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com

Payment for participation in research: a pursuit

for the poor?
M Stones and J McMillan

J Med Ethics 2010 36: 34-36

doi: 10.1136/jme.2009.030965

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Research ethics
1
Hull York Medical School,
University of Hull, Hull, UK;
2
School of Medicine, Flinders
University, Adelaide, Australia
Correspondence to:
Associate Professor J McMillan,
Faculty of Health Sciences,
STURT GENERAL, Flinders
University, GPO Box 2100,
Adelaide, Australia; john.
mcmillan@flinders.edu.au
Received 7 May 2009
Revised 22 July 2009
Accepted 24 July 2009
Downloaded from jme.bmj.com on October 20, 2010 - Published by group.bmj.com
Payment for participation in research: a pursuit for
the poor?
M Stones,1 J McMillan2
ABSTRACT
Poor people predominate as a subgroup of those who
take part in healthy volunteer research. They are
subjected to minimised but unknown risks and unpleasant
burdens so that the safety of new medicines can be
evaluated. This is prima facie unfair especially given that
the poor are often unable to access expensive medicines.
Although participants in this kind of research often do
receive compensation for their time, these payments are
usually capped at a very low level. This paper defends a
version of a reimbursement model for the payment of
research subjects. This model is practical, would benefit
those without an income who take part in research, and
would make it possible for those in regular work to take
part in phase 1 research.
Poor people predominate as a subgroup of those
who take part in healthy volunteer research.1 They
are subjected to minimised but unknown risks and
unpleasant burdens so that the safety of new
medicines can be evaluated. When shown to be
effective new medicines will be used to combat
disease, but access to new medicines is often
limited to those who can afford them. Successful
medicines grow the coffers of private industry and
their shareholders. Although participants in this
kind of research often do receive compensation for
their time these payments are usually capped at a
very low level. Given the profits that drug
companies make and the importance of wealth
for access to many medications, is there a case for
permitting higher levels of payment to those who
take part in this kind of research?
One common objection to allowing significant
payments for research participation is that they
mean that participants are induced into participating
in research. After examining arguments developed by
Wilkinson and Moore,2 3 McNeill4 and Titmuss5 we
will argue that the principal reason to be concerned
about inducement is because it might result in
participants being subjected to unacceptable levels
of risk. However, rather than not allowing payments
to subjects, ethics committees and regulatory agen-
cies are more effective ways to ensure that risk is
minimised and that consent is of the highest quality.
We will argue that payment at levels that might be
considered to be ‘‘inducing’’ can be acceptable and
suggest a suitable model for these payments.
It is important to clarify that the type of research
under discussion here is first-in-man clinical trials
(phase 1, healthy volunteer). There are a number of
reasons for this. Phase 1 trials are often the riskiest
type of trial, largely because much less is known
about the effects of the trial medication. Research
involving patients (phases 2, 3 and 4) raises other
questions about the appropriateness of paying
participants, given that they are likely to be receiving
care at the same time as they are taking part in
research. We are also not considering research that is
negligently dangerous, scientifically invalid or other-
wise obviously non-ethical studies such as those
considered by Beecher.6
INDUCEMENT AND CONSENT
Many ethics committees and professional bodies
warn against payments that might induce research
participants into taking part in research because it
might encourage them to enrol even if it is contrary
to their best interests.
In their 1997 paper Wilkinson and Moore2 argue
that the prima facie case for permitting payment
for research participation is that both parties
benefit from the contract. Researchers offer money
to participants for taking part in their research,
thereby recruiting research participants, whereas
research participants are made better off by the
money. In Wertheimer’s terms,7 8 payment for
research participation appears to be a mutually
advantageous transaction in that both parties are
likely to be made better off. A common objection
to this claim is that undue inducements invalidate
informed consent. Some worry that financially
induced participants will not consider the risks
involved carefully and are likely to agree to do
something that they otherwise would not and
which might be contrary to their interests.9
However, as Wilkinson and Moore2 point out,
people often do things for money that they would
otherwise not do, for example unpleasant work.
Unpleasant work can often be riskier than other
jobs, yet we do not assume that people are
rendered incapable of misjudging whether or not
it is in their interests to accept this level of risk.
Nonetheless, when research participants are
harmed it raises important questions about the level
of risk they agreed to and whether they were
adequately informed. In The TeGenero (TGM1412)
incident some healthy volunteers were seriously
injured during a first-in-man study of a biological
agent.10 Media reports after the event discussed the
levels of payment that these subjects received and
whether they compromised their understanding of
the potential side effects.11 The poor level of under-
standing among research participants is well docu-
mented.12 One important difference between
payment for research participation and being paid
for risky employment is that in the latter case the
employee might have a fairly good understanding of
the risks involved and thereby be able to make a
reasonable judgement about whether or not it is in
their interests. The primary reason why many
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research participants struggle to give adequately informed consent
is because the relevant information is so difficult to understand
and in the case of phase 1 trials, which aim at quantifying risk, the
risks are necessarily unknown.
Steinbrook13 emphasises that, at least in the UK and USA, the
consent process should ensure that participants understand that
there may be certain side effects/injuries and as such are not
entitled to compensation if they should occur. It is their (the
research subject’s) responsibility to make their own healthcare
provision. In the UK that provision would fall to the National
Health Service. No compensation is due although the Association
of the British Pharmaceutical Industry recommend that compen-
sation is provided.13 In France, Germany and Spain clinical trial
insurance is mandatory whatever the cause. In our view it seems
ethically problematical not to provide such protection. Although
participants might know that they are signing away their right to
compensation, this seems unfair if they commonly do not
understand the risks that they are taking.14
While the general difficulties about participant understanding
would appear to raise serious difficulties for a more permissive
approach to payment, we think that there is a solution that is
better than disallowing those who could benefit financially by
taking part in research. In our view, the most morally
significant question to ask of the TeGenero study is not: did
all participants understand the risks of the study? but rather:
did those designing and conducting the trial do all that they
could to manage and minimise any potential risks, as well as
ensuring that the level of risk was not unacceptably high?
INDUCEMENT AND RISK
Paul McNeill4 gives an account of a moral test that many would
find plausible for weighing up whether or not research
participation is acceptable. He describes how he gave his
daughter money while she was travelling in England so as to
persuade her against taking part in a phase 1 trial. Whether or
not we would be happy for one of our loved ones to take part in
research for money seems like a relevant test for whether or not
we should expect other people to do this. McNeill4 says that she
had been unduly influenced to ignore the potential risk of the
study because of the money offered by the trial company. It is
hard not to empathise with this position: who would not be
concerned for the welfare of their child when they were
desperate for money and touring a foreign country.
Nonetheless, it might be that McNeill4 thinks that the risks
inherent in trials are higher than they are.
Wells15 summarises compensation claims made using the
Association of the British Pharmaceutical Industry compensa-
tion scheme. Of the 415 000 participants in studies during the
period 1990–5, only 21 made claims. In half of the cases claims
were for less than £1000. Although it is possible there have been
additional private claims that were not been picked up by the
survey, the numbers are low, which suggests that it is
surprisingly rare for people to be harmed during research. If
research is typically not very risky then why should we be
concerned about people being induced by payments? In the next
section we will consider whether there is something different
about the nature of research participation that might make
payments wrong even when research is not risky.
INDUCEMENT, ALTRUISM AND COMMODIFICATION
It might be that there is something about the nature of research
that is different from work, which makes it unacceptable to be
paid for the former but not for the latter.
Research ethics
We think that there are some parallels between research
participation and blood donation. To that end it is worth briefly
reminding ourselves of the arguments of Titmuss in ‘‘The gift
relationship: from human blood to social policy’’ (1970).5
Titmuss5 makes a number of useful and important points. First,
market-driven systems redistribute blood from the poor to the
rich, this is exploitative and unjust. Payment for research
participation will often produce knowledge that is exploited by
pharmaceutical companies for the benefit of shareholders and
those who can afford the medication, this too appears exploita-
tive. However, there does appear to be an important difference
with research participation: whether or not participants are paid is
not likely to have any bearing on whether or not companies,
shareholders and rich patients benefit. In fact, it appears worse
that participants do not benefit financially when so many others
can because they are only permitted to act on altruistic motives.
Titmuss’s main worry is that a paid market in blood is
imperialistic and will win out over an altruistic system.
Margaret Radin16 has developed this line of thinking and argued
that once commodification has taken place and blood has a
market value it can no longer be seen as a gift but only for its
monetary value. When the blood is no longer seen as a gift, the
motivation to give will be lost.
This appears to be, at least partly, an empirical argument and
evidence is needed really to settle this point. We are sceptical
about whether payment that is inducing but not exhorbitant
would actually have this effect. The amount paid for a pint of
blood is relatively small but enough to encourage the poor to
choose to give. Those who are better off are able to give
independently of the financial incentive as it is relatively
insignificant to them (their motivations lie elsewhere). We are
not convinced that unpaid purely altruistic and paid blood
donation cannot take place in parallel as is the case in the USA.
However, there is something right about Titmuss’s observation
that altruism may not come naturally and is something to be
nurtured by the institutions of society. Nonetheless, we remain
unconvinced that this is a reason against payment.
Many of us have donated blood regularly and are happy to do
this as long as it is convenient to do so. There are minimal risks
associated with giving blood and it takes less than half an hour.
The costs to the donor are low and the benefits to society
(which may include the donor or his family) are high.
Blood donation in terms of burden may be compared with
small-scale research studies in which the demand is not too
great upon time. Many of us will take part in research of this
kind and be permitted to do so during working hours,
particularly those of us who work in health care. However,
this kind of research demands much less time than some phase 1
research, which requires that people altruistically give up 1, 2 or
3 weeks of their lives. It is hard to imagine any employers giving
their workers this amount of time off work or employees giving
up their vacation time to do this. It seems impractical and
unlikely that anyone would do this unless they are paid. One of
us has visited clinical trials units in the UK, and typically
volunteers are not in full-time employment, they tend to be
medical students, back-packers taking a year out or unemployed
people. Because of the importance of these trials there is a
strong argument in favour of payment. To say that payment
cannot be permitted is to say that these trials cannot run, which
is not something that we should accept.
HOW MUCH SHOULD PARTICIPANTS BE PAID?
Rhodes17 and Harris18 both argue that we have a moral duty to
take part in clinical research in return for the benefits we receive
 Downloaded from jme.bmj.com on October 20, 2010 - Published by group.bmj.com
Research ethics
from previous medical advances that we now enjoy (and future
medicines that we will enjoy from current research). Not to
reciprocate by taking part in research (with all the inherent
risks) is free-riding and unfair. Rhodes17 imagines a jury process
in which citizens are periodically called upon to take part in
trials. They would be given the opportunity to decide what kind
of trial they take part in, which would allow them to avoid
research that they strongly disagreed with. This suggestion is an
interesting thought experiment but it is very hard to see how
this could work, particularly in a country such as the UK,
where, post-Creutzfeldt–Jakob disease, people tend to be very
cautious about reassurances from the state. Given that there are
no significant problems with recruitment to phase 1 trials at
present there does not appear to be any need to move to such a
system. If there was a desperate need to recruit research
participants and a pressing need for a particular kind of research,
this kind of measure might be worth considering, but it does not
seem relevant to our present situation. What is good about
Rhode’s proposal is that avoids the present injustice in
recruitment to clinical trials: the burdens of research tend to
be carried by the poor. While her scheme is unlikely to work we
believe that there is another fair way to make it possible for
others in society, especially those in full-time employment, to
take part in research.
There are some good reasons for thinking that it is acceptable
to offer payments to research participants but that there should
be some upper limit on what is an acceptable level of payment.
Following Dickert and Grady19 we think that a reimbursement
model in which participants are paid according to their income
is appropriate. Participants should be allowed to take paid leave
from work in order to volunteer to take part in research. When
the study is carried out by a commercial drug company, the
volunteer’s employer could be reimbursed their salary by the
drug company. This model has some similarities to those of the
volunteer Reservist Armed Forces in the UK. Employers are
encouraged to give volunteers paid time off from work. One
initial problem is that this system might mean that those who
were being given time off work were being paid while the
unemployed were not. Perhaps those who are not in employ-
ment could be paid in line with what those who were given
time off work would get, perhaps the unskilled salary. Ideally,
the appropriate reimbursement would be at a level that the non-
economically disadvantaged would consider fair and would be
prepared to participate in exchange for. This approach also has
the potential to reduce inequity between rich and poor taking
part in research. Some disadvantages of this model are that the
employer is inconvenienced and costs may be increased to the
drug company, presumably costs that could be passed on to the
final purchaser. However, it should be noted that phase 1 trials
are not a particularly costly part of the drug development
process as numbers of participants are small.
The participant pay rates should be pro-rata so that
participants still get paid for their efforts even if they need to
drop out of a study. Completion bonuses should be small so
that the participant is not induced to mask adverse reactions.
It is possible that payment might encourage participants to
mask pre-existing medical conditions in order to gain access to
studies. However, unpaid participants are also unable to declare
a pre-existing condition if it were undiagnosed. This should be
overcome by prestudy screening and access to medical records,
which should also be useful in detecting cases in which people
have not mentioned known conditions.
CONCLUSIONS
Payment to take part in research should be permitted as it
increases the options and freedom of poor people to make money
and increases the number and variety of potential participants
available. It may or may not influence the quality of their
informed consent (autonomy) as may other factors. In our view
this makes it imperative that risks are fully minimised and
accounted for but does not constitute a reason to ban payment.
Paying research participants is not the same as other kinds of
work: it has more in common with paid blood donation. The
risks in phase 1 research are different because they are not
known in advance. However, like work, effort is made to
mitigate and predict risk and to manage harms if they do occur.
The empirical evidence suggests that approved clinical research
is not that risky, although there have been some high-profile
exceptions. When you compare this to very risky jobs such as
deep sea diving or being a member of the armed services,
research is not risky enough to justify banning payment.
A modified version of the reimbursement model was
considered in which the employer rather than the employee
was reimbursed by the study organiser. This compromise allows
for altruistic volunteering in exchange for time off work.
It seems unacceptable that a person in dire circumstances
should accept very high levels of payment from a researcher.
However, the bottom line is: could an unscrupulous researcher
persuade a potential research participant to undertake a
dangerous study in exchange for a large sum of money? The
answer is no, not unless they were prepared to act illegally. The
bona fide ethics committee would not allow a dangerous study
to take place. That said, the ethics committee and regulatory
agencies are only as good as their component parts, and
however good are not infallible.
Competing interests: None.
Provenance and peer review: Not commissioned; externally peer reviewed.
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