Beyond Nuremberg: a critique of 'informed consent' in Third World human subject research.

• Author: Schuman, Jacob

1. INTRODUCTION: FROM NUREMBERG TO KANO A. The Birth of Informed Consent B. Global Challenges to Informed Consent C. Proposal for a Critique of Informed Consent in Third World Research II. THE PRINCIPLE OF INFORMED CONSENT: THEORY, POLICY, AND ADVOCACY A. The Theoretical Bases of Informed Consent B. The FDA's Informed Consent Policies for Foreign Research C. The Advocacy for Informed Consent in Third World Research III. A CRITIQUE OF INFORMED CONSENT IN THIRD WORLD HUMAN SUBJECT RESEARCH A. A Contextualization of Third Worm Research B. A Critique of the Right to Informed Consent in Third Worm Research C. A Critique of the Possibility of Informed Consent in Third Worm Research IV. BEYOND INFORMED CONSENT: DISTRIBUTIVE JUSTICE IN THIRD WORLD HUMAN SUBJECT RESEARCH V. CONCLUSION: TOWARD A "KANO CODE". The hidden Yes in you is stronger than all Nos and Maybes that afflict you and your age like a disease--Friedrieh Nietzsehe (1)

1. INTRODUCTION: FROM NUREMBERG TO KANO

   1. The Birth of lnformed Consent

      The principle of "informed consent" forms one of the "basic ethical protections for research involving human participants." (2) Informed consent requires that a human subject of scientific research "willingly verif[y] his/her willingness to participate in a particular treatment, after having been informed of all aspects which are pertinent to that treatment and relevant to the subject's participation." (3) Governments around the world have adopted a variety of regulations (4) that articulate and enforce this "oldest and most universally accepted ethical standard in research." (5) In the United States, the Federal Food, Drug, and Cosmetic Act (FD&C) mandates that scientists who test new drugs first inform human subjects about the experimental nature of the studies and obtain their consent. (6) The U.S. Food and Drug Administration (FDA), the federal agency charged with administering and enforcing the FD&C, (7) has promulgated a series of regulations to implement this requirement. (8)

      The informed consent requirement originated in the Nuremberg Trials following World War II. (9) Under the Third Reich in Germany, Nazi scientists conducted a variety of involuntary and often fatal medical experiments on concentration camp inmates, (10) mainly Jews, Roma, and Slavs. (11) After the war ended, the United States prosecuted twenty Nazi scientists (12) before the International Military Tribunal in Nuremberg, Germany for war crimes and crimes against humanity. (13) Ultimately, seven of the Nazi scientists were sentenced to death and eight to varying prison terms (14) As part of its final judgment, the Tribunal promulgated a set of ten principles, later known as the "Nuremberg Code," that provided the first international rules for scientific research on human subjects. (15) The Nuremberg Code's first and most important principle (16) directed:

      The voluntary consent of the human subject is absolutely essential. This means that the person involved should have legal capacity to give consent; should be so situated as to be able to exercise free power of choice ... and should have sufficient knowledge and comprehension of the elements of the subject matter involved as to enable him to make an understanding and enlightened decision. (17) Later international guidelines, such as the World Medical Association's 1964 "Declaration of Helsinki," (18) provided further direction for medical researchers. Nevertheless, the Nuremberg Code "remains the most authoritative legal and ethical document governing international research standards." (19) Supreme Court Justice William Brennan once remarked, "[t]he medical trials at Nuremberg in 1947 deeply impressed upon the world that experimentation with unknowing human subjects is morally and legally unacceptable." (20)

   2. Global Challenges to Informed Consent

      The globalization of the pharmaceutical industry, especially the clinical testing process for new drugs, (21) has undermined enforcement of the informed consent requirement. When the FDA first began to regulate clinical studies in the 1960s, it hesitated to approve new drugs based on research conducted abroad, which caused pharmaceutical companies to rarely sponsor overseas trials. (22) But as the FDA gradually liberalized this policy, especially in its 1994 decision to allow new drug applications based entirely on foreign research data, (23) the industry responded by moving its experiments offshore. The number of foreign investigators seeking FDA approval for new drugs increased sixteen-fold over the 1990s, while U.S.-based researchers declined. (24) In 1999, over a quarter of new drugs approved by the FDA were first tested abroad, (25) and by 2008 that figure had jumped to more than three quarters of new drugs. (26)

      Pharmaceutical companies based in First World countries have sought to conduct their research in the Third World, (27) drawn by lower costs and a more permissive regulatory environment. (28) The most popular new locations for foreign studies are developing regions such as the former Soviet Union, Latin America, India, China, South East Asia, and Africa. (29) Between 1995 and 2005, U.S. pharmaceutical companies conducted nearly one-third of their clinical studies in poor and low-income countries, and by 2005, approximately 40% of all international clinical trials occurred in these developing regions. (30) One journalist explained, "rich countries have the drugs and hypotheses, while poor countries have vast numbers of patients." (31)

      Yet the "outsourcing" of medical research to the Third World has made it more difficult to regulate the ethics of human subject research. There are no binding international treaties that regulate human experimentation, (32) and the international ethical guidelines, such as the Nuremberg Code, lack any sanctions or enforcement mechanisms. (33) Government regulators in the Third World are "generally ill-equipped to oversee, much less manage, the clinical trials being held within their borders." (34) Moreover, these poorer countries have "strong incentives to encourage leniency in national and local oversight of the research" (35) to attract drug companies and obtain the financial benefits of clinical studies. (36) The "resulting 'regulatory vacuum' makes it difficult to ensure the welfare of trial participants," (37) and effectively permits inadvertent, or even intentional, abuse of human subjects. (38) A series of recent headline articles in the Washington Post revealed that, in several instances, pharmaceutical companies had conducted clinical trials in the Third World in which researchers forged consent forms, lied to subjects about the nature of the study, or failed to reveal the potential dangers of the experimental drugs. (39) Unfortunately, cases like these may not constitute isolated aberrations--a 1996 study found that nearly half of the clinical trials conducted in Chile that year suffered from "ethical problems," most commonly a failure to obtain the subjects' consent. (40) In addition, international variations in acceptable experimental protocols allow for studies in the Third World that would not satisfy First World regulatory scrutiny. (41) Even in the absence of clear ethical violations, language barriers and cultural differences between First World scientists and Third World human subjects make it difficult for investigators to ensure that their patients legitimately consented to participating in research . (42)

      One high profile case of allegedly unethical pharmaceutical research occurred in Kano, Nigeria in 1996, when the American drug company Pfizer, Inc. sponsored a study of the experimental drug Trovan on hundreds of children during a meningitis outbreak in Northern Nigeria. (43) After eleven children died and many more were injured, (44) a group of Nigerian children and their guardians sued Pfizer in an American court, claiming that the company had tested the drug on them without disclosing the experimental nature or dangers of the research. (45) The lawsuit ultimately led to the Second Circuit case of Abdullahi v. Pfizer, Inc., (46) in which the court declared that the prohibition on nonconsensual medical research constituted a universally accepted norm of international law, (47) and held that violation of this norm--even when it occurred abroad--was sufficiently heinous to support the universal jurisdiction of an American court. (48) The Second Circuit concluded "the norm prohibiting nonconsensual medical experimentation on human subjects has become firmly embedded and has secured universal acceptance in the community of nations." (49) The Abdullahi decision offered a source of both hope and despair--half a century after the Nuremberg Trial first announced the principle of informed consent, and the requirement became a widely accepted tenant of international law, violations continued to occur in the Third World.

   3. Proposal for a Critique of lnformed Consent in Third World Research

      Concerns about the welfare of human subjects in developing countries have led activists, academics, and government officials in the United States to call for reinforcement of the informed consent requirement in Third World pharmaceutical research. (50) This paper offers a critical analysis of that approach. Although the assurance of experimental subjects' voluntary participation in Third World clinical studies is certainly a laudable goal, a rights-based notion of autonomous consent ignores the actual context in which that consent takes place--a terrain defined by the absence of essential medical treatment, desperation for healthcare, and important cultural differences. These circumstances belie the notion of an inalienable and universal right to freely assent to medical experimentation. As an alternative, this paper proposes that advocates concerned about the interests of human subjects in developing countries address the distributive consequences of globalized pharmaceutical testing. This...