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Noncompliance in AIDS research.

Noncompliance in AIDS Research

From Nuremberg to the mid-1980s, the ethics of research has concentrated exclusively on the rights of patient-subjects. Noncompliance with protocols--either lying to get in a study or, once in, failing to adhere to its requirements--has always been a nuisance, but never a major problem requiring public discussion. In the past, noncompliance could largely be chalked up to the frailty inherent in human nature. Subjects usually broke the rules because of carelessness, despair of getting better, or adverse reactions.

The advent of AIDS and AIDS research has transformed a pervasive but minor problem into a major ethical-political issue. Although reliable statistics on noncompliance are unavailable, for obvious reasons, anecdotal reports of rampant "lying and cheating" are numerous. [1] Participants lie to get into studies (often with the help of their own physicians) [2] and, once enrolled, lie about their medical condition and level of compliance. They attempt to frustrate the use of placebos by dropping out of studies if randomized to the placebo arm; by analyzing the drugs they receive, thereby unblinding the study; and by pooling drugs, which ensures that they will receive some portion of the active substance while playing havoc with assigned dosage levels. This latter problem is often exacerbated by subjects who, fearful of receiving excessively high amounts of experimental drugs, substitute their own notions of appropriate dosages for the terms of the protocol. Finally, participants frequently take other nonvalidated therapies in addition to the drugs under study, thereby possibly masking the beneficial or harmful effects of those drugs. [3] Clearly, the magnitude of noncompliance in AIDS research threatens the validity of many important ongoing clinical trials.

Why has noncompliance become such a serious problem in the age of AIDS? Three complementary explanations come to mind. First, the desperate quest for access to health care has largely eclipsed altruism as a motive for participating in clinical trials. In spite of the fact that the drugs under study are experimental, persons with AIDS (PWAs) and HIV-infected persons have come to view them either as the exclusive source of therapeutic benefit or else (as in studies using placebos) as their only chance of such benefit. Some potential subjects are primarily interested in access to experimental drugs, many of which have been unavailable off protocol. Others may be able to purchase a drug through the market or so-called "guerrilla clinics," but desire entry into trials to acquire the needed drug free of charge. Still others, mostly the poor and uninsured, may be relatively disinterested in obtaining experimental drugs, but keenly desirous of obtaining the modicum of primary care that often comes with participation in hospital-based clinical trials. For all such patient-subjects, advancing their own self-interest--rather than the future of medical science or the plight of future sufferers of AIDS--seems to be the driving motivational force.

Secondly, many infected persons and PWAs are desperate to obtain help. Rightly cognizant of AIDS as a lethal threat to their very existence and of the impotence of current medical science, many infected persons will "do anything," including lying and cheating, to obtain what they think they need to live. Access to clinical trials is the "only hope" for such patients, for whom noncompliance is not so much an ethical problem as a means of personal survival.

Thirdly, many potential subjects are profoundly alienated from "mainstream" society. Unlike most cancer patients, who are often equally desperate for "last chance" cures, the ranks of AIDS patients are largely filled with persons who, prior to their illness, had been entirely marginalized. While some gay men and drug users might still identify very strongly with the majority culture, many no doubt are openly hostile to the larger society that has criminalized and stigmatized their way of life. Why should they honor their particular "contract" with researchers, many reason, when they have been effectively excluded from the larger "social contract"? Why place their lives at further risk for a society that reviles them, ignores their interests, and basically leaves them to die? [4]

Those who violate research protocols (or defend those who do) offer two distinct sorts of moral argument. Some claim that many research designs are inherently unethical and that it is therefore morally permissible to violate their unconscionable terms. AIDS activists have cogently argued, for example, that researchers should never resort to placebo-controlled trials in certain circumstances or forbid subjects to take prophylactic drugs that might forestall opportunistic infections while confounding the effects of experimental anti-viral agents. Such critics tend to see noncompliance as a symptom of immoral research designs, rather than as a moral problem in its own right. "Give us ethical protocols," they say, "and compliance will naturally follow. Until you do, our noncompliance will be entirely justified." [5]

By shifting our focus from noncompliance to the ethics of research design, this justification strategy points us in the direction of important issues that cannot be settled in this paper. Suffice it to say that if any particular accusation of unethical research turns out to be well-founded, then the case for noncompliance with that protocol would be significantly enhanced. In that case, however, the study itself should never have been undertaken in the first place.

A second line of defense for noncompliant behavior contends that even if a study is ethically designed according to the canons of informed consent and risk/benefit analysis, noncompliance is justified in the presence of unfair or unjust background conditions that have a "coercive" effect on the participants' freedom. Many participants in AIDS trials see themselves as having "no real choice" but to accept the researchers' offer. Severely ill or threatened by the AIDS virus, unable to pay for expensive drugs, or desperate to gain access to drugs otherwise unavailable, many HIV-infected persons argue that their circumstances constrain their will and vitiate the validity of their consent. Given the injustice of the choice imposed upon them, they conclude, they should not be held accountable to the terms of their agreement with researchers.

In the following sections, I shall critically examine noncompliance in AIDS research as an ethical problem. I shall first state the case against noncompliance and then assess the attempt to justify protocol violations on grounds of coercion. Reflecting on the results of this ethical inquiry, I shall conclude that, while moral condemnation of noncompliance might be justified in many instances, a purely prudential account of the problem already tells us just about everything that we need to know for purposes of social policy.

What's Wrong with Noncompliance?

Noncompliance involves two distinct but equally problematical moral wrongs. Those who fudge (with the help of their physicians) information about their medical condition to gain entry into studies violate the moral rule that prohibits lying. They deceive researchers into thinking that they (the participants) are either better off or worse off than they actually are in order to fit the study's inclusion/exclusion criteria.

By contrast, participants who, once admitted to a study, proceed to ignore the specified terms of the protocol violate the moral rule against breaking promises. [6] Whereas we are (almost) always obligated not to lie, promising creates a new obligation where none existed before. No one is obligated to make promises, but once made they must be kept. Likewise, no one has a duty to become a research subject in the first place, but by entering a protocol, subjects enter into a moral relationship with researchers by promising or "contracting" to abide by certain restrictions in return for the benefits of participation. Dropping out of an ethically designed study merely because one has been randomized to placebo, pooling drugs, or taking unapproved remedies all amount to violations of this promise.

The fact that the DHHS research regulations assure subjects that they have a legal right to "discontinue participation at any time without penalty or loss" should not obscure the moral seriousness of violating a promise to abide by the terms of an agreement. [7] Having a right is not equivalent to doing the right thing.

What, then, is wrong with lying and breaking promises? In the first place, they both amount to using other persons, other rational agents, for our own instrumental purposes. By lying or making a false promise we take advantage of the trust that others place in us--trust nurtured either by the general background presumption of truthtelling or by our own free commitment to bind ourselves in the future--and then abuse that trust to achieve our own purposes. In Kantian terms, this betrayal of trust violates the autonomy of other persons. Subjects thus wrong researchers by engaging in noncompliant behavior.

In addition to wronging others by lying and breaking promises, we can also harm their interests. Noncompliance involves multiple harms to a variety of parties, all of which are rooted in the fundamental harm of threatening the integrity of clinical trials. Consequently, the approval of desperately needed effective therapies could be slowed or sidetracked forever, while many initially promising but unacceptably toxic drugs could command center stage for years before their true effects are revealed. In the midst of a worldwide epidemic of such devastating and tragic proportions, it is no longer possible to think of medical progress as a merely "meliorist" [8] venture whose results we can await at our leisure. Effective drugs are desperately needed now and must be developed as soon as possible lest hundreds of thousands more suffer and die. By delaying the successful and timely completion of vitally important clinical trials, noncompliance thus threatens to deprive present and future AIDS sufferers of effective palliative, curative, and preventive measures against the virus.

Noncompliance impinges upon further important interests of present patients. If someone lies about his health condition to gain entry into a trial, he not only risks distorting the results but also occupies a place that could have been taken by someone else just as needy who also fits the required medical profile. Assuming that the inclusion/exclusion criteria are themselves necessary, reasonable, and fair, taking the place of genuinely qualified candidates constitutes an injustice to them.

Likewise, those who unblind studies, drop out, alter dosages, and take off-protocol drugs threaten to harm their fellow research subjects by altering the risk-benefit ratio of the study. Although many PWAs have come to see experimental drugs as therapy, they all have some toxic side-effects and taking them within the context of clinical trials poses definite risks to research subjects. We permit subjects to take such risks in large part because of the anticipated benefits of the trial. But when the noncompliance of some threatens the integrity and results of a trial, the compliant subjects are put at equal risk for less potential gain. Indeed, if the results of a study are completely vitiated by noncompliance, then "we" (i.e., researchers and society) have subjected human beings to significant risks for no real social benefit. That too constitutes an injustice to other persons.

Finally, clinical trials are extremely expensive undertakings in both dollars and human resources. A typical trial of an anti-viral, immune system modulator or prophylactic agent costs hundreds of thousands of dollars, not to mention all of the time and energy expended by statisticians, physicians, nurses, and social workers in the design of such studies. While noncompliance is defended as a matter of individual need, it obviously implicates and threatens a whole network of important social interests.

Noncompliance and Coercion

As we have seen, even if we agree for the sake of argument that a particular trial is ethically designed, it could still be claimed that subjects should not be held accountable for their commitment to participate in conformity with the protocol due to the coercive nature of their circumstances. It is often said, for example, that PWAs are desperate, that they have no other choice, and that they are "forced" to lie and cheat merely to stay alive.

One would have to be completely insensitive and bereft of moral imagination not to be at least partially swayed by such claims. While it is easy for the uninfected, white, straight, comfortable majority to denounce noncompliance, it is perhaps not too hard to imagine how "we" would feel in the shoes of a desperate PWA confronting a medical establishment that seems to move at glacial speed. In spite of this intuitive and sympathetic appeal, the "coercion defense" remains puzzling and problematical. Is it really true that desperate circumstances inevitably coerce, destroy all voluntariness, and vitiate all contractual agreements?

A "Coercive Offer"? Whether or not we call it coercive, the proposal that researchers make to potential subjects is clearly an "offer" as opposed to a "threat." Threats are proposals that have the effect of undermining someone's present, normal, or morally correct "baseline situation," while offers hold out the prospect of improving one's situation or enlarging one's options. [9] Thus, the gunman who (credibly) demands, "Your money or your life!," is issuing a threat; he intends to worsen your normal or morally correct situation, which includes both being alive and having your wallet in your own pocket. By contrast, the lecherous millionaire who says to the desperate, impoverished mother of a dying child, "I will pay the entire cost of your child's operation if you will agree to be my mistress for one year," [10] is making the woman an offer. Unlike the gunman, he is expanding her realm of freedom by giving her a new choice, albeit a particularly distressing one, between losing her daughter and sleeping with an exploitative creep.

Against this background, it is clear that AIDS researchers are making an offer to potential participants. They are saying, in effect, "If you play by the rules, we will give you access (or at least the possibility of access) to promising new drugs. If you refuse to play by the rules, we won't give you such access." The researchers are thus offering participants the prospect of improving their baseline situation; and most potential subjects are more than happy to move from what might be called their "pre-proposal baselines" to the situation created by the proposal to participate.

The difficult and yet crucial questions are whether such offers are "coercive" and, if so, whether they vitiate consent and justify noncompliance. Since the tangled debate over the concept of coercion is much too complex to canvas here, let alone resolve, (11) I shall simply apply, without justification, my own preferred view to some of the main contentions and counterarguments regarding the coercion defense in the context of AIDS research. That view contends, with Alan Wertheimer, that structural features of a situation--e.g., the valence of the alternatives (i.e., whether the choice is between an evil and a good, or merely between evils) and their proximity on the chooser's scale of preferences--add little to the moral analysis of coercion claims and that everything depends upon the fairness or justice of the chooser's initial baseline situation.

An important consequence of this view is that the concept of coercion turns out to be considerably "moralized"--that is, it cannot be described in purely descriptive, non-moral terms that might function as independent premises in moral arguments. Instead, coercion claims rely for their soundness upon prior arguments bearing on the ethical correctness of the baseline situation. More simply put, we first have to know whether an offer is ethical to know whether it is coercive. [12]

"No Choice." The first defense of the coercion claim emphasizes the HIV-infected person's lack of acceptable alternatives. His or her back up against the wall, the potential research subject "has no choice" but to accept an offer that couples access to possibly effective drugs with unwelcome restrictions. The latter are perceived as an "evil," but they do not come close to the ultimate evil of death. Hence, it is often said that because HIV-infected persons have no real choice, they have no moral obligation to conform to the terms of research protocols.

This is a bad argument. Having "no choice" is not a sufficient condition of being coerced. Suppose that a particular U.S. senator was utterly miserable in his job, failing at just about every task and suffering the ridicule of his colleagues. Out of the blue, he is offered the vice-presidency of the United States! While we might agree that the senator had "no choice" but to trade his untenable situation for this offer, we would most likely say that he was "enticed" rather than "coerced."

Even if the offer presents someone with a choice between two evils, one of which is much worse than the other--rather than between an evil and a good--it it is still far from clear that such an offer is necessarily coercive. Suppose that Bill, a notorious juvenile delinquent in a small town, is hauled before the judge following a particularly destructive rampage. He is given the option to either go to jail for a year or to join the army. Clearly, Bill has "no choice" in the sense that he would do just about anything to avoid going to jail. But has the judge "coerced" him? Would Bill be justified in deserting the army once he joined on the ground that the judge failed to give him a more acceptable alternative?

The answer is clearly "no" on both counts. Since Bill was guilty of a serious offense meriting a year in jail, the judge had every right to make him that offer, and Bill has no right to complain or back out of the deal he made. The fact that he had "no choice" is irrelevant. It would have been relevant, however, if Bill had independent grounds for thinking that the judge had a duty to provide him with a better alternative. [13] Suppose, for example, that Bill was really innocent of the charges against him and the judge made him the "jail or army" offer just to get rid of a "troublemaker." In that case, the judge would have had an independent duty to provide Bill with a third "option," his freedom, and Bill would clearly have been morally justified in reneging on his commitment to the army.

The question, then, is not whether potential research subjects have "no choice," but rather whether AIDS researchers or "society" have an independent obligation to provide HIV-infected persons with better alternatives than those contained in current protocols.

Unjust Baseline. Are HIV-infected persons entitled to a better offer from researchers or society? This is essentially a question about the moral adequacy of HIV-infected persons' "baseline situation." The claim is that their "pre-proposal baseline" is itself unjustly low, and that against this deplorable background the researchers' offer poses unfair and unreasonable alternatives. Hence, HIV-infected research subjects should not be held accountable for their promise to abide by the terms of protocols.

This objection raises the important question of how to assess potential subjects' baseline situation. Specifically, should we take their situation as we find it, minus the offer, as the starting point for our analysis; or should we rather project some other, more desirable state of affairs from which they ought to be allowed to respond to the researchers' offer? If we decide to fix on their actual circumstances as the appropriate baseline, we are in effect saying that their position and the offer itself are fair enough to make their commitments binding. But if we decide that the subjects' actual circumstances are not merely unfortunate but unjust as well--i.e., that they have a right to a different baseline--then the researchers' offer would be coercive.

Suppose, for example, that a researcher (R) offers an HIV-infected person (P) something to which he is already entitled but of which he has been unjustly deprived. For the sake of argument, let us suppose that P (who is seropositive but asymptomatic) has a right to an "adequate level of health care," but due to societal and governmental neglect he has no effective access to it. R comes along and says, "We'll give you some primary care in our hospital, as well as some experimental drugs, if you'll agree to play by our rules (which include respect for our inclusion/exclusion criteria)." In a case like this, one is sorely tempted to say that R as a representative of society through its "ministry of health," has no right to impose such a choice upon P. Given P's desperate need for primary care, it is unfair to force him to take risks with experimental drugs to obtain something to which he is already entitled, and it's hard to hold P responsible for his lying promise. (One could argue, however, that P has no right to lie to R if R wasn't the party who deprived him of his right of access.)

Consider next the situation of PWAs with access to primary care who nevertheless desperately seek to obtain experimental drugs. R's protocol is their only route of access either to the drugs themselves or to their free provision. (Assume that paying the full market price for the same drugs will impose severe financial burdens.) Their spokesperson, SP, argues "This country ought to have a system that makes a wide variety of experimental AIDS drugs readily available at reasonable cost to anyone who needs them. Were such a system in place now, then R's offer would not be at all coercive; but since it isn't, since we have to act out of desperation, the offer is coercive."

As stated, SP's argument is ambiguous with regard to the word "ought." On the one hand, he could mean "It would be highly desirable for our country to develop a better system than we have now." If this were the ultimate point of SP's coercion claim, very few would disagree. As Wertheimer points out, coercion claims can have disparate moral objectives. [14] Sometimes they are merely intended to call attention to the need to change someone's baseline situation. To demonstrate the truth of such a claim, one need not show that the relevant baseline is unfair or unjust; rather one must simply show that improvements are both possible and desirable.

The ultimate point of SP's coercion claim goes much deeper, however, for SP is claiming not only that a change in his baseline would be desirable, but that he should not be held responsible for any agreements reached at the baseline. To justify this much stronger and more controversial claim, SP must show that his baseline situation is actually unfair, unjust, or violates his rights.

The obvious problem with equating "society ought" with "it would be highly desirable" for this rhethorical purpose is that it would tend to vitiate the vast majority of agreements that people make. All of us would rather come to the bargaining table better off than we are; many of us come to contractual situations in a deeply wounded state. Yet the mere fact that one is not as well off as he would like or as the principle of utility would demand, the mere fact that he can envision a better position from which to make contracts and promises, does not render him unable morally to commit himself. [15] As Wertheimer puts it, the moral question is whether someone is responsible for his actions, not whether he is happy about it. [16]

Thus, a more plausible interpretation of SP's claim would hold that he has a right to a system that would make a wide variety of experimental drugs available at reasonable cost. While this standard avoids the arbitrariness of the former interpretation, its substantive point is highly debatable. We must recall here that we are dealing, not with proven therapies, but rather with non-validated, experimental drugs. While we might all agree (I certainly do) that everyone should have a right to basic health care, it is not at all obvious that non-validated drugs fit this description. [17] Even though PWAs and other infected persons havecome to view clinical trials primarily as vehicles for delivering medical "treatment," the sad fact remains that the vast majority of drugs under study will turn out to be either unsafe, ineffective, or both.

Indeed, a discernable strain in the advocacy literature implicitly acknowledges the non-therapeutic character of most sought-after drugs. For example, in calling for increased access to experimental drugs for AIDS patients, Mathilde Krim, Donald Abrams, and Alvin Novick [18] all emphasize the psychological advantages of obtaining such drugs. Fully cognizant of the limited therapeutic potential of most drugs under study, these observers nevertheless stress the positive feelings of empowerment that come with greater access to experimental substances. It is a positive benefit, they note, to "take control" of one's illness and of one's life, to shed passive dependency upon an impassive medical bureaucracy, by actively seeking out and determining one's own treatment plan.

While the claimed psychological benefits of obtaining access to experimental drugs are undeniable and vitally important to those who seek them, it is hard to see how they ground a justified right-claim. If we have a right to basic medical treatments, this must be due to their purported ability to meet our health care needs. If we have a right to chemotherapy for leukemia, this must be because it has been shown to work well enough according to the standards of the medical community. Leukemia patients most likely also feel significantly empowered by electing effective therapies, but that is not the reason we should make them available as a matter of right. One need not attempt to impugn the seriousness or the intensity of patients' desire for feelings of empowerment--indeed, one can have the utmost sympathy and respect for such a need--to note that desires, no matter how strong, are not the same as rights.

Although much obviously remains to be done in improving the baseline situation of potential subjects with regard to the increased availability of experimental drugs, their present lack of access is perhaps best described, in the words of H. Tristram Engelhardt, Jr., as "unfortunate but not unjust." [19] Consequently, their present baseline situation is an ethically appropriate measure of the coerciveness of R's proposal. By that standard, R's offer does not appear to be either unfair or coercive.

A Libertarian Challenge

An alternative critique of the present baseline of HIV-infected research participants would have us forget about specific rights to health care and concentrate instead on a more general right to be free of governmental interference. Rather than putting the burden of proof on the research participant to show that he has a specific right to experimental drugs, this gambit places that burden on government bureaucrats who would interfere with the private choices of individuals seeking desperately to extend their own lives. According to this argument, the government has no right to exercise a monopoly over access to experimental drugs, especially when those seeking broader access are dying and willing to assume the risks of unproven treatments. The latter's current baseline is, therefore, unjust.

This libertarian argument for unfettered access to experimental drugs encounters two problems. In the first place, it ignores the potential for exploitation that an unregulated system would foster. Given the utter desperation of many HIV-infected individuals, and given the inevitable profusion of highly expensive but worthless "cures" designed to exploit that desperation, many people would be driven to expose themselves to costly but highly toxic and useless drugs. Although our present regulatory structures could be relaxed somewhat without subjecting HIV-infected persons to such harmful exploitation--indeed, they have already been considerably relaxed--we must recall that those structures were initially put there for the eminently good reason of protecting desperate and vulnerable patients from highly predictable harms.

The second problem with the libertarian argument is that it ignores the larger social context. Although unrestricted access to unproven drugs for HIV-infected persons would no doubt satisfy the immediate desires of many persons, it could have the highly undesirable side-effect of derailing vital controlled trials of the very same drugs. If unproven remedies were to suddenly become available to any HIV-infected person who could get a doctor to prescribe them, it is highly unlikely (though not, of course, impossible) that sufficient numbers of patients would enroll in crucially important clinical trials. An interesting case in point is a recent San Francisco trial of DDI, a promising anti-viral agent. According to Donald Abrams, a prominent AIDS researcher, this study will most likely not yield good data due to inadequate recruitment in the wake of expanded access to the drug. Although researchers needed eighty participants in the trial, they had only been able to enroll six. [20]

If enacted in a thoroughgoing way, the libertarian agenda could thus pose a classic conflict between the perceived needs and desires of present HIV-infected individuals and the needs of a much larger group of future patients for genuine, minimally toxic, and maximally efficacious drugs--needs that will only be satisfied quickly by means of rigorously designed, randomized clinical trials. But once we understand the conflict in this way--rather than as a struggle between desperate individuals and a meddling, overly protective Federal government--the burden of proof would appear to shift back upon those calling for unfettered access. Why, indeed, should the immediate desires of some for unproven, largely toxic and inefficacious drugs outweigh the needs of all HIV-infected persons, present and future, for genuine remedies, especially when the two groups have desires of equal intensity and the latter vastly outnumber the former? It seems to me that in such a situation society would be perfectly justified in seeking scientifically validated remedies for the larger group even at the expense of the smaller group's intense desires.

Coercion and the Validity of Promises

In his illuminating discussion of coercion, Joel Feinberg argues that the validity or invalidity of any particular consenting act cannot simply be deducted from prior accounts of coercion and voluntariness. [21] In other words, even if we were to assume that R's offer was coercive and SP's will was somewhat diminished, it doesn't automatically follow that SP's promise to R is invalid for any given purpose. Whether any particular consenting act is sufficiently involuntary to be deemed invalid will always depend upon a pramatic assessment of what our purpose in judging is, what is at stake (i.e., the amount of social harm threatened by one's ocnduct), and the context of choice. Like judgments of "competency" to consent to medical treatment, judgments about the validity of promises or contractual agreements will always be "decision specific" and context dependent.

The importance of purposes and context is highlighted in the analogous problem of consent to research in prisons. Here too we have subjects who are desperate (for money, release, relief from boredom, etc.), who inhabit a severely coercive situation, and whose voluntariness is likewise suspect. Yet it has been effectively argued that, so long as no one subjects the potential participants to deception, duress, or manipulation--and so long as strenuous safeguards against abuse are in place--their consent to participate should be deemed valid enough.

The brouad outlines of this argument look like this: Even though prisoners' normal baseline is rather impoverished compared to that of free citizens, it should, assuming that independent criteria of decency are met, provide the standard for assessments or coercion and voluntariness. True, their actions are much less voluntary than they would be on the street, but that is not where they are. They are in prison, and so long as they are there for a good reason--i.e., so long as their incarceration is just and fair--the circumstances of their confinement should provide the background for assessments of the validity of their consent. Given that the rewards of participation are highly prized by the prisoners themselves (they often go to court to defend their right to participate!) and given the significant social benefits to be derived from research on such stable populations, the prisoners' consent can be judged voluntary enough in the circumstances. [22]

Coming to our question, then: Should the promises of AIDS research subjects be deemed invalid for the purpose of holding them to their commitment to abide by the terms of the protocols? If we take their present situation as the appropriate baseline for assessing the offer, adn fi we recall that no one has a right to non-validated therapies, then such subjects' agreement might well be deemed voluntary enough in the circumstances. This conclusion is further buttressed by the fact that noncompliant behavior threatens grave social harms. [23] Participants' failure to keep their word would have serious repercussions for the integrity of vitally important and extremely expensive clinical trials. Given the magnitude of this threatened harm, it would seem perfectly reasonable for society to require a showing of much greater coercion before conceding the justification of noncompliant behavior.

This is not to say that the present system of allocating experimental drugs (and thus the subjects' "normal baseline situation") cannot or should not be significantly changed. If any one of a number of excellent current proposals were implemented [24] subjects would have greater access to nonvalidated therapies. With more options to choose from, participants would be less desperate, and their choices less coerced. Such improvements may even give a second life to altruism as a dominant motive for participation in AIDS research.

No matter how much the present system is improved, however, it can never be modified to the point where it can accommodate every strong desire of every research subject. Some placebo studies may well be necessary in the absence of any efficacious prophylactic agents against certain opportunistic infections. Dosage requirements and restrictions on extraneous drugs will still have to be maintained. And the much vaunted parallel track may not in the end prove compatible with enrolling sufficient numbers of subjects to complete important clinical trials in a timely fashion. Even with the new and better systems in place, subjects will still have to limit their desires and make binding promises to insure the eventual success of AIDS research. The major difference between now and then, however, is that such a system will make it much easier for subjects to keep such promises.

Noncompliance and the Erosion of

Political Community

The "coercion defense" fails to show either that the researchers' offer of potentially effective drugs in exchange for compliance is coercive, or that subjects are not bound by their promises to comply. Notwithstanding this failure on the level of theory, the coercion defense remains a valuable signal of deep and disturbing social realities.

I can well imagine a gay PWA or infected Latina from the south Bronx responding to the above conclusions in the following way: "Your arguments about baselines and no right of access to experimental drugs are too narrowly focused and therefore miss the point. We are desperate for anything that offers some prospect of help and find ourselves confronted by a system that doesn't work for us, that indeed oppresses us. Soem of us have been systematically excluded from the benefits of American Life on account of race or class; others, while benefitting from middle-class life in most respects, have been the objects of fierce societal discrimination on account of their sexual preference. Why should we keep our commitments to agents of a society that excludes and oppresses us? Why should we be moral when our entire situation is profoundly immoral and unjust?"

In contrast to the coercion defense, this sort of claim cannot be easily disarmed through philosophical analysis, for it points to a deep-seated and justified sense of political alienation. This is the voice of people who no longer feel that they have a stake in mainstream society, or that they are bound to the usual terms of the social contract. Coming from them, the coercion defense functions not so much as a convincing philosophical argument as a disturbing symptom of a rift in the social fabric. "them" against "us," this rift threatens to balkanize our society into ethical subcultures that know no responsibilities or obligations to one another. It is a chilling prospect.

Certainly, representatives of the larger society will insist, rightly to some extent, that promises ought to be kept, even if they are made against a backdrop of serious and pervasive injustice. Even if many poor, minority youths enter the military only because racial and economic injustice have precluded other alternatives, we don't conclude that they are ethically entitled to desert or otherwise renege on their commitment. As Wertheimer puts it, "it does not follow that all moral bets are off simply because the world is not just." [25]

It is highly doubtful, however, whether this point will have much impact on people who already see themselves as belonging to a different "moral community," a community of exiles struggling to stay alive. In order to rekindle a sense of political obligation in such people, in order to bring them back into moral communion, more than philosophical argumentation will be necessary. Actions must be taken that manifest the larger society's commitment to the autonomy and well-being of HIV-infected persons.

Noncompliance and Social Policy:

From Ethics to Prudence

At this point, one might well observe, "At most you have shown that iths wrong for research subjects to lie and cheat. So what? Where exactly does this take us with regard to special policy?" The answer to this question is, "Not very far." I shall conclude by observing that, having labored to reach a defensible moral judgement, we can easily find in the notion of prudence everything we need to know about noncompliance and social policy.

Our overriding social objective, we must recall, is the development of effective preventative and therapeutic measures against HIV. The successful and prompt completion of important clinical trials of AIDS drugs is vital to the accomplishment of this objective. But to do that, researchers must obtain the requisite degree of compliance, and this means that researchers must become more aware of what motivates the behavior of participants.

While this is obviously not the place for a detailed empirical examination of research subjects' motivational structures, we can make the following modest points. First, it is highly unlikely that mere appeals to ethical standards of right and wrong widely shared in the community will significantly alter present patterns of noncompliance. Subjects who see themselves as fighting for their very lives will not likely be swayed by appeals to the values of an oppressive majority culture. Stern ethical condemnations of promise breaking and anti-social conduct, while perhaps entirely justified, are not going to change behavior.

To secure heightened compliance, two rather obvious steps must be taken. First, researchers must work toward the establishment of greater trust between themselves and HIV-infected subjects. Although there are no doubt numerous imaginative ways to pursue this goal, eliciting greater community participation in the design of clinical trials would be a top priority. [26] Subjects who recognized that they or their representatives have had a say in the planning and design of research protocols will most likely be less suspicious and more committed to the project. What better way to encourage subjects truly to be "coadventurers" in medical science than to give them a voice in determining the very terms of that adventure?

Secondly, research participants should, whenever possible and consistent with the overriding goal of completing clinical trials in a timely fashion, be given more choices through greater access to nonvalidated therapies. Assuming they are willing to accept the increased risks that inevitably come with earlier distribution of experimental drugs, subjects will welcome the lessening of coercive pressure that comes with greater choice. More choice will mean less desperation, less resetment of protocol requirements, and more cooperation. Subjects will simply find it easier to abide by the terms of protocols that pose less restrictive alternatives and require fewer personal sacrifices. We know all this independently of and prior to any moral analysis.

Given such improvements in their baseline situation, research participants would most likely respond far more responsibly to the moral entreaties of researchers. Whether they are currently acting irresponsibly and inexcusably is, in a sense, beside the point. The question is how we can foster greater trust and cooperation. Name calling, while perhaps morally justified, is not the answer. The answer, at least in developing a social policy, lies in fostering conditions under which traditional appeals to the altruism of research subjects can again become meaningful.


[1] "Wayne," "Lying and Cheating to get in a Protocol," PWA Coalition Newsline 45 (June 1989), 37-38.

[2] Alvin Novick, "Noncompliance in Clinical Trials II: Primary Care Physicians," discussion paper prepared for AmFar Working Group on Research Ethics. See also Harry Y. Vanderpool and Gary B. Weiss, "False Data and Last Hopes: Enrolling Ineligible Patients in Clinical Trials," Hastings Center Report, 17:2 (April 1987), 16-19.

[3] Alving Novick, "Noncompliance in Clinical Trials I: Subjecs," (unpublished manuscript).

[4] Novic, "Noncompliance in Clinical Trials I."

[5] According to activist Rebecca Smith, "Even if you have a supply of compliant martyrs, trials must have some ethical validity." Quoted in Joseph Palca, "AIDS Drug Trials Enter a New Age," Science 246 (October 6, 1989), 19.

[6] Lisa Newton, "Agreement to Participate in Research: Is that a Promise?" IRB 6:2 (March/April 1984), 7-9.

[7] Robert J. Levine, "The Doctor's Unproven Beliefs and the Subject's Informed Choice: Another Commentary," IRB 11:3 (May/June 1989), 9-11.

[8] Hans Jonas, "Philosophical Reflections on Experimenting with Human Subjects," in Paul A. Freund, ed., Experimentation with Human Subjects (New York: Braziller, 1970), 1-31. Even in the midst of the AIDS crisis, however Jonas's conclusion that informed consent is a moral prerequisite to the enrollment of research remains valid.

[9] See Joel Feinberg, The Moral Limits of the Criminal Law, Vol. 3: Harm to Self (New York: Oxford University Press, 1986), 219-28; and Roger Wertheimer, Coercion (Princeton: Princeton University Press, 1987), 204-217.

[10] See Feinberg, Harm to Self, 229.

[11] In addition to the important works by Feinberg and Wertheimer, see: Robert Nozick, "Coercion" in Sidney Morgenbesser et al., eds. Philosophy, Science, and Method (New York: St. Martin's Press, 1969), 440-72; David Zimmerman, "Coercive Wage Offers," Philosophy and Public Affairs 10:2 (Spring 1981) 121-45; Daniel Lyons, "Welcome Threats and Coercive Offers," Philosophy 50 (Octover 1975), 425-36; and Charles Fried, Contract as Promise (Cambridge, MA: Harvard University Press, 1981).

[12] Other theories (e.g., Zimmerman's) attempt to account for coercion without resorting to normative moral judgments. While I do not agree, they are plausible theories. Caveat lector!

[13] Wertheimer, Coercion, 231.

[14] Wertheimer, Coercion, 184-91.

[15] Feinberg, Harm to Self, 196.

[16] Wertheimer, Coercion, 305.

[17] Benjamin Freedman et al., "Nonvalidated Therapies and HIV Disease," Hastings Center Report 19:3 (May/June 1989), 19.

[18] Freedman, "Nonvalidated Therapies," 16; Donald Abrams, "Alternative Therapies," in HIV Infection and Disease (Chicago: American Medical Association, 1990), 172; Novick, "Noncompliance in Clinical TrialsI."

[19] H. Tristram Engelhardt, Jr., "Health Care Allocations: Responses to the Unjust, the Unfortunate, and the Undesirable," in Earl E. Shelp, ed., Justice and Health Care (Dordrecth: D. Reidel Publishing Co., 1981), 121-37.

[20] Remarks of Donald Abrams, MD, at AmFar Working Group on Research Ethics, Citizens Commission on AIDS, New York City, January 18, 1990.

[21] Feinberg, Harm to Self, 261-62.

[22] Feinberg, Harm to Self, 261. It could be cogently argued, however, that research on prisoners should be disallowed on other grounds than the validity of their consent. One could claim that such a practice establishes an unjust distribution of benefits and risks between the civilian and prison populations or the widespread abuse cannot be avoided in practice.

[23] As Feinberg, puts it, the greater the projected harm to others, the greater the coercion necessary to excuse the conduct. Harm to Self, 261.

[24] Freedman, "Nonvalidated Therapies"; Nathaniel Pier, "The Emperor Has No Clothes," AIDS Patient Care 3:1 (February 1989), 2-5; Gina Kolata, "Radically Wider Testing of AIDS Drugs is Urged," New York Times (March 26, 1990), Al ff.

[25] Wertheimer, Coercion, 238.

[26] See Nancy Dubler, Carol Levine, and Robert Levine, "Consensus Report of the AmFar Working Group on the Ethics of AIDS Research," (tentative title, document in preparation); Herbert R. Spiers, "Politics and Philosophy of Community Consultation," discussion paper prepared for AmFar Working Group on Research Ethics; Gary Melton et. al, "Community Consultation in Societally Sensitive Research: Lessons from Clinical Trials of Treatments for AIDS," American Psychologist 43 (1988), 573-81.

John D. Arras is associate clinical professor of bioethics, Montefiore Medical Center--Albert Einstein College of Medicine, New York, NY.
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Author:Arras, John D.
Publication:The Hastings Center Report
Date:Sep 1, 1990
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