide subjects with less than the best possible care. Research ethics committees should be willing to grant exceptions for research studies that satisfy four conditions: (1) scientific necessity, (2) relevance for the host community, (3) sufficient host community benefit, and (4) subject and host community nonmaleficence. (Amer. J. Public Health)

Post-trial access

Moral Standards for Research in Developing Countries: From “Reasonable Availability” to “Fair Benefits” - Guidance documents such as CIOMS’ International Ethical Guidelines for Biomedical Research Involving Human Subjects require that interventions proven effective in a study should be made “reasonably available” to the study population after the trial. The authors argue that the reasonable availability requirement is mistaken. Reasonable availability is intended to prevent the exploitation of a study population, e.g., by exposing them to the risks of research without giving them any of its benefits. However, exploitation occurs when one party takes “unfair advantage” of another. Thus, what is needed to avoid exploitation is that the study population receives a fair amount of benefits. Reasonable availability therefore addresses the wrong question: it is concerned with what people receive, but we should be concerned with how much they receive. The authors propose a “fair benefits framework,” which substitutes three criteria for the reasonable availability requirement: (1) fair benefits to the population at risk for exploitation; (2) collaborative partnership with the host population; (3) a public database of benefit agreements to ensure transparency.(Hastings Center Report 34, no. 3 (2004): 17-27, See, also, Participants in the 2001 Conference on Ethical Aspects of Research in Developing Countries, Fair Benefits for Research in Developing Countries Science. 2002; 298: 2133-2134). 

Community participation

Ethics in International Health Research: A Perspective From the Developing World (2002) - This paper by Bhutta argues that much of recent international research in the developing world has lacked adequate participation by the developing country hosts.  The current challenge is to expand ethics debates to the larger issues of global equity and justice, and to make the process as participatory and democratic as possible.  The actions required to move ahead in this field include strengthening bioethics capacity in developing countries; linking health research to community needs in a transparent and participatory process; and increasing communication between scientists and ethicists in industrialized and developing countries. The clear goal in all these activities must be the reduction of global inequities in health (adapted from abstract, WHO Bulletin).

Regulatory issues

Ethical Oversight of Research in Developing Countries (2003, The Hastings Center IRB: Ethics and Human Research) – This article by Kass, Dawson and Loyo-Berrios (article not freely available on the web), is the product of a study commission by the National Bioethics Advisory Commission (NBAC). The survey study investigated the experiences and attitudes of U.S. investigators about ethics review and regulatory oversight of research they have conducted in developing countries. Issues identified by focus groups informed the design of a survey. Survey results are reported and recommendations are made about review and oversight of research in developing countries. Some of the results of the survey are available in the NBAC report Ethical and Policy Issues in International Research: Clinical Trials in Developing Countries (2001).

Report of the Equivalent Protections Working Group (2003) – This report from a DHHS Working Group was formed in response to recommendations made by the National Bioethics Advisory Commission (NBAC) and the DHHS Office of the Inspector General (OIG) that OHRP “assess whether other countries’ laws and practices afford equivalent protections to those that apply to human subjects participating in clinical trials in the U.S…(p.2). The Report provides a framework for equivalent protections in the context of protections in the U.S. regulations (45CFR46). A five step approach is proposed to assess equivalence of protections, along with an assurance from the foreign institution that the procedures will be followed.

Coercion and undue inducement

Undue Inducement in Clinical Research in Developing Countries: Is it a Worry (2005) – Emanuel, Currie and Herman, on behalf of Project Phidisa, note four major controversies surrounding research in developing countries: standard of care used in the control condition; ancillary care provision during the trial; availability of interventions at the end of the trial and quality of informed consent. An emerging concern is that undue inducements to participants may impair voluntary participation. The article posits that if an ethics review committee assesses the risks as reasonable and that other criteria for ethical research are met, inducements to participate are unlikely to lead to substantial risk of harm and are not undue. Links to related articles are provided. (The Lancet)

Biological samples

The Use of Human Biological Samples in Research: A Comparison of The Laws in the United States And Europe (2003) – This link to an article written for a Working Group on Tissue Banks and Resources from the National Cancer Institute, NIH and the European Organization for Research and Treatment of Cancer Data Center compares laws and identifies trends in bio-banking. Tissue research is regulated through different and sometimes conflicting laws, and the trend is toward increasing regulation at the same time that collaborative projects are increasing. The article includes references to numerous laws and policies. (Pharmalicensing.com)

African Malaria Network Trust (AMANET) – This site includes a web-based course: Basic Health Research Ethics. It was developed by the African Malaria Network Trust. Modules cover fundamental principles, operation of review boards, informed consent, ethical requirements of research studies, vulnerable groups in research, standard of care, researcher responsibilities, scientific misconduct and current issues in genetics research and stored specimens. Registration is required to access the course but there is no charge.

Collaborative Institutional Training Initiative (CITI) - The CITI International Training Platform at www.irbtraining.org is a public access site providing basic, foundational information for researchers, research staff and research ethics committee members involved in international research. This program now includes two learner tracks. Track 1 targets the international investigator (International Modules) while Track 2 is intended for non-US investigators, involved in U.S. Federally funded international research (US Federal Modules). Topics for both tracks include History and Ethics, Research Review Processes, Informed Consent, International studies (Resource information/country specific information), Course documents (Ethical guidance documents and links to research compliance information)

Ethics Around the World (UNESCO) – This site describes a UNESCO/National Commission for UNESCO activity involving a series of conferences that will educate participants, build capacity, and raise awareness of ethical issues in science and technology.

Ethics Education Program (UNESCO) – This site links to background information and an overview of the UNESCO ethics programs, and to its publications and activities.

Eubios Ethics Institute - This site links to reports, educational resources for students and teachers, conference abstracts, ongoing research projects, and UNESCO documents and declarations. The links focus on international activities, particularly Asian resources.
Family Research International Research Ethics Training Curricula –  Training curricula for international scientists and for community representatives are posted along with slide presentations, notes, handouts for students and test questions. The curricula cover basic ethical principles, ethics committee review, and responsible conduct of research.

Health Training: Postgraduate Training Programmes in International Health – This site is Medicus Mundi Switzerland's internet inventory of postgraduate training educational opportunities in the field of International Health. The user can query by topic, educational institution, location and/or type of educational program and locate training opportunities.

International Issues in Biomedical Research: A Casebook (2007) – This book on ethics of research involving human subjects in developing countries is the work of staff of the NIH Department of Clinical Bioethics and of the Unversity of Toronto Center for Bioethics. Using 21 actual case studies, it covers the topics, including the ethics of placebo research in Africa, what benefits should be provided to the community after completion of a research trial, how to address conflicts between IRBs in developed and developing countries, and undue inducement of poor people in developing countries. Each case is accompanied by two expert commentaries
International Health Research (in the Department of Population and

International Research Ethics - The Phoebe R. Berman Bioethics Institute at Johns Hopkins University site includes information on training programs in international ethics research, including a summer intensive summer course. The Institute also conducts empirical research on international issues.

Online Course On Ethical Issues in International Health Research – This course by the Harvard School of Public Health introduces major ethical topics in international health research, poses questions for students and scholars to consider, and also provides research resources and case studies.  CD-Rom is available. 

Strategic Initiative for Developing Capacity for Ethical Review –This WHO initiative conducts a network of regional fora for ethics committees and researchers to improve human subjects protections. The site links to other organizations and publications.

Training and Resources in Research Ethics Evaluation for Africa (TRREE) – This site aims to assist ethics evaluation and to build ethics review infrastructure in developing African countries.  It focuses on internationally recognized ethical principles and regulations while integrating local African issues and perspectives that are relevant to the protection of research participants. An electronically accessible curriculum is under development. Links to many training programs and policy resources are available.  The site was developed by the European and Developing Countries Clinical Trials Partnership, a group of European and African countries that to develop clinical tools for AIDS, malaria and tuberculosis.

UK Clinical Ethics Network – The Network’s main mission is to provide information and support to UK clinical ethics committees. It links to many resources relevant to ethical issues in general and to international research. The site includes clinical case studies, a link to ethical issues, a practical guide to clinical ethics support and educational resources

International Organizations

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