Medical Research: Establishing International Guidelines
by Michael P. Hamilton
Canon Hamilton is on the staff of Washington Cathedral (Episcopal) in Washington, D.C. This article appeared in the Christian Century October 20, 1982, p. 1047. Copyright by the Christian Century Foundation and used by permission. Current articles and subscription information can be found at www.christiancentury.org. This material was prepared for Religion Online by Ted & Winnie Brock.
“Would it be all right if we used the native population as patients in order to test a drug which we hope will better treat a particular tropical disease?” he asked. It seemed an innocent enough inquiry, and the usual interrogation followed. We asked whether adequate animal testing of the drug would take place before it was given to humans, whether the subjects would be fully informed about what was going to happen to them and about any possible danger of side effects from the drug prior to giving their consent, whether they were going to be paid for participating in the experiment and, if so, how much. We also wondered whether some patients would be in a “control” group given only the current standard treatment so that a comparison could be made between their progress and the response of the patients who were given the new drug. All the answers regarding the scientific merit and the ethical nature of the proposed research seemed satisfactory. We were about to applaud the enterprise and encourage its spokesman to see that it was carried out when a final question occurred to me. “What will happen if the drug is found to be helpful?” I asked.
“The experiment will be a success, of course, and we will use it,” he answered.
“That’s good. Will the patients themselves continue to be given the drug as long as they need it?”
“I suppose so.”
“Will supplies of the drug be made available on the market for the citizens of the country where we have done this research?”
After a long pause, he answered, “We haven’t thought about that.”
I then objected to the research on the grounds that we would be using people as guinea pigs solely for our own benefit. In conducting such research, we would have a moral obligation not only to complete treatment of the patients involved but also to see to it that supplies of the drug, if it were efficacious, would be made available on the local market. We never did learn whether the research was carried out or not. Upon reflection I presume that its mysterious proponent was employed by the Department of Defense, which was interested in finding a treatment for members of our armed forces should they be exposed to the disease.
The Geneva-based Council for International Organizations of Medical Sciences (CIOMS), an institution which works with the World Health Organization (WHO), has been working for some years to develop comprehensive, international guidelines for medical research. In the process Dr. Zbigniew Bankowski, executive secretary of CIOMS, sent out over 100 questionnaires to Third World countries. He discovered that whatever restraints were placed upon research, whether domestically or internationally funded, arose from indigenous ministries of health, university policies and hospital codes and varied greatly in quality. In addition, he learned that the responsibility for both the scientific and ethical approval of approximately 23 per cent of the research was vested in individual medical investigators.
An extreme example of this haphazard dispersion of control was an experiment to test the effects of tetracycline on a rickettsial disease. The subjects of this experiment were to be healthy members of the subordinate staff of a medical institution in a Third World country; they were to be exposed to the disease by the bites of infected insects. Despite being informed that even with the proposed antibiotic treatment, rickettsial infection might be persistent in their bodies -- and that there was “a small risk of death” -- people “volunteered.” It sounded like a form of medical banditry: not “your money or your life” but “your health or your job.”
However, it should be noted that abuses are not restricted to developing countries. They take place even in the United States, our guidelines notwithstanding. The experiment that permitted retarded children to contract hepatitis at the Willowbrook State School in New York state and the injection of live cancer cells into elderly patients at the Jewish Chronic Disease Hospital in New York City are two illustrations.
An example of unethical behavior involving two developed countries occurred in July 1980 when Dr. Martin J. Cline, a member of the staff of the School of Medicine at the University of California in Los Angeles, conducted the first gene therapy in humans on two terminally ill thalassemia patients in Israel. Criticism of Dr. Cline by American scientists came quickly after the procedure was announced, and it focused on two issues. First, the insertion of combined genes into a patient was not authorized by Dr. Cline’s protocol, nor was it envisaged under the conditions of his grant. Second, the experiment itself was scientifically premature and should have been preceded by more animal studies. In his defense, Dr. Cline at first claimed that his experiment was not really novel, but later (in a letter to the National Institutes of Health) he wrote: “I greatly regret my decision to proceed with the DNA experiment. . . . I exercised poor judgment in failing to halt the study.” Subsequently, most of the government funds for research over which Dr. Cline had responsibility were withdrawn.
One could argue on behalf of Dr. Cline that because national cultures differ, their medical and ethical standards should also. Why should medical research and treatment as practiced in the industrial nations be mirrored in emerging, Third World, agricultural nations? Should Western, Judeo-Christian values be promulgated in non-Western nations? Is this not an example of cultural imperialism? Can one realistically require individual free consent to participation in research when decisions in the tribal community are basically communal and expressed through a single spokesperson? Should a scientist be subject to penalty if he or she conducts research forbidden in his or her own nation in another country? If the benefits from a successful new treatment would be much greater in a country where the disease is prevalent than in another where it is rare, cannot one rightly take more risks in researching that treatment where the disease is prevalent?
While the need for some form of international guidelines has long been recognized, CIOMS first proposed a draft in October 1980. After amendment by international participants at the numerous CIOMS Roundtable Conferences, the guidelines were finally endorsed in October 1981 by the WHO Advisory Committee on Medical Research. They are consonant with previous international codes and draw quite heavily upon recent American Health, Education and Welfare and Health and Human Services regulations. The new CIOMS international guidelines incorporate the two central aspects of all contemporary national guidelines: the free and informed consent of the participants and the prior scientific and ethical review of the research protocols by an independent body of scientific experts and community representatives.
The central philosophic question of whether differing national cultures should have different medical ethics is not addressed by the CIOMS guidelines, but the answer is implied. The new guidelines -- as did the Nüremberg Code and other declarations before them -- simply assume the basic Western humanist standards, particularly as they place a high value on the welfare of the individual. If the authors of the guidelines were asked to be self-conscious about their assumption, they might offer the following justification: Western medicine has evolved with, and been motivated by, Judeo-Christian and Greek values. Since it is the procedures of Western medical research that are now being adopted throughout the world, the values must go with them. It is doubtful that Western medicine would be effective without the trust these values have elicited in patients. Only a few maverick physicians, or a nation possessed by something as evil as Nazism, would deliberately try to separate the procedures from the values. To this justification, I would add my personal opinion that medical investigators should be expected, wherever they work, to live up to their own personal beliefs and to the spirit of at least their own national standards. Such behavior is not imperialistic; it is just conscientious.
Specifically the guidelines call for research to be conducted by “appropriately qualified and experienced investigators” who will describe their project in protocols outlining its purpose, risks, proposed means of gaining consent, and position on confidentiality. Children are to be included in research only if there can be no substitutes for them. Pregnant women and mentally ill people must be excluded unless the research relates to their particular status. Employees of drug companies or dependent personnel such as medical students should not be recruited if undue influence is involved. In a departure from the recent regulations of most European nations, prisoners are permitted to be subjects.
The guidelines do provide for some flexibility in interpreting their standards according to available domestic resources and social customs. This flexibility constitutes a recognition of the differing cultural and ethical values obtaining between nations, but not an abandonment of central Western standards. Thus, the consent of the subject may in some developing countries be exercised by one or more representatives of the community rather than by the individuals themselves. But such an exception to the rule must be made only by those whose traditional role is to speak for and to protect the welfare of the whole community.
The process of review is to be conducted by one or two independent review boards, depending upon availability of resources. One “multidisciplinary advisory committee operative at the national level” should have responsibility for assessing the safety and quality of all new medicines and devices intended for use in their country. Another recommendation is for an “Ethical Review Committee,” also interdisciplinary and including community representatives, which would be responsible for evaluating all foreign and domestic research protocols. The countries that don’t have many trained medical-research personnel may have only a single board to perform both of the above functions.
The section on the task of ethical review states that “an experiment on human subjects that is scientifically unsound is ipso facto unethical.” In other words, bad science is bad ethics -- something we Americans are still arguing about. Another element which is not yet included in U.S. regulations is the requirement that compensation for injury received as a result of participation in medical research is to be on a no-fault basis. In America one still must go through the difficult process of suing for malpractice before compensation can be gained.
The promulgation of these international guidelines is a major achievement, and Dr. Bankowski, and many others who worked with him, deserve commendation. Although the guidelines obviously have no mandatory power in themselves, they do provide reference points and goals for individual governments to adopt, and they are also standards by which a nation’s performance may be judged. One hopes that the new guidelines will encourage the development of domestic medical review procedures where they are presently inadequate, and that’ their publication will reveal and censure some of the abuses caused by foreign exploitation.
However, there are some technical problems which these guidelines, and indeed current American ones, have not yet resolved. If there is no consensus in an International Review Hoard or Ethical Review Committee, does the minority have any right to appeal, and, if so, to whom? A second problem is the monitoring of the conduct of research after the protocol has been approved. Nobody in the United States does such monitoring on a systematic basis, partly because it is a very time-consuming process and partly because it is unpopular with the investigators, whose pride is hurt, because it implies a lack of confidence in their continuing competence and integrity.
Another unresolved problem is how research whose goal is the relief of diseases which occur primarily in Third World countries is to be encouraged and funded. The poverty of many of these nations precludes the funding of their own research, and drug companies have understandably been reluctant to embark on such ventures because the potential profits are not sufficient to cover the costs of development and marketing. Perhaps all drug companies involved in international research should be assessed dues which, along with donations from WHO, would help in subsidizing such programs. Meanwhile, as an incentive to provide treatment as well, as research, use of people as guinea pigs only should be prohibited.
A related problem is that the CIOMS guidelines do not clarify the issue of whether or not the same standards of risks should obtain in a poorer country where a disease is prevalent as in the funding country where the disease seldom occurs. On page six of the guidelines appears a statement regarding the risks of research on new drugs in developing countries: “Decisions relating to their investigation and subsequent use should be made in the light of local judgment and experience, and directed to practicable options rather than unobtainable ideals.” This recommendation suggests that ethical leeway is intended in the degree of risk which is acceptable in one community or nation as compared to another. However, on page 32, in a section of the guidelines titled “Externally Sponsored Research,” the following statement is also made: “The ethical standards applied should be no less exacting than they would be for research carried out within the initiating country.” In my opinion a risk/benefit analysis should always be made, but where a greater benefit is potentially available, a greater risk can be ethically taken.
Finally, the publication of international guidelines for medical research illuminates the need for similar guidelines in related fields. For instance, there is no internationally accepted minimum standard for the labeling of pharmaceutical drugs. False claims and inadequate warnings of dangers are common for drugs marketed in South America; the result is often tragic. The export of toxic chemicals, particularly pesticides, to developing countries without information regarding their dangers has, long been a problem for them. If domestic, environmental and safety regulations require the closing of an asbestos manufacturing plant in one country, on what moral grounds can the moving of such a plant to another country be justified?
Much has now been achieved in developing standards for medical research around the world; now these standards need to be applied. Much is still left to be done in the matter of international regulation; those remaining tasks must now be addressed.