November 1989 XI/3
AIDS RESEARCH: INNOVATIVE METHODS
Recent developments in the testing of drugs for AIDS patients portend significant changes in the way clinical trials will be conducted in the United States. The developments and changes in question give rise to serious ethical issues. Traditionally, the standard procedure for testing drugs requires clinical trials in which one group of people, the control group, receives placebos, (or the standard treatment), and another group of people receives the drug being tested. In order to avoid the "placebo effect" participants in the trial do not know whether or not they are receiving the placebo (or standard treatment) or the drug being tested. If the researcher working with the participant of the study is also unaware of the substance the subjects receive, this is known as a double-blind study.
In addition, new drugs are not approved for public use until three series of clinical trials are conducted. The first trial tests the safety of the substance; does any serious harm befall the first people to receive the drug? The second test is for effectiveness; does the new drug combat the illness or disease in question? The third trial investigates side effects; what unwanted symptoms result from varying doses of the drug?
The aforementioned methods were followed in the first clinical trials testing drugs for the alleviation of AIDS. But the recent response of AIDS activists to traditional clinical trials has hampered drug trials and called into question ethical principles upon which they are based (Science, 10/6/89). In some cases patients in the clinical trial have had their pills tested. If they are receiving the placebo or a treatment they consider unsatisfactory, they dropout of the trial. Fewer and fewer AIDS patients are willing to volunteer for clinical trials, stating that they do not wish to be guinea pigs for science. Moreover, AIDS activists are calling for a faster method of making new drugs available and demanding that they be made available to more people, maintaining that persons in danger of death will not be concerned about stringent safety standards.
In order to improve the situation of AIDS patients, AIDS activists are demanding of the Federal Agencies that clinical trials be considered as primarily therapeutic; that all patients in a clinical trial be given the drug being tested; and that experimental drugs be released to any patient who wishes to use them. Not only has the request been made for agencies of the Federal government to change their policies for testing drugs, several physicians and people affected with AIDS have initiated private studies of drugs which might alleviate AIDS without observing the research safeguards. Unlike government funded clinical trials, the private studies are not overseen by impartial committees (IRE) which analyze risk, benefit and informed consent in order to protect subjects from being harmed by research. Clearly, the demands of AIDS patients and their proponents challenge the usual way of conducting research in the scientific community.
Principles
The ethical questions underlying the request of the AIDS activists to change the method of testing drugs are:
1) What is the purpose of clinical trials? Should they be designed to acquire scientific knowledge, or should they be structured, in order to deliver therapy? For years, clinical trials were considered first and foremost as research projects; that is, the primary purpose was to discover knowledge which would benefit the human community. If the subjects of the protocol would receive some therapeutic benefit in the course of the trial, well and good. But the clinical trial would be designed in such a way as to insure that the desire for therapeutic benefit for the subject would not endanger the discovery of knowledge. In clinical trials for cancer drugs for example, the subjects are often limited to those who are seriously ill; and while there is a remote chance that the drug being tested may be of some help to the subjects, the clinical trial is not designed to be primarily therapeutic.
2) What is needed to insure informed consent on the part of a person participating in a clinical trial? Briefly, the person participating in a clinical trial should be aware of the goals, procedures, risks and, benefits of the research project and should have these goals, procedures, risks and, benefits explained in his or her own language. Finally, the subject should make a free decision; hence, coercing one to participate in a clinical trial is unethical. If these norms are observed, then one may assent ethically to participate in the trial.
Discussion
From an ethical perspective, how evaluate the requests of the AIDS activists? First of all, no matter what the purpose of a clinical trial, the well being of the participants must be the foremost concern of those who design the protocol. Even if the principal purpose is to obtain scientific knowledge, the risks to the subject must be proportionate to the benefits derived from the trial. Though people with AIDS may indeed be desperate, researchers are not allowed to expose them to totally unknown risks. Private trials which do not evaluate the safety of the drug in question before distributing it to people even if these people may die as a result of AIDS, would seem to be unethical.
Secondly, it does seem unfair to ask AIDS victims to join a clinical trial in which they may receive a placebo instead of a drug which may improve their condition. When the clinical trials for AZT were conducted, they were evaluated by computing the number of AIDS patients who died in the group which received AZT compared to the number of those who died in the group which received the placebo. Would it have been possible to give all participants in the trial the drug being tested and then compare their physical condition and longevity with results predicted from experience with AIDS patients in the past? Or, could a factor short of death be utilized for measuring the efficiency of the drug, making the test more flexible and open to more people? Certainly the scientific knowledge gained from a test in which all receive the drug being tested would not be as easily acquired nor as conclusive as knowledge gained from the traditional double-blind clinical trial. But is it not possible to design trials in which the goal of therapy is more prominent, even though scientific knowledge remains the principal goal?
While a double-blind study is ethically acceptable if the subject understands the essential elements of the study and freely commits to participation in the study, the need for such studies may not be as great in the future. As a result of objections from AIDS activists, the Biostatistics Research Committee at the NIH is using computers to design clinical trials which will produce statistically valid data without using placebo.
Conclusion
The Federal Agencies in charge of drug research have responded favorably to the requests of the AIDS activists (NY Times 9/28/89 p.10). Whatever the innovations and changes being initiated in the clinical trials for drugs that will combat AIDS, one ethical principle should remain paramount. The most unethical type of trial is one which does not yield a reliable answer. Hence, as clinical trials become more therapeutic, the need to acquire certain scientific knowledge must not be forgotten.
Kevin O'Rourke, OP
| INDEX | © Kevin O'Rourke, O.P.