Social Benefits of Human Subjects Research

Introduction

One of the primary ethical justifications for conducting research with human subjects is to benefit society.[1-5] This normative principle is explicitly stated or implied in many codes, guidelines, and regulations pertaining to research with human subjects.[6-10] According to the Nuremberg Code, an experiment with a human subject should “be such as to yield fruitful results for the good of society” and “[t]he degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment.”[6] The CIOMS Guidelines put the matter this way: “The ethical justification of biomedical research involving human subjects is the prospect of discovering new ways of benefiting people's health.”[8] According to the U.S. federal research regulations, the risks of research must be reasonable in relation to the benefits to the subjects and the knowledge that may be gained, which is generally understood as a social benefit of research.[2, 10] The federal regulations also require investigators to inform subjects about the benefits of the research to the subjects or others.[10]

Although there is a broad consensus that research with human subjects should benefit society, there has been relatively little in-depth discussion in the bioethics literature about the social benefits of research.[11] Investigations of social benefits tend to focus on topics related to social benefits, such as individual benefits, the ratio of risks to benefits, or the distribution of benefits, not on social benefits per se.[12-16]

One also finds very little discussion of social benefits in typical informed consent documents in biomedical research. In a pilot study of a random sample of 44 informed consent forms from U.S. oncology clinical trials, the average number of words describing social benefits was 19.7, as compared to 49.3 words describing individual benefits and 930 words describing risks. Five documents (11.4%) did not even mention how the research could benefit others. Many of the documents used generic language to describe social benefits, such as “this research may benefit other patients in the future.”[17] Since this is only a pilot study, further investigation is warranted to determine whether the results stand up.

What Are Social Benefits?

A “social benefit” of research can be defined as a socially valuable (or good) outcome received by someone other than the research subject, such as other patients with the subject's disease, researchers, sponsors, or society as a whole. People frequently disagree about whether particular research projects involving human subjects produce socially worthwhile results because they have different understandings of what is good for society, which often reflect disagreements about moral, political, or religious values. For example, a pacifist might hold that research on vaccines to protect soldiers against biological weapons does not offers any significant social benefits, because the research would aid the military.[11] Someone who opposes birth control would not consider research on new methods of contraception to be a social benefit, because it could increase the use of birth control. An atheist might have little interest in a study on the effects of prayer on recovery from heart surgery. Someone who takes a utilitarian approach to ethics may have a very different view of the social benefits of the use of placebo-controls in clinical trials than someone who adheres to a human rights or Kantian approach to ethics.[5] As long as people disagree about fundamental moral, political, or religious values, they are likely to also disagree about the social benefits of research.

It is commonly assumed that research produces social benefits by generating knowledge with practical applications. Sometimes the road from research to practical applications is clear, smooth, and immediate. For example, a study of a method for reducing errors related to pharmacotherapy in the hospital could produce life-saving applications soon after it is completed. The road from human research to social benefits is often long, uncertain, and attenuated, however.[18] For example, Phase I clinical trials on healthy subjects can be justified on the grounds that they are an important step in the development of new treatments that will help other people with diseases.[19] Yet most drugs that are tested in Phase I trials never make it to the marketplace because they do not advance past the other phases of clinical testing, due to lack of safety or efficacy.[20] Some studies using human subjects contribute to general knowledge about human biology or behavior, but are not expected to yield practical results for quite some time, if ever. For example, the Human Genome Project (HGP), an effort to sequence and map the DNA in an entire human genome, was begun in 1990 and completed in 2002. Although the HGP has provided researchers with a wealth of information about human DNA, it may take several decades to translate this research into medical treatments and diagnostic tests.[21] Some of the practical applications of research with human subjects include:

• New drugs, biologics, surgical techniques, and other medical therapies

• Public health interventions, practices, and policies

• Nutrition and exercise

• Psychological counseling and social work

• Social or economic policy

• Environmental or other regulations

• National security

• Law enforcement and criminal justice

• Public education

• Food, recreation, consumer products

• Workplace safety and ergonomics

• Transportation and communication

Assessing Social Benefits

Another standard requirement for research with human subjects is that the risks imposed on the subjects must be justified by virtue of potential benefits for the subject or society. One way of putting this is to say that risks must be reasonable in relation to benefits or that the risk/benefit ratio is acceptable.[1, 2, 13] In the U.S., committees known as an institutional review boards (IRBs) are charged with approving research studies that fall under the federal regulations. Other countries have similar committees. To decide whether risks are reasonable in relation to benefits, IRBs must assess and compare risks and benefits. Because people disagree about how to compare risks and benefits, quantitative methods of comparing risks and benefits, such as cost-benefit analysis or expected utility theory, are sometimes not very useful in making decisions about research with human subjects.[9, 13] To compare risks and benefits, IRBs must carefully describe the risks and benefits and make holistic judgment about them.

A great deal has been written about the assessment of risks in research, so I will not explore that topic here.[2, 22] Much less has been written about the assessment of benefits and even less about the assessment of social benefits. To help illuminate our understanding of social benefits, I will outline a process that IRBs and investigators can use to assess benefits systematically. (See Table 1.)

Table 1.

Assessing Social Benefits in Research: Key Questions

Benefits identification	What are the possible benefits to society?
Benefits estimation	What is the social significance of the benefits?
	How likely are the benefits to occur?
Benefits distribution	Who will receive the benefits?

The assessment of benefits has much in common with the assessment of risks. The first step of risk assessment in human subjects research is risk identification.[2, 13]. Likewise, the first step in benefits assessment is to identify the benefits (see Table 1). Will the research project help test a new medical therapy? Will it lead to a new public health intervention? Will it help to improve an educational program? Will it have important implications for social or economic policy? As we have already seen, there are many different types of benefits that a project might produce for society.

The next step in benefits assessment is benefits estimation, which involves determining the social significance of the benefits and the probability that they will materialize. When estimating the social significance of a potential benefit one may consider such questions as, are the benefits important or trivial? Will they affect many people or only a few? Will they save human lives? Relieve suffering? Have economic impacts? Improve human knowledge in some area? And so on. Since people often disagree about whether research has social benefits, they may also disagree about the social significance of the potential benefits of research. For example, someone who opposes that death penalty may agree that some useful knowledge may be gained by interviewing people about the deterrent effects of the death penalty, but they might not consider that knowledge to be very worthwhile, since it might be used to justify the death penalty. Someone who opposes birth control might admit that a study on the safety of intrauterine devices might improve women's health, yet still object to the research.

People who agree about the social significance of benefits may disagree about the probability that benefits will materialize, due to lack of knowledge about the impact of the research. Some may regard a potential benefit as likely while others may judge it to be unlikely or only a remote possibility. The fact that people disagree about the probability that benefits will occur need not be an impediment to benefits assessment, however. Though it would be unethical to use human subjects in research that cannot produce any benefits (individual or social), human subjects may be used when the benefits have a realistic (i.e. more than merely speculative) chance of occurring.[2] Investigators should help IRBs assess social benefits by including evidence concerning the probability and social significance of social benefits in their research proposals.

Another important step in benefits assessment is to ascertain how benefits will be distributed. Who may benefit from the research? Will other patients benefits? Healthy people? School children? Soldiers? Private companies, universities, or other organizations? People in other countries? Questions about the distribution of benefits are important to the assessment of benefits because they have implications for the moral significance of the benefits and overall fairness of the research project. In many instances, disagreements about the social benefits of a research project will center on questions about who will benefit from the project. For example, many commentators and organizations have expressed the concern that pharmaceutical clinical trials conducted in developing nations may benefit people in developed nations more than they benefit people in developing nations, because people in developing nations may not be able to afford the drugs being tested.[15, 16] International codes of research ethics, such as the Helsinki Declaration and the CIOMS guidelines, have provisions that address the distribution of the benefits of research. The CIOMS guidelines require research conducted in resource-poor countries “is responsive to the health needs and the priorities of the population or community in which it is to be carried out; and any intervention or product developed, or knowledge generated, will be made reasonably available for the benefit of that population or community.”[8]

Analysis of a Current Controversy Concerning Social Benefits

I will briefly illustrate how the process of assessing social benefits that I have just described can be applied to a current controversy concerning research with human subjects, testing pesticides on human subjects.[23, 24] In the 1990s, several private companies sponsored over a dozen experiments the U.K. and the U.S. in which human subjects ingested small doses of pesticides. One of the purposes of the research was to generate data to convince the Environmental Protection Agency (EPA) to increase the amount of allowable levels of pesticide residues on food. The U.S. Congress had passed a law in 1996 that required pesticide residue on foods to be decreased by a factor of ten, to provide extra protection for children. The companies submitted their data to the EPA, but the agency declined to accept the data until the ethical and regulatory issues were resolved. The agency asked the National Research Council (NRC) to study the issues. The EPA had been making its decisions concerning pesticides on animal toxicology experiments, not on human experiments. In 2001 an agricultural interest group, Croplife America, sued the EPA for engaging in improper rule-making without public comment, and in 2003 a federal court sided with Croplife. The court ordered the EPA to issue new rules, following appropriate public comment. The EPA complied with the court's order and issued new rules for accepting data from human experiments sponsored by private companies in 2006.[25] The EPA's new human subjects rules have generated considerable controversy, and are opposed by environmental groups.[25]

Environmental interest groups and other critics of the pesticide experiments argued that they were poorly designed, statistically underpowered, coercive (some experiments used company employees), dangerous to the subjects, and offered no useful social benefits.[23, 26, 29] Other commentators, including the NRC, argued that while these particular experiment were flawed, pesticide testing on human subjects was not inherently unethical and could be carried out under stringent scientific and ethical standards.[25, 27] Some of these standards were that 1) experiments should be well-designed; 2) the experiments should be expected to provide information that contributes to our understanding of how pesticides affect human health and could be used by regulatory agencies to protect the public from the hazards of pesticide exposure; 3) experiments should not expose research subjects to a dose that would be expected to cause any permanent harm or damage, 4) subjects should give their fully informed consent, 5) subjects should not be members of a vulnerable group, such as children or pregnant women. Opponents of the experiments contended these scientific and ethical standards were insufficient to permit human pesticide testing, because even well-designed experiments would needlessly expose human subjects to significant risks with benefits only accruing to pesticide companies and agribusiness interests. The research would offer no useful results for society and could lead to a weakening of pesticide regulations.[28, 29] (See Table 2.)

Table 2.

Assessing Social Benefits in Pesticide Research

Benefits identification	Increased knowledge about how pesticides affect human beings
	Stricter (safer) pesticide regulations
Benefits estimation	Research is likely to produce knowledge about how pesticides affect human beings but that knowledge may not be very significant, since we already have safety data from animal studies
	Research could lead to safer pesticide regulations but it also could be used to justify laxer regulations
Benefits distribution	Benefits are likely to accrue to pesticide companies, farmers and other agribusiness interests
	The public may benefit from stricter pesticide regulations or the public could be harmed by laxer regulations

Although this dispute involves a number of different issues related to research with human subjects, much of the controversy has centered on questions about the social benefits of pesticide experiments on human subjects, or lack thereof. Some opponents of the research claimed that pesticide experiments can never yield any morally worthwhile consequences for society.[26] Other opponents conceded that some experiments might produce valuable results, but that they results would not be important enough to justify intentionally exposing human subject to pesticides.[23] Finally, opponents were also concerned about the distribution of benefits. They argued that pesticide companies and agribusiness interests would benefit more than other people in society.[23, 29] Defenders of pesticide testing on human subjects argued that well-designed studies that expose people to low-doses of pesticides under carefully controlled conditions could yield important knowledge about how the human body absorbs, distributes, metabolizes, and eliminates pesticides, and that this knowledge could help to protect people from the harmful effects of pesticides.[24, 27] The benefits of testing would outweigh the risks, provided that human subjects are not exposed a dose that would cause any permanent damage.[24]

A systematic approach to assessing the social benefits of human pesticide testing could enhance our understanding of this controversy and point the way toward a resolution of some of the issues. By focusing on questions concerning the identification of benefits, the estimation of benefits, and the distribution of benefits, it may be possible to pinpoint the disputants’ sources of disagreement. The opposing parties may, in fact, agree on matters relating to research design, the minimization of risks, and informed consent, but may have some major disagreements concerning whether the experiments could have social benefits and whom the experiments might benefit.

Conclusion

While few people dispute the idea that research with human subjects should have social benefits, people often disagree about whether particular research projects will produce good results for society. Though considerable attention has been devoted to the assessment of risks in research, relatively little attention has been directed toward the assessment of social benefits. In this article I have attempted to shed some light on social benefits in research and have proposed a method for examining social benefits systematically. I encourage others to investigate some of the issues explored in this article.