Research Ethics: “Excessive” Offers Threaten Voluntariness

Voluntary consent has long been considered a foundational requirement for ethical research recruitment. The Nuremberg Code, the Declaration of Helsinki, and the Belmont Report all flatly condemn coercion, or obtaining consent through “an overt threat of harm.”⁹ But when the Belmont Report was issued in 1978, it introduced an additional concern of a very different nature: “undue influence,” which the authors framed as offering “an excessive, unwarranted, inappropriate or improper reward or other overture in order to obtain compliance.”¹⁰

Faden and Beauchamp built on this foundation in their early work, A History and Theory of Informed Consent.^{Reference Faden and Beauchamp11} In their view, an offer of a reward or incentive in exchange for research participation compromises the voluntariness of consent if the subject finds the offer both “unwelcome” and difficult to resist.¹² To illustrate the potential for unwelcome offers to undermine autonomy, the authors offer the example of a financially desperate woman named Mary. Researchers offer Mary $25 per day in exchange for her participation in research involving repeated, painful medical procedures.¹³ Mary is terrified of participating in the research, but feels she must accept because she badly needs the money. In Faden and Beauchamp's analysis, Mary's consent is not sufficiently voluntary; her desperation and the researcher's offer place her substantially under the researcher's control.

This conception of the way payment affects voluntariness has been enormously influential, finding its way into the guidelines governing research on human subjects and spawning a vast literature seeking to define the circumstances under which offers may unduly induce research participation.¹⁴ However, supporters of this conception of voluntariness have been unable to identify the precise contours of undue influence. Not every inducement that influences an individual's decision to participate in research is improper; the ethical issue only arises when the influence is “undue.”¹⁵ Yet the Belmont Report itself “does not specify when or for what reasons an offer should be considered excessive, unwanted, inappropriate or improper.”^{Reference Largent, Grady, Miller and Wertheimer16} More than three decades later, many observers lament the lack of progress on this issue in the literature.^{Reference Appelbaum, Lidz and Klitzman17}

The widespread adoption of “undue influence” has distorted the debate over paid studies in three important ways. First, by framing the ethical issue as one of payment rather than selection of subjects, it locates the problem solely in the size of the paycheck while excluding the wider circumstances that are often far more important to the subject's decision — in particular, the background conditions of poverty or desperation that might lead someone to accept a bad offer. In the example offered by Faden and Beauchamp, for instance, it is surely Mary's financial desperation that is the problematic issue, rather than the size of her $25 payment. This kind of desperation appears repeatedly in the interviews of 178 Phase I trial subjects conducted by Cottingham and Fisher, who found that many subjects dismissed their concerns about study risks because of their extreme financial need. “I guess the desperation far outweighed the concerns,” one subject said. “You know, when someone's desperate, like they are not even gonna think twice, so I guess that's where I was at.”¹⁸

Second, the insistence on avoiding undue influence by lowering payment undermines the core ethical principle of justice in the selection of subjects, which demands that those who bear the risks and burdens of research should be in a position to share in its benefits.¹⁹ Requiring that payments be kept low virtually ensures that the subject population in paid trials will be disproportionately made up of people with lower incomes.^{Reference Lemmens and Elliott20} This concern is borne out by a substantial body of research indicating that paid trials largely attract minority men with low incomes and low rates of health insurance.^{Reference Stunkel, Benson, McLellan, Sinaii, Bedarida, Emanuel and Grady21} Indeed, drug companies and CROs have repeatedly drawn the ire of critics by targeting homeless people and undocumented immigrants to serve as research subjects.^{Reference Elliott22} As a result of these recruiting practices, the very people who test drug safety are less likely to have access to medications the research may help produce.^{Reference Elliott and Abadie23}

Third and most importantly, framing the problem as “undue influence” concentrates attention solely on issues surrounding the voluntariness of a subject's consent while ignoring the question of whether the offer is fair. Not every ethical concern can be shoehorned into a worry about autonomy. The fact that a competent subject has voluntarily accepted an unfair offer does not make the transaction ethically sound. Competent subjects can make fully informed, rational, and voluntary decisions to enter into exploitative studies simply because they are desperate and taking part in the study is their least bad option.

Forced to operate within this narrow framework, many commentators have struggled to reconcile a desire to protect vulnerable subjects with a conceptual apparatus focused on the voluntariness of the subjects' consent. Oversight bodies have been unable to offer meaningful guidance as to what amount of compensation constitutes an undue influence.²⁴ The Office for Human Research Protection's IRB Guidebook frankly acknowledges that “[f]ederal regulations governing research with human subjects contain no specific guidance for IRB review of payment practices.”²⁵ Indeed, OHRP admits that “[o]n a practical level, it is probably impossible for an IRB to determine what amount of money or type of reward would unduly influence a particular individual to accept a given degree of risk.”²⁶ Thus it is left to IRB members themselves to interpret when an offer is excessive, improper or undue.²⁷

The absence of effective guidance has produced mass confusion among researchers and IRBs. Most research entities have no written policies regarding payment practices, and most written policies that do exist “do not describe how investigators or IRBs should determine when money is ‘undue.’”^{Reference Dickert, Emanuel and Grady28} A 2012 survey of IRB members and research ethics professionals found that 80% believed that merely offering payment “constitutes undue influence simply because it motivates someone to do something they otherwise would not.”^{Reference Largent, Grady, Miller and Wertheimer29} Nearly two-thirds (65%) believed this kind of payment constituted not just undue influence, but full-blown coercion.³⁰

A rule that no one knows how to abide by — including the entity promulgating it — cannot be effective, and is probably defective. In our view, the difficulty encountered in crafting standards for avoiding undue inducement is a symptom of flaws in the underlying conceptual premises.

Contract Law: Higher Compensation Enhances Fairness

When subjects are paid to participate in research, they enter into agreements that broadly resemble employment contracts.³¹ Contract law requires voluntariness as a condition of a valid agreement, and accordingly the law imposes protections against coercion and excessive pressure. Unlike research guidelines, however, which warn against offering participants too much, contract law looks with skepticism only at agreements in which one side seems to gain too little.^{Reference Lynch32}

Although contract law recognizes “undue influence” as undermining voluntariness, that legal concept does not apply to overly generous offers. Rather, the essence of this legal claim is “excessive pressure,” including such features as “discussion of the transaction at an unusual or inappropriate time,” “extreme emphasis on untoward consequences of delay,” and “the use of multiple persuaders by the dominant side against a single servient party.”³³ In other words, the contract law view of undue influence refers to situations in which one party obtains another's agreement by badgering or wearing down the other or by taking advantage of the other's weakness of mind. But inducing agreement by simply offering the other party very generous compensation would never signal excessive pressure.

On the contrary, in some cases contract law views compensation that is too low as evidence that suggests a party may not have entered into an agreement voluntarily. For example, the “unfairness” of an agreement can serve as potent evidence that a contract was the result of improper threats.³⁴ Likewise courts consider “inadequacy of consideration” — meaning one party received too little value from the transaction — an important factor in deciding whether to invalidate a contract as “unconscionable.”³⁵ But nowhere does the law suggest that “excessive” consideration threatens voluntariness.³⁶ Rather, the more compensation a party receives, the less likely a court is to invalidate the agreement on the grounds of involuntariness.

Accordingly, contract law would clearly bless as voluntary the consent given by Mary in the scenario Faden and Beauchamp describe as a paradigmatic case of undue influence. Under their account, Mary's consent is not sufficiently voluntary because she finds the offer unwelcome and cannot easily resist it because she needs the money.³⁷ By contrast, contract law makes no distinction between “welcome” and “unwelcome” offers. Nor does it ask whether offers are “irresistible” (unless the offer actually represents a veiled threat, such as the occasion in The Godfather when Don Corleone made Johnny Fontane “an offer he couldn't refuse”). Absent the kind of badgering that constitutes “excessive persuasion,” the mere offer of money — present in nearly every contract — clearly could not qualify as undue influence.

Nor would Mary's desperate financial straits undermine the conclusion that Mary's consent was voluntary. While a court may invalidate a contract on the basis of a party's “economic duress,” this doctrine only comes into play if the defendant has committed a “wrongful act,” such as “the assertion of a claim known to be false” or “a bad faith threat to breach a contract.”^{Reference Wertheimer38} “Merely being put to a voluntary choice of perfectly legitimate alternatives” — such as an opportunity to participate in research in exchange for money, or to decline — “is the antithesis of duress.”³⁹ The researcher's offer of payment to Mary in exchange for her research participation clearly does not constitute a “wrongful act” that would invalidate her consent, even if her refusal to accept would leave her destitute.

Most importantly for present purposes, the larger the benefits offered to Mary in exchange for her consent, the less likely a court would be to find duress or undue influence.⁴⁰ Rather than undermining Mary's voluntariness, courts generally view larger offers as enhancing the fairness of agreements, making it more likely that an individual willingly chose to enter into the contract. It is low payment that is more likely to raise questions of unfairness.

The approach to compensating research subjects suggested by contract law provides IRBs with guidance that is far more coherent than the dominant view in research ethics. Rather than grappling with what level of payment might cause subjects to accept an offer that they do not “want to want,” IRBs should adopt a much easier rule of thumb that higher pay is better for subjects than lower pay. And while raising compensation may not be sufficient on its own to ensure fair selection of research participants (as discussed below), discarding concerns about undue inducement would remove a requirement that seems to all but ensure that participating in phase I trials is attractive primarily to financially desperate people.

Exploitation: More Than (Un)Just Compensation

Some scholars have understandably embraced a view of compensation similar to that of contract law, arguing that subjects should be paid whatever the market will bear.⁴¹ Yet although abandoning concerns about excessive payments would benefit research subjects, it is by no means sufficient to protect them from exploitation. For evidence one need look no further than the poor industrial working conditions that prevailed in the United States in the early twentieth century, when the market operated largely free from government interference. This laissez faire approach to the labor market was endorsed by the United States Supreme Court in Lochner v. New York, in which the Court struck down a state law that limited the number of hours bakers were allowed to work.⁴² The court concluded this regulation violated due process by interfering with citizens' “freedom of contract.” In the years that followed the Court rejected multiple additional attempts by federal and state governments to protect workers, including laws imposing minimum wages, restricting the labor of children, and enshrining workers' rights to join labor unions.⁴³ This unfettered freedom of contract produced sweatshops, child labor, and unsafe working conditions, not to mention subsistence wages. The regulations that today govern wages, hours, and workplace safety were put in place specifically to combat the exploitative conditions that prevail when parties are left “free” to contract regarding the terms of labor.

In our view, protecting research subjects requires an understanding of exploitation that extends well beyond what subjects are paid. Exploitation typically involves taking unfair advantage of another person, often someone in a position of vulnerability.^{Reference Wertheimer, Emanuel, Grady, Crouch, Lie, Miller and Wendler44} For example, few would dispute that the Public Health study at Tuskegee was exploitative: Public Health Service doctors used the offer of burial insurance to lure impoverished, uneducated black men with syphilis into a deceptive study where they would get no treatment for a dangerous illness.^{Reference Jones45} Although exploitation can involve coercion and threats, a person might also willingly — even eagerly — agree to an exploitative offer, simply because the unfair offer is still superior to her other choices.⁴⁶ This helps explain why many poor people are willing to enroll in paid clinical trials, irrespective of their potential risks and discomforts.⁴⁷

Wertheimer calls transactions such as these “mutually advantageous exploitation,” in order to distinguish them from cases of “harmful exploitation.”^{Reference Werthheimer48} Using the threat of involuntary commitment to coerce a mentally ill patient into a dangerous study would be “harmful exploitation.”⁴⁹ By contrast, paid clinical trials can represent “mutually advantageous exploitation.” Rather than being coerced to participate, subjects join because they expect to benefit from the transaction — even if they are being taken advantage of.

Whether a mutually advantageous transaction counts as exploitative depends on whether the transaction is fair. Price-gouging, for instance, is widely considered exploitative; a truck driver who offered to tow an injured, stranded driver from an isolated snowbank for a price of $10,000 would be taking unfair advantage of the driver.⁵⁰ But the ethics of many other mutually advantageous transactions — such as paid clinical trials — are highly contested.

Some bioethicists who concede that some trials are potentially exploitative mistakenly believe that the remedy is simply to increase payment. Just as fairness demands that workers in dangerous jobs be rewarded with higher payment, they argue, so too should research subjects be rewarded for longer, risk-ier, and more unpleasant studies. As Emanuel writes, “So when one is tempted to charge ‘undue inducement’ because of too many poor people enrolling and the possibility of exploitation, the response should be to increase the inducement.”^{Reference Emanuel51}

Yet merely increasing payment does not ensure that an offer is fair. Just as there are many ways for sweatshop labor to be unfair to workers apart from low wages, there are many ways for research studies to be exploitative apart from inadequate compensation. For instance, a research study might be exploitative because it exposes vulnerable subjects to conditions that are excessively dangerous, demanding, painful, or degrading. Simply paying those subjects more money would not be sufficient to ensure that they are being treated fairly. The solution, rather, is to fix the conditions that make the transaction unfair.

In our view (as described below) many research studies in the United States are currently exploitative and would remain so even if compensation were increased. Making those studies fair will require significant changes to the current oversight system and the structure of many research studies.