Journal of Alzheimer’s Disease 79 (2021) 1443–1449 1443

DOI 10.3233/JAD-201378
IOS Press

Review

Sleep Deprivation, a Link Between

Post-Traumatic Stress Disorder and
Alzheimer’s Disease
Vedad Delica , Whitney A. Ratliffb and Bruce A. Citrona,c,∗
a Laboratory of Molecular Biology, VA New Jersey Health Care System, Research & Development, East Orange,

NJ, USA
b Laboratory of Molecular Biology, Bay Pines VA Healthcare System, Research and Development, Bay Pines,

FL, USA
c Department of Pharmacology, Physiology, & Neuroscience, Rutgers-New Jersey Medical School, Newark, NJ,

USA

Accepted 7 December 2020

Pre-press 11 January 2021

Abstract. An estimated 5 million Americans are living with Alzheimer’s disease (AD), and there is also a significant impact
on caregivers, with an additional 16 million Americans providing unpaid care for individuals with AD and other dementias.
These numbers are projected to increase in the coming years. While AD is still without a cure, continued research efforts
have led to better understanding of pathology and potential risk factors that could be exploited to slow disease progression.
A bidirectional relationship between sleep deprivation and AD has been suggested and is well supported by both human and
animal studies. Even brief episodes of inadequate sleep have been shown to cause an increase in amyloid-␤ and tau proteins,
both well-established contributors to AD pathology. Sleep deprivation is also the most common consequence of post-traumatic
stress disorder (PTSD). Patients with PTSD frequently present with sleep disturbances and also develop dementia at twice the
rate of the general population accounting for a disproportionate representation of AD among U.S. Veterans. The goal of this
review is to highlight the relationship triad between sleep deprivation, AD, and PTSD as well as their impact on molecular
mechanisms driving AD pathology.

Keywords: Alzheimer’s disease, amyloid-␤, post-traumatic stress disorder, sleep deprivation, tau

INTRODUCTION of endocrine and neuroendocrine processes that input

Sleep is a reoccurring period of restorative uncon-
sciousness necessary for normal human function. The
cycle of consciousness and unconsciousness is under
the control of the circadian clock, a complex system
∗ Correspondence to: Bruce A. Citron, PhD, VA New Jersey
Health Care System, Laboratory of Molecular Biology, Research
and Development, Building 16, Room 16-176, 385 Tremont Ave.,
East Orange, NJ 07018, USA. Tel.: +1 973 676 1000 /Ex1-3686;
E-mail: bruce.citron@rutgers.edu.
ques from the environment to create a sleep-wake
rhythm. Significant variability exists in when peo-
ple sleep and how frequently, termed chronotypes.
However, sleep duration less than 5 hours per night
corelates with poor cardiovascular health, type 2 dia-
betes, and obesity across different populations [1, 2].
Individuals with chronotypes far outside the average
are considered to have sleep disorders [3]. Require-
ment for sleep is evolutionarily conserved and is
present in invertebrates and vertebrates [4]. Chronic

ISSN 1387-2877/21/$35.00 © 2021 – IOS Press. All rights reserved.

1444 V. Delic et al. / Sleep, PTSD, and Alzheimer’s Disease
lack of adequate sleep leading to sleep deprivation
can cause both systemic and neurological problems
ranging from metabolic disruption and obesity to
stroke, and impaired learning [5, 6]. Sleep deprivation
is associated with neurodegenerative disorders like
Alzheimer’s disease (AD) [7] as well as neuropsychi-
atric disorders such as post-traumatic stress disorder
(PTSD) [8], but it remains unclear if sleep deprivation
is a cause or a consequence for these disorders.
Quality sleep has been shown recently to be neces-
sary in helping coordinate the clearing of metabolic
waste and toxic proteins involved in AD and inad-
equate sleep may therefore accelerate or cause
AD. Non-rapid eye movement (Non-REM) sleep
presents on an electroencephalogram (EEG) with
low-frequency (less than 4 Hz) oscillations, important
in supporting consolidations of new memories and
neuronal processing [9–11]. During Non-REM sleep,
low frequency oscillations in neuronal activity were
found to co-occur with large influx of cerebrospinal
fluid (CSF) into the brain and hemodynamic changes
[12]. In mice, sleep is associated with clearance of
metabolic waste from the CSF which is stronger dur-
ing low-frequency EEG oscillation associated with
Non-REM sleep [13, 14]. Sleep has been found to
regulate CSF levels of AD related proteins amyloid-
␤ (A␤) and tau [15, 16]. Even a single night without
sleep can cause accumulation of A␤ in otherwise
healthy human brains suggesting a close relation-
ship with sleep disruption and key components of
AD pathology [17]. AD is the most common neu-
rodegenerative disorder that disrupts neural circuits,
leading to a progressive loss of neurological function
and death. Disruption of neural circuitry and neurode-
generation is in part driven by accumulation of “senile
plaques” made up of misprocessed A␤ protein and
also neurofibrillary tangles consisting of hyperphos-
phorylated tau. Studies suggest that the incidence of
AD is higher in those individuals diagnosed with
PTSD [18, 19], a psychiatric disorder triggered by
exposure to one or more traumatic events which can
lead to a number of neurological and physiological
problems, though there have been few studies inves-
tigating the factors that may contribute to observed
correlation between PTSD and AD. While PTSD
patients can present with a number of characteris-
tic symptoms, one of the most common complaints
is the presences of sleep disturbances. Large studies
suggest that sleep disruption is present in 70–87%
of patients with PTSD [20–22]. In this review, we
discuss the important role of sleep deprivation in the
pathogenesis of AD and as a component of PTSD
that may drive the higher incidence of AD in PTSD
patient population. We examined primary literature
over the past two decades spanning human and ani-
mal studies on PTSD, sleep deprivation, and AD, that
together implicate sleep deprivation as the likely link
between PTSD and increased susceptibility to AD.
SLEEP DEPRIVATION
Disruption of sleep-wake cycle is frequently
caused by work and lifestyle choices [23]. Persis-
tent disruption of sleep-wake cycle can result in
chronic sleep deprivation which has been linked to
systemic and neurological problems including dis-
ruption of normal metabolism, obesity, heart disease,
high blood pressure, and stroke [5, 6]. The conse-
quences of sleep deprivation are not simply a result
of wear and tear but also due to long lasting hor-
monal, genetic, and epigenetic changes [5, 6, 24].
Brain is particularly affected by sleep deprivation,
resulting in diminished learning and memory even
after brief periods of sleep deprivation [25–27]. Even
among college athletes sleep deprivation causes dete-
rioration in learning, vigilance, mood, and athletic
performance [28]. By altering gene expression and
hormone levels, and by disrupting normal metabolic
function, sleep deprivation can predispose, cause, or
worsen neurodegenerative and neuropsychiatric dis-
orders including AD.
Sleep deprivation and AD
A bidirectional relationship between sleep disrup-
tion and AD has been proposed and is supported
by mounting evidence, demonstrating that sleep
deprivation increases AD related pathology and that
increasing AD pathology further causes sleep disrup-
tion [29, 30]. Sleep cycles between non-REM and
REM sleep stages, several times during a typical
night. Non-REM is the longer of the two sleep stages
and is further subdivided into 3 successive sub-stages,
that occur before the shorter REM period is reached.
Non-REM sleep is characterized by low-frequency
(less than 4 Hz) oscillations, important in supporting
consolidations of new memories and neuronal pro-
cessing [9–11]. Non-REM sleep is also accompanied
by large influx of cerebrospinal fluid (CSF) into the
brain and also with hemodynamic changes [12]. In
mice, as in humans, diurnal variation in A␤ levels
were found to occur, with higher A␤ levels detected
in the CSF during waking hours, that decrease fol-
lowing sleep or in case of mice higher levels of A␤
 V. Delic et al. / Sleep, PTSD, and Alzheimer’s Disease
were detected during their active dark phase com-
pared to light phase [15]. Chronic sleep disruption
in mice resulted in significantly higher levels of A␤,
that decreased following sleep suggesting that A␤
levels are dependent on wakefulness rather than time
of day [15]. Orexin is a molecule involved in regulat-
ing wakefulness and is released from hypothalamic
neurons promoting wakefulness [31]. Diurnal fluc-
tuations in orexin correspond to A␤. Brain infusion
of orexin in mice resulted in increased A␤ levels,
while inhibition of orexin receptors abolished diur-
nal A␤ variation [15]. Chronic sleep deprivation
of APP transgenic mice that develop A␤ plaques,
resulted in increased plaque burden, while block-
ing orexin receptors decreased plaque burden [15].
Sleep duration of less than 5 hours or greater than
11 hours per night have been linked to increased risk
for cognitive impairment [32, 33]. Prospective study
looking at sleep demonstrated that sleep fragmen-
tation increases the risk of developing AD [7]. AD
related pathology is thought to start decades before
the onset of symptoms and eventual diagnosis. Iden-
tifiable pathological changes in AD include reduction
of soluble A␤42 levels in the CSF 10–15 years before
the onset of cognitive symptoms associated with AD
[35]. Asymptomatic individuals with reduced soluble
A␤42 levels, which is an indication of A␤ sequestra-
tion into insoluble senile plaques, have worse sleep
quality compared to their peers with normal A␤42 lev-
els [36]. These clinical observations were replicated
in two different mouse models (APPSWE and APP-
SWE/PS1DE9) where sleep deprivation accelerated
deposition of A␤ into amyloid plaques and enhanced
sleep showed decrease in A␤ plaque deposition [15].
Sleep deprivation in PTSD as a risk factor for AD
Individuals with PTSD are reported to have exag-
gerated cognitive changes with aging, and increased
incidence of AD; however, well-controlled studies
in this area are relatively few in number. Admin-
istrative data from the Veterans Integrated Service
Network (VISN) of Department of Veterans Affairs
healthcare facilities revealed that the prevalence and
incidence of a dementia diagnosis remained nearly
two times as high in Veterans with diagnosed PTSD
compared to the control group consisting of Veter-
ans without diagnosed PTSD [18]. Another study
of Veterans aimed at determining whether PTSD is
associated with increased risk for developing demen-
tia reported that during a 7-year follow-up, Veterans
with PTSD had a cumulative incident dementia rate
1445
of 10.6% whereas those without PTSD had a rate of
6.6%. These results were similar even after those with
a history of head injury, substance abuse, or clinical
depression were excluded [19]. While PTSD is com-
mon among Veterans, it is also present in the general
population. A study of 600 older persons revealed
that individuals that were categorized as being in
the 90th percentile of “distress-proneness” were 2.7
times more likely to develop AD than those not prone
to distress (10th percentile). In this study, “distress-
proneness” was also associated with overall cognitive
decline [37].
PTSD and AD have also been studied in animal
models. Studies in animals have shown that various
stressors can be associated with accelerated develop-
ment of amyloid plaques [38–41], increased levels of
A␤ [42, 43], and tau hyperphosphorylation [44–46].
One study in mice found that a PTSD-like induction
chronically elevated levels of A␤ in the CSF, exacer-
bating ongoing AD pathogenesis [47]. Justice et al.
demonstrated that A␤ resulted in hyperexcitation of
corticotropin-releasing factor (CRF) neurons and that
lowering of A␤ levels attenuated the PTSD-like phe-
notype. Their data demonstrated that exposure to
PTSD-like trauma can drive AD pathogenesis and
perturb CRF signaling, important in stress activated
responses, thereby enhancing chronic PTSD symp-
toms and increasing the risk for AD.
PTSD patients can present with a number of
psychiatric symptoms, including nightmares and
hyperarousal, which invariably impact sleep dura-
tion and quality [48]. PTSD and sleep quality deficits
are common among combat Veterans. One study of
Operation Iraqi Freedom (OIF) and Operation Endur-
ing Freedom (OEF) Veterans found that 89% were
reported as “poor sleepers” according to the Pitts-
burgh Sleep Quality Index (PSQI) and that sleep
quality was worse among Veterans presenting with
PTSD symptoms [49].
Neuroimaging studies have long shown that
neuronal excitability plays a key role in PTSD
pathogenesis [50–52]. One study demonstrated that
patients with PTSD exhibited a mean conditioned
motor evoked potential amplitude higher than that
observed in control groups. They demonstrated that
PTSD can give rise to abnormalities in intracortical
inhibition which leads to cortical hyperexcitabil-
ity [53]. Similarly, changes in neuronal excitability
may underlie the effects of sleep deficit on AD
pathogenesis. In a Drosophila model of AD, A␤ accu-
mulation led to fragmented and reduced sleep, while
chronic sleep deprivation led to increased A␤ burden.
1446 V. Delic et al. / Sleep, PTSD, and Alzheimer’s Disease
Fig. 1. PTSD can cause altered gene expression, altered hormone
levels, and disrupted metabolism, thereby creating an environment
that can promote amyloid-␤ (A␤) aggregation and neurodegen-
eration associated with Alzheimer’s disease. Sleep deprivation
resulting from PTSD can cause a positive feedback loop where
sleep deprivation increases likelihood of Alzheimer’s disease and
in turn, progression of Alzheimer’s disease can result in further
sleep disturbances.
Moreover, neuronal excitability was found to mimic
the effects of reduced sleep on A␤ accumulation.
Suppressing neuronal excitability reduced the effects
of sleep deprivation on A␤ accumulation [54]. These
results suggest that both neuronal excitability and
sleep deprivation exacerbate the accumulation of
A␤ and may provide a link between the neuronal
excitability and sleep deprivation in PTSD patient
populations which can eventually lead to develop-
ment of AD. We summarize the relationship between
PTSD, sleep deprivation, and AD in Fig. 1.
MOLECULAR MECHANISMS OF AD
DRIVEN BY SLEEP DEPRIVATION
The hallmark plaques observed in AD brains
are the result of an accumulation and inability to
clear the protein A␤, a metabolic waste product.
Though the mechanisms by which A␤ is cleared in
healthy human brains is not well understood, there
is evidence that sleep may play a role in clear-
ance of waste products from the brain including
A␤ [13]. Animal models provide further evidence
that A␤ levels and sleep quality and duration are
tightly linked. In mice, measurement of hippocam-
pal A␤ levels using in vivo microdialysis revealed
that A␤ levels were positively correlated with the
amount of time spent awake and negatively cor-
related with the amount of time spent asleep.
This negative correlation was even stronger with
non-REM sleep [15]. In a human study, even a single
unrestricted night of sleep led to a 6% decrease in CSF
A␤ levels in cognitively normal middle-aged men
and just one night of total sleep deprivation counter-
acted this decrease, interfering with the physiological
morning decrease in A␤ levels [55].
The increased risk for AD associated with chronic
sleep deficit appears to be modulated through multi-
ple molecular pathways of neuronal injury in addition
to the effect on A␤ accumulation. Two-month sleep
deprivation in mice not only altered the A␤ protein
precursor processing but also raised the phosphory-
lated tau (p-Tau) level and resulted in impairment
of cognitive performance compared to non-sleep
deprived controls. In addition to increased A␤42 pro-
duction and more senile plaques in the cortex and
hippocampus, sleep deprivation also caused neuronal
mitochondrial damage, caspase cascade activation,
and mediated neuronal apoptosis. These changes
were long-lasting and were irreversible during a
3-month follow-up under normal conditions [56].
Transgenic mice that were sleep deprived showed
significant increase in the insoluble fraction of tau,
lower levels of postsynaptic density protein 95, and
increased glial fibrillary acidic protein levels [57].
Sleep-deprived mice displayed increased A␤ and
p-Tau levels in the cortex and higher circulating
levels of the hormone corticosterone, responsible
for energy, immune, and stress response regulation,
compared to controls [58]. Other animal models of
chronic sleep deprivation have shown depletion of
glycogen stores and increase in oxidative stress and
free radical formation [59], thus emphasizing that
multiple molecular pathways are involved in neu-
rodegeneration in response to chronic sleep deficit.
Orexin
Orexin, the neuropeptide that promotes wake-
fulness, appears to play a significant role in A␤-
mediated neurodegeneration. APP/PS1 transgenic
mice, in which the orexin gene was knocked out,
display a marked decrease in the amount of A␤
pathology in the brain with an associated increase in
sleep time. In contrast, sleep deprivation or increas-
ing wakefulness by rescue of orexinergic neurons in
APP/PS1 mice lacking orexin increase the amount
of A␤ pathology in the brain [60]. Orexin activa-
tion has also been shown to play a role in behavioral
fear expression in an animal model [61]. Similarly,
another animal study showed that orexin adminis-
tration impaired fear extinction [62]. These studies
suggest that inappropriate excitation of this path-
 V. Delic et al. / Sleep, PTSD, and Alzheimer’s Disease
way may account for the fear generalization observed
in PTSD. Additionally, altered orexin signaling
may lead to sleep disturbance and changes in A␤
pathology.
Alzheimer’s disease, sleep, and the immune
system
Sleep deprivation is associated with increased risk
of cardiovascular disease, diabetes, hypertension, and
obesity with a 45% increase in the risk of a fatal heart
attack. These consequences of sleep loss are char-
acterized, in part, by inflammatory processes [63].
Sleep deficit-induced proinflammatory response is
considered a risk factor for neurodegenerative dis-
eases such as AD [64]. Sleep appears to have a
bidirectional relationship with the immune system
and over the past few decades it has become increas-
ingly apparent that sleep is closely intertwined with
the immune system. In 1975, Pappenheimer et al.
[65] reported isolating a substance which they termed
sleep-promoting factor (factor S) and later research
identified this substance as a bacterial cell wall pep-
tidoglycan fragment known as muramyl peptide, a
pyrogenic cytokine. This substance was shown to
induce sleep in non-sleep deprived animals and it also
induced inflammatory cytokines [66]. These findings
led to further research to delineate the role of sleep,
in immune responsiveness and the findings have con-
firmed a bidirectional relationship between sleep and
immune function. It has been found that through
neuro–immune interactions, sleep loss alters immune
function and immune challenges alter sleep pattern.
As more became known about the sleep response to
infectious challenge, it became clear that IL-1␤ and
TNF-␣ are among the inflammatory markers that are
involved in the central nervous system regulation of
physiological sleep [67].
SUMMARY
Individuals diagnosed with PTSD are at least twice
as likely to develop AD than those without PTSD.
Sleep deprivation is the most commonly reported
consequence of PTSD and has been reported as a
major accelerant of AD pathology in patients and
in AD animal models. Sleep deprivation appears to
affect multiple molecular pathways leading to higher
risk for neurodegeneration and therefore interven-
tions aimed at improving sleep patterns will have a
much broader impact than medications targeting any
single molecular mechanisms. It has been established
1447
that neurodegeneration in AD begins years before
symptom manifestation presenting an opportunity for
intervention prior to onset of symptoms.
ACKNOWLEDGMENTS
We thank Dr. U. Nalla B. Durai for useful dis-
cussion and inspiration. This review was supported
by the Department of Veterans Affairs (Veter-
ans Health Administration, Office of Research and
Development, Rehabilitation/Biomedical Laboratory
Research and Development (RX001520, RX003253,
BX005015), the Assistant Secretary of Defense for
Health Affairs through the Congressionally Directed
Gulf War Illness Research Program (W81XWH-16-
1-0626), The Bay Pines Foundation, and the Veterans
Bio-Medical Research Institute.
The contents do not represent the views of the
Department of Veterans Affairs or the United States
Government and the opinions, interpretations, con-
clusions and recommendations are those of the
authors and are not necessarily endorsed by the
Department of Defense.
Authors’ disclosures available online (https://
www.j-alz.com/manuscript-disclosures/20-1378r2).
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 PERSPECTIVE
published: 05 February 2020
doi: 10.3389/fmed.2020.00027

Artificial Intelligence in Medicine:

Today and Tomorrow
Giovanni Briganti 1,2*† and Olivier Le Moine 1,3†
1
Medical Informatics, School of Medicine, Université Libre de Bruxelles, Brussels, Belgium, 2 Unit of Epidemiology,
Biostatistics and Clinical Research, School of Public Health, Université Libre de Bruxelles, Brussels, Belgium, 3 Hopital
Erasme, Université Libre de Bruxelles, Brussels, Belgium

Artificial intelligence-powered medical technologies are rapidly evolving into applicable

solutions for clinical practice. Deep learning algorithms can deal with increasing amounts
of data provided by wearables, smartphones, and other mobile monitoring sensors
in different areas of medicine. Currently, only very specific settings in clinical practice
benefit from the application of artificial intelligence, such as the detection of atrial
fibrillation, epilepsy seizures, and hypoglycemia, or the diagnosis of disease based on
histopathological examination or medical imaging. The implementation of augmented
medicine is long-awaited by patients because it allows for a greater autonomy and a
more personalized treatment, however, it is met with resistance from physicians which
were not prepared for such an evolution of clinical practice. This phenomenon also
creates the need to validate these modern tools with traditional clinical trials, debate
Edited by:
Enrico Capobianco, the educational upgrade of the medical curriculum in light of digital medicine as well
University of Miami, United States as ethical consideration of the ongoing connected monitoring. The aim of this paper is
Reviewed by: to discuss recent scientific literature and provide a perspective on the benefits, future
Marco Diego Dominietto,
Paul Scherrer Institut (PSI),
opportunities and risks of established artificial intelligence applications in clinical practice
Switzerland on physicians, healthcare institutions, medical education, and bioethics.
Marian Klinger,
Opole University, Poland Keywords: digital medicine, mobile health, medical technologies, artificial intelligence, monitoring

*Correspondence:
Giovanni Briganti
giovanni.briganti@hotmail.com
1. INTRODUCTION
† These authors have contributed The expression “Medical Technology” is widely used to address a range of tools that can enable
equally to this work health professionals to provide patients and society with a better quality of life by performing early
diagnosis, reducing complications, optimizing treatment and/or providing less invasive options,
Specialty section: and reducing the length of hospitalization. While, before the mobile era, medical technologies
This article was submitted to were mainly known as classic medical devices (e.g., prosthetics, stents, implants), the emergence
Translational Medicine,
of smartphones, wearables, sensors, and communication systems has revolutionized medicine with
a section of the journal
the capability of containing artificial intelligence (AI) powered tools (such as applications) in very
Frontiers in Medicine
small sizes (1). AI has revolutionized medical technologies and can be commonly understood as
Received: 03 November 2019
the part of computer science that is able to deal with complex problems with many applications in
Accepted: 17 January 2020
areas with huge amount of data but little theory (2).
Published: 05 February 2020
Intelligent medical technologies (i.e., AI-powered) have been met with enthusiasm by the
Citation:
general population partly because it enables a 4P model of medicine (Predictive, Preventive,
Briganti G and Le Moine O (2020)
Artificial Intelligence in Medicine:
Personalized, and Participatory) and therefore patient autonomy, in ways that could not be possible
Today and Tomorrow. (3); smartphones are becoming for instance the go-to item to fill and distribute an electronic
Front. Med. 7:27. personal health record (4), monitor vital functions with biosensors (5) and helping to reach optimal
doi: 10.3389/fmed.2020.00027 therapeutic compliance (6), therefore gifting the patient with the spot as the main actor in the

Frontiers in Medicine | www.frontiersin.org 1 February 2020 | Volume 7 | Article 27

Briganti and Le Moine
care pathway. The development of intelligent medical
technologies is enabling the development of a new field in
medicine: augmented medicine, i.e., the use of new medical
technologies to improve different aspects of clinical practice.
Several AI-based algorithms have been approved in the last
decade by the Food and Drug Administration (FDA) and could
therefore be implemented. Augmented medicine is not only
enabled by AI-based technologies but also several other digital
tools, such as surgical navigation systems for computer-assisted
surgery (7), virtuality-reality continuum tools for surgery, pain
management and psychiatric disorders (8–10).
Although the field of augmented medicine seems to encounter
success with patients, it can be met with a certain resistance
by healthcare professionals, in particular physicians: concerning
this phenomenon, four widely discussed reasons should be
provided. First, unpreparedness as to the potential of digital
medicine is due to the evident lack of basic and continuing
education regarding this discipline (11). Second, the early
digitization of healthcare processes, very different from the
promise of augmented medicine came with a steep increase of the
administrative burden mainly linked to electronic health records
(12), which has come to be known as one of the main components
of physician burnout (13). Third, there is increasing fear as to
the risk of AI replacing physicians (14), although the current and
mainstream opinion in the literature is that AI will complement
physician intelligence in the future (15, 16). Fourth, the current
world-wide lack of a legal framework that defines the concept
of liability in the case of adoption or rejection of algorithm
recommendations leaves the physician exposed to potential legal
outcomes when using AI (17).
As of the lack of education in digital medicine, several
private medical schools are preparing their future medical leaders
to the challenge of augmented medicine by either associating
the medical curriculum with the engineering curriculum or
implementing digital health literacy and use in an upgraded
curriculum (18).
The aim of this paper is to summarize recent developments of
AI in medicine, provide the main use-cases where AI-powered
medical technologies can already be used in clinical practice,
and perspectives on the challenges and risks that healthcare
professionals and institutions face while implementing
augmented medicine, both in clinical practice and in the
education of future medical leaders.
2. CURRENT APPLICATIONS OF
ARTIFICIAL INTELLIGENCE IN MEDICINE
2.1. Cardiology
2.1.1. Atrial Fibrillation
The early detection of atrial fibrillation was one of the first
application of AI in medicine. AliveCor received FDA approval
in 2014 for their mobile application Kardia allowing for a
smartphone-based ECG monitoring and detection of atrial
fibrillation. The recent REHEARSE-AF study (19) showed that
remote ECG monitoring with Kardia in ambulatory patients is
more likely to identify atrial fibrillation than routine care. Apple
also obtained FDA approval for their Apple Watch 4 that allows
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AI in Medicine: Today and Tomorrow
for easy acquirement of ECG and detection of atrial fibrillation
that can be shared with the practitioner of choice through a
smartphone (20). Several critiques of wearable and portable ECG
technologies have been addressed (21), highlighting limitations
to their use, such as the false positive rate originated from
movement artifacts, and barriers in the adoption of wearable
technology in the elderly patients that are more likely to suffer
from atrial fibrillation.
2.1.2. Cardiovascular Risk
Applied to electronic patient records, AI has been used to
predict the risk of cardiovascular disease, for instance acute
coronary syndrome (22) and heart failure (23) better than
traditional scales. Recent comprehensive reviews (24) have
however reported how results can vary depending on the sample
size used in research report.
2.2. Pulmonary Medicine
The interpretation of pulmonary function tests has been reported
as a promising field for the development of AI applications in
pulmonary medicine. A recent study (25) reported how AI-based
software provides more accurate interpretation and serves as a
decision support tool in the case on interpreting results from
pulmonary function tests. The study received several critiques,
one of which (26) reported how the rate of accurate diagnosis in
the pulmonologists participating in the study was considerably
lower than the country average.
2.3. Endocrinology
Continuous glucose monitoring enables patients with diabetes
to view real-time interstitial glucose readings and provides
information on the direction and rate of change of blood
glucose levels (27) Medtronic received FDA approval for their
Guardian system for glucose monitoring, which is smartphone-
paired (28). In 2018, the company partnered with Watson
(AI developed by IBM) for their Sugar.IQ system to help
their customers better prevent hypoglycemic episodes based on
repeated measurement. Continuous blood glucose monitoring
can enable patients to optimize their blood glucose control and
reduce stigma associated with hypoglycemic episodes; however,
a study focusing on patient experience with glucose monitoring
reported that participants, while expressing confidence in the
notifications, also declared feelings of personal failure to regulate
glucose level (27).
2.4. Nephrology
Artificial intelligence has been applied in several settings in
clinical nephrology. For instance, it has been proven useful for the
prediction of the decline of glomerular filtration rate in patients
with polycystic kidney disease (29), and for establishing risk
for progressive IgA nephropathy (30). However, a recent review
reporters how at this moment research is limited by sample size
necessary for inference (31).
2.5. Gastroenterology
The specialty of gastroenterology benefits from wide range of
AI applications in clinical settings. Gastroenterologists made use
of convolutional neural networks among other deep learning
models in order to process images from endoscopy and
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Briganti and Le Moine
ultrasound (32) and detect abnormal structures such as colonic
polyps (33). Artificial neural networks have also been used
to diagnose gastroesophageal reflux disease (34) and atrophic
gastritis (35), as well as to predict outcomes in gastrointestinal
bleeding (36), survival of esophageal cancer (37), inflammatory
bowel disease (38), and metastasis in colorectal cancer (39) and
esophageal squamous cell carcinoma (40).
2.6. Neurology
2.6.1. Epilepsy
Intelligent seizure detection devices are promising technologies
that have the potential to improve seizure management through
permanent ambulatory monitoring. Empatica received FDA
approval in 2018 for their wearable Embrace, which associated
with electrodermal captors can detect generalized epilepsy
seizures and report to a mobile application that is able to
alert close relatives and trusted physician with complementary
information about patient localization (41). A report focused on
patient experience, revealed that, in contrast to heart monitoring
wearables, patients suffering from epilepsy had no barriers in the
adoption of seizure detection devices, and reported high interest
in wearable usage (42).
2.6.2. Gait, Posture, and Tremor Assessment
Wearable sensors have proven useful to quantitatively assess gait,
posture, and tremor in patients with multiple sclerosis, Parkinson
disease, Parkinsonism, and Huntington disease (43).
2.7. Computational Diagnosis of Cancer in
Histopathology
Paige.ai has received breakthrough status from FDA for an
AI-based algorithm that is capable of diagnose cancer in
computational histopathology with great accuracy, allowing
pathologist to gain time to focus on important slides (44).
2.8. Medical Imaging and Validation of
AI-Based Technologies
A long-awaited meta-analysis compared performances of deep
learning software and radiologists in the field of imaging-based
diagnosis (45): although deep learning seems to be as efficient
as radiologist for diagnosis, the authors pointed that 99% of
studies were found not to have a reliable design; furthermore,
only one thousandth of the papers that were reviewed validated
their results by having algorithms diagnose medical imaging
coming from other source populations. These findings support
the need of an extensive validation of AI-based technologies
through rigorous clinical trials (5).
3. DISCUSSION: CHALLENGES AND
FUTURE DIRECTIONS OF ARTIFICIAL
INTELLIGENCE IN MEDICINE
3.1. Validation of AI-Based Technologies:
Toward a Replication Crisis?
One of the core challenges of the application of AI in medicine in
the next years will be the clinical validation of the core concepts
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AI in Medicine: Today and Tomorrow
and tools recently developed. Although many studies have
already introduced the utility of AI with clear opportunities based
on promising results, several well recognized and frequently
reported limitations of AI studies are likely to complicate such
validation. We will hereby address three of such limitations, as
well as provide possible ways to overcome them.
First, the majority of studies comparing efficiency of AI vs.
clinicians are found to have unreliable design and known to
lack primary replication, i.e., the validation of the algorithms
developed in samples coming from other sources than the one
used to train algorithms (45). This difficulty could be overcome
in the open science era as open data and open methods are bound
to receive more and more attention as best practices in research.
However, transitioning to open science could prove difficult for
medical AI companies that develop software as a core business.
Second, studies reporting AI application in clinical practice
are known to be limited because of retrospective designs and
sample sizes; such designs potentially include selection and
spectrum bias, i.e., models are developed to optimally fit a given
data set (this phenomenon is also known as overfitting), but do
not replicate the same results in other datasets (32). Continuous
reevaluation and calibration after the adoption of algorithms that
are suspected of overfitting should be necessary to adapt software
to the fluctuation of patient demographics (46). Furthermore,
there is a growing consensus as of the need of development of
algorithms designed to fit larger communities while taking into
account subgroups (47).
Third, only few studies are known to compare AI and
clinicians based on same data sets; even in that scenario, critiques
have been made pointing at lower diagnostic accuracy rate than
expected in specialty doctors. (26). Opposing AI and clinicians
is, although well represented in the scientific literature, probably
not the best way to tackle the issue of performance in medical
expertise: several studies are now approaching the interaction
between clinicians and algorithms (47) as the combination of
human and artificial intelligence outperforms either alone.
3.2. Ethical Implications of Ongoing
Monitoring
Medical technology is one of the most promising markets
of the 21st century, with an estimated market value rapidly
approaching a thousand billion dollars in 2019. An increasing
percentage of the revenue is due to the retail of medical
devices (such as heart monitoring devices) to a younger
population, which is not the primary target consumer profile
(because health problems such as atrial fibrillation are less
likely to appear). Because of this phenomenon, the Internet of
Things (IoT) is redefining the concept of healthy individual
as a combination of the quantified self (personal indicators
coded in the smartphone or wearable) and series of lifestyle
wearable-provided parameters (activity monitoring, weight
control, etc.).
Furthermore, in the last couple of years several wearable
companies have been concluding important deals with either
insurance companies or governments to organize a large-scale
distribution of these products: this kind of initiatives are mainly
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Briganti and Le Moine
aimed to induce lifestyle change in large populations. While
western countries are continuing to evolve toward health systems
centered around the patient’s individual responsibility toward
its own health and well-being, the ethical implications of
ongoing medical monitoring with medical devices through the
Internet of things are frequently discussed. For instance, ongoing
monitoring and privacy violations have the potential to increase
stigma around chronically ill or more disadvantaged citizens
(48) and possibly penalize those citizens that are unable to
adopt new standards of healthy lifestyle, for instance by reducing
access to health insurance and care; little to no debate has
been focused on these potential and crucial pitfalls in health
policy making.
In this techno-political framework, the issue of data protection
and ownership becomes more and more crucial, although
more than two decades old (49). Several attitudes toward
data ownership are described in the literature: although some
works argue for common ownership of patients data to profit
personalized medicine approaches (50, 51), consensus is shifting
toward patient ownership, as it has positive effects on patient
engagement as well as may improve information sharing if a data
use agreement between the patient and healthcare professionals
is developed (52).
3.3. The Need to Educate Augmented
Doctors
Several universities have started to create new medical
curriculum, including a doctor-engineering (18), to answer
the need of educating future medical leaders to the challenges
of artificial intelligence in medicine (53). Such curricula see a
stronger approach to the hard sciences (such as physics and
mathematics), and the addition of computational sciences,
coding, algorithmics, and mechatronic engineering. These
“augmented doctors” would count on both a clinical experience
and digital expertise to solve modern health problems, participate
in defining digital strategies for healthcare institutions, manage
the digital transition, educate patients and peers.
Society as well as healthcare institutions could benefit from
these professionals as a safety net for any processes including AI
in medicine but also as a drive of innovation and research. Aside
from basic medical education, there is a need for implementation
of ongoing educational programs regarding digital medicine and
targeting graduated physicians, so as to allow retraining in this
growing field. In most cutting-edge hospitals around the world,
such experts are charged with the mission of Chief Medical
Information Officer (CMIO).
3.4. The Promise of Ambient Clinical
Intelligence: Avoiding Dehumanization by
Technology
As reported by several studies (12, 13), electronic health records
can be an important administrative burden and a source
of burnout, phenomenon increasingly present in physicians,
both in training and trained. Although artificial intelligence
solutions such as Natural Language Processing are becoming
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AI in Medicine: Today and Tomorrow
more and more capable of helping the physician deliver
complete medical records, further solutions are needed to
solve the issue of the increasing time allocated to indirect
patient care.
Ambient clinical intelligence (ACI) is understood as
a sensitive, adaptive and responsive digital environment
surrounding the physician and the patient (54) and capable
of, for instance, analyzing the interview and automatically
fill the patient’s electronic health records. Several projects
are underway to develop an ACI, which would be a
crucial application of artificial intelligence in medicine
and much needed to solve modern problems with the
physician workforce.
One of the great barriers to the adoption of intelligent medical
technologies in physicians is the fear of a dehumanization of
medicine. This is mainly due to the increasing administrative
burden (12) imposed on physicians. However, modern
technology such as ACI and Natural Language processing
are bound to solve the issue of administrative burden and will
help clinicians focus more on the patient.
3.5. Will Doctors Be Replaced by Artificial
Intelligence?
As recently discussed in the literature (15, 16) doctors will
most likely not be replaced by artificial intelligence: smart
medical technologies exist as such as support to the physician
in order to improve patient management. As recent studies have
indicated (45), however, comparisons frequently occur between
artificial intelligence solutions and physicians, as if the two
counterparts were in competition. Future studies should focus on
the comparison between physicians using artificial intelligence
solutions with physicians without the aid of such applications,
and extend those comparisons to translational clinical trials; only
then will artificial intelligence be accepted as complementary
to physicians. Healthcare professionals stand nowadays in a
privileged position, to be able to welcome the digital evolution
and be the main drivers of change, although a major revision of
medical education is needed to provide future leaders with the
competences to do so.
4. CONCLUSION
The implementation of artificial intelligence in clinical practice is
a promising area of development, that rapidly evolves together
with the other modern fields of precision medicine, genomics
and teleconsultation. While scientific progress should remain
rigorous and transparent in developing new solutions to improve
modern healthcare, health policies should now be focused on
tackling the ethical and financial issues associated with this
cornerstone of the evolution of medicine.
AUTHOR CONTRIBUTIONS
All authors listed have made a substantial, direct and intellectual
contribution to the work, and approved it for publication.
4 February 2020 | Volume 7 | Article 27
Briganti and Le Moine
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Conflict of Interest: The authors declare that the research was conducted in the
absence of any commercial or financial relationships that could be construed as a
potential conflict of interest.
Copyright © 2020 Briganti and Le Moine. This is an open-access article distributed
under the terms of the Creative Commons Attribution License (CC BY). The use,
distribution or reproduction in other forums is permitted, provided the original
author(s) and the copyright owner(s) are credited and that the original publication
in this journal is cited, in accordance with accepted academic practice. No use,
distribution or reproduction is permitted which does not comply with these terms.
6 February 2020 | Volume 7 | Article 27
Oxman et al.
Health Research Policy and Systems (2022) 20:28
https://doi.org/10.1186/s12961-022-00828-z

COMMENTARY Open Access

Health communication in and out of public

health emergencies: to persuade or to inform?
Andrew D. Oxman1*  , Atle Fretheim1,2, Simon Lewin1,3, Signe Flottorp1,4, Claire Glenton1, Arnfinn Helleve1,5,
Didrik Frimann Vestrheim1, Bjørn Gunnar Iversen1 and Sarah E. Rosenbaum1 

Abstract 
Much health communication during the COVID-19 pandemic has been designed to persuade people more than to
inform them. For example, messages like “masks save lives” are intended to compel people to wear face masks, not
to enable them to make an informed decision about whether to wear a face mask or to understand the justification
for a mask mandate. Both persuading people and informing them are reasonable goals for health communication.
However, those goals can sometimes be in conflict. In this article, we discuss potential conflicts between seeking to
persuade or to inform people, the use of spin to persuade people, the ethics of persuasion, and implications for health
communication in the context of the pandemic and generally. Decisions to persuade people rather than enable them
to make an informed choice may be justified, but the basis for those decisions should be transparent and the evi-
dence should not be distorted. We suggest nine principles to guide decisions by health authorities about whether to
try to persuade people.
Keywords:  Evidence-informed health policy, Health communication, Risk communication, Health promotion,
Infodemic, Health education, Health information, Persuasion, Ethics

Potential conflicts between seeking to persuade
or seeking to inform
During the pandemic, governments and health authori-
ties have recommended or mandated infection preven-
tion and control measures, including social distancing,
face masks, travel restrictions, self-isolation, quarantines,
lockdowns and vaccination. Implementation of these
measures has ranged from simply informing the public,
to eliminating people’s ability to choose.
Public messaging about these control measures has
changed as the pandemic has evolved [1]. Changes may
have reflected evolving research evidence and shifting
expert opinions. However, justifications have not always
been shared candidly in communication by governments
*Correspondence: oxman@online.no
1
Centre for Epidemic Interventions Research, Norwegian Institute
of Public Health, Skøyen, Postboks 222, 0213 Oslo, Norway
Full list of author information is available at the end of the article
or health authorities to the public [2–4]. Additionally,
researchers may have hyped the certainty and potential
of their research in order to promote it [5]. As a result,
the public has sometimes experienced COVID-19 mes-
sages from these authorities as untruthful and inconsist-
ent. Thus, those messages may have exacerbated rather
than reduced confusion from the tsunami of information
that accompanied the pandemic.
Increasing compliance through persuasion
Authorities seeking to maximize compliance may design
their communication to persuade people to follow rec-
ommended or mandated control measures. However,
messages designed to persuade can limit people’s ability
to make informed choices and may erode public trust in
authorities, which in turn can negatively impact compli-
ance. There is evidence that public trust in government
increased compliance with stringent government restric-
tions in both authoritarian and democratic countries [6].

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Oxman et al. Health Research Policy and Systems (2022) 20:28 Page 2 of 9

Furthermore, research needed to reduce uncertainties
(such as randomized trials measuring the effects of clos-
ing schools) can be difficult to conduct in an environment
where those uncertainties are not acknowledged publicly.
Supporting informed choices providing options
and the pros and cons of those options
Conversely, health authorities aiming to enable people
to make informed choices (or to be transparent about
the reasons for a mandate) are more likely to include
what is known about the pros and cons of interven-
tions and the reasons for recommendations or policies
[7]. This approach respects the rights of individuals to
be informed and enables participation in public debate.
More candid communication might also make policy
changes seem less arbitrary and help preserve people’s
trust in health authorities [8, 9]. However, this approach
could reduce compliance. For example, people may be
less likely to wear face masks if they perceive them to
be ineffective, and communication of uncertainty might
reduce the perception of effectiveness [10]. It could also
increase inequities, if some people are less likely to have
access to candid information, to understand it or to be
able to use it as intended [11].
Sometimes the goals of persuading and informing peo-
ple are in conflict [11, 12]. This dilemma, brought into
sharp contrast by the COVID-19 pandemic, exists for
all types of health authorities, including public health
professionals and organizations, other healthcare pro-
fessionals and organizations, researchers and scientific
organizations.
Changing people’s behaviour through spin
One way to influence people to behave in a desired way
is to emphasize the advantages of the desired behaviour
and ignore or downplay any disadvantages or uncertain-
ties (Table  1). This is sometimes referred to as “spin” or
“hype”. It can be done intentionally or unintentionally.
Spin can be found in the scientific literature, where
reporting practices distort the interpretation of results
and mislead readers so that results are viewed in a more
favourable light [13–15]. It can be found in news reports
[16], advertisements used to promote the purchase of
health products [17], and in public health messages [18].
Spin is manipulative when it ignores or misinforms about
events or alternatives.
Governments may limit the extent to which spin can
be used by industry. For example, the European Union
(EU) Directive 2005/29/EC on unfair commercial prac-
tices prohibits misleading and aggressive advertising [19].
This includes advertising that significantly limits the con-
sumer’s ability to make an informed decision. The Blue
Guide on Advertising and Promotion of Medicines in the
UK states, “An advertisement must present information
which is factually correct, and those facts should not be
exaggerated in any way” [20]. However, such regulations
do not apply to health authorities. For example, the Food
and Drug Administration (FDA) in the United States
required producers of Relenza and Tamiflu to state in the
package labels that these drugs had not been proven to
reduce complications of influenza. However, the Centers
for Disease Control and Prevention (CDC) in the United
States could claim that these drugs reduced complica-
tions and saved lives [21].
Strategies that can be used to influence people to
behave in a desired way, either intentionally or uninten-
tionally, include using words and hyperbolic or alarming
language without presenting numbers [7, 22], presenting
risk ratios for benefits and absolute effects for harms [7,
23], leaving out the denominator [24], arousing fear or a
sense of urgency [25, 26], using narratives [27, 28], and
using expert sources to support otherwise unsubstanti-
ated claims [29].
Information designed to enable informed choices
should systematically and transparently summarize the
evidence and other considerations in relation to factors

Table 1  Ways of spinning information to influence people

Factors that can affect a decision Spin to influence people to behave in a desired way

The effects of behaving in the desired
way compared to other options
Costs of behaving in the desired way
compared to other options
Alternatives to the desired option
Emphasize or exaggerate the benefits of behaving in the desired way
Ignore or downplay the harms or undesirable effects of behaving in the desired way
Ignore or downplay uncertainty about the benefits, and emphasize or exaggerate uncertainty about the harms
Neglect to consider or point out that people may weigh desirable and undesirable outcomes differently
Assume or imply that the desirable effects far outweigh the undesirable effects
Ignore or downplay the costs and emphasize or exaggerate the savings of behaving in the desired way
Ignore or downplay uncertainty about the savings and emphasize or exaggerate uncertainty about the costs
Ignore, assume or imply the intervention is cost-effective, and ignore uncertainty
Misinform or leave out information about relevant alternatives
 Oxman et al. Health Research Policy and Systems (2022) 20:28
that might influence a decision, such as the factors listed
in Table  1 [30]. When there is compelling evidence that
the advantages far outweigh the disadvantages, the dif-
ference between persuading and informing people may
be smaller. For example, the advantages of vaccines for
measles, mumps and rubella clearly outweigh the disad-
vantages [31]. Parents want balanced information about
the benefits and harms of childhood vaccination [32], and
providing them with clear, concise, evidence-based infor-
mation may both build trust and persuade them to con-
sider the evidence when deciding.
However, the more closely balanced the advantages and
disadvantages are and the greater the uncertainty, the
more likely it is that there will be a difference between
persuading and informing people. For example, for some
women it is not clear whether the advantages of breast
cancer screening outweigh the disadvantages. Conse-
quently, communication to increase uptake differs sub-
stantially from information designed to enable informed
decisions [33].
The ethics of persuasion
When considering the ethics of information designed
to persuade, it is helpful to recognize a continuum from
information to coercion (Fig.  1). Persuasion, manipula-
tion and coercion are the predominant categorizations of
various types of influence in bioethics, although not all
ethicists agree with these categories [18, 34]. Importantly,
it has been argued that “manipulation” includes many
Fig. 1  A continuum from information to coercion
Page 3 of 9
forms of influence and needs conceptual refinement and
ethical analysis to address the use of behavioural science
to influence health behaviours. Also, these words may be
confusing, since they can have different meanings and
connotations in other contexts. Nonetheless, the distinc-
tions or spectrum can be helpful when considering the
ethics of persuasion.
Information that respects individual autonomy but considers
collective burden
Information designed to inform people builds on a basic
principle of respect for people’s autonomy [35]. Some
autonomous choices that people make entail risks, such
as riding a motorcycle. In societies that value autonomy,
such choices are respected if they do not harm other peo-
ple or create undue collective burden. In the context of
a pandemic, many choices that people make can harm
others and add to the collective burden (for example, on
healthcare systems). Consequently, health authorities
have frequently advocated policies that restrict auton-
omy and governments have implemented restrictive
measures.
Information that is not manipulative
Information designed to influence people’s behaviour
does not necessarily infringe on their autonomy, but
it can if the information is manipulative [18]. Spin is
manipulative if it promotes disinformation or with-
holds important information to direct people’s choices.
Oxman et al. Health Research Policy and Systems (2022) 20:28
For example, withholding important information
about a well-documented, serious vaccine side effect
that may lead people to choose not to be vaccinated
or not to vaccinate their children would be manipula-
tive, even if there is compelling evidence that the ben-
efits far outweigh the harms. Providing information
designed to arouse fear or other emotions, such as
guilt or urgency, can also be manipulative. For exam-
ple, during the COVID-19 pandemic, informing peo-
ple about the gravity of the situation has been used to
motivate people to adhere to control measures. People
should be made aware of the seriousness of the situa-
tion so that they can make informed choices. However,
exaggeration can exacerbate fear, anger and anxiety
unnecessarily [36].
It can be argued that people’s choices are not truly
“autonomous” when they are unknowingly shaped by
their environment or by misinformation provided
by actors with special interests [11], for example the
food industry [37]. In addition, people do not always
rationally weigh their options, and decisions are often
affected by cognitive biases [38]. However, this alone
does not justify manipulation of information or peo-
ple’s emotions by health authorities or governments.
Information that is honest and transparent
When authorities deliberately design information to
be persuasive or “manipulative” (using behavioural
science), there is an underlying assumption that they
know what problems should be addressed, what pref-
erences and goals people have, and what is best for
people and the community. If these assumptions are
well founded, authorities may be justified in recom-
mending, persuading or even restricting people’s
behaviour, despite some disagreement. For example,
seat belt laws, traffic regulations and information to
promote adherence to those are widely accepted as
well founded in many countries, although not every-
one agrees.
However, when there are important uncertainties
or disagreements, not being honest and transparent
can inhibit research and perpetuate practices that are
wasteful and may be harmful. This includes uncertainty
or disagreements about social, economic and other
consequences not directly related to health. Moreover,
one key asset for obtaining public health goals, trust,
may be undermined if health authorities are not trans-
parent or perceived to be honest by the public. Changes
in policies because of changes in the evidence are likely
to be more acceptable to the public if the authorities
were transparent about the uncertainties of the evi-
dence when the original policy was made.
Page 4 of 9
Information that does not “blame the victim”
Health information that is designed to influence peo-
ple’s behaviour can also result in victim-blaming and
stigmatization. For example, well-intended informa-
tion campaigns to reduce obesity and the health con-
sequences of obesity may have contributed to blaming,
shaming and stigmatizing obese people [39]. Health
communication about HIV and AIDS that used threats
or scare tactics contributed to stigmatization [40]. The
use of threats or scare tactics during the COVID-19
pandemic also may have contributed to stigmatization
[36].
Information that is “actionable”
Not everyone wants to be informed or to make their
own decisions about many of the behaviours that affect
health [41]. Most people want clear, actionable messages,
and for some people that is sufficient. For example, when
there is a high COVID-19 infection rate, a recommenda-
tion to “wear face masks when it is not possible to main-
tain social distancing” is a clear actionable message. Not
everyone is interested in the justification for such rec-
ommendations. Nonetheless, the justification should be
reasonable, should be communicated transparently and
should be available to anyone who is interested [46, 47].
Information that is developed through systematic,
transparent and evidence‑informed processes
It may be justified to design messages to persuade peo-
ple to adhere to such recommendations. Health authori-
ties who make decisions about what to recommend and
whether to use persuasive messages should use system-
atic procedures informed by the best available evidence
[30]. Systematic procedures should be used to decide
how to communicate important recommendations, as
well as for deciding what to recommend [42, 43]. Sys-
tematic procedures and transparency do not guaran-
tee reasonable decisions any more than they guarantee
that the results and interpretation of research are valid.
Nonetheless, they can help to ensure accountability and
reasonableness.
When is it justified to persuade people to change their
behaviour?
Generally, the more uncertainty there is about the bal-
ance between the advantages and disadvantages of a
behaviour, the less likely it is that it is justified to try
to persuade people to behave in that way (Fig.  2). On
the other hand, the greater the potential impacts of a
behaviour are on others (e.g. transmission of infectious
diseases or drunk driving), the more likely it is that
 Oxman et al. Health Research Policy and Systems (2022) 20:28
Fig. 2  Factors underlying the justification for persuading people to
change their behaviour
persuasion is justified [44]. Similarly, the greater the
risk, the more likely it is that persuasion is justified.
Communication in the context of public health
emergencies
Health authorities who communicate to the public in
the context of health emergencies, such as the COVID-
19 pandemic, must take account of ethical considera-
tions and the extent to which persuasion is justified.
The extent of uncertainty combined with the need to
respond urgently may limit the ability of health authori-
ties and governments to use systematic and transpar-
ent processes to decide what to recommend and how to
communicate recommendations. However, they can be
prepared for emergencies by having established system-
atic processes for rapidly reviewing the evidence and
making recommendations and policy decisions that are
informed by existing evidence [45, 46], and by imple-
menting evidence-based guidance for communicating
risk and evidence [1, 7, 47]. They also can have in place
processes for generating evidence to address important
uncertainties [48].
Another way in which they can be prepared is by fos-
tering critical thinking [49, 50]. The COVID-19 pan-
demic has been accompanied by an “infodemic”—an
overabundance of information, some accurate and
some not. By fostering critical thinking skills, health
authorities and governments can help to reduce peo-
ple’s susceptibility to misinformation and enhance their
ability to recognize and use reliable information. Cur-
rently many people lack those skills [49–51].
Page 5 of 9
Principles to guide decisions by health authorities
about whether to persuade
Health authorities and others responsible for commu-
nicating health information to the public should reflect
carefully on the purpose of the information they com-
municate to the public—whether it is intended primar-
ily to persuade people or to inform them. This should
include consideration of long-term consequences as
well as immediate effects on behaviour. For example,
authorities who aim to persuade the public and there-
fore downplay uncertainty about the risk of side effects
of a vaccine may increase uptake. However, if side
effects are discovered over time, this could undermine
trust and people’s willingness to be vaccinated in the
future.
Before designing information to influence people’s
behaviour in a specific direction, health authorities
should be confident that the potential advantages out-
weigh the potential disadvantages and that most well-
informed people would agree with their justification for
wanting to persuade people. Deciding how to influence
people parallels how to make recommendations based
on evidence of variable quality [30, 52–54]. Generally,
when there is low confidence in the evidence, strong
recommendations and persuasion are not warranted.
However, there are circumstances where a strong rec-
ommendation or persuasion is warranted despite
important uncertainties [52–54]. Principles that can
help guide decisions about when it is justifiable for
health authorities to try to persuade people to behave
in a certain way are summarized in Table  2. Answer-
ing the questions in Table  2 requires evidence, inter-
pretation of the evidence, and judgements. Having in
place an efficient system for summarizing the evidence,
involving stakeholders and making transparent judge-
ments can help to ensure that decisions and recom-
mendations by public health authorities do more good
than harm. Experience with such systems for deciding
what to do or recommend can facilitate making simi-
larly transparent judgements about how to communi-
cate those decisions and whether to persuade people.
The principles in Table  2 could also be applied to
decisions about whether to restrict people’s behaviour
or mandate that people behave in a certain way. When a
behaviour is mandated, messages may still be designed
to persuade people to adhere to the mandate, or they
may be designed to inform people. For example, in the
context of a mask mandate, messages may be designed
primarily to persuade people to adhere to the mandate
(e.g. Fig. 3) or to inform people about the rationale for
the mandate (e.g. a guide to when and where masks are
mandated, why, and how to select and use masks).
Oxman et al. Health Research Policy and Systems (2022) 20:28 Page 6 of 9

Table 2  Principles to guide decisions by health authorities about whether to persuade

Principles Questions Explanations

Evidence What is known about the potential impacts of the behaviour? Decisions about what to recommend should be based on the
best available scientific evidence about the effects of the targeted
behaviour, based on up-to-date systematic reviews whenever
possible [58]. This is not always possible in the context of public
health emergencies, but such reviews can be done rapidly [59],
and experience using a structured approach to make and justify
recommendations outside of emergencies can make it easier to do
this in an emergency
What is known about the potential impacts of the communica- Decisions about how to inform or persuade people should also be
tion strategy? informed by the best available scientific evidence. It is possible to
systematically review this evidence outside of the context of emer-
gencies, so that it is readily available as evidence-based guidance
[1, 6, 50], and experience using a structured approach outside of
emergencies can also make it easier to do this in an emergency
Participation Does the message reflect the values of those affected? Decisions about whether and how to persuade depend on judge-
ments about how much people value the potential benefits and
harms. Stakeholders—those who are affected by the decision—
should be involved in those decisions.
For this to be practical in the context of emergencies, it is likely
necessary to have established effective mechanisms to facilitate
participation or participation in planning when not in the emer-
gency [55–59]
Equity Are the potential impacts of the message on different popula- A decision to persuade (or not to persuade) should not affect seg-
tions fair? ments of the population, particularly disadvantaged ones, unfairly.
The benefits, harms and burden should be distributed fairly
Transparency What is the justification for the message? The justification for a decision to persuade should be transparent
and readily available to the public. This should include the criteria
used to make the decision, the judgements that were made for
each criterion, and the basis for the judgements [30]
Precaution Is there a credible threat of serious harm that warrants an urgent In response to urgent and credible threats of serious harm, pro-
message? portionate precautions should be taken. This principle is especially
relevant in the context of public health emergencies. This is a
complex principle that requires judgements about the urgency of
a threat, the credibility of the threat, the likelihood and seriousness
of the potential harms, and the potential benefits and harms of the
intervention [60].
When the precautionary principle is applied, it should include
evaluation to address important uncertainties, so far as possible
[48]
Proportionality Is the message appropriate for the level of risk? The proportionality principle is used in a variety of contexts and
has been defined in different ways [61]. The general idea underly-
ing the principle is that responses to threats or risks should be
appropriate for the level of risk and not excessive
Flexibility Is the message tailored to key target audiences and their Messages should be tailored to address important cultural, socio-
contexts and can it be modified as new information becomes economic and language differences. Attention should be paid to
available? minority groups, their ability to access and understand messages,
and their ability to act on messages. Choice of communication
channels (e.g. websites, social media, mass media) should also be
tailored to targeted audiences. Thresholds (e.g. for COVID-19 infec-
tion rates) and other reasons for changing the message should
be communicated as clearly as possible, and it should be possible
to reconsider and change messages and how they are communi-
cated in response to changing conditions or new evidence
Testing Has the message and how it is communicated been tested? Important public health messages—whether they are designed
to inform or persuade—and ways of communicating them should
be tested with people from key targeted audiences, including
minority groups, to ensure that they are correctly understood and
helpful [42, 43]
Uncertainty Are there important uncertainties about the impacts of the Important uncertainties should be identified. When there are
message? important uncertainties, the impacts of decisions should be evalu-
ated as rigorously as possible
 Oxman et al. Health Research Policy and Systems (2022) 20:28
Fig. 3  In the United States, an ad campaign compared masks to
helmets and seatbelts. The campaign, which was initiated after
wearing a mask had been made mandatory in most public places but
only 66% of residents said they always wore a mask, was based on a
survey that showed this was an effective message
Conclusion
Both persuading people and informing them are reason-
able goals for health communication. However, those
goals can be in conflict. Decisions to persuade people
may be justified, but the basis for those decisions should
be transparent, and persuasive messages should not dis-
tort the evidence. Key messages should be upfront, using
language that is appropriate for targeted audiences. In
addition, it should be easy for those who are interested to
dig deeper and find more detailed information, including
the evidence and the justification for a recommendation
or decision [7].
When there is a public health emergency, persuasion
may be justified despite important uncertainties about
the balance between the potential benefits and harms.
However, when there are important uncertainties, they
should be acknowledged. Not disclosing uncertain-
ties distorts what is known, inhibits research to reduce
important uncertainties, and can undermine public trust
in health authorities. When there are important uncer-
tainties about whether it is justified to persuade people,
the impacts of persuading people should be evaluated as
rigorously as possible.
Acknowledgements
We would like to thank Bjørn Morten Hofmann, Steven Woloshin, Julia Lüh-
nen, Anke Steckelberg, Christina Lill Rolfheim-Bye, Knut Forr Børtnes and Frode
Forland for helpful comments on an earlier version of this paper.
Authors’ contributions
Our interest in health communication that is designed to inform decisions,
and how that differs from communication that is designed to persuade peo-
ple, grew out of research over the past 30 years developing and evaluating
ways of helping people make informed choices about healthcare, including
Page 7 of 9
working with the GRADE Working Group. We drew on this experience and
a broad range of literature, including recent analyses in the context of the
COVID-19 pandemic, to prepare this article. ADO conceived of the idea and
discussed it with the other authors. He prepared a first draft. All the authors
contributed equally to revising the manuscript and agreed with the final
content. All authors read and approved the final manuscript.
Funding
No specific funding was received for this work. All the authors are employees
of the Norwegian Institute of Public Health. SL receives additional funding
from the South African Medical Research Council.
Availability of data and materials
Not applicable.
Declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Author details
1
 Centre for Epidemic Interventions Research, Norwegian Institute of Public
Health, Skøyen, Postboks 222, 0213 Oslo, Norway. 2 Faculty of Health Sciences,
Oslo Metropolitan University, Oslo, Norway. 3 Health Systems Research Unit,
South African Medical Research Council, Cape Town, South Africa. 4 Depart-
ment of General Practice, Institute of Health and Society, University of Oslo,
Oslo, Norway. 5 Centre for Evaluation of Public Health Measures, Norwegian
Institute of Public Health, Oslo, Norway.
Received: 7 December 2021 Accepted: 11 February 2022
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