The Obligation to Participate in Biomedical Research

A patient has a chronic condition for which there is apartially effective standard treatment. Her physician tells her of a study testing a new therapy. Physicians are uncertain whether the new therapy improves on the standard treatment. Participation requires the patient to be randomly assigned to receive either standard treatment or experimental treatment as well as receive extra blood draws and magnetic resonance imaging scans. Should this patient enroll in the study? Does she have a duty to enroll?

According to the standard view, her participation is above and beyond the call of duty. It would be good for her to participate, but not wrong if she refuses. According to the obligation view, the patient has a moral duty to participate. Assuming that the burdens and risks of participation are not excessive, it would be wrong to refuse to participate.

This article defends the obligation view. Its purpose is not to make a philosophical point, but to stimulate support for a major cultural shift in the way physicians, researchers, patients, and society at large think about participation in research.

According to the standard view, participation in research is akin to giving blood or donating to charity.^{1 - 5} Participation that benefits society is supererogatory—while participants who put themselves at risk or inconvenience deserve praise, those who refuse to participate in research are not acting wrongly or unethically.

Although the standard view dominates current thinking, 2 arguments have been proposed for the obligation view: beneficence and free riding.

Beneficence. According to the beneficence argument, if an individual can prevent something bad or produce some good that individual has a duty to perform that action.^{6 - 8} Any action beneficial to society overall would be obligatory. Participation in many clinical trials is therefore obligatory merely because doing so helps society at large.

It is certainly good to be beneficent, but the beneficence argument is excessively demanding as a basis for an obligation to participate in research.⁹ It implies not only that individuals have an obligation to participate in research, but also to perform numerous acts that are normally considered supererogatory and to donate a portion of their wealth for the sake of nobler causes. Indeed, participation would be morally obligatory even if there were a significant risk of harm provided the expected societal benefit was sufficiently great. This argument is unreasonably demanding.

In addition, if a weaker version of the beneficence argument in which individuals have an obligation to perform a limited number of beneficent acts is accepted, the beneficence argument would not explain why anyone has a special obligation to participate in biomedical research when contrasted with other beneficent acts such as donating to charity.¹⁰

Free Riding. According to another argument, the failure to participate in research is a form of free riding.^{6 ,11 - 14} Free riding occurs when an individual receives a benefit that others pay for and takes advantage of the contributors by refusing to share the burden of obtaining it. An example is the speed bump: a neighborhood has a problem with speeders, and all the residents agree that a speed bump would make everyone much safer. Their municipality will allow the speed bump to be built only if the residents of the street pay for it. The cost of one individual helping the neighborhood pay for the speed bump is worth the bump's benefit to him, but he knows his neighbors want the bump so much that they will pay for it even if he does not contribute. Surely he should help pay.

The free-riding argument claims that individuals benefit from the fruits of biomedical research. Usually they actively seek out the benefits, consuming safer, more effective medical treatments. Sometimes they benefit passively, as exemplified by herd immunity due to vaccination. By refusing to participate in biomedical research but accepting these benefits, those individuals are free riding on those who participate.

Although this free-riding argument appears attractive, it fails for participation in research. The burdens of participating in biomedical research that current participants assume are not alleviated when other individuals participate.^{4 - 5} Implicit in the free-riding argument is the claim that doing one's fair share will relieve others in society of the burdens of participation. Although this is true for the speed bump, it is not true with respect to biomedical research. Participants would not be paying back any actual participants—they are benefiting others who will in fact not participate. Unlike the free-riding case, more participation helps society at large and future generations, but does nothing to relieve the burdens on those who are actually participating in the research.

Individuals have an obligation to participate in biomedical research because the knowledge produced by the system of biomedical research is what economists call a “public good.” A public good has 2 characteristics. First, one individual's use of that good does not diminish another's use of that good; and second, it is impractical to prevent individuals from using the good.^{15 - 17} Conversely, a good is private if one individual's use diminishes another's use or if it is feasible to provide it to some but withhold it from others. Typical examples of public goods are national security, a fireworks display, street cleaning, and clean air.¹⁸ One citizen's benefit from a fireworks display or national security does not diminish another's benefit, and an individual cannot be prevented from benefiting from a fireworks display or national security even if he or she does not contribute to its provision. Who provides the good is irrelevant to whether it is public or private. A private company might provide a public good like fireworks, whereas a government could provide unemployment benefits, which is a private good because it can be given to unemployed individuals but not to others.

Generating Public Goods. There is normally no incentive for any individual to contribute to a public good even if the benefit of that public good to the individual is greater than the cost of contribution.¹⁶ No individual can be denied the benefit of a public good no matter how much or how little he or she has contributed. For that reason, public goods tend to be undersupplied.¹⁹ To overcome this problem, society sometimes compels individuals to contribute. For instance, society mandates that cars come equipped with catalytic converters to provide the public good of clean air. In other cases, society gives individuals positive incentives to contribute, such as subsidizing administration of the influenza vaccine to provide the public good of herd immunity. In still other cases, individuals contribute because they believe they have an obligation to do so. Many individuals vote not because they think that their vote will make a difference to an election's particular outcome but because they believe they have an obligation to support the public good of electoral democracy.^{20 - 21}

Biomedical research is devoted to generating the public good of generalizable biomedical knowledge.²² Assuming that the knowledge is made public, one individual's use of that knowledge does not deprive others of using it. Moreover, the benefit of that knowledge cannot be withheld from the public. The significant benefits of medical research to the public over the past century include the eradication of smallpox and near eradication of polio, and the development of penicillin, modern surgical techniques, and other lifesaving discoveries. In addition to developing new interventions, biomedical research produces important public knowledge of conditions and already available treatments, as exemplified by research demonstrating that a lumpectomy is often just as effective as mastectomy in the treatment of breast cancer.^{23 - 24}

Clinical investigators, research institutions, and funding agencies were indispensable to these advances. Equally important were the millions of individuals who agreed to participate in the research that proved the effectiveness of the interventions that worked and, no less importantly, the ineffectiveness of those that did not.

Because the enterprise of biomedical research produces the important benefit of medical knowledge that is an advantage to all, every individual has an obligation to support that system of knowledge generation by participating in biomedical research. If it turned out that biomedical research with human participants was not that important after all—that society would not be much worse off if all research on humans were to cease—there would be no obligation to participate. But barring convincing evidence that such research is in fact unimportant, there is a duty to participate in research.

Free Riding vs Public Goods. Although the classic free-riding argument and the public goods argument both appeal to a duty to do one's fair share, there are crucial differences between them. First the public goods argument aids the cause instead of merely splitting the bill. For example, suppose the catalytic converter on a car has deteriorated. The owner has benefitted greatly from the reduction in air pollution produced by catalytic converters. Should the owner replace the catalytic converter? The free-riding argument is not applicable here because replacing the converter would not ease the burden of air pollution control on others. But according to the public goods argument, the car owner should do his or her part in contributing to the public good of air pollution control.

Second, a free-rider obligation requires relief for individuals currently contributing. By comparison, discharging a public goods obligation makes society better off in the future. This is why the public goods argument applies in the case of the patient participating in research while the classic free-rider argument does not. The patient's participation helps supply present and future generations with important medical knowledge while not necessarily reducing the burden on those participants who made the knowledge available for her treatment.

Nature of the Obligation. The obligation to participate in research is not absolute. Rather, individuals have what philosophers call a prima facie obligation to participate.²⁵ In other words, there may be circumstances or reasons that override or mitigate the force of the duty. For example, a parent may permissibly break a promise to meet a friend to care for a sick child. Similarly, if participating in a trial requires the patient to violate a sincere religious belief about bodily integrity or is excessively burdensome, then that patient's obligation to participate in research has been overridden and he or she is not morally required to participate.

It is difficult to specify the strength of the obligation to participate in research with any precision. Is it more important to spend a few hours with an individual's family or participate in research? Does the obligation hold if the individual lives far away from the research center? As with most theories of obligation, there is no mathematical algorithm. Tensions between obligations are an inevitable feature of moral lives.^{26 - 27} This does not undermine or negate the obligation, but only highlights the complexity of ethical decisions. Nonetheless, the obligation has force. The obligation requires starting from the assumption that the patient ought to participate in the study. If he or she were to refuse, that patient should have a good reason for doing so.

How much is a patient required to do? He or she has an obligation to fulfill his or her “fair share” of participation.⁹ The patient is not required to enter every trial for which he or she is eligible. By analogy, how often must an academic agree to review manuscripts for journals? Given that scholars benefit from the peer review system, they have a prima facie obligation to do their fair share of reviewing when asked. Yet they need not accept every request. Although there is no formula to determine how often such requests must be accepted, or what factors can legitimately override the obligation, such moral uncertainty does not undermine the claim that academics have such an obligation. Similar uncertainty should not undermine the claim that every individual has a duty to participate in biomedical research.

Enforcement. To say that any patient has a moral obligation to participate in a clinical trial does not mean that the patient should be legally compelled to do so. It is perfectly coherent to argue that there is a duty to vote but that individuals should not be compelled to do so, and no nation enforces an obligation to keep promises to friends even though most think that there is an obligation to do so. Legal coercion may be a legitimate tool in certain circumstances, such as paying taxes for national security or making cars with catalytic converters, but it is not so for biomedical research. There are sound moral reasons for thinking that all individuals should be able to decide what happens to their body even if they decide not to do what they are morally obligated to do, the kind of right to privacy inferred from the US constitution^{28 - 29} and explicit in the European Convention on Human Rights.³⁰ An individual's right over his or her body can justly be overridden in some circumstances, such as when society compels individuals to be vaccinated. But the need for biomedical research today does not qualify as such an extraordinary circumstance. It is important to be wary of broader societal implications of compulsory participation.

An obligation to participate in biomedical research also would not alter the requirements of informed consent. If a carpenter has loaned his woodworking tools to a neighbor on several occasions, it can be said that the neighbor has an obligation to loan comparable tools to the carpenter. Nonetheless, it would still be wrong for the carpenter to take the neighbor's tools without consent. Similarly, although an individual may have an obligation to participate in research, there should still be insistence that the participant provide informed consent to do so.

The obligation to participate in research does not undermine the right to withdraw from participation in a trial.³¹ To say that participants have a right to withdraw is not to say that they have no prima facie obligation to remain in a study. It is to say that they should not be penalized for withdrawing even if withdrawal is wrong.

Personal Obligation. Individuals ought to participate in clinical trials when presented with the option. Well-functioning institutional review boards ensure that the risks are not excessive relative to the benefits of research. When the risks are significant, the obligation may be weaker. The obligation to participate applies to both healthy volunteers and patients. Both are needed to advance biomedical knowledge. For patients, there is an obligation to agree to participate in a study involving their condition when appropriate. Healthy individuals should participate in a fair share of the research for which they are eligible and needed.

Cultural Change. Just as many claim that citizens have an obligation to vote even though they are not legally required to do so, society should recognize that everyone has an obligation to participate in research when it is not excessively burdensome to do so. The current default position is that an individual does not have to participate in research if he or she does not want to. Instead, the default position should be that an individual should participate unless he or she has good reasons not to. This article advocates a cultural and moral change, not a legal one.

One strategy to affirm and reinforce the belief that individuals have an obligation to participate in research would be a publicity campaign analogous to get-out-the-vote efforts, which have helped convince 90% of US citizens that there is a duty to vote.²¹ The language of current advertisements could change from calling participants everyday heroes, which implies participating is supererogatory, to using language similar to recycling advertisements, which state “do your part” or “it's your turn to participate.”

Another strategy operates at the individual level. Researchers could use moral encouragement when attempting to recruit participants instead of emphasizing benefits to the individual as reasons to join studies.^{32 - 33} Additionally, physicians should be more willing to actively recruit patients to participate in important clinical trials.³⁴ Such encouragement would have to be given carefully; there is a risk that the patients would fear abandonment by their physician if they refused to participate. In the very least, researchers can legitimately inform patients about how important biomedical research has been and will be to everyone's well-being.

Paying Others to Participate in One's Stead. In theory, the obligation to participate could be fulfilled by paying someone else to participate. Most UK and US citizens discharge their obligation to defend their country by paying for an all-volunteer army through taxes. In principle, research participants could be paid enough so that no one would have to be asked to make any sacrifice by participation. But there are practical and moral limitations to this strategy. It would be inordinately expensive to increase payment to research participants enough to attract the millions of individuals who are needed above current participation levels.

In addition, there is the concern about undue inducements. Offering someone enough to participate when that individual would otherwise prefer not to might lead that individual to misunderstand the burdens and risks of participation. Additional concerns over exploitation and data reliability emerge if participants are recruited abroad for the sake of speed and budget savings.³⁵ But if individuals in the United States are reluctant to pay participants abroad, more effort and participation will be required by those in the United States.

The public goods argument is admittedly a minority position, and advocates of the standard view are likely to raise several objections.

Alternate Contribution. One might argue that certain individuals can discharge their obligation to participate by contributing financially to other public goods, or societal goods in general. Instead of participating in research, an individual could donate to Oxfam or the Special Olympics.¹⁰

However, it is practically infeasible to attempt a moral “accounting” when someone weighs the good deeds he or she has recently performed to see if they are sufficient. Even if such an accounting was possible, it is problematic to have contributions in one sphere of action offset duties to contribute to other spheres. For example, an individual's duty to recycle does not diminish even if he or she has donated vast sums of money to charity. Similarly, participation in biomedical research is a separate sphere of activity from charitable contributions. Aiding in the sphere of charitable donations would not be a way to offset the obligation to assist through participation in the sphere of biomedical research.

Current Contribution. Some say the obligation to support biomedical research is fulfilled by paying taxes that support research at the National Institutes of Health or the Medical Research Council, paying drug prices, and buying health insurance.^{36 - 37}

Biomedical research needs participants as well as financial support.³⁸ There are too few participants and adding more funding will probably not solve that problem. A shortfall of participants in biomedical research impedes the completion of clinical trials more than lack of funding.^{39 - 40} By one estimate, if the proportion of patients with cancer who agree to participate in clinical trials were to increase from its current 5% to 10%, the usual study completion rate would decrease from around 4 years to 1 year.⁴¹ Another estimate suggests that at least 16 million more individuals are needed to participate in research trials each year.⁴²

The obligation to support research is preserved even if an individual has paid for insurance, purchased drugs, etc. The situation is in some ways analogous to a wartime call to arms in which not just money but soldiers to fight are needed.

Equity. One might argue that wealthy individuals receive more benefits from biomedical research than poorer individuals; they are more able to afford new, expensive drugs and interventions. A poorer individual does not have an obligation to support an institution that primarily benefits the wealthy.^{43 - 44}

The public goods argument maintains that an individual has an obligation to participate in research only if the burden of participation is less than the overall benefit of biomedical research to the individual. It is an open empirical question whether or not wealthy individuals ultimately get more benefit out of biomedical research than poorer individuals, but it is likely that the benefit from research to the poor exceeds the burden of participation for the poor. There is some evidence that while poor populations lag behind in health improvements compared with the wealthy, the poor populations often manage to catch up as interventions become inexpensive and widely available.⁴⁵

This is partially because medical knowledge is a public good; wealthy individuals' access to medical knowledge does not preclude poorer individuals from having access to it. Even if their access is delayed, poorer individuals still receive benefits from interventions originally targeted at the wealthy. Access to a tuberculosis vaccine or antiretroviral therapy, for example, may be delayed for the less affluent, but they eventually get access and ultimately a greater improvement in their lives from the research because less affluent individuals are more threatened by diseases such as tuberculosis, human immunodeficiency virus, and AIDS.^{46 - 47}

Excessive Burden on the Sick. Because much research can be conducted only with those who have a particular disease or condition, the obligation to participate in biomedical research falls disproportionately on sick individuals who already have suffered. It may be argued that an obligation for the sick to participate in trials is unreasonably demanding.⁵

While it is unfortunate that the sick bear a disproportionate burden of participation in research, it is not unfair. It is an unavoidable fact of life that some obligations fall on some and not others. It is not unfair that a witness to a crime has an obligation to report it and testify in court, whereas individuals who happen not to be witnesses have no such obligation. Individuals sometimes acquire obligations simply because of the circumstances in which they find themselves.

Patent Protection. Three-quarters of all clinical research is sponsored by pharmaceutical companies.⁴¹ While there may be an obligation to participate in publicly funded research, it could be objected that patented biomedical knowledge is not a public good, and hence participation in industry-sponsored research that may produce patented knowledge is not an obligation.

Patents on medications eventually expire. For example, brand-name widely used statins, such as Lipitor, will soon be available at generic prices. Moreover, a patent protects the production of a drug or device, but the knowledge of its effects is the public good. That knowledge is a core value of biomedical research and is the result of public and private research alike. Indeed, a private company can provide a public good. What matters is that the good is available to everyone, not that a public institution provides it. Consequently, there can be obligations to help private companies produce public goods. By analogy, someone might support the public good of national defense by working for a private company producing bulletproof vests instead of a more lucrative profession. In the case of biomedical research, even private companies have an incentive to spread the knowledge of effectiveness of a drug or device because it is an effective way to get physicians to recommend those interventions. Whether a study is publicly or privately financed has little bearing on the obligation to participate in that study.

Unsuccessful Research. Much research benefits no one. Only a small percentage of drugs tested will ever make it to market. Negative results are often not even published. Given the small chance any particular research study has to generate an effective intervention, the obligation would seem to be weak.⁴¹

A negative result that is unpublished and unreleased is not a public good. However, negative results disseminated to the medical community are indeed a public good. That is a good reason to encourage the dissemination of the results of all studies. Knowing what does not work can be useful in itself and can contribute to other studies.

Even if many studies would not, in hindsight, be worth the effort, it only matters that the benefits of the research are expected to be worthwhile before the research is completed. Given that the research enterprise overall produces valuable public goods, and institutional review boards have determined that any particular research study has an overall positive expected social value, the obligation remains in force. As Beecher said, “an experiment is ethical or not at its inception; it does not become ethical post hoc.”⁴⁸ The same can be said of obligations—the importance of contributions should be evaluated from an ex ante perspective.

There is a prima facie obligation to participate in biomedical research. This obligation arises because biomedical research produces the public good of biomedical knowledge—a good that everyone has access to and that retains its value no matter how many individuals have access to it. The results of research do not just help the rich or powerful—all take advantage of this public good such as with vaccines, drugs, or medical devices. Many individuals owe their lives to the biomedical knowledge that could only be produced with the contribution of many willing participants. The obligation to participate in biomedical research makes reasonable demands on all individuals in a society. Participating in research is much less burdensome than contributing to many other public goods; joining the army is more risky and time-consuming than any clinical trial that has been approved by a well-functioning institutional review board. Indeed, paying taxes may be much more burdensome than participating in many research trials.

This is not to suggest that individuals have an obligation to become full-time research participants. Instead, there needs to be a cultural shift in the moral framework that is brought to participation in research. The standard view of research participation must be changed from one in which participation is supererogatory to one in which individuals need to give a good reason not to participate. The shift should be from participation in biomedical research being, like charity, above the call of duty, to such participation being a moral obligation for everyone to do his or her part.