The Utilitarian Argument: Ashley Ferguson
When policymakers draft policies and argue for certain initiatives, laws, or programs,
they often contend that their policy will benefit the greatest number of people. This argument is
grounded in utilitarianism, which theorizes that one should pick options that produce the greatest
good for the greatest number [1]. The “good” could be happiness, satisfaction, protection of
human rights, and other benefits brought to humanity. In the context of healthcare, utilitarian
decisions prioritize protecting the health of the greatest number of people. In clinical trials and
research, a utilitarian approach regarding the use of placebos is necessary to protect general
welfare and health. If we want to maximize the care and development of drugs for all, then
placebos must be included in clinical trials and research.
Placebo controls, often used in clinical trials for new drugs, allow for comparison
between two groups: those taking the experimental drug and those not receiving any treatment
[1]. In contemporary clinical medicine, placebo controls have been revered as the “gold
standard” as they enhance accuracy in statistical analysis in clinical trials. Placebos statistically
“yield the strongest efficacy data in drug testing” where bias is minimized and the rigorous
examination of the cause-and-effect relationship between a drug and its outcome is maximized
[2, 3]. The American Medical Association contends that placebo controls can indeed be an
ethical practice, particularly when physicians obtain informed consent [4].
When comparing placebo-controlled trials (PCTs) with other trials that exclude placebos,
specifically active-controlled trials (ACTs), there are severe discrepancies in data that point to
flaws in the methods of ACTs. In antipsychotic drug trials for schizophrenia, the ACTs had a
degree of improvement that was almost double that of drugs in placebo-controlled trials [5]. This
study included 32 trials of typical antipsychotic medications for patients with schizophrenia, and
the degree of improvement, measured by the Brief Psychiatric Rating Scale (BPRS), revealed
that ACTs drastically exaggerated the impacts these medications had on the improvement
patients experienced. ACTs improved about 15 points in the BPRS, and PCTs had mean BPRS
improvements from around 3 to 7 points, with a 6.35 mean difference between the ACT and PCT
scores [5]. In studies comparing two or more active medications without the use of a placebo, the
response rates for active antidepressants were 65.4%—almost 8% higher than similar studies that
have a placebo arm [6]. These results demonstrate that active-control studies have questionable
validity and can overstate and magnify trial results. If these drugs were introduced to the market,
patients would be at risk of consuming drugs that provide no benefit and could, in turn, harm
their health.
The Sean M. Healey & AMG Center for Amyotrophic Lateral Sclerosis (ALS)
Massachusetts General Hospital (MGH) report emphasizes why misinformation and erroneous
data are so damaging. MGM asserts that this data can lead to ineffective or harmful treatments
marketed to the public. It specifically reports that the use of placebos in trials for ALS is
imperative to prevent ineffective or harmful ALS treatments arising in the market [7]. An ACT
for ALS patients indicated that lithium helped slow the disease, but a placebo-controlled, double-
blind trial, proved that lithium had no effect on ALS [7]. This erroneous data arises from trials
that don’t include placebos. If a PCT had not been conducted on lithium for ALS patients, then
this medication would have infiltrated the market.
Interventions that can harm patients are already at risk of being offered and advertised to
the public. A cardiology study examined the impact of a cardiac pacemaker on the risk of
vasovagal syncope, a fainting spell that occurs when the body overreacts to emotional distress
[9]. Unblinded controlled trials of pacemaker therapy compared to an active (standard) treatment
for syncope demonstrated a decrease in the incidence of syncope [9]. The researchers
subsequently interpreted these results as favorable for the use of a pacemaker in reducing
vasovagal syncope. In a follow-up study, however, researchers compared an active pacemaker to
a surgical sham control, a fake surgical intervention—a placebo [9]. This study proved that
active pacing did not reduce the effects of vasovagal syncope [9]. If the original study used a
surgical sham control, fewer patients would have been exposed to the risk of complications of
inserting a pacemaker. If this follow-up study had not been conducted, millions of people
throughout the world could have considered or undergone surgery for a pacemaker that does not
improve their condition and would result in life-threatening risks from unnecessary surgery.
The discussion encompassing placebo use can merge into one false presumption: that the
ethics in PCTs must mirror the ethics of the physician-patient relationship, where the physician
strives for beneficence. Beneficence, the ethical and moral obligation to promote the well-being
of the patient, involves actions to maximize the welfare of the individual a physician is treating.
In the physician-patient relationship, the patient expects the physician to act in his best interest—
to prescribe drugs that will ostensibly benefit the patient. In clinical trials, such as PCTs, the
ultimate goal is to produce a drug that raises and amplifies the well-being of the public—of
society. PCTs, specifically, prioritize producing a drug that will confirm scientific validity so that
the safety of the public—anyone who could receive the drug—is prioritized. Healthcare must
separate the ethics in PCTs and physician-patient relationships because the priority in PCTs to
ensure scientific validity should not be confused by the beneficence expected and required in
physician-patient interactions.
PCTs provide the best insight into whether an active treatment is effective or harmful.
They ensure that the drugs and treatments entering the market are safe, and this fosters trust in
the healthcare system, thus encouraging more people to seek medical care and drugs available on
the market. To further garner this trust, clinical trials should prioritize public safety instead of
sacrificing the validity of research data in the name of ethical research.
The Deontological Argument: Nicholas Cormas
Clinical trials boast prospects of personalized care, financial compensation, and
innovative treatment opportunities for patients with treatable conditions such as Chronic
Obstructive Pulmonary Disease. Unfortunately, rather than receive the novel medications or even
the clinically-accepted treatments, half of clinical trial subjects receive the control treatment––a
placebo pill. A 2017 analysis of all FDA-logged experimental drug and biological product trials
found that 76.9% of Chronic Obstructive Pulmonary Disease trials and the majority of other
medical trials investigating conditions already have pre-existing treatments [1]. Placebo controls
can potentially expose subjects to detrimental side effects of non-treatment, such as ill symptoms
and the worsening of pathology [2]. Accordingly, the implementation of a placebo control often
violates clinical equipoise: an ethical requirement in clinical studies that declares placebo
controls may only be utilized if there is no standard treatment [3]. For example, the principal
investigators of an Indian HIV study of Risperidone as a potential treatment of acute mania were
widely criticized for their choice of a placebo control that exposed subjects to the risks of
untreated HIV during the duration of the study. The principal investigators responded by
claiming that the placebo control was necessary to yield statistically significant results from the
study. This sparked the central point of contention: is it ethical to risk research subjects’ health
via the administration of placebo controls for improved statistical viability of the study [4]?
Given their observed violations of clinical equipoise and patient autonomy, strict placebo
controls in clinical trials are largely unethical and require meticulous scrutiny under the context
of a pre-existing accepted therapy.
To explore the ethical basis of placebo control, I will begin by examining the code of
conduct all physicians swear by: the Hippocratic Oath. The original Hippocratic Oath states that
physicians must “prescribe regimen for the good of [their] patients”, which is often interpreted as
a physician’s pledge to always act in the best interest of their patients [5]. The Hippocratic Oath
is inherently deontological: “a range of rights and obligations [established] because every person
has inherent dignity” [6]. Deontological philosophy is foundational to medical ethics,
encouraging a prioritization of beneficence towards the individual over broader societal concerns
by requiring physicians to ascribe to a specific code of infallible moral values. Accordingly,
withholding treatment via placebo control violates the duty of a physician on two fronts: their
responsibility to act to uphold both the health and autonomy of the individuals they treat [7].
Given the Hippocratic principle of beneficence, it is unethical for a physician to
knowingly withhold a clinically accepted medicine that could function as a control treatment
from a research subject for the betterment of scientific knowledge. This interpretation of the
ancient Hippocratic Oath is corroborated by modern medical institutions. One notable line from
the contemporary Pennsylvania State College of Medicine and the Oceania University of
Medicine Hippocratic Oath reads “I shall not let any lesser public or professional consideration
interfere with my primary commitment” of providing wellness to individual patients [8,9]. In
other words, the sacrifice of complete care for an individual is not ethically justifiable by a claim
that it improves public health for the “greater good.” A physician’s conscious decision to
withhold a clinical accepted therapeutic control treatment by administering a placebo control
goes against the very principle of nonmaleficence that binds physicians to do no harm.
Placebo controls fall short in their ability to maintain patient autonomy. The ideal ethical
standard of any clinical trial is informed consent: research subjects must be fully informed of all
positive and negative consequences of receiving a treatment. Therefore, subjects in a PCT must
be fully informed of the consequences of potentially receiving a placebo treatment. However,
this is often not the case, as seen in a study that analyzed informed consent materials provided to
subjects in 45 large randomized clinical trials [10]. The study found that there was statistically
significant evidence that informed consent materials highly prioritize giving information about
the experimental target treatments over the placebo treatment, deliberately leading patients to
overestimate the potential positive benefits of the experimental treatment whilst underestimating
the possible drawbacks of receiving the placebo control. Only 9% of studies actually described
placebo treatments’ beneficial or adverse effects, and no studies provided subjects with any
rationale as to why or how placebo treatments could affect the subjects’ health [10].
Furthermore, a recent Finnish study found that “an explanation as to why placebo [that] was
necessary [was] featured in only 23% of the sets of participant-information materials, and only
12% of the documents discussed the possible risks associated with placebo” [11]. The global
lack of detailed communication between physicians and research subjects about the rationale and
consequences of placebo control treatment is highly unethical. This failure of clear
communication deals a severe inhibitor of patient autonomy, especially when subjects are
unaware of their clinical right to full autonomy.
These concerns regarding the administration of placebo controls in clinical trials not only
call into question the theoretical ethical basis of PCTs as they have tangible effects on individual
health and public opinion toward medical research. There are still significant gaps in medical
knowledge and consensus about the long-term risks and impact of placebo treatments [12].
Furthermore, patients who receive a placebo control rather than an experimental medicine
designed to treat their condition can quickly lose confidence and trust in the medical system if
complications such as short-term symptoms and long-term developments in their conditions
arise. These emotional complications can be detrimental as the physical effects of placebo
treatment must be seriously addressed. Before we can comfortably administer placebo controls in
good faith, larger strides in communication with patients must be implemented to maximize
autonomy: informing patients of not only what the physiological impacts of placebos but also
why they may receive a placebo control. This must go hand-in-hand with further intensive
research on the long term effects of placebo controls in specific pathologies so that patients are
fully informed of all of the potential consequences of a placebo treatment they may receive.
Among these complexities, one thing remains certain: the very foundation of ethical medicine
crumbles when the wellness and autonomy of patients are compromised for overarching societal
interests in Placebo Controlled Trials.
Ashley’s References:
1. McCombs School of Business. (2024). Utilitarianism. Ethics Unwrapped.
https://ethicsunwrapped.utexas.edu/glossary/utilitarianism
2. Sharona, H. (2001). Connecticut Law Review. Heinonline.org.
https://heinonline.org/HOL/Page?collection=journals&handle=hein.journals/conlr33&id=
462&men_tab=srchresults
3. Brower, V. (2001). Science versus ethics. European Molecular Biology Organization.
https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC1083897&blobtype=pdf
4. Hariton, E., & Locascio, J. J. (2018). Randomised controlled trials - the gold standard for
effectiveness research. BJOG: An International Journal of Obstetrics & Gynaecology,
125(13), 1716. https://doi.org/10.1111/1471-0528.15199
5. American Medical Assocation. (n.d.). Ethical Use of Placebo Controls in Research | ama-
coe. Code of Medical Ethics. https://code-medical-ethics.ama-assn.org/ethics-
opinions/ethical-use-placebo-controls-research
6. Woods, S. W., Gueorguieva, R. V., Baker, C. B., & Makuch, R. W. (2005). Control
Group Bias in Randomized Atypical Antipsychotic Medication Trials for Schizophrenia.
Archives of General Psychiatry, 62(9), 961. https://doi.org/10.1001/archpsyc.62.9.961
7. Hasnain, M., Rudnick, A., Bonnell, W. S., Remington, G., & Lam, R. W. (2018). Use of
Placebo in Clinical Trials of Psychotropic Medication. The Canadian Journal of
Psychiatry, 63(5), 338–341. https://doi.org/10.1177/0706743717752917
8. Sean M. Healey & AMG Center for ALS. (n.d.). Placebo-Controlled Trials.
Massachusetts General Hospital.
https://www.massgeneral.org/neurology/als/research/placebo-
trials#:~:text=So%2C%20why%20use%20placebos%20in
9. Castro, M. (2007). Placebo versus Best-Available-Therapy Control Group in Clinical
Trials for Pharmacologic Therapies: Which Is Better? Proceedings of the American
Thoracic Society, 4(7), 570–573. https://doi.org/10.1513/pats.200706-073jk
Nicholas’s References:
1. Sorscher, S., AbuDagga, A., Almashat, S., Carome, M. A., & Wolfe, S. M. (2018, April
24). Placebo-only-controlled versus active-controlled trials of new drugs F: OAJCT.
Open Access Journal of Clinical Trials. https://www.dovepress.com/placebo-only-
controlled-versus-active-controlled-trials-of-new-drugs-peer-reviewed-fulltext-article-
OAJCT
2. Millum, J., & Grady, C. (2013). The ethics of placebo-controlled trials: methodological
justifications. Contemporary clinical trials, 36(2), 510–514.
https://doi.org/10.1016/j.cct.2013.09.003
3. Cassidy, J. T., Petty, R. E., Laxer, R. M., & Lindsley, C. B. (2010). Textbook of Pediatric
Rheumatology E-Book. Elsevier Health Sciences.
4. Basil B, Adetunji B, Mathews M, Budur K. Trial of risperidone in India--concerns. Br J
Psychiatry. 2006 May;188:489-90; author reply 490-1; discussion 491-2. doi:
10.1192/bjp.188.5.489-b. PMID: 16648540.
5. Association of American Physicians and Surgeons. (n.d.). Various physicians oaths.
https://www.aapsonline.org/ethics/oaths.htm#lasagna
6. Centre, T. E. Ethics Explainer: What Is Deontology? https://ethics.org.au/ethics-
explainer-deontology/ (accessed 2024-04-23).
7. Alexander, L., & Moore, M. (2020, October 30). Deontological ethics. Stanford
Encyclopedia of Philosophy. https://plato.stanford.edu/entries/ethics-deontological/
8. Oath of Modern Hippocrates. Penn State College of Medicine Current Students. (2021,
May 11). https://students.med.psu.edu/md-students/oath/
9. Current-2023-Oum Student Handbook. (n.d.).
https://oum.edu.ws/documents/2023/03/oum-student-handbook.pdf/
10. Bishop, F. L., Adams, A. E., Kaptchuk, T. J., & Lewith, G. T. (2012). Informed consent
and placebo effects: a content analysis of information leaflets to identify what clinical
trial participants are told about placebos. PloS one, 7(6), e39661.
https://doi.org/10.1371/journal.pone.0039661
11. Keränen, T., Halkoaho, A., Itkonen, E., & Pietilä, A. M. (2015). Placebo-controlled
clinical trials: how trial documents justify the use of randomisation and placebo. BMC
medical ethics, 16, 2. https://doi.org/10.1186/1472-6939-16-2
12. Wyatt, R. J., Henter, I. D., & Bartko, J. J. (1999). The long-term effects of placebo in
patients with chronic schizophrenia. Biological psychiatry, 46(8), 1092–1105.
https://doi.org/10.1016/s0006-3223(99)00227-9