AbstractAlthough information about risks, benefits, alternatives and costs is offered to human research participants in informed consentdocuments, information about how much the tested medical intervention is expected to cost future patients is not routinely madeavailable to research participants. Two arguments are offered in support of including this information. First, justice demands thatparticipants are given this information so that they do not inadvertently sign up for studies to test interventions that in the futurewill be out of their financial reach, or the reach of their family or community. Second, the cost of an intervention is rightly partof the risk/benefit profile of any medical intervention, and as such should be included so that research participants can make ajudgment comparing the tested intervention against the current standard of care, if one is available. Several objections to this newpractice are raised. Sharing the future costs of the treatment under investigation may be prohibitive to study sponsors who don'tyet have that information; it may be unhelpful to participants who won't know what to make of the information; finally, theinformation may not be relevant to current participants. Replies are offered to each objection. It is concluded that researchparticipants should be given information about the future costs of the medical interventions they are testing so that they mightbe fully informed about the risks and benefits of the medical intervention under study.
significant bearing on whether participants would actually
Prior to medical treatment patients are provided
volunteer for clinical research studies. Here I propose an
information about the risks, benefits, alternatives, and costs
additional piece of information that should be integrated
of the treatment. The patient's voluntary agreement to the
into future informed consent documents: Informed consent
treatment on the basis of an understanding of this
documents for clinical research studies should disclose
information is what is meant by informed consent.
how much the new intervention is expected to cost future
When research subjects, often referred to as
research participants, give informed consent to participate
In the course of my career I've served on three
in a clinical trial, they are offered the same type of
IRBs, I've chaired two, and currently chair one and sit on
information. In terms of risks, informed consent
another. And yet I have no recollection of ever seeing an
documents may include lengthy discussions of the possible
informed consent document that let prospective
risks, the likelihood of those risks, and what to do to avoid
participants know the sponsor's estimate of the future cost
certain risks. In terms of benefits, Institutional Review
Boards (IRBs) are very careful to make sure that thebenefits of a study are not over-sold, so that participants
don't fall into a therapeutic misconception. Participants are
Having this information would be important for
told about the alternatives: If a potential participant does
two reasons. First, participants should know if they are
not wish to enroll, what other courses are available to him
helping to gain approval for a medical intervention that
or her? If the participant wishes to cease participation at
would be financially out of reach for them as patients.
any time, what is the orderly means of withdrawing from
Many bioethicists believe that it is morally wrong and
the study? When it comes to costs, participants are told
exploitive to have a cohort of research subjects test a drug
who is paying for the study (the "study sponsor"), whether
or device that is beyond that cohort's ability to obtain in the
their time or efforts will be reimbursed, and whether
future. This perceived injustice was the basis for many
compensation is available for injuries incurred during the
people's criticisms of the short-course AZT trial for
vertical HIV prevention (Glantz, et al, 1998). This study
For a long time now I've believed that detailing
protocol recruited participants from Africa and Thailand.
only the above information about costs does not
The protocol was successful in demonstrating that a
sufficiently inform research participants. People are
shorter course of AZT was superior to a placebo. The
enrolling in clinical research studies, testing a new drug or
short course study did not randomize subjects against the
device, without a crucial piece of information about costs.
longer course, which had been demonstrated to work in the
Furthermore, that missing piece of information may have
076 trial. However, the rates of vertical HIV transmission
in the short course were found to be comparable to the
Participants should be told up front how much
more expensive long course of AZT in preventing
sponsors expect to charge for the new drug, in comparison
mother-to-child transmission of HIV [1]. Many took issue
with Tamiflu, as part of the overall cost/benefit profile of
with the short course trial because even though it
the drug. After all, the costs of the drug are part of the
costs and benefits that will be taken into account by future
patients and practitioners. This information would also be
helpful to IRBs: Sponsors who are undertaking a
non-inferiority trial of new, wildly expensive drug X, in
comparison with relatively cheap standard of care drug Y,
should be asked a lot of hard questions by IRBs. Using the
above example, the risks of using human research subjects
to study a new drug which is expected to cost $2,000 a
though it was tested in developing countries. There is an
dose, to determine that the drug is no better than an
injustice in allowing one group of people to bear the risks
existing treatment that costs less than $500 a dose, do not
of the study, while another group benefits from the
appear to outweigh the benefits at all. Even if the trial
demonstrates that the two drugs are of equal value
Some may argue that the research subjects in the
medically, the fact that one costs between four and nine
short course trial were not exploited, and there was no
times as much as the other significantly alters the
injustice, as long as participants were given the
cost/benefit analysis. Subjects will have been asked to test
information needed to make an informed decision. If they
a drug that no one is going use, without any benefit, the
were given information about the risks, benefits, and costs,
IRB should judge that risks of the trial are too high to
and yet they still chose to participate, that was not
exploitation. However, one of the essential pieces ofinformation they should have been given was that while
they were testing the drug, the drug would be financially
One objection to this proposal is that sponsors
unavailable to their family and friends if ultimately
may claim that they don't have the information about how
approved. Participants in all clinical trials should be given
much the drug while it is still under study, and they cannot
information about how much a study drug is expected to
be expected to give participants information they do not
cost, so that they are not in the position of the African and
have. I find this objection disingenuous [3]. First, many of
Thai participants discussed above, experiencing the risks
the drugs tested in clinical trials have already been
of the research without their cohorts being able to gain
approved for one condition, and now are being tested for
from the expensive treatments if they are ultimately
other conditions. As such, the sponsors have a very good
idea how much the drugs would cost in the future, basedon current costs.
The Argument From Disclosure of Risks and Benefits
Sponsors may reply that there are too many
Second, the costs of a new drug or device are
unknowns to extrapolate future costs from current costs. If
rightly part of the overall cost/benefit profile of that
a drug is shown to work well for other conditions, the price
intervention. If a sponsor knows that a new drug will cost
may rise as demand exceeds supply, or the price may fall,
four times as much as a competitor, but the medical
as production of that drug increases and production costs
benefits of the new drug are only marginally better than the
are proportionally lowered. Even the best predictions can
competitor, it isn't clear that the new drug is that much
become obsolete as new information emerges. However,
better. Fleck (2006) and Brock (2006) make this point in
there is already a system that is designed to handle just
articles discussing the costs of the anti-cancer drug
such moving targets: IRBs are routinely given information
Avastin, but similar points can be made when dealing with
about changes in risk profiles, and adverse events, while
medical conditions that are typically not as serious as
clinical trials are underway, as new information emerges.
cancer. Imagine a new drug under development that
If new medical information changes the risk/benefit profile
promises to cut in half the days that people with the flu
of a drug, then participants are given this information, as
experience symptoms. The drug is being developed as a
part of an ongoing process of informed consent. So, if new
competitor for Tamiflu, and is being tested to determine if
developments alter the predicted cost of a drug,
the medical risks and benefits of the new drug are
participants can still be given that information.
comparable to Tamiflu. However, the new drug is expected
Second, even for those interventions that are
to cost $2,000 a dose, which is far more than Tamiflu,
being newly introduced, sponsors have already run
which can cost between $222 and $445 without insurance
analyses as to how much the intervention would cost to
develop, to produce, to store, to ship, etc. It is hard to
believe that the sponsors haven't already done this
participants, thus, this information should be included.
calculation, numerous times, in an attempt to determine
Second, the costs of the new treatment under study are part
what is best for their bottom line. To plea utter ignorance
of the overall risk/benefit profile of the new treatment.
about the future costs of therapies currently under study is
Participants should only enroll in clinical studies for which
there is a positive overall risk/benefit ratio, but the benefits
A second objection is that this information may
of the study may accrue only to future patients, and not the
not be helpful. Perhaps participants won't initially know
participant him or herself. And yet, knowing that those
what to do with these cost figures, and will be misled into
benefits may exist is part of being informed. By the same
falsely thinking a more expensive treatment is always
token, knowing the risks of a new therapy, including its
better (Angell, 2004, pp. 95-97). While this may happen,
costs to future patients, is part of the overall risk/benefit
it isn't a reason to leave the information out. Participants
ratio. Knowing the cost of a new therapy to future patients
probably don't know what to do initially with the
is as essential to being informed as knowing that some
information about numerous medical risks of experimental
drugs. That doesn't mean that the information should be
In keeping with the relevancy objection, some
left out. Rather, having that information is part of an
sponsors may be concerned that if participants knew how
informed decision whether to enroll in a trial.
much the experimental drugs might cost in the future that
Participants should have the opportunity to
the participants might demand their share of the profits,
discuss with their healthcare provider, and the members of
and as such, my recommendation would do more harm
the research team, any information in an informed consent
than good. In other words, if participants were reminded
document about medical risks and costs. If participants
that this was a profit-making enterprise they would
don't have their questions answered, they haven't truly
demand their share of profits, so perhaps it is best not to
offered informed consent to research participation.
remind them. Whether or not participants are fairly
Similarly, information should be included about the future
compensated for their efforts is a hotly-debated question
financial costs of the treatments under study. Participants
(Abadie, 2010). Perhaps they are justly compensated, in
should have the opportunity to ask questions about these
which case telling participants of the costs to future
facts and figures. Those discussions can help show that a
patients should make no difference. Perhaps they are not
more expensive intervention isn't always the best, just as
justly compensated, in which case raising the issue may
they can help explain other complex aspects of research
correct a current injustice. Finally, it is perhaps the case
participation, such as randomization or the weighing of
that there is a disconnect between appearance and reality:
maybe participants think they are being exploited, when
A similar objection is that information about
they really aren't, or maybe they don't think that they are
future costs is not relevant to the participant, unlike
being exploited, but they really are. Again, this is why it is
information about current risks and costs. The side-effects
essential for informed consent to include all of the
of treatment are those the participant himself may have to
information, as well as the opportunity for participants to
bear, and reimbursement for cost (or lack thereof) directly
ask questions, so that they can make a decision for
impacts the financial situation of the participant. But
themselves whether to participate in what may appear to be
telling the participant about the future cost of the
intervention, if the intervention is approved, is telling theparticipant about costs to future patients, not to the
participant himself or herself. Why would this be relevant
As it stands, there appear to be two good
arguments in favor of including future costs of new
There are two responses to this objection. First,
medical interventions in informed consent documents, and
researchers and IRBs may have no idea what is relevant to
the objections to this new practice are unsound. If today's
the participant, but it isn't their job to leave things out of a
research participants volunteer to test medical
consent form on the assumption that the participant won't
interventions that someone else will pay for in the future,
find it relevant. If there is any uncertainty, we should err
they should be told how much those interventions are
on the side of informed consent, and include the
information. Researchers and IRBs should not have the lastword as to what is and is not relevant to research
Notes1.See http://www.ed. umich.edu/pediatrics/ebm/cats/zdv.htm for a summary of the comparison between long course and short course results. My thanksto Franklin G. Miller for his helpful clarification of this example.
2. According to Massachusetts General: http://www2.massgeneral.org/pharmacy/Newsletters/1999/November%201999/How%20much%20is%20a%20day%20worth%20Relenza%20and%20Tamiflu.htm; accessed 12-29-2010. 3. Marcia Angell and Jerry Avorn are two sources who agree with my skeptical stance towards the study sponsors.
ReferencesAbadie, R. (2010). The Professional Guinea Pig: Big Pharma and the Risky World of Human Subjects. Durham: DukeUniversity Press. Angell, M. (2004). The Truth About the Drug Companies. NY: Random House. Avorn, J. (2004). Powerful Medicines: The Benefits, Risks, and Costs of Prescription Drugs. NY: Knopf. Brock, D. W. (2006). How much is more life worth? Hasting Center Report, 36, 3, 17-19. Fleck, L. M. (2006). The costs of caring: Who pays? Who profits? Who panders? Hasting Center Report, 36, 3, 13-17. Glantz, L. H. et al (1998). Research in developing countries: Taking benefit seriously. The Hastings Center Report, 28,6, 38-42.
abzuwarten, bevor sie mit der Einnahme vonweiteren empfängnisverhütenden Maßnah-Eine Filmtablette enthält 0,03 mg Ethinyl-estradiol und 2 mg Chlormadinonacetat. Nach der üblichen Einnahmepause oder derletzten wirkstofffreien Tablette aus der Pa-präparat zur hormonalen Kontrazeption soll-trazeptive Wirkung des Produkts beeinträch-Die vollständige Auflistung der sonstigente unmitt
R E S E A R C H A N D D E V E LO P M E NT Where Is the New Science most new science in developed rather thandeveloping economies for reasons that may not in Corporate R&D? always characterize the U.S. situation. Jerry Thursby and Marie Thursby* The idea that the United States domi- or currently planned R&D facility both views of corporate R&D. For example,outside and inside
in the short course were found to be comparable to the
Participants should be told up front how much
more expensive long course of AZT in preventing
sponsors expect to charge for the new drug, in comparison
mother-to-child transmission of HIV [1]. Many took issue
with Tamiflu, as part of the overall cost/benefit profile of
with the short course trial because even though it
the drug. After all, the costs of the drug are part of the
costs and benefits that will be taken into account by future
patients and practitioners. This information would also be
helpful to IRBs: Sponsors who are undertaking a
non-inferiority trial of new, wildly expensive drug X, in
comparison with relatively cheap standard of care drug Y,
should be asked a lot of hard questions by IRBs. Using the
above example, the risks of using human research subjects
to study a new drug which is expected to cost $2,000 a
though it was tested in developing countries. There is an
dose, to determine that the drug is no better than an
injustice in allowing one group of people to bear the risks
existing treatment that costs less than $500 a dose, do not
of the study, while another group benefits from the
appear to outweigh the benefits at all. Even if the trial
demonstrates that the two drugs are of equal value
Some may argue that the research subjects in the
medically, the fact that one costs between four and nine
short course trial were not exploited, and there was no
times as much as the other significantly alters the
injustice, as long as participants were given the
cost/benefit analysis. Subjects will have been asked to test
information needed to make an informed decision. If they
a drug that no one is going use, without any benefit, the
were given information about the risks, benefits, and costs,
IRB should judge that risks of the trial are too high to
and yet they still chose to participate, that was not
exploitation. However, one of the essential pieces ofinformation they should have been given was that while
they were testing the drug, the drug would be financially
One objection to this proposal is that sponsors
unavailable to their family and friends if ultimately
may claim that they don't have the information about how
approved. Participants in all clinical trials should be given
much the drug while it is still under study, and they cannot
information about how much a study drug is expected to
be expected to give participants information they do not
cost, so that they are not in the position of the African and
have. I find this objection disingenuous [3]. First, many of
Thai participants discussed above, experiencing the risks
the drugs tested in clinical trials have already been
of the research without their cohorts being able to gain
approved for one condition, and now are being tested for
from the expensive treatments if they are ultimately
other conditions. As such, the sponsors have a very good
idea how much the drugs would cost in the future, basedon current costs.
The Argument From Disclosure of Risks and Benefits
Sponsors may reply that there are too many
Second, the costs of a new drug or device are
unknowns to extrapolate future costs from current costs. If
rightly part of the overall cost/benefit profile of that
a drug is shown to work well for other conditions, the price
intervention. If a sponsor knows that a new drug will cost
may rise as demand exceeds supply, or the price may fall,
four times as much as a competitor, but the medical
as production of that drug increases and production costs
benefits of the new drug are only marginally better than the
are proportionally lowered. Even the best predictions can
competitor, it isn't clear that the new drug is that much
become obsolete as new information emerges. However,
better. Fleck (2006) and Brock (2006) make this point in
there is already a system that is designed to handle just
articles discussing the costs of the anti-cancer drug
such moving targets: IRBs are routinely given information
Avastin, but similar points can be made when dealing with
about changes in risk profiles, and adverse events, while
medical conditions that are typically not as serious as
clinical trials are underway, as new information emerges.