ETHICAL CONSIDERATIONS FOR

NURSES IN CLINICAL TRIALS

Kathleen Oberle and Marion Allen
Key words: beneficience/non-maleficence; clinical trials; ethical issues; moral obligation;
therapeutic obligation
Ethical issues arise for nurses involved in all phases of clinical trials regardless of whether
they are caregivers, research nurses, trial co-ordinators or principal investigators. Potential
problem areas centre on nurses moral obligation related to methodological issues as
well as the notions of beneficence/non-maleficence and autonomy. These ethical concerns
can be highly upsetting to nurses if they are not addressed, so it is imperative that they are
discussed fully prior to the initiation of a trial. Failure to resolve these issues can place both
the conduct and the results of research in jeopardy.

Introduction
There has been a recent upswing in interest in the ethics of research. Much has been
written about the topic, most of it focusing on the protection of vulnerable participants
from harm. Little attention has been paid to the ethical considerations for nurses
involved in long-term placebo-controlled clinical trials. By far the most frequent
clinical studies are drug trials, with a physician as the principal investigator and a
nurse employed as a research nurse or project co-ordinator. However, not all clinical
trials are medical and many clinical studies have nurses as principal investigators.
Ethical issues can arise for nurses in their capacity as research nurse, trial co-ordinator
or principal investigator. The purpose of this article is to raise some ideas and generate
thought so that nurse researchers and their research staff are prepared for issues that
could arise. It will also serve to help nurses who are working as research nurses or
project co-ordinators to be alert to the ethical problems they may experience during the
conduct of a clinical trial.
Many of the issues we discuss arose in the context of our recently completed clinical
trial of the efficacy of elk velvet antler (a product that has been in use in traditional
Chinese medicine for over 2000 years) in rheumatoid arthritis.1 From our perspective
there are two major areas to contemplate. The first is around nurses moral obligations
related to methodological issues and the second is centred on the notions of
beneficence/non-maleficence and autonomy. We will discuss each in turn, although
Address for correspondence: Kathleen Oberle, Faculty of Nursing, University of Calgary, 2500
University Drive NW, Calgary, Alberta, Canada T2N 1N4. Tel: /1 403 220 6268; Fax: /1 403 284
4803; E-mail: oberle@ucalgary.ca

Nursing Ethics 2006 13 (2) # 2006 Edward Arnold (Publishers) Ltd

10.1191/0969733006ne836oa

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we understand that our categorization is artificial as there is considerable overlap

between problem types.

Moral obligation and methodological issues

To consider the ethical issues related to clinical trials methodology, one must first have
a clear understanding of the structure of controlled trials. Generally, they are set up to
test a hypothesis related to a new or revised drug or intervention. Patients are
randomly assigned to either an experimental or a control (placebo) group or arm. The
experimental group receives the new drug or intervention, while the control group
receives the placebo, and both the researcher and research participant are blinded to
the group in which the participant is placed (the classic double-blind study). In that
way, it is assumed that researcher bias will be minimized and the results will remain
uncontaminated by prior beliefs about the effectiveness of the drug. Alternatively,
when there is a known effective treatment for the clinical problem, the comparison
may be between the new intervention and standard care. In all instances, participants
are seen regularly, generally much more often than for routine or standard care, and
are carefully monitored. Most of the ongoing contact is with the so-called research
nurse, who recruits participants, collects data and maintains all records. The same
design is also used for treatments such as nursing interventions, for example, the
effectiveness of therapeutic touch versus ordinary touch in relieving pain or speeding
wound healing. In this instance, the placebo would be a kind of sham therapeutic
touch but it would not be possible to blind the individual doing the touch, so the study
would be single-blind. Typically, drug trials are double blind and of longer duration
than nursing trials, sometimes lasting for two or three years.
Tensions can arise for nurses in several aspects of clinical trials, depending on their
role. They may experience conflict between their obligations to the study and their
obligations to patients.2 For example, an interesting methodological and ethical issue
in this type of research design is the concept of the nurse as a therapeutic tool. As
mentioned above, most clinical trials employ a research nurse as data collector and
project manager. The research protocol is carefully outlined and it is assumed that the
nurse will follow it to the letter. Outcome measures are most often a combination of
biological tests such as blood analysis, physical tests such as functional abilities related
to the treatment, and psychological and quality of life indicators. It is assumed that
well-tested instruments will reduce investigator bias and be sensitive to changes,
and that the placebo will control for the well-known Hawthorne effect (ie changes
that arise simply as a result of believing one is being treated). With these controls in
place, it is understood that observed differences between groups can be related
confidently to the intervention. However, it is interesting to note that the potentially
therapeutic value of a nurses presence, and the moral obligation of nurses to provide
support to individuals with health care needs, are seldom taken into account in
protocol design. This could become a problem in that simple nursing actions
performed by the nurse researcher or research nurse could enhance the placebo effect
and thereby attenuate the therapeutic differences. An example may be a situation in
which the experimental treatment is effective. In this situation, it is quite possible that
patients in the control (placebo) group may express more concerns about their health
or experience more symptoms, which could lead them to seek more support from the

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nurse in the form of symptom management, advice, or merely a listening ear. In

considering whether to provide this support in response to a perceived professional
obligation, the nurse should be aware that the interventions could act as therapy, thus
increasing the sense of wellness of those receiving the placebo and decreasing
differences between experimental and control groups. Nurses are taught to offer a
therapeutic presence and create a healing environment in interactions with patients3
and merely being in relationship with patients could cause improvement in their
symptoms. With this in mind, the nurse might question whether it would contravene
the protocol to offer support to the patient, but at the same time the nurse could ask
whether failing to act on his or her best knowledge of what might be helpful to the
patient would constitute abdication of a professional obligation. The nurse might well
feel conflicted, being obligated on the one hand to follow the therapeutic protocol and
on the other to intervene in a meaningful way. These issues should be recognized and
discussed prior to the studys inception, as decisions need to be made in advance
about how they should be handled.
A second methodological issue can arise for nurses as data collectors when they
observe that significant physiological, psychological or social elements of participants
experience with the study intervention are not being captured. This can happen, for
example, when participants describe to the nurse certain responses that they perceive
to be directly linked to the intervention, but are neither measured by the study tools
nor categorized as adverse events. If the participant is concerned and wants these
experiences recorded and considered, the nurse has some decisions to make: should he
or she record the observations and bring them to the attention of the principal
investigator? What if that has no effect, that is, if the principal investigator does not
attend to the concerns? For example, the observed effects could be important enough
to warrant changing the instruments and/or the consent form. The nurse has an
advocacy role in patient care and is morally obligated to ensure that patient concerns
are heard. This could present the nurse with a difficult dilemma. If he or she is
persistent and insists that the issues be addressed, it could damage relationships with
the study team, which ultimately could affect smooth conduct of the study. On the
other hand, if the nurse allowed himself or herself to be silenced, thus also silencing
and potentially causing harm to the patient, the nurse could experience considerable
moral distress. Clearly, if the issues are related to patient safety, the nurse would have a
moral obligation to report to the research ethics board if no action were taken. This is
another example of a concern that could be anticipated by the principal investigator
and mechanisms put in place at the inception of the study to ensure that such
problems are dealt with effectively.

Issues of beneficence/non-maleficence and autonomy

A second set of issues revolves around the risk/benefit ratio of involvement in a study.
Here again, the nurse may well experience tensions between obligations to the study
(and presumably, the greater good) and obligations to the individual patient. One
concern is related to the concept of clinical equipoise. This is the notion that, in
conducting a clinical trial, the researcher must be genuinely uncertain about whether
or not the new treatment is superior to the old. In other words, the researcher must not
have evidence that the new treatment is superior, for in the presence of such evidence

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it would be unethical not to offer it to all patients.4 At the beginning of a trial, nurses
can assume equipoise because the new intervention is not yet tested, and there is
consequently no evidence about its efficacy. However, as the trial proceeds, it is
possible that the nurse may begin to observe differences between patients, and could
make assumptions about which patients are in the experimental and which are in the
control arms of the study. The nurse may feel that the study is denying some patients a
superior treatment. Even more problematic is the nurses belief, based on clinical
observations, that one of the study treatments is causing harm to the patient. The nurse
will feel morally conflicted if he or she is required to give both treatments. There could
be a perceived obligation to the advancement of science, and a parallel obligation to do
good (beneficence) and do no harm (non-maleficence).5 The nurse could be placed in a
morally difficult position when having to make a decision about whether to act on
perceptions of patients best interests or to follow the study protocol. However, in a
blinded study, it is impossible to know which patient is in which group, and the
nurses assumptions could be incorrect. The nurse may actually be observing chance
differences, not systematic between-group differences. It is important that the nurse
should understand this fundamental feature of a clinical trial; there may be large
differences between individuals, but when all the results are averaged, there may not
be differences between groups. In other words, there could be large individual
variations in both groups. However, it is possible that one treatment is indeed superior
to the other. It is unethical to continue a trial if it means one group is denied a
substantially more effective treatment or is being harmed.
When faced with perceived study effects of benefit or harm, the nurse could select
from a number of potential actions. He or she could simply ignore any perceived
differences in the realization that they might well be occurring by chance. Alternatively, the nurse could act to sidestep or even subvert the research by refusing to follow
the experimental protocol, or by encouraging patients to withdraw from the study.
However, neither of these options seems acceptable. Nurses have an obligation to
report their observations when they feel strongly that one treatment is superior to the
other or is causing harm to patients. Again, the nurse has an advocacy role in bringing
a perceived pattern to the attention of the principal investigator. If the principal
investigator chooses not to attend to these concerns, the nurse will have to consider
other actions. It may be reasonable to expect the nurse to contact the institutions
research ethics committee, particularly if the issue is one of perceived harm. Although
this could well make working relationships with the principal investigator less
comfortable, the nurse must always remember that the first obligation is to the patient.
This example points to the necessity of excellent communication between principal
investigators, study co-ordinators, research nurses and clinical staff. All must understand the research process, and must be prepared to raise difficult issues in the face of
perceived benefits or harms resulting from the research. It is also important to realize
that most clinical trials have stopping rules included in the protocol. Usually there is
provision for interim analysis, and if a difference of a certain magnitude is observed
between groups, the study is stopped. However, not all studies have such rules in
place. A nurse researcher (principal investigator) would be well advised to take into
account the potential need for stop rules before the study commences and include
details for interim analysis in proposals submitted for ethics review. This will eliminate
the need to return to the ethics committee to request a change in protocol. Finally, it is
essential that all nurses involved in the study as data collectors and caregivers have an

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excellent understanding of the possibility of wide individual variations within both

groups. They need to realize that it is only through systematic observation of large
groups of patients that true between-group differences can be identified.
Perceptions of between-group differences may also become a problem in recruiting
patients into a study. Again the issue is one of balancing scientific rigour with
understandings of beneficence/non-maleficence. The nurse who is doing the recruiting may have few moral qualms at the inception of the study. However, as the study
progresses and he or she begins to observe differences between groups, a new
understanding of the risk/benefit ratio may begin to emerge. The following can serve
as an example.
Mrs Holden is an 84-year-old widow with advanced rheumatoid arthritis and severe
hypertension. She meets all the inclusion criteria for entry into a study of a new
antihypertensive. However, the study will impose a significant burden on her, as she is not
easily mobile and does not drive. All follow-up visits for the study take place in the
hypertension clinic. It is mid-winter and the outdoor temperatures are regularly well
below freezing. Marty, the study nurse, knows she should try to recruit Mrs Holden into
the study, and is quite sure that she will agree, as from Martys experience in the clinic, she
knows Mrs Holden always wants to help out. However, Marty has observed that patients
in one arm of the study seem to have large reductions in their blood pressure, while those
in the other group have little change. She knows, also, that Mrs Holden is quite well
controlled on her current medication. Marty really questions whether it would be right to
recruit Mrs Holden into the study, knowing that she would experience significant
difficulty in attending for follow-up appointments, may be placed at risk in trying to
navigate icy streets and sidewalks, and may well experience no benefit from the study
treatment.

Here, again, the nurse must confront issues of conflicting obligation.6 Martys
concern for Mrs Holdens welfare extends beyond the study protocol and conflicts
with it. As a study employee, Marty feels a duty to follow the protocol, but as a nurse
she feels an obligation to act in the patients best interests. Again, the notion of nurse as
advocate suggests that Marty has an obligation to act to ensure that the patient is not
harmed in any way. She may also experience similar unease when it becomes clear that
there is no difference between the groups and that participants are experiencing a
significant burden, for example, invasive tests such as lumbar punctures or bone
marrow biopsies, as part of the study follow-up. Marty may worry that speaking up
about her concerns could put her job in jeopardy or generate conflict with the principal
investigator. At the same time, as in the earlier example related to therapeutic
presence, she may experience considerable moral distress if she feels compelled to
ignore her concerns. Her role as advocate for the individual patient conflicts with her
role in the service of science. At the same time, her concerns may have methodological
implications because patients who are likely to be jeopardized by participation in the
study may not be the best candidates from a scientific perspective. Clearly there are
many sides to the issue, which again points to the need for open communication
among all study personnel and thoughtful consideration of potential problems. The
researcher developing a protocol must use imagination in envisioning possible
scenarios such as the one described above, and work out solutions to such problems
a priori. The objective must be to reduce potential harm to participant and nurse alike.
For example, the investigator might discuss with research staff the kinds of issues that
could arise, and together they can establish creative guidelines for dealing with them.

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Another instance in which a nurse could experience disconnection between nursing

obligations and research obligations again concerns recruitment. Here the concern is
what has been termed the therapeutic misconception. Studies have shown that
participants in placebo-controlled trials, despite having signed a consent form, often
have little understanding of the placebo process. Nor do they understand that the
experimental treatment has unproven efficacy. That is, it has been demonstrated that
patients have limited understanding of the concept of clinical equipoise. Instead, they
enter a study with the full expectation that they will receive a new improved
treatment, even though they have been informed that they will be randomly assigned
to a treatment or a placebo arm, and that the new treatment is not necessarily
effective.7 It may be difficult for patients to understand that their physician or nurse
would administer a treatment with no benefit. The nurse may be aware that potential
participants do not fully understand the study design, yet may feel obligated to recruit
anyway. Here again the obligation to do good and to do no harm, especially in the
form of burden on the participant, dictates that the nurse takes a different action to that
called for by obligation to promote the study. In this case the nurses obligation is
relatively clear: nurses are obliged to practice in accordance with their professional
code of ethics. The Canadian Nurses Association Code of Ethics for Registered Nurses
has choice as one of the primary values of nursing. In order for true choice to be
exercised, one must be fully informed, but in the situation described above one cannot
say that the participant is fully informed. Therefore, the nurse would be obligated not
to recruit until it was clear that the patient fully understood the potential risks and
benefits, and the commitments required. Issues of consent should be discussed fully
with the principal investigator.
A final concern for this discussion arises when participants complain to the nurse
about inappropriate or unsafe care that may be unrelated to the study as such. In many
clinical trials patients are recruited from within a particular population, and may be
cared for by a variety of physicians and other health care providers. If participants
develop a close relationship with the nurse, they may express concerns about their
care. The nurse must then decide what, if anything, to do about it. This is particularly
problematic in that there is almost never documented evidence to support the
participants complaints. Certainly, if there are perceived safety issues, and particularly
if more than one participant makes the same complaint, the nurse should request the
participants permission to report to the principal investigator or appropriate
authority, whether it is a professional association or the institution. Similarly, the
nurse may uncover illegal practices in the process of conducting the study. Some of
these, such as child or older person abuse, must be reported under law. This
requirement should be revealed to the participant as part of the informed consent
process.

Conclusion
We have highlighted some of the ethical issues of which nurses as principal
investigators, research nurses or trial co-ordinators must be aware in clinical trials.
We did not want to provide an exhaustive list but rather to increase sensitivity to the
possibility of ethical issues arising in the research context. It is important to examine
potential conflict between a nurses obligation to provide care and the obligation to

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advance knowledge to improve care. It could be argued that an individual patients

needs can and should be overridden in some instances in the interests of the greater
good. However, nurses have a moral obligation to meet individual needs. One may
question, then, whether nurses can indeed have the necessary objectivity to allow them
to overlook possible harms, even if minor, in the interests of science. It seems
important to engage in this debate, as there is a very real potential for creating moral
distress in nurses who are providing care for individuals enrolled in clinical trials. We
have suggested that it is the responsibility of the principal investigator, together with
the research team, imaginatively to envision potential problems and work out ways of
dealing with these problems prior to the studys inception. This may not be sufficient
to deal with nurses dual and conflicting obligations, but may go some distance
towards preventing moral distress among nurses as researchers, data collectors and
caregivers. We hope to have raised some possibilities and made evident some of the
very real concerns of nurses engaged in any aspect of a clinical trial.
Kathleen Oberle, University of Calgary, Calgary, Alberta, Canada.
Marion Allen, University of Alberta, Edmonton, Alberta, Canada.

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