# Presentation: 368332

## Payment, Coercion, and Undue Inducement

*October 28, 2004*
- Neal Dickert
- Johns Hopkins School of Medicine and
- Bloomberg School of Public Health

**Notes:**
Hi, I’m Neal Dickert, and I appreciate the chance to talk with you about a topic that I’ve thought about for some time now and still find very interesting and challenging, the topic of paying subjects for participation in clinical research.  In particular, I want to talk about issues of coercion and undue inducement, concerns often raised regarding payment and in the conduct of research in general.  I want to start by acknowledging in particular Christine Grady and Zeke Emanuel, with whom I have done most of this work and whose thoughts  over the past 8 years have been essential and exceedingly helpful to me in developing the views expressed in this talk.

## Alexis St. Martin

- “The Intrepid Guinea Pig of the Great Lakes”
- In 1822, accidentally shot in the gut and left with a permanent gastric fistula.
- William Beaumont paid him room, board, and $150 a year for use of his stomach.

- http://www.guineapigzero.com/AlexisStMartin.html

**Notes:**
Most of you have probably never seen or heard of the man on the right.
His name is Alexie St. Martin, and he has been called the “intrepid guinea pig of the Great Lakes.”
You see, in 1822, St. Martin, a voyageur for the American Fur Trading Company, was accidentally shot in the gut and, though miraculously saved by an army surgeon named William Beaumont, was left with a permanent gastric fistula.
While the fistula was less than ideal for Alexie, Beaumont saw a phenomenal opportunity, as St. Martin’s wound provided a window into the functioning of the human GI system.
As a result, Beaumont paid St. Martin room, board,and $150 a year for use of his stomach, making him to my knowledge the earliest paid research subject.

## Walter Reed

- Paid $100 in gold for participation.
- $100 bonus for successful infection with yellow fever.
- Payable to family in the event of death.

- http://etext.lib.virginia.edu/healthsci/reed/commission.html#vol

**Notes:**
Likely more familiar than St. Martin and Beaumont, this picture shows Walter Reed in Cuba in 1900 with the group of research subjects that he used in his work on Yellow Fever.
Reed paid each subject, most of whom were Spanish immigrants to Cuba, $100 in gold, with a $100 bonus if they were successfully infected.  Incidentally, were anyone to die, the amount would be paid to their family after death.

I cite these historical examples to illustrate that paying research subjects is far from a new practice.  However, it has surely grown in recent years with rapid rate of research in general.

## Tensions Today

- 	“Because payment for participation can have coercive or exploitative effects on potential subjects, institutional review boards (IRBs) generally take into consideration the amount and distribution of proposed monetary payments to subjects to ensure that subjects in the study will not be unduly influenced to participate.”
- 	Schonfeld, et al., *IRB*. 2003.

**Notes:**
Despite the fact that payment has occurred for many years, it remains a contentious practice, with significant ethical tensions reflected in discussions about payment in IRB meetings and in the literature.
The presence of these tensions, as well the confusion that exists around them, are evidenced in this passage from a recent issue of IRB...
Because payment for participation can have coercive or exploitative effects on potential subjects, institutional review boards (IRBs) generally take into consideration the amount and distribution of proposed monetary payments to subjects to ensure that subjects in the study will not be unduly influenced to participate

While the desire to protect vulnerable subjects is unanimous, this excerpt illustrates what I believe to be an important and common mistake in talking about research recruitment in general, and payment in particular.  Namely, these authors fail to distinguish and carefully analyze the important ethical concerns of coercion, exploitation, and undue influence or inducement.  Defining and employing these terms clearly is, I think, crucial to the effective analysis of the issues at stake in considering payment and other recruitment strategies in clinical research.

## Overview

- State of payment in the US
- Ethical Concerns
- Coercion
- Undue Inducement
- Exploitation
- Data on ethical concerns in practice
- Recommendations

**Notes:**
In this talk, I’ll start by providing some data that we at the NIH have gathered on the state of payment in the United States today, some of which is contained in the Annals paper I included in your packet.
Then, I want to examine the often raised concerns of coercion and undue inducement.  I hope to persuade you that payment cannot be coercive and that coercion is actually rare in research in general.  
And, I hope to clarify and define the often used but rarely defined concept of undue inducement and argue that it too is a rare occurrence but one that has significant impact for how we ought to pay subjects.

While I will not explore the concept of exploitation in depth, I hope to highlight it as a concern and show that concerns about exploitation can exist in tension with concerns about undue inducement, but that concerns about exploitation are generally not ameliorated by alterations in payment.

Then, I’ll discuss some of the limited data that have been published on the degree to which some of these ethical issues are borne out in practice and close with recommendations about how I think we ought to proceed.

## The Common Rule

- 	“An investigator shall seek such consent only under circumstances that provide the prospective subject or the representative sufficient opportunity to consider whether or not to participate and that minimize the possibility of coercion or undue influence.”
- 	45 *CFR* 46.116

**Notes:**
In evaluating the state of payment in the US, I want to start with the federal regulations.  In short, there are no clear regulations regarding payment.

The Common Rule is completely silent on concerns about payment, requiring only that
An investigator shall seek such consent only under circumstances that provide the prospective subject or the representative sufficient opportunity to consider whether or not to participate and that minimize the possibility of coercion or undue influence.”
So, it highlights concerns of coercion and undue influence but neither defines them nor gives any suggestions as to how they may be avoided with regard to payment.

## FDA

- 	“Payment to research subjects for participation in studies is not considered a benefit, it is a recruitment incentive... The IRB should review both the amount of payment and the proposed method and timing of disbursement to assure that neither are coercive or present undue influence.”
- 	FDA Information Sheets, 1998

**Notes:**
The FDA addresses payment directly, but the guidance it offers is hardly any clearer.  It reads:
Payment to research subjects for participation in studies is not considered a benefit, it is a recruitment incentive...  The IRB should review both the amount of payment and the proposed method and timing of disbursement to assure that neither are coercive or present undue influence.”
These guidelines are at best vague, again giving no insight in what types of incentives would be coercive or unduly influential or what those terms even mean.

## OHRP

- 	“... the IRB should review both the amount of payment and the proposed method of disbursement to assure that neither entails problems of coercion or undue influence. Such problems might occur, for example, if the entire payment were to be contingent upon completion of the study or if the payment were unusually large. Payments should reflect the degree of risk, inconvenience, or discomfort associated with participation.“
- 	Office of Human Research Protection. *IRB Guidebook*.

**Notes:**
OHRP also addresses payment in this section of the IRB Guidebook.
“... the IRB should review both the amount of payment and the proposed method of disbursement to assure that neither entails problems of coercion or undue influence. Such problems might occur, for example, if the entire payment were to be contingent upon completion of the study or if the payment were unusually large. Payments should reflect the degree of risk, inconvenience, or discomfort associated with participation.“

This guideline does at least give a helpful example of large completion bonuses as potentially problematic, but the last sentence is especially confusing.  In particular, stating that payment should reflect the degree of risk entailed in a study is contrary to the views of many in the field and calls into question what the meaning of coercion or undue inducement might be.

## Payment in the U.S.

- Only 4 of 9 academic institutions surveyed kept track of which studies pay subjects.
- Average of 23% of protocols at these academic institutions paid subjects.
- Likely an underestimate.
- Frequency of payment higher at independent IRBs and pharmaceutical companies.
- “most” and “about 80%”

**Notes:**
Given the lack of clear guidance on the practice of payment, Christine Grady, Zeke Emanuel, and I conducted a review of policies and practices regarding payment at 32 US academic institutions, independent IRBs, Contract Research Organizations, and pharmaceutical companies.  The data from this project are reported in the Annals paper that I included in your packet.
At 11 of the academic institutions and independent IRBs, we and Tom Jawetz systematically reviewed a random sample of paid protocols approved during 1997.  In total, we reviewed 467 protocols.
With regard to how many studies pay subjects, we found that, at the 4 academic institutions that had some way to identify which studies paid subjects, 23% of protocols offered payment.  However, I think based upon the crudeness of the systems in place, the number of 23% is likely an underestimate.
We were unable to obtain similar data from independent IRBs or pharmaceutical companies, but representatives suggested payment likely occurred more often, with one represetnative saying “most” and another “about 80%” of studies pay subjects.

## Types of Studies Paying Subjects (n=467 studies)

- Grady, Dickert, Jawetz, and Emanuel. *under review*

| Phase I | 26 | 5.6% |
| --- | --- | --- |
| Phase II | 58 | 2.4% |
| Phase III | 100 | 21.4% |
| Phase IV | 36 | 7.7% |
| Physiologic | 88 | 18% |
| Behavioral | 82 | 17.6% |
| Other | 77 | 16.5% |
| Total | 467 | - |

**Notes:**
This table is, I think, particularly interesting, as it dispels the common view that only healthy subjects are paid and only in studies of no benefit.  If you look in the right column, you see that, of the 467 paid studies that we reviewed, only 5.6% were Phase I, and over 30% were Phase II, III, and IV studies, typically studies only enrolling patients with the condition under study and often involving a prospect of direct benefit to subjects.  In fact, in the protocols that we reviewed, over 75% enrolled and paid patients.

## Amount of Money Being Paid (n=467 studies)

| < $100 | 30.4% |
| --- | --- |
| $100-249 | 33.6% |
| $250-499 | 21.2% |
| $500-999 | 10.5% |
| $>1,000 | 4.3% |
| Mean | $266 |
| Median | $155 |

*Amounts shown in U.S. dollars*
- Grady, Dickert, Jawetz, and Emanuel. *under review*

**Notes:**
In this slide, you see the amounts of money paid in the studies we reviewed.  Again, these are all studies conducted in the US.  And, I think the slide is remarkable primarily for how modest the payments really are.  As you can see, almost 65% of studies paid less than $250, with only 4.6% of studies paying over $1,000.

## Payment in the U.S.

- 8/32 institutions had any guidance.
- Significant variation within and between institutions in amount of payment for particular procedures, inpatient days, outpatient visits.
- Rarely itemized.
- MRI with contrast- $25-$120
- Wide variation in multi-site studies.
- Up to $840 difference for the same study.

**Notes:**
There are several other findings that I want to point out.  First, only 8 of 32 institutions, of all types, had any particular guidance regarding how payment ought to be done, a fact reflected in the lack of description in most protocols for how payment was arrived at or itemization of what payment is for.

Second, there was significant variation, both within and between institutions, in the amount of payment offered for particular procedures, inpatient days, and outpatient visits.  For example, when itemized, the payment for an MRI scan with contrast ranged from $25-$120.

Finally, there was wide variation (up to $840) among payment offered at different sites for the same study in multi-site studies.

## What do the Data Show?

- Payment is very common.
- Payment is erratic with little institutional guidance or consistency.
- Payment is generally modest.

**Notes:**
What do these data say about the state of payment in the United States?  They tell us that payment is indeed very common, that it involves healthy subjects and patients, that payment is erratic with little institutional guidance or consistency in how it is carried out, and that payment is generally pretty modest in amount.
.  

## Ethical Concerns

- Concerns focus on the enrollment of vulnerable populations.
- Poor and homeless
- Sick patients
- Children
- Often cast as worries about coercion, undue inducement, and exploitation.

**Notes:**
Having laid out this picture of how payment appears to be be thought of and carried out in the US, I now want to jump into addressing the ethical concerns that the practice of payment has raised.

In general, concerns recently have focused on the enrollment of vulnerable populations, in particular
Poor and homeless people
Sick patients
Children 
While several types of concerns have been raised regarding payment, by far the most common are concerns about undue inducement and coercion.  Exploitation concerns have also been expressed and warrant particular attention.
I’ll start by addressing the issue of coercion, which is, I think, an often misunderstood concept, particularly with regard to payment

## Coercion

- 	“By now it is an unquestioned ethical precept of biomedical and behavioral research practice that subjects should not be coerced into participating... Those who choose to participate in research should be capable of choosing freely; they must do so voluntarily, willingly, without duress, and without being subjected to threats or the promise of too great a reward.”
- 	Macklin, *IRB. *1981.

**Notes:**
In this quotation from her very important early work on payment, Ruth Macklin expresses the view that coercion may take place in the presence of too great a reward or a threat.

## Coercion

- 	“... [A] patient suffering from a life-threatening disease may feel as though she has little choice regarding treatment.  Physicians should be aware of how vulnerable patients may be to the coercive influence of unrealistic hope, especially those suffering from chronic, life-threatening disorders.”
- 	Berg, Appelbaum, Lidz, and Parker, *Informed Consent: Legal Theory and Clinical Practice.* 2001.

**Notes:**
Though not in the context of payment, this quotation also evidences the common view that coercion can take place in any setting in which individuals’ options are constrained.

## Coercion

- Used in many different circumstances.
- Often misunderstood as simply meaning involuntary or under strong influence.
- Because coercion is not a benign accusation, the concept is in need of clarification and should be used carefully.

**Notes:**
The concern about coercion, as you know, is raised in many different circumstances, and I think it is often misunderstood as simply referring to settings that undermine voluntariness or involve strong influence.

But, because coercion is not a benign accusation, it is a concept that should be clear and used very carefully.

## Coercion Requires a Threat

- Classic case- “your money or your life”
- Structure- *A* wants *B* to do *X*.  If *B* does not do *X*, *A* will make *B* worse off than *B* was before the interaction.
- 	Wertheimer, *Coercion*. 1987.
*If B refuses, B will be worse off than if A had never approached him.*
- Strictly speaking, B’s decision may be voluntary but is being made while being threatened with harm.

**Notes:**
Though not entirely settled within the philosophical community, coercion is generally taken to be a specific type of circumstance in which there is a presence of a threat.
The classic case of coercion is thus the mugger who approaches you with a gun and demands “your money or your life.”
Alan Wertheimer very helpfully defines the structure of coercion as the following:
Person A wants person B to do some activity X.  If B does not do X, A will make B worse off than B was before the interaction.
So, the defining feature of coercion is that If B refuses to do X, B will be harmed.  He will be made worse off than if he had never run into A in the first place.  Note that this is not the same as saying B is worse off for refusing rather than accepting.  If you offer to pay me $300 to cut your grass, I’m better to accept the $300 than to refuse.  But, if I refuse, I’m not any worse off than if you had never asked me in the first place.  For a situation to be coercive, B must be worse off than if the proposition had never been made at all.
Note also that one may claim that B’s decision in a coercive circumstance is not involuntary.  I might voluntarily give up my wallet rather than get shot.  Regardless of whether you think this is voluntary, the problem is that I am making that decision under an unjustifiable threat of harm.
While coercion may be justified with regard to taxation, for example, it is never justified in research and constitutes a serious accusation.

## Can Payment be Coercive?

- Payment is an offer and not a threat.
- To be coercive, a subject who refuses must be made worse off than if he or she would have been if never asked.
- Payment for research is not coercive.

**Notes:**
The question, then, is whether payment is ever coercive.  I think that payment alone is not coercive, primarily because payment for research is, to my knowledge, always an offer and never a threat.  There may be bizarre circumstances such as a threat to withhold an employee’s regular salary if the employee does not participate in a study, but this is not what we are talking about regarding payment for research.

The key is that, in order to be coercive, a subject who refuses must be made worse off than he or she would have been if never asked.
For this reason, I think we should not speak of payment as raising concerns about coercion.

## Coercion is Rare in Research

- Cases where retribution is conceivable.
- Inmate may receive poor treatment for refusing.
- A physician may threaten to abandon a patient who refuses to participate in a study.
- Perceived coercion is possible.
- Patient participates in a study run by his PCP because the patient fears his care is contingent on participation.
- Recommendation: use “coercion” carefully and not regarding payment.

**Notes:**
I want to go a bit further, however.  Not only do I think that payment is not coercive.  In fact, I think that coercion is rare in clinical research in general.
There are some cases where retribution for refusal is conceivable.  For example, it is possible that an inmate may receive poor treatment for refusing to participate in a study conducted in a jail.  It is also possible that a physician may threaten to abandon a patient with whom there is an existing relationship if that patient refuses to participate in a study.  These situations are certainly coercive.
Similarly, I think that it is crucial to recognize the possibility of perceived coercion even in the absence of a true threat.  For example, a patient may participate in a study run by his PCP because the patient fears his care is contingent upon participation.  Even if this threat is not real, it may seem to be real to the patient.
Regarding the concept of coercion, then, I think we need to be very careful in how we use the term and avoid using it regarding payment.

## Inducement

- Inducements are offers that get people to do things they would not otherwise do.
- Acceptable inducement
- Higher salaries or other perks for jobs.
- Giveaways by stores induce us to shop.
- Inducements in research
- Any activity to encourage participation.
- Pure reimbursement- pay for parking.
- What inducements are acceptable?

**Notes:**
If the concept of coercion is murky, the notion of inducement and undue inducement is even murkier.  
First of all, I think it is important to recognize that all inducements are offers intended to get people to do things they would not otherwise do.  So, the notion that there is such a thing as undue inducement clearly means that some inducements are ok, and others are not.
Examples of acceptable inducements pervade everyday life.  Higher salries or other perks for jobs, and giveaways that stores offer to get us to shop are both entirely acceptable forms of inducement.
In considering inducements in research, I think it is important to recognize that any activity that encourages participation ought to be considered an inducement.  Even such obviously benign things as simply paying for participants’ parking count if they are designed to encourage participation.  The challenge is sorting out which, if any, inducements are undue, or unacceptable

## Undue Inducement

- 	“...monetary inducements may be undue if they alter patients’ decision-making processes such that they do not appropriately consider the risks of participating.”
- 	Halpern, et al., *Arch Intern Med*. 2004

**Notes:**
I want to read a few definitions of what might constitute undue inducement.
Halpern and colleagues offer this definition.
“...monetary inducements may be undue if they alter patients’ decision-making processes such that they do not appropriately consider the risks of participating.”

## Undue Inducement

- 	“An offer one could not refuse is essentially coercive (or "undue"). Undue inducements may be troublesome because: (1) offers that are too attractive may blind prospective subjects to the risks or impair their ability to exercise proper judgment; and (2) they may prompt subjects to lie or conceal information that, if known, would disqualify them from enrolling -- or continuing -- as participants in a research project.”
- 	Office of Human Research Protection. *IRB Guidebook*.

**Notes:**
OHRP, in the IRB Guidebook, gives the following definition of undue inducement.
An offer one could not refuse is essentially coercive (or "undue"). Undue inducements may be troublesome because: (1) offers that are too attractive may blind prospective subjects to the risks or impair their ability to exercise proper judgment; and (2) they may prompt subjects to lie or conceal information that, if known, would disqualify them from enrolling -- or continuing -- as participants in a research project.”
Note that coercion and undue inducement are used interchangeably in this definition, and the defining features of undue inducement have to do with blinding subjects to risk, impairing judgment, and leading to hiding of information.

## Undue Inducement

- 	“Payment in money or in kind to research subjects should not be so large as to persuade them to take undue risks or volunteer against their better judgment.  Payments or rewards that undermine a person’s capacity to exercise free choice invalidate consent.”
- 	CIOMS, 2002, Guideline 7.

**Notes:**
In its guidelines for international research, CIOMS offers the following definition.
Payment in money or in kind to research subjects should not be so large as to persuade them to take undue risks or volunteer against their better judgment.  Payments or rewards that undermine a person’s capacity to exercise free choice invalidate consent.
This definition focuses on concerns about freedom or voluntariness, encouraging risk, and impariment of judgment.

## Undue Inducement

- Individuals induced by large amounts of money are acting involuntarily and may be exposed to significant risk.
- They may be blinded to the risks of participation and thus make uninformed decisions.
- They may lie or conceal information.

**Notes:**
As you can see, these definitions differ in important ways. Taken together, they express three sorts of concerns. 
First, Individuals induced by large amounts of money  act involuntarily and may be exposed to significant risk
Second, they may be blinded to the risks of participation and thus make uninformed decisions.
Third, they may lie or conceal information, exposing themselves to signficant risk or undermining the integrity of the study.

## Undue Inducement

- There is an offered good.
- The good is excessively attractive.
- It leads people to exercise *poor judgment*.
- Participation involves a *risk of serious harm*.
- 	Emanuel, *J Law Med Ethics*. 2004.

**Notes:**
In the paper that I included in your packet, Zeke Emanuel very helpfully considers these different notions of undue inducement in offering a new definition of this poorly understood concept.  His definition is a 4-part definition that I think is a significant improvement on previous attempts.  On this slide is a paraphrased version of Zeke’s definition.
First, there must be an offered good
Second, the good must be excessively attractive
Third, the offer leads people to exercise poor judgment 
Finally, participation must involve a risk of serious harm.

## Undue Inducement

- Payment cannot be undue inducement in an appropriately approved study.
- Enrolling in such a study cannot represent poor judgment.
- IRBs should not approve studies that expose subjects to serious risk of harm.
- 	Emanuel, *J Law Med Ethics*. 2004.

**Notes:**
Zeke concludes that payment cannot be undue inducement in an appropriately approved study for two reasons.
First, enrolling in such a study cannot represent poor judgment.  This is primarily for the reason that IRBs should not approve studies that expose subjects to serious risk of harm.

## Undue Inducement

- Concern seems misdirected if a study involves no risk.
- Concerns about voluntariness are counter-intuitive.
- Concerns about consent argue for improving the consent process.
- 	Emanuel, *J Law Med Ethics*. 2004.

**Notes:**
I agree with Zeke’s view that worries about undue inducement seem largely misdirected in studies involving no risk at all.  It seems awfully odd to me, for example, to worry about a study that pays $500 to ask people about their favorite color.
In addition, I think Zeke rightly argues that concerns about voluntariness are counter-intuitive.  After all, it does seem odd to say that someone who makes a decision in order to gain money is acting involuntarily.
Finally, he points out that if the concern is about the quality of consent, the solution should be to improve the consent process and not change payment.

## Undue Inducement

- Two concerns with this definition
- Reasonability of risks to different people varies.
- Non-risk determinants of poor judgment that involve violations of fundamental values.

**Notes:**
While I agree in all of these ways with Zeke’s analysis, I have two concerns about the definition that he offers, both of which lead me to think that undue inducement remains an important issue when considering paying subjects.

First, the I think the reasonability of risks to different people varies
Second, I am concerned about non-risk determinants of poor judgment that involve violations of fundamental values

## Reasonability of Risk Varies

- Risk tolerance lies on a spectrum from extreme daredevil to extreme caution.
- IRBs simply cannot, and should not, accommodate the whole range of risk tolerance.
- But, as studies get riskier, and as payment goes up, it becomes more likely to induce people to take risks that make them very uncomfortable.

**Notes:**
As Zeke mentions, risk tolerance clearly lies on a spectrum from extreme tolerance to extreme caution.  And, as he points out, IRBs simply cannot, and should not, accommodate the whole range of risk tolerance.  They must evaluate risk on the basis of what reasonable people would take to be reasonable.

My worry, however, is that, within the range of approvability, as studies get riskier and payment increases, it becomes more likely to induce more people to take risks that make them very uncomfortable

## Non-Risk Determinants of Judgment

- Values other than risk may make people significantly averse to particular studies.
*Example: *Some people have value-based objections to getting undressed in front of members of the opposite sex.  A study paying a lot of money but requiring them to disrobe may lead them to act contrary to those values.
- They may not be *wrong* to override these values, but it may be worrisome to institutionalize practices that encourage them to do so.

**Notes:**
I have a similar worry that there are values other than risk that may make people significantly averse to particular studies.

Example: Some people may have stong value-based objections to getting undressed in front of members of the opposite sex.  These values may be religious or cultural, for example.  But, they are stongly held.  A study paying a lot of money and requiring them to disrobe may lead them to override their objection and participate in the study, acting contrary to important values.

I don’t want to say that people are necessarily wrong to override these values, nor would they be doing so involuntarily, but it seems worrisome to me to allow, at an institutional level, practices that encourage people to act contrary to fundamental values.

## Undue Inducement- New Definition

*	**Undue inducements are excessively attractive offers that lead people to do something to which they would normally have real objections based on risk or other fundamental values.*
- Acting contrary to important values better captures the nature of undue inducement concerns.
- In most cases, risk will be the primary objection but is not the only consideration.

**Notes:**
As a result of these considerations, I want to propose a new definition of undue inducement that is very similar but slightly different from the one Zeke put forth.  I think it is a sort of friendly amendment to his definition.  I propose that we define undue indcuements as excessively attractive offers that lead people to do something to which they would normally have real objections based on risk or other fundamental values.

In short, I think that acting contrary to fundamental values better captures the nature of undue inducement concerns.
I agree with Zeke that, in most cases, risk will be the primary objection, but other values may be at stake
As a result, risk of harm is not the only consideration nor is it the only determinant of poor judgment.

## Is Undue Inducement a Concern?

- Rare in protocols approved by diligent IRBs.
- Can neither be completely dismissed nor completely eliminated.
- A reason for caution at the ends of the spectrum of risk or in settings where subjects likely have values in conflict with the research.
- Not just the IRB’s responsibility.

**Notes:**
The question now is whether, on this definition, undue inducement is a concern.
I think it will be rare in protocols approved by diligent IRBs
But, I think concerns about undue inducement can neither be completely dismissed nor completely eliminated
As a result, this concern gives us a reason for caution with payment at the ends of the spectrum of risk or in settings where subjects likely have values that conflict with the research.
But, I think it is important to note that it is likely not  the IRB’s responsibility to accommodate all potential cases of undue inducement.  
I think it is the case that Idiosyncratic values carry some risk of being threatened.
While they must attend to the values held by most reasonable people, IRBs can’t, and shouldn’t have to accommodate all sets of values.

## Exploitation

- Raised as a concern when paying vulnerable populations
*Example*- Paying the homeless
- “An exploitative transaction is one in which A takes unfair advantage of B.”
- Wertheimer, *Exploitation. *1999.

**Notes:**
While I do not have time in this talk to elaborate on concerns of exploitation extensively, I do want to highlight it as an important issue and point out some of the problems that exploitation poses regarding payment.

Exploitation tends to be raised as a concern when paying vulnerable populations.  In fact, many would argue that vulnerability is essential to exploitation.  The populations that are seen as particularly vulnerable to offers of payment tend to be poor individuals such as the homeless, participants in developing countries, and prison inmates.

I don’t pretend that there is a single definition of exploitation, but I think Alan Wertheimer’s definition of exploitative transactions as ones in which A takes unfair advantage of B seems to get at the heart of exploitation concerns.  The question is what advantage is unfair, and what is the remedy?

## Exploitation

- Solution- pay more?
- Hardly satisfies most opponents.
- Significant tension exists between concerns about exploitation and undue inducement.

**Notes:**
In particular, if the argument is that the terms of the bargain between a homeless participant and a wealthy institution are unequal, it seems like the solution may well be to pay the homeless participants more.  However, this hardly satisfies most people levelling charges of exploitation against investigators who pay participants for participation.
Rather, it highlights an important tension between concerns about exploitation and undue inducement that I think is nicely articulated in this section of the IRB Guidebook.

## Exploitation and Undue Inducement

- 	“Paying prisoners the same amount that would be paid to nonprisoners may, however, be seen as unduly influential in a setting where inmates can earn only a small fraction of that amount for any other "work" activity. On the other hand, paying prisoners a fraction of what would be paid to nonprisoners can be seen as exploitative.”
- 	Office of Human Research Protection. *IRB Guidebook*.

**Notes:**
“Paying prisoners the same amount that would be paid to nonprisoners may, however, be seen as unduly influential in a setting where inmates can earn only a small fraction of that amount for any other "work" activity. On the other hand, paying prisoners a fraction of what would be paid to nonprisoners can be seen as exploitative.”

## Exploitation

- Issues of exploitation are complicated and warrant further attention.
- Many potential subjects, for many different reasons, live under background conditions that may be problematic to start with, most of which are not within the investigators’ power to fix.

**Notes:**
In short, concerns about exploitation are very complicated and warrant further attention.  The crux of the problem is that many potential subjects, for many different reasons, live under background conditions that may be problematic to start with, most of which are not within the investigators’ power to fix.

## What do the Data Show?

- Motivations of paid subjects
- Money is important but not the only factor.
- 50-95% of subjects motivated primarily by money.
- 	Bigorra and Banos, 1990; Vrhovac, Francetic, and Rotim, 1990; van Gelderen, et al., 1993; Novak, Seckman, and Stewart,*.* 1977; Martin,  et al., 1968; Hassar and Weintraub, 1976; Aby, Pheley, and Steinberg*,* 1996.
- Very little data on the kinds of tradeoffs subjects will make for money.

**Notes:**
I want to spend just a few minutes before wrapping up going over some of the data that have been published regarding the degree to which some of the ethical concerns that have been mentioned about payment are borne out in practice.
First, there is very little empirical work out there on the important questions regarding payment.  For example, there really aren’t good studies on how much payment even increases recruitment in clinical research.  There has been some work in the survey literature and CROs and pharmaceutical companies have collected some of these data in clinical research, but they are unpublished.
There are quite a few studies, prompted by a concern about why people might enter paid studies, that have assessed paid subjects motivations for participation.  Not surprisingly, these studies generally found payment is an important factor but not the only one.  Depending on which patients were asked, some studies found as low as 50% and others as much as 95% of subjects motivated primarily by money.  The problem is that most of these studies only sought subjects’ primary motivations and none provide much insight into the kinds of tradeoffs subjects are willing to make for money, which is certainly the most important information regarding concerns about undue inducement

## What do the Data Show?

- Payment influences willingness to participate.
- Influence of payment may level off.
- Relative influence of payment seems stable as risk increases.

**Halpern, S. D. et al. *****Arch Intern Med*****. 2004**

**Notes:**
This study, by Halpern and colleagues, published earlier this year, did attempt to measure the influence of different amounts of money on willingness to participate by asking potential participants for hypertension research how likely they were to participate in different studies paying different amounts and involving different risks of adverse effects. 
As you can see from the graph to the right, paying more did increase willingness to participate at every risk level.
However, the influence of money seemed to level off, as the difference in willingess to participate, at every level of risk, was greater between $100 and $1000 than between $1000 and $2000.  Finally, the influence of increasing amounts of payment seemed to be about the same as the risks of side effects went up, so the relative influence of payment seems stable as risk increases.  It’s worth noting, though, that exactly what level of influence increasing amounts of money ought to have at each level is unclear
Though preliminary and not conclusive, these data at least suggest that money may not have a disproportionate influence on willingness to participate at different levels of risk.

## What do the Data Show?

- No empirical support for an impact of payment on subjects’ perceptions of study risks.
- No interaction between amount of money and risk rating.
- 	Bentley and Thacker, *J Med Ethics. *2004.
- Public thinks other people are more likely to be impaired in judgment/understanding as a result of payment than they are themselves.
- 	Casarett, Karlawish, and Asch, *J Gen Intern Med. *2002.

**Notes:**
Again, though the data is limited, I am not aware of any empirical support for the concern that payment undermines the level of understanding that subjects have about studies.
In a study in which pharmacy students were given hypothetical scenarios regarding paid studies, Bentley and Thacker found no interaction between the amount of money offered and subjects’ rating of the risk level of the study, suggesting that payment doesn’t blind subjects to risks.

I think one of the most interesting findings regarding payment and informed consent was reported in a 2002 study in which jurors were asked about the degree to which payment for research participation would affect their ability to understand and make good decisions and the degree to which it would affect others’ ability to understand and make good decisions. Interestingly, though maybe not surprisingly, subjects thought other people were more likely to be impaired by payment in their judgment or understanding than they would be themselves. I wonder if many ethicists worried about payment’s effect on informed consent harbor the same sort of belief.

## Summary

- Coercion requires the presence of a threat of harm if a subject refuses participation.
- Payment cannot constitute a threat.
- Undue inducements are excessively attractive offers that lead people to do something to which they would normally have real objections based on risk or other fundamental values.
- Exploitation involves unfair advantage.

**Notes:**
In summary, I want to review the definitions that I proposed for each of these terms and give some recommendations for how to proceed from here.

First, coercion requires the presence of a threat to make someone worse off. Payment cannot constitute a threat

Undue inducements are excessively attractive offers that lead people to do something to which they would normally have real objections based on risk or other fundamental values.
Undue inducement is rare but is an important concern

Exploitation involves unfair advantage
Exactly what advantages are unfair is difficult to define.  Exploitation concerns exist in tension with undue inducement.  And, investigators are often not in a position to fix the conditions which give rise to concerns about exploitation.

## Recommendations

- More empirical work
- Tradeoffs people will make for money.
- Reasons people don’t participate in research.
- Impact of pay on safety and data integrity.
- Clear policies and practices at the institutional and possibly federal level
- Wage payment model
- Provides consistency.
- Treats research participation as labor.
- Offers protection from undue inducement.

**Notes:**
In concluding, I have 3 types of recommendations.
First, there is a need for more empirical work.  In particular, we need more and better data on
The kinds of tradeoffs people will make for money
The Reasons people don’t participate in research in order to know if fundamental values are at stake
Impact of payment on subject safety and data integrity
Second, there is a need for clear policies and practices at the institutional and possibly federal level.  This will help investigators and IRB members immensely and ensure uniformity in an ethically important area.
Third, in terms of the content of such guidance, Christine Grady and I have argued, in the paper I included in your packet, for the wage payment model, that involves treating research participation as unskilled labor and paying participants wages according to the unskilled labor market.  I think this model is the right one, primarily because it.
Provides consistency
Treats research participation as the kind of work that I think it is.
And, it offers the right level of protection from concerns about undue inducement and exploitation.