The case for reimbursing study participants
for the extra costs they incur from study participation
while avoiding undue influence
The goal of this proposal is to remove financial barriers to
participation in studies,
NOT to influence the decision.
participation of lower-income patients would allow trials to
be conducted more quickly, speeding the development of new
Joseph M. Unger, Hershman, MD, et al
patient's participating in a clinical trial, the extra costs in
terms of both time and money may make it difficult for low and
middle income patients to participate. A recent report from JAMA
shows that lower income patients are not equally represented in
We are proposing that some reimbursement to patients for documented
expenses like travel and time off work may increase participation and help
reduce income related sample bias.
we can get this right without subjecting lower
income persons to undo influence we might: 1) increase participation
in clinical trials; 2) reduce income disparity in study samples
thereby improving generalizability of results. 3) Improve access to
investigational therapies and; 4) improve trial accrual rates.
Clinical trials can require much more of the patient than what is
asked of them when receiving regular care.2
This may include numerous research-related blood tests, extra
monitoring scans, and /or additional biopsies.
The physical, social, and financial burden of cancer itself and the
extra demands of trial participation can be overwhelming - the
latter is especially true for persons who can barely make ends meet.
This is supported by a recent JAMA report on a prospective study on
the barriers to trial participation, which concluded:
* lower-income patients were less likely
to participate in clinical trials. Lower-income
patients are likely more sensitive to marginal financial
expenditures than higher-income patients.
Incentives or reimbursements may be appropriate, though they
should not be coercive to patients.
* One approach to
alleviate the financial risk associated with clinical trial
participation would be to cover the excess costs of
participation, including copayments and coinsurance.
Direct compensation to clinical trial participants has also
* Considerations with respect to time off
from work, child care, and transportation could also improve
access to clinical trials for lower-income patients. Future
research should investigate how to overcome financial
barriers to clinical trial participation.
The identification of patient income level as an independent
predictor of trial participation is important for multiple
If income is associated with health status, then
improving representativeness of lower-income patients in
trials would improve the generalizability of study outcomes.
Also, greater participation of lower-income patients would
allow trials to be conducted more quickly, speeding the
development of new treatments. Crucially, since clinical
trial treatments represent the newest available treatments,
access to this vital resource should be available to
individuals of all income levels."
Source: Patient Income Level and Cancer Clinical Trial Participation: A
Prospective Survey Study 1:
Here we propose that
reimbursement for expenses be provided to study participants.
The goal is to remove financial barriers to
participation in studies without it being an incentive to take part.
propose that the sponsors reimburse for the following expenses
needed to take part in extra research-related tests and
For the cost of preparing the study drug
When the participant's insurance does not pay for this.
(on a per diem basis)
the patient's time off from work if employed
(on a per diem rate, perhaps based on what is due to citizens
who serve on jury duty.
Requiring documentation that the participant has taken
time off work.
the cost of care for the participant's
under-age or elderly dependents*
Requiring documentation that the participant has such
Note: It is standard practice for the sponsor
to pay for research-related tests and procedures, AND for regular tests that are
given more frequently for research purposes. Typically,
these extra tests are done to gain knowledge and not for the direct
benefit of the study participant.
It's time to recognize
the service to society provided by the participants of
clinical research ... not by words, but by our policies and actions.
Current practice is well-intended to avoid coercion and undue
influence, but failing to reimburse the participants for their
expenses could well exclude lower-income persons from taking part in
clinical research, which can be the only prudent choice for an
individual when regular treatments are proven to be ineffective.
This omission also delays progress that is needed to test and find
better treatments for life-threatening diseases, and limits the
generalizability of study findings.*
In Medicaid (low-income) populations access to transportation and
child care are known to be established causes of missed appointments
and, thus, poorer outcomes.4
We canít let the perfect
be the enemy of the improved. That patients may well be priced out
of participation, or must pay extra out of pocket to participate
(for the benefit of us all) is clearly wrong ... and is costing us
all. The devilish details have to be worked out to everyoneís near
satisfaction. Common sense and now evidence from a prospective study
is saying the same thing: there's a pressing need to stop imposing
financial penalties on study participants - for their sake and
What about costs?
That reimbursing patients for their expenses might
increase the expense of doing clinical research ought not be the
issue -- after all every stakeholder in research receives
compensation and what they realize vastly exceeds their expenses or
they would not do it. But the question has been raised so let's
examine it. Per patient cost of running trials is rising and has
been estimated to be about "$40,000 per patient" for late-phase
The most significant factor for the increase cited in the 2011
report was "patient recruitment." For discussion sake, if the
average reimbursement to the patient is about $1,000,that would
increase the cost per patient by 2.5% -- which could be completely
offset by more efficient patient recruitment! (More patients would
be able to participate.)
What about undue influence?
If we get it right (what is reimbursed matches well
with the patients expenses for research-related tests and
procedures), it's a difficult to understand how this amounts to undo
influence. The patient has a life-threatening illness and will also
be guided in many cases by his or her independent treating
physician. Are we to believe that the patient would choose a study
over regular care simply because she will get reimbursed (and
modestly) for the expenses she would not otherwise have?
What about the administrative burden?
The policies and procedures can be standardized in order to minimize
the administrative burden to the centers and to facilitate IRB
approvals. Standard forms, instructions, and per diem reimbursements can be used for
meals, travel, lodging, and time.
What is the impact of current
Mike's story (below)
suggests that failing to reimburse the participant for his or her
expenses (substantial in his case) might reduce participation rates
overall - across other income groups.
comment or ask a question
JAMA Oncology, 2015:
Patient Income Level and Cancer Clinical Trial Participation: A
Prospective Survey Study
The ASCO Post, April 2015 by By Lee M. Krug, MD
On trial participation: ďDoctor, is this all worth it?Ē The tests,
procedures, can be burdensome
the following scenario:
Hello, Ms. Smith. Thanks for coming in today. As we
discussed at our last visit, the computed tomography
(CT) scan showed that the chemotherapy has stopped
working, and we need to come up with a plan for your
next course of therapy. There are other chemotherapy
options, or we could consider a clinical trial with
a new drug.
Smith: I canít say Iím too enthusiastic about
getting more chemotherapy. Tell me more about the
We have seen excellent results with this drug in
other cancers, and we think it has a good chance of
working in your cancer also. You are in good shape,
so I think you would make an excellent candidate for
Smith: That sounds encouraging. Can I start that
No. First you need to have some testing done to make
sure you are eligible to participate. You will need
to come back later this week to get some blood work
and three electrocardiograms (ECGs).
Smith: Can I get the blood work done today while
I am here?
No. It needs to be collected in the morning after
Smith: Ugh, okay. Itís just that I live an hour
away. Can I start after that?
Well, you also need a biopsy of the tumor in your
Smith: Donít we already know this is cancer?
Yes, but this biopsy is being done for research
Smith: When will I get the results of this
You wonít. The samples are sent to the
pharmaceutical company for analysis.
2011 report -- probably higher still:
Per-Patient Clinical Trial Costs Rise 70% in Three Years
"But the largest increases in
per-patient costs came in Phase IIIa and Phase IIIb, which saw an
average 88 percent and 86 percent rise, respectively. The study
found that both Phase IIIa and Phase IIIb per-patient costs now top
$40,000 compared to approximately $25,000 three years ago. Phase IV
(post-marketing studies) costs also rose, but at a more modest 31
percent, on average.
"The most significant factor for increased clinical trial costs
is patient recruitment," said Adam Bianchi, chief operating
officer of Cutting Edge Information. "This comes as no surprise
because clinical development teams have struggled to enroll
sufficient volunteers to fill trials for several years now. But
other factors, such as site recruitment challenges and vendor
management, also play a big part in the rising costs we now see."
Health Disparities Based on Socioeconomic Inequities:
Implications for Urban Health Care: Academic Medicine
As a trial participant , I note that although some of the extra
costs associated with the trial were borne by the trial (primarily
the cost of the study drugs and associated health care costs), most
My maintenance treatment extended several years longer than that
usually scheduled, and as a result, I paid several thousand dollars
out of pocket to pay for the added treatment. I'm hopeful that this
will be a beneficial result of the trial, but it would be incorrect
to say that this hasn't placed a financial burden on our family.
Fortunately, the company has instituted a co-pay card which helped
cover the cost of extended treatment, but did not cover all the
I personally would not ask for total reimbursement of costs in my
financial position (wage earner with decent, but by no means
extravagant health insurance), but I could see where those that have
a need for extra transportation over longer distances, etc. could
find a barrier to trial participation when these expenses are not
Typical language in a consent form on the costs of taking part
in a clinical trials
What are the costs of taking part in this study?
Both XYZ and ABC will be supplied at no charge while you take
part in this study. It is possible that XYZ and ABC may not
continue to be supplied while you are on the study. Although not
likely, if this occurs, your study doctor will talk to you about
You will not be charged for any costs related to the blood
samples that are collected for research purposes. These samples
are not used for testing that affects your care.
You and/or your health plan/insurance company will be billed
for all standard costs of treating your cancer, including
the cost of tests, procedures, or medicines to manage any side
effects. Before you decide to be in the study, you should check
with your health plan or insurance company to find out exactly
what they will pay for.
You will not be paid for taking part in this study.
[In this example there is no offer to reimburse for travel
or taking time off work in order to have
study-related tests or procedures.]