The moral permissibility of randomized clinical trials hinges on several distinct but related considerations. Firstly we will consider the importance of medical research and examine the potential conflicts between the administration of medical research and the protection of human rights. Then we will investigate the case where research on human subjects is morally acceptable, that is, when there is not a clearly superior choice among treatments. Lastly we will inspect satisfactory methods of recruiting subjects for medical experimentation.

The benefits of medical research are indisputable: The emergence of antibiotics allowed the treatment of infection with methods other than amputation; Salk's discovery of the Polio vaccine has virtually exterminated a disease that killed or crippled millions; recent advances in the treatment of AIDS has immeasurably improved and extended the lives of millions more. The difficulty with research arises when humans are used as subjects. In medicine, the introduction of human subjects is ultimately necessary in any research project because, as Hans Jonas notes, "in the end man himself must furnish knowledge about himself." (Jonas, p524b) The conflict emanates from the Kantian notion that inherent in all humans is a dignity that requires each person be treated as an end and never as a means only. (We will treat this inherent dignity as a premise) The use of human beings as instruments of learning constitutes such a moral transgression. In order to reconcile research with this transgression, scientists assert that, based on past achievements, society can not afford not to pursue research. Jonas rejects this - he contends that as long as a favorable birth/death ratio is maintained, society "can go on flourishing in every way." (Jonas, p525b) He declares that progress is not the responsibility of any society, but merely the object of value and as such demands far less consideration than the maintenance of human dignity. It is plausible that society may be able to "afford" the deaths resulting from a cessation of medical research, but Jonas does not account for factors coincident with death, such as the suffering of family and friends and the process of dying, that may call for a moral response greater than death itself. Leon Eisenberg declares that although critics of research are quick to point to the existential reality of death (that research can not and should not attempt to obstruct), they fail to view the pursuit of research in the appropriate context, that is the context of not pursuing research. Eisenberg points to the alternatives to research: usual and customary procedures. He reviews examples of human suffering effected by questionable or harmful usual and customary procedures such as tonsillectomy and blood-letting and concludes that relying on intuition and tradition is a greater moral violation than any possible infringement on the rights of subjects. He supports his claim with the observation that most of the critics of research are the recipients of adequate health care, and that the health care abominations that plague much of the world are morally significant and unignorable - "Not to act is to act." (Eisenberg, p520b) Jonas would reply that although these conditions are regrettable, they do not justify the abrogation of individual rights. In conclusion, though we are morally bound to pursue research because it "stands alone in its ability to avert human suffering and death" (Eisenberg, p517b) we must not abridge individual rights in the process.

The most obvious candidate for such research is therapeutic research, where the subject receives treatment for a given condition. Therapeutic research is most productively administered through randomized clinical trials, where the subject is given one of two treatments with the goal of attaining a statistical measure of the relative effectiveness of each treatment. This transforms the physician into the [now proverbial] physician-researcher, establishing a potential conflict of interest. While the physician must always act in the best interest of the patient, the researcher is concerned with determining the validity of formally constructed hypotheses; when the demands of the respective roles do not coincide a conflict of interest results. (Hellman&Hellman, p164a) Even in a case where the physician believes that the large number of people that would be served by learning from the patient justifies sacrificing the good of the patient, she is morally obligated to ignore those potential benefits and serve her patient individually because that is the assignment which the patient hires her to execute and the role the patient trusts she will fill. Therefore, when there is a clearly best treatment the physician must never administer another because she would then be acting contrary to her patient's best interests and thus remiss in her responsibilities as the patient's unqualifiable advocate.

The question then becomes, of course, what constitutes a clearly best treatment. It is clear that if a well-informed physician has exactly no preference between two treatments, randomization of the treatments among subjects is not ethically questionable because there is no preferable treatment for the patients. The situation where the physician's propensity to choose between two treatments is balanced is called theoretical equipoise. (Freedman, p170b) Theoretical equipoise is a problematic criterion for judging the permissibility of randomized clinical trials because physicians are fallible. Quite simply, to shorten a trial because an individual doctor develops a treatment preference demonstrates excessive regard for individual doctor's preferences. It is important to note that a common objection to the use of theoretical equipoise as a criterion for judging the permissibility of randomization of treatments, that it is impossible to obtain or maintain ("balancing on a knife's edge," according to Freedman), is not morally relevant. If randomization is impermissible without theoretical equipoise, and theoretical equipoise is never obtained or maintained, then randomization is never permissible. It is the fallibility of individual physicians that renders theoretical equipoise an unsuitable criterion. The Hellmans rightly note that physicians are recruited in part for their judgments, but that does not make the judgments sufficient arbiters of equipoise. Indeed, physicians are at least equally recruited for their representation of the opinion of the medical community. Freedman, applying this 'spokesman' model, introduces the more permissive clinical equipoise. Clinical equipoise exists when there is not a consensus among competent medical practitioners, meaning that those who hold the majority preference at least recognize the credibility of those who hold the minority preference. For clinical equipoise not to exist, the minority would have to be implicated by the majority as irrational or dogmatic. Freedman defends this notion of equipoise by comparing it to the historically social or consensus-based nature of medicine, and noting how it allows the type of medical research he desires. The deficiency of clinical equipoise, as Dr. Becker points out, is the same as that of theoretical equipoise - just as the individual physician is fallible, the consensus is fallible. Dr. Becker alludes to famous cases where the medical consensus was wrong, such as blood-letting in the nineteenth century. If we were to abide by clinical equipoise as our criterion, then blood-letting might still be used today because the research needed to judge the procedure would be impermissible. As a remedy, Dr. Becker proposes an even milder criterion, research equipoise, which exists whenever "credible scientists" feel there is a need for research. This notion of equipoise allows randomization in all but the most indisputable medical theories, of which there are few, and there is an unshakable feeling of adhocness accompanying research equipoise: When does a research program degenerate? Must a physician randomize treatments when she and the majority of the medical community have a longstanding treatment preference? Clearly research equipoise as a criterion crosses the line of acceptable leniency.

The moral physician, when deciding whether to randomize treatment, must use her judgment while actively recognizing her fallibility. Thus if she has a preferential treatment, but recognizes the credibility of the alternative, she may ethically randomize treatment, or she can choose to abide by her inclination and ethically reject randomization. This notion of equipoise also addresses the problem of interim results opinion modification (I.R.O.M.), where the physician changes her opinion of the research based on accumulating results of the ongoing trial. In this case, the physician may randomize treatment until she considers one of the treatments implausibly effective, preserving her responsibility to act in her patients' best interests.

The question of who should be recruited and in what way is not relevant when the subject is the patient (therapeutic research). Whenever equipoise exists, randomization is permissible. In the case where the subject does not potentially medically benefit, or nontherapeutic research, the question of who and how to recruit subjects emerges. Part of the dignity inherent in all humans is the willful control over one's body. Following, it is immoral to force any person to participate in medical research. "Research extremists" advocate forced participation on the grounds that the present generation benefits from the results of medical research on past generations. Jonas replies that one is not indebted to society but to the past research subjects, a debt that society has no right to collect by deepening its own; that gratitude is not enforceable, and certainly does not mandate repetition of the deed; and finally that if it was wrong in the past it's still wrong. (Jonas, p527a) Since research entails bodily risks, one would only subject herself to those risks if there were a more powerful motivating force pulling her 'toward' research. What constitutes an acceptable motivating force? Certainly altruism must qualify - if someone feels exceptional compassion for those who suffer, or enthusiasm for knowledge or progress, we must not deny her the opportunity to accept the risks and 'donate' her body to research. (Jonas, 528b) The controversial motivating force is money. Money is deemed by some as an unsuitable reward for participating in research because it constitutes a force to the poor and has created the clearly objectionable present condition of disproportionate representation of the indigent as research participants. This concept of 'force,' though, slides down the famous philosophical slippery slope. Dr. Becker noted that anorexic women have a particular inclination to participate in medical research as part of their self-destructive disease. Should researchers investigate the mental health of all their potential subjects? More clearly: a particularly selfless person would be 'forced' to participate in medical research if she knew her participation would surely ameliorate suffering -- someone afflicted with a more severe case of generosity would be 'forced' to participate if she knew her participation could potentially ameliorate suffering! The evaluation of the motive for participation breaks down because it is impossible to draw a line between force, coercion, and reason. Since researchers have interests in their research beyond the public good, however, (e.g. tenure, fame, etc.) a third party should be responsible for the recruitment of subjects to assure objectivity, and proper oversight of research projects must be implemented to maintain their compatibility with the ethical imperative.