|
| Franklin G. Miller*, David Wendler, Leora C. Swartzman
Franklin G. Miller and David Wendler are in the Department of Clinical
Bioethics, National Institutes of Health, Bethesda, Maryland, United States of
America. Leora C. Swartzman is in the Department of Psychology, university of
Western Ontario, London, Ontario, Canada. The opinions expressed are those of
the authors and do not necessarily reflect the position or policy of the
National Institutes of Health, the Public Health Service, or the Department of
Health and Human Services.
Competing Interests: The authors declare that no competing interests exist.
Published: September 6, 2005
DOI: 10.1371/journal.pmed.0020262
Copyright: © 2005 Public Library of Science. This is an open-access article
distributed under the terms of the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided
the original work is properly cited.
Citation: Miller FG, Wendler D, Swartzman LC (2005) Deception in Research on the
Placebo Effect. PLoS Med 2(9): e262
*To whom correspondence should be addressed. E-mail: fmiller@nih.gov
The placebo effect is a fascinating yet puzzling phenomenon, which has
challenged investigators over the past 50 years. Recently, it has been defined
as the “positive physiological or psychological changes associated with the use
of inert medications, sham procedures, or therapeutic symbols within a
healthcare encounter” [1]. Increasing scientific inquiry has been aimed at
elucidating the mechanisms responsible for placebo effects and determining how
inert interventions can lead to positive changes in patients [1,2]. The majority
of placebo mechanism research has been done within the context of experimental
and clinical pain.
Patients' expectations for improvement, also referred to as “response
expectancies,” are thought to be one of the central mechanisms responsible for
placebo effects [3–5]. Brain imaging techniques are being used to explore both
the neurophysiological correlates of these expectations and the mechanisms
underlying placebo effects in a variety of contexts, including pain relief in
healthy participants, relief of symptoms of depression, and motor functioning in
patients with Parkinson disease [6–8]. Understanding these mechanisms is an
important step in harnessing the placebo effect in patient care. In the words of
a National Institutes of Health request for applications, “understanding how to
enhance the therapeutic benefits of placebo effect in clinical practice has the
potential to significantly improve healthcare” [9]. Toward that end, the
National Institutes of Health invited submissions for systematic studies aimed
at discerning the psychosocial factors (including expectancy) in the
patient–clinician relationship and/or in the health-care environment that can
potentiate healing.
A common feature of research investigating the placebo effect is deception of
research participants about the nature of the research. This use of deception is
considered necessary to understanding the placebo effect, but has received
little systematic ethical attention. In this article, we examine ethical issues
relating to deception in research on the placebo effect, with a particular focus
on experiments involving patients in clinical settings. We propose a method of
informing participants about the use of deception that can reconcile the
scientific need for deceptive research designs with the ethical requirements for
clinical research.
Altering Expectations to Examine Placebo Mechanisms
Response expectancy is seen to be a major driving force behind the placebo
effect. Therefore, a common (and some would argue, necessary) feature of
research aimed at elucidating placebo mechanisms is the use of deception in
experimental manipulation of participants' expectations (e.g., about whether or
not they will receive a “powerful pain killer” or a “sugar pill”), while holding
constant the pharmacological (or other) properties of the administered
intervention. This research has clearly shown (across a wide range of clinical
conditions) that altering expectancies for improvement has an impact on
therapeutic outcomes [8,10–13].
The tension between scientific methods for elucidating the placebo effect and
ethical norms for conducting research involving human participants is
illustrated most clearly by “the balanced placebo design,” an approach designed
to disentangle the relative effects of pharmacology and response expectancy.
Table 1 displays the balanced placebo design in a way that highlights the
deception of participants that occurs in two of the four arms of the design.
In the balanced placebo design, investigators manipulate both expectancies
(e.g., informing participants that they will receive a drug versus informing
them that they will receive placebo) and the pharmacological agent (giving a
drug versus giving a placebo). As reviewed by Swartzman and Burkell, researchers
using this paradigm with healthy volunteers have shown that expectation plays a
role in the subjective and behavioral effects of a range of psychoactive
substances [14]. These substances include dexamfetamine, alcohol, caffeine,
nicotine, and tetrahydrocannabinol [15–19].
The balanced placebo design offers a powerful and elegant approach to evaluate
drug versus expectancy effects and their interactions. As Kirsch notes, this
design yields information that cannot be obtained from conventional clinical
trials [20]. It provides a direct assessment of the drug effect, independent of
expectancy, and the nondeceptive arms are more ecologically valid than the
double-blind administration in conventional randomized trials (i.e., they mimic
what goes on in the real world of clinical practice). Thus, it is not surprising
that Caspi recently suggested that the balanced placebo design “be used more
often in clinical trials of drug efficacy” [21]. Despite the methodological
virtues of the balanced placebo design, and its prior use in healthy volunteers,
we are unaware of any trials that have employed this approach with patients.
Clinical investigators likely have avoided use of the balanced placebo design
out of concern for the ethical acceptability of deceiving patients.
An often cited article on the balanced placebo design characterized the
deception in the following way: “Although deception is involved, it is no
greater than is involved in any study using placebos” [22]. However, this
defense of the balanced placebo design confuses the ethical issues it raises.
Placebo-controlled trials aimed at evaluating the efficacy of treatments may be
regarded as having an element of deception, since the placebo control is
designed to appear indistinguishable from the active treatment under
investigation. Nevertheless, when these studies are conducted under effective
double-blind conditions, participants are told that they will receive either a
drug or a placebo, and neither the investigators nor the research participants
know which intervention is received by any of the participants. Accordingly,
administering the study interventions, unlike the situation of the balanced
placebo design, does not involve intentionally false communication; it requires
investigators to withhold information, but not to lie to participants about the
interventions they will receive.
When deception is used, a conflict between the means and ends of scientific
investigation ensues.
Research designed to understand the placebo effect by deceptively manipulating
the expectations of participants holds great promise for understanding the
psychological and neurobiological dimensions of healing. However, to pursue this
research while respecting participants, it is necessary to develop an approach
that reconciles the outright deception involved in placebo research, including
the balanced placebo design, with the ethical norms governing clinical research.
What Makes Deception in Scientific Investigation Ethically Problematic?
At the outset, it is useful to appreciate the conflict between the ethos of
science and the use of deceptive techniques. Science aims to discover and
communicate the truth about the natural world and human conduct. There are sound
methodological reasons for using deception to probe for the truth about human
attitudes and beliefs and their effects on behavior. It follows, however, that
when deception is used, a conflict between the means and ends of scientific
investigation ensues: the end of discovering the truth is pursued by the means
of deliberate untruth.
It might be argued that deception in scientific investigation is no more
problematic than the pervasive and accepted use of deception in daily life and
in social contexts [23]. In a recent news article reporting advances in the
design of computers to simulate human responsiveness, Clifford Nass, a professor
of communication at Stanford University, endorses the deception involved in this
project: “We spend enormous amounts of time teaching children to deceive—it's
called being polite or social. The history of all advertising is about
deceiving. In education, it's often important to deceive people—sometimes you
say, ‘Boy you are really doing good,’ not because you meant it but because you
thought it would be helpful” [24].
Deception in ordinary life typically is justified on the grounds that it is for
the benefit of the individual who is being deceived. For instance, the polite
and social deception that Nass cites is justified on the grounds that it is
better to deceive someone slightly than to criticize the person or to hurt the
person's feelings. Notice, however, that this condition is not relevant to
placebo research, including the balanced placebo design. In placebo research,
participants are not deceived for their own benefit. Rather, they are deceived
for the benefit of science and society in general, through the development of
generalizable knowledge.
Deception of research participants also clearly conflicts with the ethical norms
governing clinical research [25,26]. First, it violates the principle of respect
for persons by infringing on the right of prospective research participants to
choose whether to participate in research based on full disclosure of relevant
information. Second, it may manipulate individuals to volunteer when they
otherwise would not have chosen to do so had they been informed accurately about
the nature of the research, including its use of deception. For these reasons,
deception, as it is currently practiced in the conduct of research on the
placebo effect, is incompatible with informed consent.
Third, although scant systematic data have been collected on the effects of
deception on clinical research participants, some available evidence indicates
that when the deception is revealed, as in the debriefing process that often
accompanies deceptive research, it causes distress to at least some participants
[27]. The adverse impact of deception in psychological research, and whether it
can be reversed adequately through a debriefing process, is a subject of debate
[28–31]. Furthermore, deception in research involving patients in clinical
settings may prove more upsetting. This is because participants in deceptive
psychological research are, for the most part, psychology undergraduates who
often are aware that deception is sometimes used in psychological research [32].
Patients, in contrast, legitimately expect to be able to trust in, and receive
truthful communication from, clinicians and clinical investigators. This trust
is violated by the use of deception. Especially problematic is the use of
deception in experiments conducted by clinicians who have a prior
clinician–patient relationship with the patients enrolled in the study. When
patients learn about the use of deception in the process of debriefing, which is
a common feature of deception research, they may feel that their trust has been
violated. Consequently, deception of patients may have deleterious effects on
the willingness of patients to volunteer for future clinical research. More
importantly, by undermining patients' faith in the truthfulness of physicians,
deception might interfere with the future medical care of those who have
experienced deceptive research.
Deception may be harmful not only to those who are deceived but also to those
who practice it.
Finally, deception in research raises ethical concern because it can be
corrupting for the professionals who practice it, and for those who witness it.
According to an ancient perspective in moral philosophy, moral character depends
on habits of conduct [33]. The use of deception in research may interfere with
the disposition not to lie or deceive persons. This problem is compounded when
the study design requires deception at the initiation of the trial as well as
repeated deception of participants while conducting the research. Those who
witness deception, especially if performed or sanctioned by professionals in
positions of authority, may develop skewed perceptions of the ethics of
deception, which may have negative consequences for the development of moral
character. In sum, deception in research is prima facie wrongful, and it may be
harmful not only to those who are deceived but also to those who practice or
witness it.
The American Psychological Association's guidelines [34] are perhaps the most
prominent attempt to reconcile the use of deception with the ethical norms of
human participant research. According to guideline 8.07 (Deception in Research),
“(a) psychologists do not conduct a study involving deception unless they have
determined that the use of deceptive techniques is justified by the study's
significant prospective scientific, educational, or applied value and that
effective nondeceptive alternative procedures are not feasible; (b)
psychologists do not deceive prospective participants about research that is
reasonably expected to cause physical pain or severe emotional distress; (c)
psychologists explain any deception that is an integral feature of the design
and conduct of an experiment to participants as early as is feasible, preferably
at the conclusion of their participation, but no later than at the conclusion of
the data collection, and permit participants to withdraw their data.”
We have argued elsewhere that these three conditions are not sufficient to
address the ethical concerns raised by deceptive research [25,26]. In
particular, these conditions fail to address the fact that concealing the use of
deception itself may affect individuals' decision to participate in research and
precludes individuals from deciding whether they want to participate in
deceptive research. To be sure, the use of debriefing may mitigate the potential
harmful consequences of deceitful communication by explaining the rationale for
deception. However, just as compensation for damages caused by negligence or
restitution for crime does not cancel an infringement of a person's rights,
debriefing does not cancel the violation of the principle of respect for
persons. To consider how these ethical concerns arise in actual practice, and
what steps might be taken to address them, it will be helpful to consider
specific examples of the use of deception in placebo research (Table S1).
Examples of Deception in Placebo Research
First, in an experiment investigating suggestion and expectation relating to
placebo analgesia, 13 women with irritable bowel syndrome were recruited, and
were subjected to visceral pain evoked by rectal distention, using a balloon
attached to a rectal catheter. The experiment took place under five experimental
conditions: (1) natural history (no intervention relating to or disclosure about
the pain stimulus), (2) rectal placebo (a sterile surgical lubricant placed on
the balloon, described as effective in relieving pain), (3) rectal lidocaine,
(4) oral lidocaine, and (5) rectal nocebo (a placebo intervention accompanied by
a disclosure that the intervention often causes increased pain) [13]. Notably,
the research report stated that “the gastroenterologist who performed the study
was the doctor the patients normally consulted in the clinic.”
The investigators described their disclosure to the participants as follows:
“The patients were told that four drugs that reduced and increased pain in
relation to IBS [irritable bowel syndrome], respectively, were being tested, and
that they had been proven effective in preliminary studies” [13]. In reality,
the participants were administered two different forms of only one drug, along
with two placebos. Hence, the participants were deceived by being informed that
they would receive drugs that in fact were placebo interventions.
Second, investigators recruited patients with asthma, from an academic medical
center, to participate in an experiment examining changes in forced expiratory
volume in one second following administration of inhaled saline described
deceptively as either a bronchoconstrictor or a bronchodilator [12]. The purpose
was to determine the impact of suggestion on a placebo intervention in patients
identified as suggestible or suggestion-resistant, based on a validated rating
scale. The disclosure to the research participants was described in the article
reporting the experimental results as follows: “Patients were contacted via
telephone and informed that the investigators were hoping to understand how
medications produce beneficial effects in asthma, including whether telling
subjects about the potential effects of various medications would alter response
to these agents. Patients were not told that they would be exposed to placebo
interventions.” The study thus used elaborate deception, which involved an
inaccurate account of the nature of the research and false descriptions of a
placebo intervention. It is therefore puzzling that the authors reported that
“all patients gave informed consent to participate in the study,” especially
since there was no indication that the participants were informed that deception
would be employed. Instead, the participants were debriefed about the study at
the end of the experiment.
Authorized Deception
Can deceptive research be made compatible with informed consent? Use of
deception is not consistent with fully informed consent. If participants are
told the true purpose of research and the nature of all procedures, there would
be no deception. However, participants can be informed prior to deciding whether
to volunteer for a study that the experimental procedures will not be described
accurately or that some features of these procedures will or may be misleading
or deceptive [25,26]. This approach, which we call “authorized deception,”
permits research participants to decide whether they wish to participate in
research involving deception and, if so, to knowingly authorize its use.
Authorized deception is compatible with the spirit of informed consent. It
fosters respect for persons, despite the use of deception, by alerting
prospective participants to the fact that some or all participants will be
deliberately deceived about the purpose of the research or the nature of
research procedures.
For example, investigators using the balanced placebo design to study expectancy
and pharmacological effects of dexamfetamine described the informed consent
disclosure as follows: “For ethical reasons it was stated in the consent form
that ‘…some information and/or instructions given [to the participant] may be
inaccurate’” [15]. This statement recognizes the ethical force of authorized
deception, but does not seem to go far enough. As illustrated above, the
balanced placebo design involves lying to participants in two arms of the study:
some participants are told that they are being administered a particular drug
when in fact they receive placebo, and others that they are being administered
placebo when in fact they receive the drug. Consequently, it is at best an
understatement to describe the disclosure in this experiment as possibly
involving “inaccurate” information. It would be more accurate to inform the
prospective participants that some research participants will be misled or
deceived.
Use of deception is not consistent with fully informed consent.
Variants of the authorized deception approach have been advocated, and sometimes
evaluated experimentally, since the 1970s [23,35–37]; however, it has not become
a routine feature of research using deception [38]. In order to solicit informed
authorization for the use of deception, the informed consent document could be
worded as follows: “You should be aware that the investigators have
intentionally misdescribed certain aspects of the study. This use of deception
is necessary to obtain valid results. However, an independent ethics committee
has determined that this consent form accurately describes the major risks and
benefits of the study. The investigator will explain the misdescribed aspects of
the study to you at the end of your participation.”
When deception of study participants is necessary and justified by the
scientific value of the study, the use of authorized deception makes the process
of deceptive research transparent. Participants are informed that they will be
misled or deceived, though obviously the exact nature of the deception cannot be
disclosed. They are assured that the research has been reviewed and approved by
an ethics oversight committee that has no vested interest in the research in
question, and that no important risks, other than the risks of the deception
itself, have been concealed. Finally, they are informed that debriefing will
occur.
Methodological Objections and the Need for Future Study
One possible objection to the technique of authorized deception is that it is
liable to defeat the purpose of using deception to obviate potentially biased
responses of research participants to research interventions. Informing
participants that deception will occur (particularly in a study that involves
administration of a placebo) is apt to make them suspicious and wary, thus
possibly contributing to biased data. This methodological risk is avoided in
most deceptive research, which does not employ this technique, provided that
prospective participants do not otherwise suspect that deception will be used.
However, limited available research indicates that the anticipated biased
results from disclosing the possibility of deception do not necessarily occur.
Holmes and Bennett assessed this methodological concern experimentally.
Psychology students were exposed to a deceptive experiment in which they were
falsely informed that two to eight “painful electric shocks” would be
administered at random times after a red signal light appeared [35]. No shocks
actually were administered. Measures of self-reported anxiety and physiological
arousal (pulse and respiration rates) were obtained. Prior to the deceptive
shock intervention, one experimental group was informed that deception is
occasionally used in psychology experiments to assure unbiased responses. The
other group exposed to the deceptive shock intervention did not receive any
information about the possibility of deception. No outcome differences were
observed for participants informed of the possibility of deception versus those
not informed.
The information about deception in this experiment, however, falls short of the
authorized deception approach that we recommend. It disclosed to prospective
participants that deception is a possibility in “a few experiments,” rather than
informing them that deception would actually be employed for all or some
participants in the particular experiment in which they were invited to enroll.
In contrast, Wiener and Erker directly tested the authorized deception approach,
described as “prebriefing,” in an experiment evaluating attributions of
responsibility for rape based on transcripts from an actual rape trial [37].
Participants (68 undergraduate psychology students) were either correctly
informed or misinformed about the jury verdict regarding the defendant's guilt.
Half of participants received an informed-consent document stating that “you may
be purposefully misinformed.” The other half was not alerted to the possibility
of deception. No differences on attribution of responsibility were observed
depending on whether or not the participants were prebriefed about the use of
deception.
The effects of the authorized deception approach on study outcomes merit
investigation.
A second methodological objection to authorized deception is that it has the
potential to reduce the comparability to previous research on placebo mechanisms
that did not employ this technique. There is no way to avoid this problem. But
to argue that consequently the authorized deception approach should not be
adopted would suggest that past ethical lapses justify current ethically
deficient practice. Finally, disclosure of the use of deception may lead to
reduced participant enrollment, making it more difficult to complete valuable
studies and possibly reducing their generalizability. At the extreme, it is
possible that too few prospective participants will be willing to volunteer,
especially for experiments recruiting patients. One clinical research study
using the authorized deception approach (in this case, informing participants
that details about the purpose of the research were withheld) found no
substantial impact on enrollment [39]. This remains to be studied further. But
if this approach reduces participant enrollment, it would indicate that eligible
prospective participants do not wish to be deceived, casting doubts on the
legitimacy of using deception without disclosing its use.
The results of psychology experiments that alerted participants to the
possibility of deception and used prebriefing are encouraging, but may not be
generalizable to the situation of patients in clinical research. The null
findings obtained by Weiner and Erker and Holmes and Bennet need to be
interpreted with caution [35,37]. Given that their study participants were
psychology undergraduates, even those who were not prebriefed about the use of
deception could have anticipated that they might be deceived [32].
Accordingly, the effects of the authorized deception approach on study outcomes
merit investigation with respect to research on the placebo effect in a clinical
setting. For example, a methodological experiment comparing the authorized
deception approach to the traditional approach that does not reveal the use of
deception might be attached to a study using the balanced placebo design to
evaluate expectation effects relating to placebo analgesia among patients
recovering from surgery. Patients would be randomized to the two methods of
disclosure, which would be assessed in terms of their impact on reported pain
relief among patients in the various arms of the underlying study. This would
allow investigators to examine the extent to which the authorized deception
approach biases the study outcomes. It might be desirable to conduct such a
methodological experiment in connection with a diversity of underlying studies
of the placebo effect and in various patient populations.
We suspect that the use of authorized deception will not bias studies of the
placebo effect. Hence, the results of such experiments have the potential to
pave the way for important research to proceed that uses the balanced placebo
design in the clinical setting along with the authorized deception
approach—research that otherwise might be rejected by ethics review committees,
owing to concerns about using deception in clinical research. If authorized
deception does produce some bias, decisions will have to be made by
investigators and ethics review committees about the importance of this bias in
compromising the validity of the research compared to the importance of
respecting the autonomy of research participants. Conducting studies to estimate
the extent of the bias will facilitate and inform these decisions.
If the use of authorized deception proved to produce seriously biased results,
then it might be argued that it would be unethical to use the balanced placebo
design in clinical research, owing to the extensive deception involved.
Nevertheless, some aspects of the role of expectancy in therapeutic responses
could still be evaluated in an ethical manner by using nondeceptive research
paradigms in clinical settings [20,40,41], such as comparing an open versus
closed [10,42] or an open versus double-blind administration of a therapeutic
agent [11]. The problem with these experimental paradigms, however, is that
because they do not fully manipulate expectancy and pharmacology in a factorial
design (as does the balanced placebo design), they do not permit a rigorous
evaluation of drug versus expectancy effects and their interaction.
Remaining Qualms about Deceptive Research
Deceptive research involving patients in the clinical setting might be
considered unethical even when all pertinent safeguards are in place, including
the use of authorized deception. This is because deception, even if authorized
in advance, violates the ethical framework of the clinician–patient
relationship, which is based on trust. It may be argued that clinician
investigators who deceive patients in the course of research are acting
fraudulently. Accordingly, professional ethics precludes participation in
deceptive research.
This objection, however, confuses the ethics of clinical research with the
ethics of medical care [43,44]. Clinical research aims at developing
generalizable knowledge in order to improve medical care in the future.
Promoting the medical best interests of particular patients is not part of the
primary purpose of clinical research. Clinical research also departs from the
ethics of medical care in the methods it uses, such as randomization,
double-blind procedures, placebo controls, and the justification of risks.
Nearly all clinical research, especially research that is not aimed at
evaluating the efficacy or safety of treatment interventions, poses risks to
participants that are not offset by potential medical benefits. Accordingly, the
researcher is not functioning as a therapist in the context of clinical
research. It follows that deceptive behavior that would be fraudulent in
clinical practice is not necessarily unethical in clinical research. The
informed-consent process should clarify that the research in question is
different from and outside the purview of medical care. The use of authorized
deception in this context makes research involving deception consistent with
ethical guidelines appropriate to clinical research.
Experiments investigating the placebo effect evoke legitimate ethical concerns.
This objection cannot be so readily dismissed, however, if the investigator or
members of the team of investigators include clinicians who have a prior
therapeutic relationship with research participants, as in the experiment
described earlier involving patients with irritable bowel syndrome [13]. When
investigators simultaneously have both therapeutic and research roles, it is
difficult, if not impossible, to avoid the violation of medical ethics
constituted by deception, even if adequate safeguards are in place to make the
deception justifiable in the context of research. In addition, the potential for
negative consequences to patients from deception is likely to be greater in this
situation. It is not clear why it would be necessary for a clinician having a
prior therapeutic relationship with participants to conduct valuable research on
the placebo effect. For example, in the case of Vase et al.'s irritable bowel
syndrome experiment, an experienced clinician would be needed to safely
administer the rectal distention procedure; however, someone other than the
treating physician could be recruited to perform this function.
Conclusion
Research aimed at elucidating the placebo effect promises to produce valuable
knowledge concerning the psychological and neurobiological dimensions of
healing. Insights gleaned from this research may contribute to the development
of clinical interventions that can enhance the therapeutic efficacy of existing
treatments. Experiments investigating the placebo effect, however, evoke
legitimate ethical concerns, owing to the use of deception.
Key safeguards to assure the ethical design and conduct of deceptive placebo
research include (1) prior review and approval by an independent research ethics
committee to determine that the use of deception
Alan
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http://www.700women.org/ is methodologically necessary and that the study
protocol offers sufficient value to justify the risks it poses to participants,
including the use of deception; (2) disclosure in the informed-consent document
that the study involves the use of deception; and (3) debriefing of participants
at the conclusion of research participation. To contribute to public
accountability, articles reporting the results of research using deception
should describe briefly adherence with these participant-protection guidelines
[45,46]. As in all clinical research, an acceptable balance must be struck
between promoting valuable knowledge and protecting the rights and well-being of
participants.
Supporting Information
Table S1. Clinical Studies on the Placebo Effect Involving Deception
(69 KB DOC).
Acknowledgments
We thank Alan Chan, who conducted the literature search for the articles
described in Table S1 and extracted the relevant information from the articles.
References
1. Kleinman A, Guess HA, Wilentz JS, (2002) An overview. In: Guess HA,
Kleinman A, Kusek JW, Engel LW, editors. The science of the placebo: Towards an
interdisciplinary research agenda London: BMJ. pp 1–32.
2. Harrington A, editor (1997) The placebo effect: An interdisciplinary
exploration. Cambridge (Massachusetts): Harvard university Press. 272 p.
3. Kirsch I (1985) Response expectancy as a determinant of experience and
behavior. Am Psychol 40: 1189–1202. Find this article online
4. Pollo A, Amanzio M, Arslanian A, Casadio C, Maggi G, et al. (2001)
Response expectancies in placebo analgesia and their clinical relevance. Pain
93: 77–84. Find this article online
5. Stewart-Williams S, Podd J (2004) The placebo effect: Dissolving the
expectancy versus conditioning debate. Psychol Bull 130: 324–340. Find this
article online
6. Wager TD, Rilling JK, Smith EE, Sokolik A, Casey KL, et al. (2004)
Placebo-induced changes in fMRI in the anticipation and experience of pain.
Science 303: 1162–1167. Find this article online
7. Mayberg HS, Silva JA, Brannan SK, Tekell JL, Mahurin RK, et al. (2002) The
functional neuroanatomy of the placebo effect. Am J Psychiatry 159: 728–737.
Find this article online
8. de la Fuente-Fernandez R, Schulzer M, Stoessl AJ (2004) Placebo mechanisms
and reward circuitry: Clues from Parkinson's disease. Biol Psychiatry 56: 67–71.
Find this article online
9. National Institutes of Health (2001) Elucidation of the underlying
mechanisms of placebo effect. Bethesda: National Institute of Health. Available:
http://grants1.nih.gov/grants/guide...AT-02-002.html. Accessed 11
July 2005.
10. Benedetti F, Maggi G, Lopiano L, Lanotte M, Rainero I et al. (2003) Open
versus hidden medical treatments: The patient's knowledge about a therapy
affects the therapy outcome. Prev Treat 6. article 1. Available:
http://journals.apa.org/prevention/...oc-jun-03.html. Accessed 21 July
2005.
11. Benedetti F, Pollo A, Lopiano L, Lanotte M, Vighetti S, et al. (2003)
Conscious expectation and unconscious conditioning in analgesic, motor, and
hormonal placebo/nocebo responses. J Neurosci 23: 4315–4323. Find this article
online
12. Leigh R, MacQueen G, Tougas G, Hargreave FE, Bienstock J (2003) Change in
forced expiratory volume in 1 second after sham bronchoconstrictor in
suggestible but not suggestion-resistant asthmatic subjects: A pilot study.
Psychosom Med 65: 791–795. Find this article online
13. Vase L, Robinson ME, Verne GN, Price DD (2003) The contributions of
suggestion, desire, and expectation to placebo effects in irritable bowel
syndrome patients. An empirical investigation. Pain 105: 17–25.
14. Swartzman LC, Burkell J (1998) Expectations and the placebo effect in
clinical drug trials: Why we should not turn a blind eye to unblinding, and
other cautionary notes. Clin Pharmacol Ther 64: 1–7. Find this article online
15. Mitchell SH, Laurent CL, de Wit H (1996) Interaction of expectancy and the
phenomenological effects of d-amphetamine: Subjective effects and
self-administration. Psychopharmacology (Berl) 125: 371–378. Find this article
online
16. McKay D, Schare ML (1999) The effects of alcohol and alcohol expectancies
on subjective reports and physiological reactivity: A meta-analysis. Addict
Behav 24: 633–647. Find this article online
17. Kirsch I, Weixel LJ (1988) Double-blind versus deceptive administration of
placebo. Behav Neurosci 102: 319–323. Find this article online
18. Perkins K, Sayette M, Conklin C, Caggiula A (2003) Placebo effects of
tobacco smoking and other nicotine intake. Nicotine Tob Res 5: 695–709. Find
this article online
19. Curran HV, Brignell C, Fletcher S, Middleton P, Henry J (2002) Cognitive
and subjective dose-response effects of acute oral delt 9-tetrahydrocannabinol
(THC) in infrequent cannabis users. Psychopharmacology (Berl) 164: 61–70. Find
this article online
20. Kirsch I (2003) Hidden administration as ethical alternatives to the
balanced placebo design. Washington (DC): American Psychological Association.
Available: http://journals.apa.org/prevention/...e0060005c.html. Accessed
11 July 2005.
21. Caspi O (2002) When are placebo medication side effects due to the placebo
phenomenon? JAMA 287: 2502. Find this article online
22. Rohsenow DJ, Marlatt GA (1981) The balanced placebo design: Methodological
considerations. Addict Behav 6: 107–122. Find this article online
23. Milgram S (1977) Subject reaction: The neglected factor in the ethics of
experimentation. Hastings Cent Rep 7: 19–23. Find this article online
24. Vedantum S (2004 June 7) Human responses to technology scrutinized:
Emotional interactions draw interest of psychologists and marketers. Washington
Post; Sect A: 14.
25. Wendler D (1996) Deception in medical and behavioral research: Is it ever
acceptable? Milbank Q 74: 87–114. Find this article online
26. Wendler D, Miller FG (2004) Deception in the pursuit of science. Arch
Intern Med 164: 597–600. Find this article online
27. Fleming M, Bruno M, Barry K, Fost N (1989) Informed consent, deception,
and the use of disguised alcohol questionnaires. Am J Drug Alcohol Abuse 15:
309–319. Find this article online
28. Broder A (1998) Deception can be acceptable. Am Psychol 53: 805–806. Find
this article online
29. Kimmel AJ (1988) In defense of deception. Am Psychol 53: 803–805. Find
this article online
30. Ortman A, Hertwig R (1997) Is deception acceptable? Am Psychol 52:
746–747. Find this article online
31. Ortman A, Hertwig R (1998) The question remains: Is deception acceptable?
Am Psychol 53: 806–807. Find this article online
32. Gallo PS, Smith S, Mumford S (1973) Effects of deceiving subjects on
experimental results. J Soc Psychol 89: 99–107. Find this article online
33. Aristotle, (2004) Nichomachean ethics. Thomson JAK, translator; Tredennick
H, Barnes J, editors London: Penguin Books. 400 p.
34. American Psychological Association (2002) Ethical principles of
psychologists and code of conduct. Am Psychol 57: 1060–1073 Available:
http://www.apa.org/ethics/code2002.pdf. Accessed 21 July 2005. Find this article
online
35. Holmes DS, Bennett DH (1974) Experiments to answer questions raised by the
use of deception in psychological research. I. Role playing as an alternative to
deception. II. Effectiveness of debriefing after a deception. III. Effect of
informed consent on deception. J Pers Soc Psychol 29: 358–367. Find this article
online
36. Bok S (1978) Lying: Moral choice in public and private life. New York:
Random House. 368 p.
37. Wiener RL, Erker PV (1986) The effects of prebriefing misinformed research
participants on their attributions of responsibility. J Psychol 120: 397–410.
Find this article online
38. Sieber JE, Iannuzzo R, Rodriguez B (1995) Deception methods in psychology:
Have they changed in 23 years? Ethics Behav 5: 67–85. Find this article online
39. Boter H, van Delden JJM, de Haan RJ, Rinkel GJE (2004) Patients'
evaluation of informed consent to postponed information: Cohort study. BMJ 329:
86–87. Find this article online
40. Colloca L, Benedetti F, (2004) The placebo in clinical studies and in
medical practice. In: Price DD, Bushnell MC, editors. Psychological methods of
pain control: Basic science and clinical perspectives Seattle: IASP Press. pp
187–205.
41. Price D (2001) Assessing placebo effects without placebo groups: An
untapped possibility? Pain 90: 201–203. Find this article online
42. Amanzio M, Pollo A, Maggi G, Benedetti F (2001) Response variability to
analgesics: A role for non-specific activation of endongenous opioids. Pain 90:
205–215. Find this article online
43. Miller FG, Rosenstein DL (2003) The therapeutic orientation to clinical
trials. N Engl J Med 348: 1383–1386. Find this article online
44. Miller FG (2004) Research ethics and misguided moral intuition. J Law Med
Ethics 32: 111–116. Find this article online
45. Pittinger DJ (2002) Deception in research: Distinctions and solutions from
the perspective of utilitarianism. Ethics Behav 12: 117–142. Find this article
online
46. Miller FG, Rosenstein DL (2002) Reporting of ethical issues in
publications of medical research. Lancet 360: 1326–1328. Find this article
online
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http://medicine.plosjournals.org/pe...oi=10.1371/jour
nal.pmed.0020262
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