Appendix 9b - Grady payment

Science and society

Payment of clinical research subjects
Christine Grady
Department of Clinical Bioethics, Clinical Center, NIH, Bethesda, Maryland, USA.

Offering payment to clinical research subjects, in an effort to enhance recruitment by providing an
incentive to take part or enabling subjects to participate without financial sacrifice, is a common
yet uneven and contentious practice in the US. Concern exists regarding the potential for payment
to unduly influence participation and thus obscure risks, impair judgment, or encourage misrepresentation. Heightening these concerns is the participation not only of adults but also of children in
pediatric research trials. Thorough assessment of risks, careful eligibility screening, and attention to
a participant’s freedom to refuse all serve to reduce the possibility of compensation adversely affecting the individual and/or the study. Institutional review boards currently evaluate payment proposals with minimal
guidance from federal regulations. Here, reasons for providing payment, payment models, ethical concerns, and
areas for further research are examined.
The payment of human subjects for their participation in scientific
research in the US is a common and longstanding practice that has
been documented for well over 100 years. As far back as the 1820s,
William Beaumont, whom many consider to be the father of gastric physiology, gave patient Alexis St. Martin — a French Canadian
voyageur suffering from an incompletely healed gunshot wound to
the stomach — food, lodging, clothing, and $150 for the opportunity to study his stomach contents for 1 year (1). In 1900, renowned
American military surgeon Walter Reed paid study participants
$100 in US gold to allow themselves to be bitten by infected mosquitoes in the famous yellow fever experiments and an additional $100
if they consequently contracted the viral disease (1). According to
Susan E. Lederer, author of Subjected to science: human experimentation
in America before the Second World War (1), in the US, “paying human
subjects for their participation in research . . . became routine in the
1920s and 1930s.” Other nonmonetary forms of compensation were
also common, such as meals, transportation, and burial costs. From
the early 1950s, when the world’s largest clinical research complex,
the NIH Clinical Center, opened, documents show that “normal”
healthy volunteers were regularly paid for their participation in biomedical research or money was given to the church or group that
organized and recruited these volunteers (2).
Today, newspaper advertisements describing studies that offer
“free treatment” for depression or asthma, for example, often state
“financial compensation provided.” Websites list possible research
trials for prospective subjects to review and commonly mention
that compensation is provided, often naming a specific dollar
amount (3). Although it is unclear exactly how common this practice is, data suggest that a sizable subset of research studies at most
organizations or institutions that conduct clinical research pay
subjects for participation (4). In addition, studies that offer payment to subjects cover a wide spectrum of types of research, from
short-term physiological studies offering no benefit to subjects to
longer, phase 3 clinical trials that may offer the prospect of direct
therapeutic benefit to subjects (5). Interestingly, there appears to be
some variation according to disease or medical subspecialty in the
frequency with which payment is offered to research subjects. For
Nonstandard abbreviations used: IRB, institutional review board.
Conflict of interest: The author has declared that no conflict of interest exists.
Citation for this article: J. Clin. Invest. 115:1681–1687 (2005).
doi:10.1172/JCI25694.

example, it is more common in the US to offer payment in asthma,
HIV, diabetes, or dermatological research trials than in oncology or
cardiovascular trials (6). There are currently no data to explain why
this variation exists. Although decisions about offering payment
could be influenced by disease severity, sociodemographic characteristics, or the availability of treatment alternatives, some of the
variation probably reflects the culture of the subspecialty.
Although the practice of paying subjects for research participation
in the US is widespread, it remains a contentious issue (Figure 1).
Some commentators believe that the act of paying research subjects is wrong (7), maybe even coercive, while others find it an
acceptable and perhaps necessary part of recruitment for clinical
investigation (8, 9); others see payment of at least healthy subjects as fair and appropriate (10, 11). In addition, only minimal
guidance exists to help investigators determine whether or how
much to pay participants in a particular study. The section of the
US Code of Federal Regulations governing clinical research does
not specifically address the issue of payment of research subjects
(12). Institutional review boards (IRBs) — committees designated
to review, approve the initiation of, and conduct periodic review
of research involving human subjects — are responsible for ensuring that the amount and schedule of proposed payment is ethically acceptable; however, these bodies also operate with minimal
and general guidance (4, 12, 13). Consequently, payment practices vary widely in the US (5).
Reasons for offering payment to research subjects and common
ethical concerns about offering payment are discussed herein.
Models of payment, payment of healthy subjects versus patientsubjects, payment in pediatric research, and practical issues related
to the payment of research subjects are also examined.
Payment of research subjects: why or why not?
Biomedical and behavioral research necessary to improve human
health and medical care depends on the participation of human
subjects. The usual justification offered for paying research subjects is that payment facilitates the timely recruitment of an adequate number and type of subject (9). Payment may be important
to research to the extent that it encourages participation. Several
studies have shown that response to written surveys is influenced
by payment (14–19), as is willingness to participate in hypothetical
studies (20, 21), but less is known about the real effect of payment
on recruitment in clinical research.

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Figure 1
Offering money to clinical research subjects for their participation is a
fairly common practice in the US. Yet there is little consensus about
why, when, or how much to pay these individuals. Getty Images.

There are several ways in which payment might enhance recruitment. First, the offer of money as reimbursement for time or
expenses incurred could help to make research participation a revenue-neutral activity for participants. In this regard, money may
enable individuals to take part who otherwise could not afford
to participate or who are not willing to make a financial sacrifice
in order to do so. Alternatively, payment could help recruit individuals who believe they should be fairly compensated for their
time and effort. Money can also serve as a recruitment incentive,
especially if the amount offered is high enough to attract subjects
to research and overcome inertia, lack of interest, as well as financial and other barriers (see Why pay clinical research subjects?). Some
say that financial incentives are also necessary to overcome barriers unique to certain subgroups in the population, such as lack

of awareness or distrust. Consequently, money may not only be
important to general recruitment but also helpful in achieving the
goals of racial, ethnic, gender, and social diversity of subjects participating in biomedical research (22, 23).
However, empirical evidence demonstrating that payment is
necessary and/or effective for the recruitment of clinical research
subjects is limited. People appear to be attracted to research and
motivated to participate for a variety of reasons. Healthy volunteers, who are frequently paid and unlikely to benefit medically
from research participation, are often attracted to research and
motivated to participate by money. Yet they appear to have a
variety of other motives besides those of a financial nature for
participation in research, including curiosity, altruism, sensation
seeking, and desire for attention provided by physicians (24–26).
Patient-subjects — those who suffer the disease or condition
under study in a particular research protocol — are often motivated to participate by the hope of personal therapeutic benefit.
When patient-subjects enroll in clinical studies and they understand the likelihood of direct medical benefit to be remote or
nonexistent, their motivations are likely to be similar to those of
healthy volunteers. Although patient-subjects are often offered
payment for their participation in clinical studies, little research
has been done to evaluate the extent to which money influences
recruitment or their willingness to participate (21). Given the
diverse motivations of subjects in clinical research and a lack of
relevant data, it is difficult to know how much paying subjects
helps to accomplish recruitment goals.
Similarly, there are few data to support the idea that paying
subjects ensures diversity. In fact, other, less fungible factors,
for example, lack of child care for women and long-standing

Why pay clinical research subjects?
Reasons to pay research subjects

Related comments and questions

Incentive necessary to recruit adequate
Limited data exist to document the extent to which money works as a
  numbers of research subjects   recruitment incentive for clinical research or to show the value of
  money for recruitment compared with other powerful incentives,
  such as treatment or access to care
Incentive necessary to overcome opportunity costs,
Limited data to support the claim that money increases diversity;
  inertia, and distrust and recruit hard-to-reach   Money may not overcome all barriers and in fact could
  subjects, especially underrepresented groups   contribute to, rather than diminish, suspicion or lack of trust
Reimbursement for expenses (and possibly
Not all research participants are reimbursed;
  lost wages) to reduce the barrier of   Payment to individuals would vary based on
  financial sacrifice for participants   their expenses and the value of their time
Fair compensation or remuneration for the time
Data suggest that time may not be the main criterion for
  and inconvenience of research participation   determining amounts of payment to subjects;
  Inconvenience is hard to quantify

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Ethical concerns about the payment of research participants
Payment may be perceived as:

Related comments and questions

Coercion
Coercion involves a threat of harm. Thus, an offer of money in return
  for research participation is not coercion.
Undue inducement
Undue inducement is not well defined
  May compromise informed consent by:   Limited data suggest that payment does not affect understanding or
  (a) reducing interest in understanding   perception of risk. The adequacy of understanding as part of informed
  risks related to research; (b) reducing the   consent can be assessed.
  voluntary nature of the decision to participate   Voluntary decisions can be made when inducements are offered, even in
  Money may unduly influence individuals   the setting of limited or poor financial options
  to misrepresent themselves   There are limited data on the influence of money on informed consent
  Other incentives may be as powerful as money
  Careful eligibility screening can minimize risk of misrepresentation
Disproportionate research burden on the poor
Sociodemographics of research participants are not well known
  Inadequate financial reimbursement might
  disproportionately exclude the poor
  Paid participation may be an opportunity, not a burden
Commodification
Services offered as part of research participation are not the same as
  “selling” body parts or sex and may be of little risk to the health and
  well-being of the participant

distrust of the research establishment by certain ethnic groups
(27–30), may be obstacles to participation that money cannot
overcome. Distrust, in fact, could plausibly be exacerbated by
an offer of money.
Ethical concerns about offering
payment to research subjects
Several ethical concerns have been raised regarding the payment
of research participants (see Ethical concerns about the payment of
research participants). The most commonly expressed concern is
that payment could be coercive or serve as undue inducement
to research participants. By definition, coercion is understood
to involve a threat of physical, psychological, or social harm in
order to compel an individual to do something, such as participate in research (31). However, money for research participation
is an offer or an opportunity and not a threat and therefore cannot be perceived as coercion. But can money be considered an
undue inducement? Existing guidelines warn against undue
inducement and its potential to compromise informed consent,
although there is disagreement about what exactly constitutes
undue inducement and consequently disagreement about the
extent to which it is a valid problem in research (32). The US
Code of Federal Regulations requires that informed consent be
obtained “under circumstances . . . that minimize the possibility
of coercion or undue influence” (12, 13). An inducement in clinical research, as defined in The official IRB guidebook (33), is deemed
undue and therefore troublesome if it is so “. . . attractive that [it
can] blind prospective subjects to potential risks or impair their
ability to exercise proper judgment . . .”
Do financial incentives blind potential research participants to the
risks of research when making decisions regarding participation?

Motivated by cash payments or an attractive financial package,
an individual could have less interest in evaluating or understanding study details, reading the consent form, or attempting
to understand the goals, purposes, and risks associated with a
study. This may be of little concern, however, if a clinical research
protocol has almost no risks or has been approved by an IRB that
has judged the level of risk to be acceptable (32). If, in addition,
there are other mechanisms in place during the informed consent
process to assure that participants adequately understand relevant risks (34), then this seems like a misplaced worry and may
even represent “unwarranted paternalism” (35). Further, limited
evidence suggests that the offer of payment does not obscure the
risk perception of potential research participants (20, 21), and
there are no data to suggest that it does.
Others worry that money can impair judgment or compromise
voluntary decision making. But voluntary decisions are motivated
by various factors, sometimes including money, and are not necessarily motivated by altruism alone. When people are choosing a
job, making purchases, or making other voluntary decisions, they
often consider the monetary aspects of their choice in the form of
salary, benefits, or sales price. Decisions are generally complex and
multifaceted, however, and are rarely based solely on monetary
considerations. Similarly, people participate in clinical research
for multiple reasons, and money may be one among those reasons
or even the main reason. Limited data suggest that the offer of
money is one factor in the decision making of some, but not all,
potential participants (21, 24, 36–40).
Even if money is one reason or the main reason to participate in
research, does the offer of money impair judgment? In one study,
most respondents (75%) thought an offer of $500 for research
participation could impair the judgment of others, but many

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Table 1
Models of payment for the participation of research subjects
Model

Payment serves as

Amount determined by

Potential advantages

Market
Incentive
Supply and demand;
(a) More rapid recruitment.

market rates
(b) Completion bonuses

encourage subject retention

and high completion rate.

(c) Possibility of profit

for participants.

(d) Little or no financial

sacrifice by subject.

Wage-
Compensation
payment

Standardized “wage” for
time and effort, suggested to be
commensurate with wages for
unskilled, but essential jobs;
additional payment for extra
burdens such as endurance of
uncomfortable procedures

(a) Recognizes contributions
of participants.
(b) Uniform payment
across studies.
(c) Equal pay for equal work.
(d) Less risk of
undue inducement.

Potential disadvantages
(a) Undue inducement possibly resulting in:
incomplete assessment of risks and
benefits by subject; subject concealing
information to ensure enrollment/retention.
(b) Competition between studies;
better-funded studies more likely to
meet recruitment goals.
(c) Different levels of payment at different
locations for multicenter trials.
(a) May have little impact on recruitment.
(b) Might undercompensate some
subjects in relation to regular wage
and preferentially attract others.

Reimbursement Reimbursement Expenses incurred (transport,
(a) Makes research
(a) May have little impact on recruitment.

meals, lodging); with or without
participation revenue neutral.
(b) Uneven reimbursement from

reimbursement for lost wages (b) Little risk of undue inducement.
subject to subject.

(c) Little or no financial
(c) Reimbursement costs for high-salaried

sacrifice for subject if
subjects may result in the targeting of

lost wages are reimbursed.
low-income populations.

(d) Financial sacrifice for subject if

lost wages are not reimbursed.
Appreciation
Reward
Token of appreciation given

at the conclusion of study

(a) Expresses gratitude
for contribution made.
(b) Not market dependent.
(c) Avoids undue inducement.

(a) Likely to have no impact
on recruitment.
(b) No basis for consistency.

Table modified from The New England Journal of Medicine (46).

fewer (20%) thought it would impair their own judgment (41).
Presumably, fewer people would think smaller amounts, say $25
or even $100, would impair judgment, yet most clinical research
studies offer considerably less than $500 for participation (6).
Some worry that individuals with limited opportunities for earning money may be most susceptible to impaired judgment when
faced with an offer of money (23). But, as Wilkinson and Moore
argue, even people with few options may still have the ability to
make decisions for themselves and thus be capable of autonomous consent (42). In fact, denying the possibility of payment
to autonomous research subjects with limited opportunities for
earning money further restricts their options rather than protecting them from a situation in which their judgment might be
impaired, especially if they would still be invited to participate
in research that did not offer compensation. Careful attention,
during the process of obtaining informed consent, to subjects’
understanding and expectations of clinical research and their
sense of freedom to choose to participate or not may be more
appropriate, albeit imperfect, than limiting the opportunity to
receive payment for participation.
On the other hand, if offering a large amount of money could
cause some people to agree to participate in research for which
they would otherwise have a profound reluctance, the offer demonstrates disrespect for their deep reservations or preferences.
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Limiting the amount of money offered for research participation might minimize the chances that it will unduly influence
participants in this way (43, 44). In my view, offering modest
amounts of money is unlikely to obscure risks or impair the
judgment of most individuals. However, investigators and IRBs
should review the offer of money and other inducements outlined in clinical research proposals, especially for research on the
margin of reasonable risk or with groups of people that are more
likely to be attracted by an offer of money. Additional empirical research would increase our understanding of the extent to
which money influences decisions about research participation
in relation to other factors; and to what extent, if at all, people
actually do agree to participate in research that compromises
their deeply held values or interests.
Concern has also been expressed about the potential for money
to unduly influence “. . . subjects to lie or conceal information
that if known would disqualify them from enrolling or continuing as participants in a research project” (43). Misrepresentation
of previous or current medical problems could jeopardize both
the safety of the subject and the quality or interpretability of the
data. For example, an individual interested in a well-paying MRI
study could jeopardize his safety by concealing the history of a
shrapnel injury that otherwise would exclude him. A participant
in a phase 1 drug study could fabricate side effects in order to stop

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study participation early without loss of payment, consequently
jeopardizing the quality of the science. One study showed a willingness of subjects to conceal information from investigators in
lower-risk studies, but this willingness was not associated with
payment (20). It is unknown how often such misrepresentation
occurs in clinical research and also unclear whether money is
uniquely capable of inducing this kind of deception. Perhaps we
should worry more about the possibility of desperate patients
engaging in deception if they perceive the therapeutic intervention
or agent under study to be their best or only remaining therapeutic option. Careful attention to eligibility criteria in the screening
history, physical examination, and laboratory tests can minimize,
although not eliminate, the possibility of misrepresentation in
order to enroll in research trials. In addition, mechanisms such as
prorating payments over time might help minimize the possibility of misrepresentation during a study.
Additional concerns about the ethics of offering payment to
research subjects have received less attention. Some worry that
payment might be more attractive to individuals with low socioeconomic status, and thus the payment of subjects could result
in a disproportionate research burden on this population. In
addition to worries about distributive justice, a skewed subject
pool could confound the generalizability of data. Unfortunately,
research subject sociodemographic information is not well documented; when documentation is available, it has been shown that
subjects in at least some studies tend to be primarily insured and
not economically disadvantaged (45). Interestingly, offering no
money or such a small amount of money that participation in
research is inaccessible to those who are economically disadvantaged also has the potential to skew the subject pool and contravene principles of distributive justice, especially for research
perceived as beneficial to participants.
Models of payment made to research subjects
Assuming that paying research subjects is ethically acceptable,
there still remain questions regarding how to pay subjects. Several possible models of payment capture the various ways that
payment could be conceptualized and the amount of payment
determined: a market model, a wage-payment model, a reimbursement model, and an appreciation model (46) (Table 1). In
a market model, payment is designed to be a straightforward
incentive. The amount of payment is determined by the market;
that is, the value necessary to recruit the number and type of
subjects needed in a given time frame. Consequently, studies
that need to recruit individuals with rare conditions or characteristics may offer more money, while studies for which there
are many willing participants may offer no money. According to
the market concept, the amount of money could be increased to
overcome aversion to risk or inconvenience. Completion bonuses and escalating incentives would be commonly employed as
incentives for subjects to meet data points or complete a study.
In contrast, in a wage-payment model, subjects are offered
payment as compensation for the time and contribution they
make to the research. Money offered to subjects is calculated by
a standardized hourly “wage” offered to compensate for their
hours of participation, with reasonable additions made for
added inconvenience. In a reimbursement model, payment is
offered to research participants to reimburse them for actual
expenses, such as travel, meals, and parking. One version of a
reimbursement model would also offer reimbursement for lost

wages. If the latter were adopted, subjects in the same study
might be reimbursed at radically different rates, depending on
their occupation and normal salary. An appreciation model
conceives of money as a reward or token of appreciation for a
subject’s contribution to research. Appreciation can be shown
by awarding a wide range of amounts of money as well as nonmonetary gifts. Unlike the other 3 models, appreciation payments may have little impact on study recruitment, as appreciation is often reserved until the study ends. Elsewhere, my
colleagues and I have argued that conceptualizing payment as
compensation in the form of a wage payment is the most ethically appropriate model because it recognizes the contribution
subjects make to research and is relatively standardized across
studies. While still possibly able to facilitate recruitment, wagelike payments are unlikely to unduly influence individuals to
enroll in research to which they object (46). Finally, offering
fair compensation for research participation also demonstrates
that society values clinical research and is grateful for subjects’
contribution to the common good.
Payment of healthy subjects versus patient-subjects
Commentators sometimes assume or assert that it is legitimate
to pay healthy subjects but not patient-subjects for their participation in research (10). Healthy subjects are often motivated
by money to participate in research, receive little or no benefit
from participation, and may appropriately be considered independent contractors in research (40). Paying money to healthy
volunteers is widely accepted, although concerns about undue
inducement and distributive justice may still pertain. In contrast, although patient-subjects are often paid to participate in
research (5), commentators worry about paying patient-subjects
because of their “vulnerability” (10). Certainly illness can make
people vulnerable in multiple ways. Presumably, patient-subjects are considered more vulnerable in research studies than
healthy subjects because of the nature of the relationship with
their physician and because of possible confusion about the
difference between participation in clinical research and the
receipt of clinical care — the so-called therapeutic misconception (47). Although this is an empirical question, it is at least
plausible that offering payment to patient-subjects in research
could help them distinguish participation in a research study
from the receipt of clinical care and thus actually decrease their
vulnerability. Offering money in return for participation might
also enable a patient to say no to the physician instead of feeling
obligated to do what the physician suggests.
Payment may not be necessary for recruiting patient-subjects
into research, especially if they are motivated by an opportunity for therapeutic benefit. However, if the goal of payment is
to reduce the financial sacrifice that research subjects have to
make, to compensate people for their time, or to show appreciation for their contribution, patient-subjects are equally deserving and should be paid comparably to healthy subjects. When
patient-subjects participate in research that offers them desirable
therapeutic benefits, money may seem irrelevant and unnecessary,
even though not morally objectionable. However, when patientsubjects and healthy subjects are both asked to undergo certain
identical study procedures for research purposes, in the interest
of fairness, the 2 sets of individuals should be compensated similarly, as both are contributing to the development of generalizable
knowledge to benefit others.

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Payment of children in research
Offering payment in pediatric research involves special challenges not found in research with consenting adults. First, research
with children is vital and promoted by both the FDA (48) and the
NIH (49). However, children do not provide their own consent to
research but are enrolled by their parents or legal guardians, generally in accord with the child’s best interests. Payment to parents for
their child’s research participation could potentially sway parental decisions in favor of participation since there is no personal
risk to themselves. To avoid making children commodities, some
argue that parents should not receive money as incentive for their
child’s research participation (50, 51). However, making it possible
for a child to participate in research can be inconvenient and costly
for parents, and the amount of risk children can be exposed to in
research is strictly limited by federal regulations (52). Consequently, some find carefully calculated payment to compensate parents
for time and inconvenience acceptable and unlikely to contribute
to significant distortions in parental judgment (53), while others
believe that compensation to parents should be limited to reimbursement for expenses (51). The American Academy of Pediatrics
recommends the giving of gifts instead of money to children in a
post-trial appreciation model (54), although many institutions do
not appear to follow these recommendations (55). Giving money
or non-cash gifts to children directly instead of to their parents is
also difficult because children appreciate money and gifts differently depending on their age. Further empirical and conceptual
research is needed to resolve when and how payment should be
offered in pediatric research.
Practical suggestions
When deciding whether to offer payment to research participants
in a study, investigators should take into account the nature of the
study, the nature of participant contributions and vulnerabilities,
institutional or organizational guidelines, and local societal and cultural norms. In the research proposal submitted to their IRB, investigators should describe the rationale for payment, how the dollar
amount was calculated, and how and when payment will be made.
Payment information should also be included in consent forms.
Although payment may be a factor in a subject’s decision
regarding research participation, IRBs do not consider payment
a benefit to offset research risks when deciding whether or not
to approve a study. IRBs evaluate whether the risks in a research
study are justified by potential benefits; otherwise unacceptable
risks cannot be made acceptable by offering money to subjects.
Therefore, discussion of payment should only arise after the riskbenefit ratio of a study is found ethically acceptable. IRBs should
review the justification for and the amount and schedule of payment and decide whether these variables are appropriate given the
particular study and the population to be recruited. In making
this determination, an IRB should consider study risks, potential
vulnerabilities of the targeted subject population, eligibility criteria and screening plans, proposed methods for assessing subjects’
knowledge of risks and ability to make voluntary autonomous
decisions, and local norms. An IRB should also review the presentation of information about payment in consent documents as
well as related advertisements and information sheets.
Plans for how and when money will be disbursed are also
important. Prorating payment for studies involving multiple
visits minimizes the possibility of inappropriately influencing
someone to remain in a study just to receive a lump sum pay1686

ment at the end. Payment according to actual time and procedures completed is consistent with offering money as compensation for a subject’s time and inconvenience. On the other hand,
in longitudinal or long-term studies, where certain data points
are critical to the study, it may be appropriate to use escalating
incentives or completion bonuses, as long as they are not offered
to compensate for increasing risk. These strategies should be
approved by the relevant IRB.
Empirical studies and unanswered questions
Although there is a growing volume of empirical research addressing issues related to the ethics of paying research subjects, many
more questions need attention. As mentioned above, evaluating
whether or under what research circumstances money might
impair a subject’s judgment would be important, as well as the
extent to which payment leads people to participate against deep
objections. Payment to clinical research populations who are particularly vulnerable to exploitation, such as children, substance
users, or those unable to consent for themselves, warrants further
attention. Sociodemographic data on research subjects in both
paid and unpaid studies would be useful. More specific guidance,
including benchmarks, would greatly assist investigators and
IRBs in making decisions about payment for participation. Additional understanding of variation in local or regional norms and
participants’ values as they relate to money, as well as how to consider the economic conditions in communities in which research
will be conducted in formulating an approach to payment, would
be useful, especially for multicenter and multinational studies.
Additionally, more attention to the influence of nonmonetary
incentives and compensation is warranted, although many of the
concerns are similar.
Concluding remarks
Payment to research subjects for their participation is a pervasive
yet uneven practice in the US. Although there is nothing inherently unethical about paying clinical research subjects, knowing more
about its effect on recruitment and its use in different research circumstances is critical. Investigators might offer money to research
subjects as an incentive to participate, as fair compensation for
their contribution, and/or as a way to reduce any related financial sacrifice. Worries about undue inducement can be reduced by
careful assessment of risks as well as attention to eligibility criteria
and to the informed and voluntary consent of research subjects.
Further dialogue, conceptual analysis, and empirical work about
payment made to clinical research subjects may serve to reduce
the divide between those who object to such payment and those
who promote payment as a sign of respect for the contributions of
research subjects and a way to facilitate valuable research.
Acknowledgments
I would like to thank Neal Dickert for important insights, for many
fruitful discussions and collaborations on this topic, and for his critical review of this manuscript. The views expressed here are those of
the author and do not necessarily reflect the views or policies of the
NIH or the US Department of Health and Human Services.
Address correspondence to: Christine Grady, Department of Clinical Bioethics, Clinical Center, NIH, Building 10/Room 1C118,
Bethesda, Maryland 20892, USA. Phone: (301) 435-8710; Fax:
(301) 496-0760; E-mail: cgrady@nih.gov.

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1. Lederer, S. 1995. Subjected to science: human experimentation in America before the Second World War. The
Johns Hopkins University Press. Baltimore, Maryland, USA. 192 pp.
2. NIH. 1959. Healthy volunteers help scientists conquer
disease. U.S. Department of Health, Education and
Welfare, Public Health Service, NIH. Bethesda,
Maryland, USA. 15 pp.
3. Center Watch Clinical Trials Listing Service. http://
www.centerwatch.com.
4. Dickert, N., Emanuel, E., and Grady, C. 2002. Paying research subjects: an analysis of current policies. Ann. Intern. Med. 136:368–373.
5. Grady, C., Dickert, N., Jawetz, T., Gensler, G., and
Emanuel, E. 2005. An analysis of U.S. practices of
paying research participants. Contemp. Clin. Trials.
26:365–375.
6. Center Watch Clinical Trials Listing Service. Clinical trial listings by medical areas. http://www.centerwatch.com/patient/trials.html.
7. McNeill, P. 1997. Paying people to participate in
research: why not? Bioethics. 11:390–396.
8. US FDA. 1998. Guidance for institutional review
boards and clinical investigators: payment to
research subjects. http://www.fda.gov/oc/ohrt/
irbs/default.htm.
9. Dunn, L., and Gordon, N. 2005. Improving
informed consent and enhancing recruitment for
research by understanding economic behavior.
J. Am. Med. Assoc. 293:609–612.
10. Lemmens, T., and Elliott, C. 2001. Justice for the
professional guinea pig. Am. J. Bioeth. 1:51–53.
11. Wilkinson, M., and Moore, A. 1999. Inducements
Revisited. Bioethics. 13:114–130.
12. US Department of Health and Human Services and
NIH Office for Protection from Research Risks. 2001.
Protection of human subjects. US Code of Federal
Regulations, title 45, part 46. http://www.hhs.gov/
ohrp/humansubjects/guidance/45cfr46.htm.
13. US FDA. 2004. Protection of human subjects.
US Code of Federal Regulations, title 21, part
50. http://www.accessdata.fda.gov/scripts/cdrh/
cfdocs/cfcfr/CFRSearch.cfm?CFRPart=50.
14. Asch, D., Christakis, N., and Ubel, P. 1998. Conducting physician mail surveys on a limited budget: a randomized trial comparing $2 bill versus $5
bill incentives. Med. Care. 36:95–99.
15. Church, A. 1993. Estimating the effect of incentives on mail survey response rates: a meta-analysis.
Public Opin. Q. 5:62–79.
16. Doody, M., et al. 2003. Randomized trial of financial incentives and delivery methods for improving
response to a mailed questionnaire. Am. J. Epidemiol.
157:643–651.
17. Halpern, S., Ubel, P., Berlin, J., and Asch, D. 2002.
Randomized trial of $5 versus $10 monetary incentives, envelope size, and candy to increase physician
response rates to mailed questionnaires. Med. Care.
40:834–839.
18. VanGeest, J., Wynia, M., Cummins, D., and Wilson,
B. 2001. Effects of different monetary incentives on
the return rate of a national mail survey of physicians. Med. Care. 39:197–201.

19. Warriner, K., Goyder, J., Gjertsen, H., Hohner, P.,
and McSpurren, K. 1996. Charities, no; lotteries,
no; cash, yes: main effects and interactions in a
Canadian incentives experiment. Public Opin. Q.
60:542–562.
20. Bentley, J., and Thacker, P. 2004. The influence of
risk and monetary payment on the research participation decision making process. J. Med. Ethics.
30:293–298.
21. Halpern, S., Karlawish, J., Casarett, D., Berlin,
J., and Asch, D. 2004. Empirical assessment of
whether moderate payments are undue or unjust
inducements for participation in clinical trials.
Arch. Intern. Med. 164:801–803.
22. Russell, M., Moralejo, D., and Burgess, E. 2000.
Paying research subjects: participants’ perspectives.
J. Med. Ethics. 26:126–130.
23. Grant, R., and Sugarman, J. 2004. Ethics in human
subjects research: do incentives matter? J. Med. Philos.
29:717–738.
24. Bigorra, J., and Banos, J. 1990. Weight of financial
reward in the decision by medical students and
experienced healthy volunteers to participate in
clinical trials. Eur. J. Clin. Pharmacol. 38:443–446.
25. Farre, M., Lamas, X., and Cami, J. 1995. Sensation
seeking among healthy volunteers participating in phase I clinical trials. Br. J. Clin. Pharmacol.
39:405–409.
26. Cunny, K., and Miller, H. 1994. Participation in
clinical drug studies: motivations and barriers.
Clin. Ther. 16:273–282.
27. Corbie-Smith, G., Thomas, S.B., and St. George, D.
2002. Distrust, race, and research. Arch. Intern. Med.
162:2458–2463.
28. Corbie-Smith, G., et al. 2003. Influence of race,
clinical, and other socio-demographic features on
trial participation. J. Clin. Epidemiol. 56:304–309.
29. Harris, Y., et al. 1996. Why African Americans may
not be participating in clinical trials. J. Natl. Med.
Assoc. 88:630–634.
30. Shavers, V.L., Lynch, C.F., and Burmeister, L.F.
2000. Knowledge of the Tuskegee study and its
impact on the willingness to participate in medical
research studies. J. Natl. Med. Assoc. 92:563–572.
31. Faden, R., and Beauchamp, T. 1986. History and
theory of informed consent. Oxford University Press.
New York, New York, USA. 392 pp.
32. Emanuel, E.J. 2004. Ending concerns about undue
inducement. J.Law Med. Ethics. 32:100–105.
33. Office for Protection from Research Risks. 1993.
IRB guidebook. Washington, DC, USA. http://
www.hhs.gov/ohrp/irb/irb_guidebook.htm.
34. Grady, C. 2001. Money for research participation:
does it jeopardize informed consent? Am. J. Bioeth.
1:40–44.
35. Newton, L. 1982. Inducement, due and otherwise
IRB. 4:4–6.
36. Aby, J., Pheley, A., and Steinberg, P. 1996. Motivations for participation in clinical trials of drugs for
the treatment of asthma, seasonal allergic rhinitis,
and perennial nonallergic rhinitis. Ann. Allergy
Asthma Immunol. 76:348–354.
37. Hassar, M., et al. 1977. Free-living volunteer’s moti-

vations and attitudes toward pharmacological
studies in man. Clin. Pharmacol. Ther. 21:515–519.
38. Korn, J., and Hogan, K. 1992. Effect of incentives
and aversiveness of treatment on willingness to
participate in research. Teach. Psychol. 19:21–24.
39. van Gelderen, C., Savelkoul, T., van Dokkum, W.,
and Meulenbelt, J. 1993. Motives and perceptions
of healthy volunteers who participate in experiments. Eur. J. Clin. Pharmacol. 45:15–21.
40. Tishler, C., and Bartholomae, S. 2002. The recruitment of normal healthy volunteers: a review of the
literature on the use of financial incentives. J. Clin.
Pharmacol. 42:363–373.
41. Casarett, D., Karlawish, J., and Asch, D. 2002. Paying hypertension research subjects. J. Gen. Intern.
Med. 17:650–652.
42. Wilkinson, M., and Moore, A. 1997. Inducement in
research. Bioethics. 11:373–389.
43. Macklin, R. 1981. On paying money to research subjects: ‘due’ and ‘undue’ inducements. IRB. 3:1–6.
44. Ackerman, T. 1989. An ethical framework for the
practice of paying research subjects. IRB. 11:1–4.
45. Pace, C., Miller, F., and Danis, M. 2003. Enrolling
the uninsured in clinical trials: an ethical perspective. Crit. Care Med. 31:S121–S125.
46. Dickert, N., and Grady, C. 1999. What’s the price
of a research subject? Approaches to payment for
research participation. N. Engl. J. Med. 341:198–203.
47. Appelbaum, P., et al. 1987. False hopes and best
data: consent to research and the therapeutic misconception. Hastings Cent. Rep. 17:20–24.
48. US FDA. 2003. The Pediatric Research Equity Act of
2003. http://www.fda.gov/opacom/laws/prea.html.
49. NIH. 1998. NIH policy and guidelines on the inclusion of children as participants in research involving human subjects. NIH Guide Grants Contracts.
http://grants.nih.gov/grants/guide/notice-files/
not98-024.html.
50. Medicines and healthcare products regulatory
agency. 2001. Clinical trials directive (2001/20/EC).
Official Journal of the European Communities. 147:41.
51. Institute of Medicine. 2004. Payments related
to children’s participation in clinical research.
Chapter 6. Ethical conduct of clinical research involving children. M. Field and R. Berman, editors. The
National Academies Press. Washington, DC,
USA. 211–228.
52. US Department of Health and Human Services
and NIH. 2001. Additional DHHS protections for
children involved as subjects in research. US Code
of Federal Regulations, title 45, part 46, subpart
D. http://www.hhs.gov/ohrp/humansubjects/
guidance/45cfr46.htm#subpartd.
53. Wendler, D., Rackoff, J., Emanuel, E., and Grady, C.
2002. The ethics of paying for children’s participation in research. J. Pediatr. 141:166–171.
54. American Academy of Pediatrics, Committee on
Drugs. 1995. Guidelines for the ethical conduct of
studies to evaluate drugs in pediatric populations.
Pediatrics. 95:286–294.
55. Weise, K.L., et al. 2002. National practices regarding payment to research subjects for participating
in pediatric research. Pediatrics. 110:577–582.

The Journal of Clinical Investigation    http://www.jci.org    Volume 115    Number 7    July 2005

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