JOHN M.
EISENBERG CLINICAL DECISIONS AND COMMUNICATIONS SCIENCE CENTER WHITE PAPER SERIES
Communicating the Uncertainty of Harms and
Benefits of Medical Interventions
Mary C. Politi, PhD, Paul K. J. Han, MD, MA, MPH,
Nananda F. Col, MD, MPP, MPH, FACP
Background. There is growing interest in shared medical
decision making among patients, physicians, and policy
makers. This requires patients to interpret increas-
ing amounts of medical information, much of which is
uncertain. Little is known about the optimal approaches
to or outcomes of communicating uncertainty about the
risks and benefits of treatments. Methods. The authors
reviewed the literature on various issues related to uncer-
tainty in decision making: conceptualizing uncertainty,
identifying its potential sources, assessing uncertainty,
potential methods of communicating uncertainty, poten-
tial outcomes of communicating uncertainty, and current
practices and recommendations by expert groups on com-
municating uncertainty. Results. There are multiple
sources of uncertainty in most medical decisions. There
are conceptual differences in how researchers define
P atients increasingly seek more active participa-
tion in health care decisions, and many groups
have called for a shift toward more meaningful dia-
logue between patients and physicians.1
3 Informed
Received 10 July 2007 from Brown Medical School/Rhode Island Hos-
pital, Providence, Rhode Island (MCP, NFC), and Outcomes Research
Branch, Applied Research Program, Division of Cancer Control and
Population Sciences National Cancer Institute, Rockville, Maryland
(PKJH). An earlier version of this work was presented at the 2006
Agency for Healthcare Research and Quality (AHRQ) Eisenberg Center
Conference: Communication of Harms and Benefits of Prescription
Pharmaceuticals to Healthcare Consumers, Rockville, Maryland, 13
September 2006. This research was conducted by the authors under
the AHRQ contract HHSA29020050013C, Rockville, Maryland. The
authors of this article are responsible for its content. No statement
may be construed as the official position of the AHRQ or the US
Department of Health and Human Services. We would like to thank
Beverly Rockhill Levine, PhD; Isaac Lipkus, PhD; Ellen Peters, PhD;
and Valerie Reyna, PhD for their insightful comments. Revision
accepted for publication 11 July 2007.
Address correspondence to Nananda Col, MD, Director, Center for
Outcomes Research and Evaluation, Maine Medical Center, 39 Forest
Ave, Portland, Maine 04101; e-mail: coln@mmc.org.
DOI: 10.1177/0272989X07307270
MEDICAL DECISION MAKING/SEP–OCT 2007
uncertainty and its sources, as well as in its measurement.
The few studies that have assessed alternate means of
communicating uncertainty dealt mostly with presenting
uncertainty about probabilities. Both patients’ and physi-
cians’ interpretation of and responses to uncertainty may
depend on their personal characteristics and values and
may be affected by the manner in which uncertainty is
communicated. Conclusions. Research has not yet identi-
fied best practices for communicating uncertainty to
patients about harms and benefits of treatment. More con-
ceptual, qualitative, and quantitative studies are needed
to explore fundamental questions about how people pro-
cess, interpret, and respond to various types of uncer-
tainty inherent in clinical decisions. Key words:
uncertainty; risk communication; decision making. (Med
Decis Making 2007;27:681–695)
or shared decision making requires that patients
understand their medical condition, know what
treatments are available, understand the expected
outcomes of treatments, and assess these expected
outcomes according to their personal values.4 One
essential component of this process is knowledge of
the scientific uncertainties that pervade and compli-
cate every step of medical decision making. A recent
summary of the state of medical knowledge reported
that nearly half (47%) of all treatments for clinical
prevention or treatment were of unknown effective-
ness and an additional 7% involved an uncertain
tradeoff between benefits and harms.5
Discussing the many uncertainties associated
with a clinical decision is thought to be a critical
element of an informed decision. Nonetheless,
empirical evidence suggests that clinicians rarely
communicate uncertainty about evidence to pati-
ents. Analysis of 1057 clinical encounters by pri-
mary care physicians and surgeons2 found that
only 16% to 18% of discussions met the minimum
criteria for an informed decision; discussion of
uncertainty about risks and benefits of treatment
was done only 1% of the time for basic decisions,
681
 UNCERTAINTY OF HARMS AND BENEFITS OF MEDICAL INTERVENTIONS
6% for intermediate decisions, and 16.6% for com-
plex decisions.
The rapid growth of medical knowledge has
spurred interest in rating the quality of medical
evidence. Sophisticated rating systems have been
developed to stratify evidence according to its scien-
tific credibility and level of uncertainty. Consider-
able progress has been made in developing such
rating systems by initiatives such as the Cochrane
Collaboration, Evidence-Based Practice Centers, US
Preventive Services Task Force, and Consumer Rep-
orts on Health. In contrast, researchers have only
begun to investigate ways to present scientific uncer-
tainty to health care consumers.
With increasing attention paid to helping patients
use research evidence to inform personal health
decisions, this review was undertaken to address
the following questions: How do we conceptualize
uncertainty? How do we assess uncertainty? What
are the best practices for communicating uncertainty
about harms and benefits of treatment? How do
patients and physicians respond to uncertainty?
Where are the gaps in the literature?
CONCEPTUALIZING UNCERTAINTY AND ITS
SOURCES
There are various definitions and interpretations of
uncertainty. The Merriam-Webster dictionary defines
uncertainty as ‘‘the state of being indefinite, indeter-
minate, unreliable, unknown beyond doubt, not
clearly identified or defined, and/or not constant.’’6
Another proposed definition of uncertainty is ‘‘a
cognitive state created when an event cannot be ade-
quately defined or categorized due to lack of infor-
mation.’’7, 8 In the health domain, Mishel9 has
broadly defined uncertainty in illness as ‘‘the inability
to determine the meaning of illness related events,’’10
which results from the ambiguity, complexity, and
unpredictability of illness10 or deficiency of informa-
tion about one’s illness and its consequences.
In measurement and science, uncertainty often
has a slightly different and technical meaning related
to imprecision in measurement. The National Insti-
tute of Standards and Technology11 defines the uncer-
tainty of a measured result as the standard deviation
of the collection of data samples approximating the
measurand, the quantity being measured. Similarly,
the International Vocabulary of Basic and General
Terms in Metrology12 defines uncertainty as ‘‘a para-
meter associated with the result of a measurement,
that characterizes the dispersion of the values that
682 • MEDICAL DECISION MAKING/SEP–OCT 2007
could reasonably be attributed to the measurand. The
parameter may be a standard deviation or the width
of a confidence interval.’’ Sources of this type of
uncertainty include data acquisition, sampling, quan-
tification, and interpolation. These groups distinguish
between uncertainty and error, in which uncertainty
represents the range of all determinations, whereas
error refers to the difference between an individual
result and the true value of the measurand. Error con-
sists of a random component and a systematic compo-
nent but is an idealized concept, and its magnitude
cannot be known exactly.
The variety of ways in which uncertainty has
been defined and conceptualized reflects its many
potential sources. Because our primary interest is in
informed decision making in the health care
domain, we have chosen to focus specifically on
uncertainties that relate to patients’ understanding
of the outcomes of medical interventions. For our
purposes, therefore, we differentiate between 5 main
types or sources of uncertainty: 1) risk, or uncer-
tainty about future outcomes; 2) ambiguity, or
uncertainty about the strength or validity of evi-
dence about risks; 3) uncertainty about the personal
significance of particular risks (e.g., their severity,
timing); 4) uncertainty arising from the complexity
of risk information (e.g., the multiplicity of risks and
benefits or the instability of risks and benefits over
time); and 5) uncertainty resulting from ignorance.
These different sources of uncertainty are not often
distinguished in the risk communication literature
but should be clarified when discussing uncertainty
in medical decision making.
Fundamental uncertainty about the future occur-
rence or nonoccurrence of a given outcome lies at
the core of the notion of risk. Risk estimates describe
this uncertainty in probabilistic terms and are
derived from empirical observations of an outcome’s
occurrence within a given population. Yet risk esti-
mates embody additional uncertainties as well.
First, because risk estimates are not truly predictive
but rather postdictive (i.e., they explain past pat-
terns of occurrence in a reference population), their
use for the purposes of informing decisions regard-
ing an individual’s outcome requires a leap of faith
that the future, and all of its deterministic elements,
will be the same as the past.
An equally important problem is that risk esti-
mates necessarily have limited applicability at the
individual level. Many argue that risk indeed loses
precise meaning with respect to individual persons
and events because individuals either will or will
not be affected.13, 14 Although risk estimates might
 POLITI, HAN, COL
accurately predict the aggregate number of outcomes
in a population, they cannot specify their exact dis-
tribution15 nor what is most critical for decision
making at the individual level: the future outcome of
any given person. No matter how much any given
person resembles other individuals statistically iden-
tified as falling into one risk category or another,
any one person’s outcome is unknowable and may
diverge from the categorical norm. The irreducible
nature of this uncertainty poses a fundamental limit
to the value of risk estimates in individual decision
making. In addition, there are some types of events
that are beyond the realm of prediction.16
The 2nd type of uncertainty in our schema relates
not to the occurrence of future outcomes but to the
quality of the risk information at hand. Decision
theorists have used the terms ambiguity and vague-
ness to describe this type of uncertainty, which
relates to the ‘‘reliability, credibility, or adequacy’’
of risk information.17;18 Ambiguity or vagueness is
high when risk information is unreliable, conflict-
ing, incomplete, unknown, unknowable, or when
expert knowledge is contested. This type of uncer-
tainty, which relates to the strength of scientific evi-
dence, has several sources, including missing or
inconsistent empirical data or conflicting expert
opinions and recommendations.
The strength of scientific evidence is affected
by many factors. These include, but are not limited
to, study design (randomized controlled trial v.
observational), blinding, duration of treatment and
follow-up, appropriateness of the outcome measures
used, controlling of confounders in design and ana-
lysis, sample size, and sample population. Inade-
quacies in any of these factors can affect the validity
(i.e., increase uncertainty) of the study’s findings,
making it more prone to bias or chance events.
Extrapolating risks derived from studies examining
one duration of treatment to another, from one for-
mulation to another, from a composite end point to
its components, or from one population to another
also introduce ambiguity, as do differences in how
the same studies are interpreted. For example, a
study examining congruence among different meta-
analyses19 found differences among reported find-
ings to be relatively small in comparison to substan-
tial disagreement in the authors’ interpretations
with regard to clinical applications of the findings.
Uncertainty regarding a risk estimate is often exp-
ressed statistically through the use of a confidence
interval (CI) around a point estimate of risk. CIs
express the dispersion around a point estimate
arising from sampling issues and sample size. The
WHITE PAPER SERIES
appropriate interpretation of a CI requires an under-
standing of the difference between accuracy, or how
close an estimate is to the actual or true value, and
precision, or the reproducibility of the estimate. CIs
reflect the precision of an estimate but not its accu-
racy. As such, CIs capture some—but not all—of the
ambiguity pertaining to a risk estimate.
The 3rd and 4th types of uncertainty in our
schema relate to the personal significance of risks
and to uncertainty arising from the complexity of
risk information, respectively. In the health care
domain, the clinical significance of risks for various
outcomes is often unclear. For example, clinicians
and patients may be uncertain about the severity of
these outcomes, their tolerability, scope, timing, or
temporal impact. At the same time, uncertainties
may arise from the sheer complexity of risk informa-
tion. For example, decision makers often need to
process and interpret multiple risks simultaneously
and to make sense of risks that change over time
and as a consequence of different actions.20 The
optimal way of processing risk information in these
circumstances is not clear even for expert decision
makers or complex computerized decision support
systems, and it depends on various assumptions
that are difficult to make explicit. Additional uncer-
tainties about the correct diagnosis and about the
natural history of a disease may further magnify
any uncertainty about the outcomes of treatment
because the likelihood of benefit (but not risk) is pre-
dicated on the patient’s having the condition in
question.
Uncertainty may also arise from ignorance of rele-
vant information. Evaluating risks, making clinical
diagnoses, and making treatment decisions within
the confines of a brief clinical encounter require that
many facts be left unknown, unspoken, or crudely
summarized. This can lead to uncertainty about the
current state of a patient. Many doctors fail to
review21 or document family history,22 and patients
have been shown to inaccurately recall important
risk factors that are used to calculate risks.22 This
type of uncertainty is common in many clinical cir-
cumstances yet is difficult to assess.
PROBLEMS IN ASSESSING UNCERTAINTY
Aside from the conceptual problems involved in
defining uncertainty and its sources, assessing
uncertainty presents an additional challenge. To
promote informed decision making in health care,
one would like to be able to specify or quantify the
683
 UNCERTAINTY OF HARMS AND BENEFITS OF MEDICAL INTERVENTIONS
uncertainty pertaining to information about the risks
and benefits of a given intervention. Yet this task is
made problematic not only by the variety of types of
uncertainty (some of which may not lend them-
selves to quantification at all) but also by methodo-
logical difficulties.
For example, even if one focuses only on uncer-
tainty pertaining to the statistical precision of a risk
estimate (a type of ambiguity), the assessment and
calculation of uncertainty through the use of confi-
dence intervals (or P values) can be challenging.
One problem is that it may be possible to apply
more than one CI when expressing ambiguity, and
the choice of CI is itself ambiguous. A data set can
be examined in its entirety (larger N, smaller CI) or
in subgroups (smaller N, larger CI), and risk esti-
mates from these alternative analyses can differ sub-
stantially in magnitude and dispersion. Although
the overall risk may appear to be more precise than
the risks associated with subgroups because of tigh-
ter CIs, a subgroup analysis may more accurately
reflect the risk pertinent to members of that sub-
group (but with less precision). For example, the
National Surgical Adjuvant Breast and Bowel Project
P-1 trial23 found that tamoxifen increased the risk of
endometrial cancer 2.5-fold (relative risk [RR] = 2.53,
CI = 1.35 − 4.97) among all women. However, age
was an effect modifier: The RR was 1.21 (0.41–3.6)
among women younger than 51 years but 4.01 (1.7–
10.9) among women 51 years or older. In such cases,
it is not clear which CI best reflects the point esti-
mate and associated uncertainty pertaining to an
individual woman: the more accurate estimate that
factors in her age, or the more precise estimate that
does not.
Another problem in assessing uncertainty is
posed by the use of composite end points, which
combine more than one clinical end point into a sin-
gle measure of impact. Composite end points typi-
cally combine more frequent but less clinically
important events (e.g., laboratory abnormalities)
with less frequent but more clinically important
events (e.g., death, stroke) to increase statistical
power (by increasing the event rate).24 However,
these events may differ substantially in terms of
their effects, the uncertainty surrounding their
effects, and their clinical significance. These differ-
ences among the events that are integrated within
composite end points make the specification of
uncertainty very difficult and may lead to biased
estimates. Composite end points that are largely
based on less important clinical end points may
684 • MEDICAL DECISION MAKING/SEP–OCT 2007
overestimate the impact and underestimate the
uncertainty of treatment on more important end
points.
A further difficulty in assessing uncertainty is
introduced by the different types of summary statis-
tics used to express risk. For example, there is gen-
eral concurrence that the risks of treatment should
be communicated as absolute risks (ARs), not RRs.25
Communicating the benefits and risks of treatment
in relative rather than absolute terms can influence
a patient’s perception of a therapy’s effectiveness,26
making the benefits of a treatment appear more
favorable27 or conversely, emphasizing its risks.28
These framing effects concerning the point estimates
of risks have been well studied and have been shown
to affect treatment decisions. However, relatively lit-
tle is known about how to estimate or communicate
the associated CI of absolute risks. Converting an RR
into an AR is relatively simple, but computing the CI
associated with the calculated AR is not.29 When
ARs are not reported, or when the patient differs
from the cohort on which the reported ARs are
based, ARs and their associated CIs must be calcu-
lated. To translate RRs into ARs, the individual’s
baseline (pretreatment) risk for a condition is com-
bined with the RR of the treatment on that condition
using simple multiplication. For example, a person
with a 10% baseline risk who takes a treatment that
has an RR of 2.5 for that condition will experience
an AR of 25% (0.10 × 2.5) with treatment.
Estimating the CI for the AR, however, is more
challenging. Simply finding the CI associated with an
individual’s baseline risk estimates can be difficult
because these often appear in monographs30 or older
journals that may be difficult to access. Once the pub-
lication is found, identifying the appropriate CI for a
risk estimate typically involves tedious multistep
table look-ups, graphical interpretations, and cross-
comparisons.29–31 Finally, these published tables and
graphs require many simplifications from the exact
calculations, thus introducing further uncertainty.
For example, a 40-year-old woman whose 30-year
breast cancer risk is calculated exactly as being 7.3%
(CI = 7–8) is estimated from the tables and graphs as
having a risk of 7.5% (6–10).32 The developers of key
risk prediction models have emphasized the uncer-
tainty associated with their models and the impor-
tance of conveying this uncertainty to patients:
‘‘All of the estimates discussed here are associated
with error; this fact should be transmitted to the
patient should any estimates be given in a clinical
setting.’’29ðp204Þ Nonetheless, when such risk models
 POLITI, HAN, COL
are promulgated,33 their associated CIs are typically
not reported.
To estimate the CI of a calculated AR, one needs
to combine the CI surrounding the patient’s baseline
risk with the CI of the RR. Although these calcula-
tions are intended to measure the uncertainty of the
AR, they also introduce a substantial amount of
uncertainty. This uncertainty stems from differences
between the study population used to develop the
risk model and the individual to whom it is being
applied, as well as the extent to which the model
may be misspecified. Misspecification may result
from omission of important but as yet unidentified
risk factors associated with the disease of interest or
failure to include specific study design elements
such as matching schemes.29 Combining the CI of
the 2 distributions assumes that the 2 are indepen-
dent, an assumption that is unlikely to be true. The
CI of risk prediction models are tightest in the mid-
dle of their prediction range (i.e., for those at average
risk) and widen the further the deviation from the
average. On the other hand, because most clinical
trials are conducted on high-risk populations, their
tightest CIs are typically among those at higher risk.
These and other methodological uncertainties
confound the quantification of uncertainty regarding
risk estimates and pose challenges for the task of
communicating uncertainty to individual decision
makers.
POTENTIAL APPROACHES TO
COMMUNICATING UNCERTAINTY
Problems in both the conceptualization and
assessment of uncertainty have important implica-
tions for the task of communicating uncertainty.
There are multiple types of uncertainty that clini-
cians may want and need to communicate to
patients, and the assessment of these uncertainties is
not straightforward. Furthermore, the communica-
tion of uncertainty to patients may serve different
purposes and goals, for example, to convey doubt or
to increase the level of confidence in a finding, to
inform patients about their estimated disease risk
and the limitations of these estimates, or to help
patients understand the general complexity or unpre-
dictability of illness and its management. Moreover,
these goals are not always consistent with one
another and may require focusing on particular types,
assessments, or approaches to communicating uncer-
tainty. Yet we know very little about the optimal
approaches and outcomes of communicating different
types of uncertainty. Although there is a growing
WHITE PAPER SERIES
literature on approaches to communicating risks (i.e.,
probabilities or likelihoods), little attention has been
given to communicating uncertainty.
In this section, we review possible approaches for
communicating uncertainty and the limited evi-
dence for the effectiveness of these approaches. For
the most part, the discussion will relate to the com-
munication of statistical uncertainty, or ambiguity,
given the existing literature. However, much of what
is written on this topic concerns communication of
risk, not uncertainty.
Uncertainty and ambiguity may be communicated
in a variety of ways, including verbally, numerically,
or visually. Verbal methods using subjective descrip-
tive words such as highly uncertain have the advan-
tage that people think they understand what is being
said; however, interpretation of such terms has been
shown to be highly variable.34
36 The use of num-
bers to depict uncertainty and ambiguity potentially
allows for more precision and avoids variable inter-
pretation. However, there are many different ways in
which information about risks may be communi-
cated quantitatively. They can be described using
RRs, ARs, frequencies, or number needed to treat;
the measure used can affect how the information is
understood and answered. Ambiguity might be com-
municated in terms of any or all of these summary
statistics; however, these possibilities have not been
evaluated.
Furthermore, many people, including experts,
have difficulty understanding and combining statisti-
cal information effectively.37 Numeracy—the ability
to comprehend quantitative information—is manifest
in the way in which people process statistical infor-
mation. One study38 found that individuals with high
numeracy were less biased by framing effects and
more influenced by affective meaning than were those
with low numeracy. Another study39 found that indi-
viduals with low numeracy tend to better compre-
hend information about the comparative quality of 2
choices when it is simplified (e.g., by highlighting
relevant or meaningful information). It is also possible
that numeracy is reflected in people’s ability to under-
stand and process information about statistical uncer-
tainty or ambiguity, but this possibility has not been
explored.
Visual depictions of data may facilitate rapid
understanding of numerical expressions of uncer-
tainty, particularly if large amounts of numerical
information must be presented. However, little
is known about how ambiguity might be depic-
ted visually. Limited work suggests that the visual
depiction of statistical uncertainty may exploit the
685
 UNCERTAINTY OF HARMS AND BENEFITS OF MEDICAL INTERVENTIONS
ability of the eye to quickly detect discontinuities in
an image and to interpret these discontinuities as
areas with distinct data characteristics. Techniques
that have been used to depict uncertainty have
incorporated discontinuities such as surface rough-
ness, blurring, and oscillations,40 depth-shaded
holes, noise, and texture,41 and the translation, scal-
ing, rotation, warping, and distortion of geometry.41
Animation effects have been used to simplify the
visualization of statistical uncertainty by not dis-
playing all of the information at once41 and by map-
ping uncertainty to animation parameters (speed,
motion blur, duration, and range of motions) and
sound effects (pitch, duration, timbre, and vol-
ume).42 Most visualizations rely on the box plot or
variants thereof, which divides the data into 4 quar-
tiles, draws a box around the central 50% of the
data, and includes lines (whiskers) encompassing
the range.43 Most visual depictions of ambiguity
attempt to portray confidence intervals around a risk
estimate, but uncertainty around other measures,
such as the number needed to treat, has also been
illustrated.44
Few of these approaches for visualizing ambigu-
ity appear to have been tested for their effect on
comprehension and choices, and existing studies
have been inconclusive. One study45 compared 9
graphics depicting ambiguity about a weather fore-
cast. They found that participants (n = 45) were
most familiar with the pie chart and histogram,
but familiarity did not correspond to improved
understanding. The pie chart and cumulative den-
sity function were best at communicating whether
a value fell within a specified range. However,
no single graph consistently dominated the others
in terms of improving the understanding of uncer-
tain data; the authors suggested using a combination
of graphics to communicate statistical uncertainty.
A 2nd study46 elicited reactions to visual depic-
tions of uncertainty about risk estimates. In one of
the depictions, participants were shown a line
graph displaying a point estimate and subsequently
one displaying both a point estimate and CIs asso-
ciated with the risk reduction of breast cancer mor-
tality. Less educated women perceived the point
estimate with CI as making the information seem
‘‘vague’’ or ‘‘wishy-washy,’’ and it decreased trust in
the information presented. More educated women,
however, were more accepting of ambiguity, and
most women in this group felt that the CI should
be presented. Thus, patient characteristics may
influence understanding of, and response to, uncer-
tainty about risks.
686 • MEDICAL DECISION MAKING/SEP–OCT 2007
Table 1 Categories of Effectiveness Used by the
BMJ Clinical Evidence Series5
Intervention Icon Description
Beneficial for which effectiveness has been demonstrated by clear
evidence from RCTs or the best alternative source of
information, and for which expectation of harmfulness is
smallcompared with the benefits.
Likely to be for which effectiveness is less well established than for those
beneficial listed under “beneficial.”
Tradeoff between for which clinicians and patients should weigh up the
benefits and harms beneficial and harmful effects according to individual
circumstances and priorities.
Unknown for which there are currently insufficient data or data of
effectiveness inadequate quality.
Unlikely to be for which lack of effectiveness is less well established than
beneficial for those listed under “likely to be ineffective or harmful.”
Likely to be for which ineffectiveness or harmfulness has been
ineffective or demonstrated by clear evidence.
harmful
PAST APPROACHES TO COMMUNICATING
UNCERTAINTY
There are many recommendations for and exam-
ples of communicating uncertainty in the literature,
although few are supported by evidence. Most have
been limited to efforts at verbally summarizing the
quality of scientific evidence pertaining to a given
health intervention. Several widely used rating
systems use simple descriptive terms to describe
uncertainty, typically combining the strength of the
evidence with the magnitude of the benefit. For exam-
ple, the BMJ Publishing Group’s Clinical Evidence5,47
reports categorize the effectiveness of interventions
as being either beneficial, likely to be beneficial, a tra-
deoff between benefits and harms, unknown effect-
iveness, unlikely to be beneficial, or likely to be
ineffective or harmful (Table 1). Similarly, the US
Preventive Services Task Force48 combines verbal rat-
ings of the strength of the evidence of effectiveness
with an estimate of net benefit (benefits minus harms;
 POLITI, HAN, COL

Table 2 How the US Preventive Services Task Force Grades Its Recommendations48

Strength of Overall Evidence and Estimate of Net Benefit Determine

the Grade

Strength of Estimate of Net Benefit (Benefits Minus Harms)

Overall
Evidence of Substantial Moderate Small Zero/Negative
Effectiveness

Good A B C D

Fair B B C D

Poor I—Insufficient Evidence

The US Preventive Services Task Force (USPSTF) grades its recommendations based on the strength of evidence and magnitude of net benefit (benefits
minus harms).

A. The USPSTF strongly recommends that clinicians provide [the service] to eligible patients. The USPSTF found good evidence that [the service]
improves important health outcomes and concludes that benefits substantially outweigh harms.
B. The USPSTF recommends that clinicians provide [the service] to eligible patients. The USPSTF found at least fair evidence that [the service]
improves important health outcomes and concludes that benefits outweigh harms.
C. The USPSTF makes no recommendation for or against routine provision of [the service]. The USPSTF found at least fair evidence that [the service]
can improve health outcomes but concludes that the balance of benefits and harms is too close to justify a general recommendation.
D. The USPSTF recommends against routinely providing [the service] to asymptomatic patients. The USPSTF found at least fair evidence that [the ser-
vice] is ineffective or that harms outweigh benefits.
I. The USPSTF concludes that the evidence is insufficient to recommend for or against routinely providing [the service]. Evidence that [the service] is
effective is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined.

The USPSTF grades the quality of the overall evidence for a service on a 3-point scale (good, fair, poor).

Good: Evidence includes consistent results from well-designed, well-conducted studies in representative populations that directly assess effects on
health outcomes.
Fair: Evidence is sufficient to determine effects on health outcomes, but the strength of the evidence is limited by the number, quality, or consistency of
the individual studies; generalizability to routine practice; or indirect nature of the evidence on health outcomes.
Poor: Evidence is insufficient to assess the effects on health outcomes because of limited number or power of studies, important flaws in their design or
conduct, gaps in the chain of evidence, or lack of information on important health outcomes.

substantial, moderate, small, zero), assigning letter
grades (A, B, C, and D) to various combinations of
these 2 rating scales (Table 2). Both systems attempt
to surmise the likelihood that the benefits outweigh
the risks and blend uncertainty with the magnitude
of the net benefit.
The popular lay publication Consumer Reports
Best Buy Drugs49 explains the benefits and risks of
treatments to consumers by using subjective terms
(‘‘about 30%,’’ ‘‘up to 7%’’) and by reporting ranges
that imply a CI but that are not explicitly defined
(‘‘between 17% and 25% are pain-free’’). Uncer-
tainty about individual variation is communicated
by stating,
It’s very important for you to know that people respond
differently to the various [treatments]. You may get lit-
tle or no relief from one and respond much better to
another . . . . But it’s possible that you would not be
helped by one of the three [treatments]. In that case,

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 UNCERTAINTY OF HARMS AND BENEFITS OF MEDICAL INTERVENTIONS
you should try one of the others. Doctors are very used
to trying another [treatment] if the first one they pre-
scribe for you does not seem to be working.
Data are lacking regarding outcomes of these
approaches to communicating uncertainty for either
physicians or patients involved in treatment deci-
sion making. According to the recent Cochrane
review of decision aids, for instance, few of the 131
decision aids reviewed included a description of the
level of uncertainty about the evidence.50
POTENTIAL OUTCOMES OF COMMUNICATING
UNCERTAINTY
To identify appropriate ways to communicate
uncertainty to patients, it is important to understand
the potential outcomes of this endeavor. Although
empirical evidence in the health domain is lacking,
there is a substantial literature on the psycho-
logical and behavioral effects of uncertainty in other
decision-making domains.
COGNITIVE AND BEHAVIORAL OUTCOMES
OF COMMUNICATING UNCERTAINTY
One concern about communicating uncertainty is
that doing so may have deleterious as well as benefi-
cial effects. To the extent that communicating
uncertainty entails the transfer of additional, com-
plex information, it has the potential to overwhelm
and confuse patients and to impair their ability to
make truly informed decisions. Ample research in
decision psychology has shown that a surfeit of
information does not necessarily facilitate informed
decision making51 and may in fact hinder it.39 Full
disclosure of all the benefits and risks associated
with a medical treatment may exceed patients’ capa-
city to process and use this information effect-
ively.52 The provision of added information about
medical uncertainty may have similar outcomes
with respect to patient understanding and decision
making.
A potentially effective way of mitigating these
negative outcomes of complex health information
may be to tailor the information to individual
patients, altering the specific type or amount of
information presented according to various charac-
teristics (e.g., gender, culture, education, psycholo-
gical factors, or behaviors of interest53
55 ) that relate
to patients’ capacity to use or respond to such infor-
mation. Presumably, such tailoring enhances
688 • MEDICAL DECISION MAKING/SEP–OCT 2007
behavior change in response to information.56
58
Health information might also be tailored according
to patients’ individual disease risks or risk factors.
For example, the provision of individualized dis-
ease risk estimates has been found to increase
patients’ uptake of screening tests, particularly in
patients at high risk for disease.59 Tailoring the com-
munication of health information according to
patients’ individual disease risks, however, is pro-
blematic given the substantial uncertainties implicit
in individual risk estimates.14 Furthermore, the tai-
loring of any type of health information according to
individual patient characteristics still raises a larger
question about the optimal amount and type of
information to be conveyed to patients from an ethi-
cal, as well as a psychological, standpoint. Until
these issues are resolved, a critical issue is to better
understand the potential outcomes of communicat-
ing uncertainty to patients in general.
Empirical and theoretical work on judgment and
decision making provides insights on the potentially
negative effects of communicating uncertainty about
risk information and the mechanisms for these
effects. A large body of past research has shown that
both laypersons and experts trained in statistics tend
to simplify and use mental shortcuts, or heuristics,
when interpreting risk information.60 Patients often
simplify probabilistic information into 2 broad cate-
gories (e.g., ‘‘I will get the disease’’ or ‘‘I will not get
the disease’’61 ). People’s reliance on heuristics and
other simplifying strategies points to inherent limita-
tions in human cognitive processing.62 These limita-
tions have been described extensively and raise
the possibility that people may not always respond
in adaptive ways to the provision of complex prob-
abilistic information. For example, some have
argued that decision makers have a fundamental pre-
ference and need to rely on mental representations
of the bottom-line meaning or gist of a choice option,
rather than the detailed or verbatim representation
that includes the accompanying details.63, 64 For
these reasons, decision makers may find details
about the uncertainty pertaining to risk information
of limited relevance or overly difficult to process or
understand.
Also relevant to the discussion of potential out-
comes of communicating uncertainty in health care
is the literature on decision psychology. A number of
studies have shown that people generally prefer to
avoid ambiguity; when confronted by ambiguous
information about risks, people tend to appraise
these risks pessimistically and avoid making deci-
sions.17, 65, 66 This phenomenon has been termed
 POLITI, HAN, COL
ambiguity aversion and has been demonstrated in a
number of decision-making settings. Ambiguity aver-
sion has been shown to persist even when odds favor
the ambiguous option,67
69 although the level of risk
appears to affect people’s reactions to ambiguity. At
very low probabilities of the unambiguous option,
decision makers become indifferent to ambiguity and
may even become ambiguity seeking.68, 70, 71 Ambigu-
ity aversion may also depend on whether gains
or losses are at stake.65, 66, 72 With potential gains
(e.g., winning money), people are ambiguity averse,
whereas with potential losses (e.g., losing money),
people are ambiguity seeking. However, this finding
has not been consistently obtained,69 and ambiguity
aversion itself varies considerably among individuals
and across different decision-making circumstan-
ces.73 Ambiguity aversion may also vary according to
how information on ambiguity is framed, for exam-
ple, in terms of gains versus losses74 or verbally ver-
sus quantitatively.73
Ambiguity aversion may have various psychologi-
cal and behavioral manifestations. For example,
ambiguity regarding estimates of risks of an adverse
outcome may lead people to perceive themselves at
higher risk75 and to have greater distrust in the infor-
mation at hand.76 However, relatively little research
has directly explored how ambiguity aversion may
be manifest in the domain of health-related deci-
sions and outcomes. Using hypothetical scenarios,
Ritov and Baron77 and Meszaros and colleagues78
showed that increasing people’s awareness of ambi-
guity about a vaccine’s safety made them reluctant to
receive it. Other studies have shown that percep-
tions of ambiguity regarding health risks and disease
prevention recommendations are associated with
ambiguity-averse perceptions and emotions and
lower uptake of screening and preventive interven-
tions.79
81 Intervention studies have demonstrated
that informing people about uncertainties surround-
ing cancer screening measures decreases their inter-
est in screening, also implying that people are
ambiguity averse.82;83 For instance, there is conflict-
ing evidence about the effectiveness of breast self-
examinations (BSEs) for early detection of breast
cancer. Following the disclosure of the uncertainty
about evidence, some patients may ignore the posi-
tive evidence about BSEs and decide not to perform
BSEs.84
Communicating uncertainty may also prompt dif-
ferent information-seeking behaviors. Some patients
may respond to uncertainty by actively seeking
information. The attempt to resolve uncertainty may
help them to cope with it; knowledge about
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uncertainty can motivate patients to seek discus-
sions with their health care providers, which may
comfort patients who prefer to take an active deci-
sion-making role in their medical care. However,
uncertainty may also lead to information avoidance
and confusion if patients lack the proper resources
to interpret available information and manage
uncertainty. In one study, for example, 13% of peo-
ple who were tested for HIV never received their
results,85 even though in a separate study, those
who initially avoided learning their HIV status
showed an improvement in mood upon receiving
their test results (regardless of their HIV status).86
Information avoidance may be used as a coping
strategy by people who have difficulty tolerating
potential but uncertain negative health conse-
quences. A similar example is those who receive or
fill prescriptions but do not take medications
because of their fear of side effects.
Emotional Outcomes of Communicating
Uncertainty
Most of the literature about emotional responses
to uncertainty pertains to uncertainty in a broad
sense that includes, but is not limited to, the specific
types of uncertainty outlined in this article. Lazarus
and Folkman’s87 stress and coping theory posits that
the cognitive appraisal of a stressor such as uncer-
tainty occurs in 2 steps. First, a person interprets the
meaning of a stressor and its relationship to his or
her experiences and values. Next, a person assesses
his or her resources and capacity for coping with a
given stressor.
This theory maintains that patients who nega-
tively appraise uncertainty might correspondingly
experience subsequent fear, anxiety, panic, and a
desire to reduce uncertainty. These negative emo-
tional responses may lead to heightened vigilance
about illness, which may further exacerbate worry
about illness.88 However, uncertainty might not
always have negative emotional effects; when con-
fronted by uncertainty about an illness or treatment,
some people are able to maintain hope and opti-
mism. Optimism can encourage patients to accept
treatments and maintain an active response to their
illness if they perceive great potential benefits.84
However, false hopes about treatments can lead some
patients to ignore real risks of other lifestyle beha-
viors. For instance, diabetic patients who believe that
insulin alone can control blood sugar levels might
not additionally alter their dietary habits.
689
 UNCERTAINTY OF HARMS AND BENEFITS OF MEDICAL INTERVENTIONS
In addition to influencing emotions during
decision making, communicating uncertainty may
influence patients’ emotional responses following a
decision. Past research has shown that patients can
experience 3 types of regret following treatment
decisions: outcome regret, which is regret about a
negative health outcome following a decision;
option regret, which is regret about the choice one
made; or process regret, which is regret about the
quality of the decision-making process (e.g., it was
too hasty).89 It is possible that communicating
uncertainty can lead to increased satisfaction in the
quality of the decision-making process, thereby
reducing option or process regret following a deci-
sion. However, it is also possible that communicat-
ing uncertainty can cause patients to blame
themselves in the case of bad outcomes, leading to
more regret.89
Although these findings relate to emotional res-
ponses to uncertainty in a very general sense, they
may also be applicable to understanding the effects
of particular types of uncertainty, such as ambigu-
ity, as they additionally apply to the particular
domain of health care decisions. These outcomes
need to be examined further.
Individual Differences in Patient Responses to
Uncertainty
Patients’ cognitive, emotional, and behavioral
responses to uncertainty are themselves uncertain
and may depend on several individual patient char-
acteristics. For example, the patient’s desired role in
his or her medical care may be important. Some
hypothesize that patients who consider themselves
knowledgeable and competent prefer to make their
own health decisions under uncertainty, and those
who consider physicians the absolute experts prefer
to defer decisions to physicians.90, 91 Others have
suggested that ‘‘patients most want to introduce their
own extra-medical values when medical factors
alone do not seem to be decisive.’’61ðp246Þ Deber and
colleagues92 found that the type of decision-making
task can affect patients’ desired role in the process;
patients may desire involvement in tasks such as
determining the acceptability of risks but may prefer
their physicians to identify treatment options, risks
and benefits of treatments, and probabilities of risks
and benefits occurring. When faced with a mismatch
in decision-making preference and physician beha-
vior, some patients might distrust their physician or
become less satisfied with their care.
690 • MEDICAL DECISION MAKING/SEP–OCT 2007
Patients’ values and preferences for medical care
may also affect how they perceive and respond to
uncertainty about health-related risks. For example,
those who are averse to medications might perceive
uncertainty about medication risks more negatively
than those who are comfortable with prescription
medications.35 As a result, they might decide not to
take the medication because of risk uncertainty.
Individual personality traits may affect pati-
ents’ responses to uncertainty. For example, social
psychologists have identified 2 personality types
that may influence information-seeking behavior
under uncertainty: uncertainty-oriented individuals,
who tend to process uncertainty and seek out rele-
vant information to allow for resolution of it, and
certainty-oriented individuals, who tend to gravitate
toward familiar situations that are less ambiguous
and who tend to rely on respected others to make
decisions.93 Similarly, cognitive processing styles
such as monitoring (vigilantly seeking and attending
to information) or blunting (distracting oneself from
information, blunting its impact) can affect the man-
ner in which patients perceive risks and uncertain-
ties surrounding their health condition.94
Finally, uncertainty may affect physicians as well
as patients, inducing anxiety and excessive concern
about bad outcomes. Physicians and medical trai-
nees tend to fear that patients will perceive them as
inadequate or ineffective,95;96 which may influence
their willingness to disclose uncertainty to patients97
as well as their use of health care resources.98
Patients’ responses to uncertainty may also be
influenced by physicians’ reactions to it. Physicians
are often concerned that acknowledging uncertainty
to patients may undermine patient trust and satis-
faction. However, some research has shown that
patient satisfaction is affected by the manner in
which the physician handles uncertainty, not
whether or not he or she presents uncertainty,99 con-
sistent with previous theories.100 When physicians
are comfortable with uncertainty and collaborate with
their patients in their medical care, patient trust and
satisfaction are actually high.61
HELPING PATIENTS COPE WITH UNCERTAINTY
Because of patients’ complex cognitive, emotional,
and behavioral responses to uncertainty, many argue
that the focus of risk communication should be on
helping patients tolerate and cope with uncertainty
rather than simply helping them understand it.84, 88
Uncertainty can be stressful and anxiety provoking
 POLITI, HAN, COL
for patients throughout the illness experience.9, 61
Some have suggested practical ways for physi-
cians to help their patients cope with uncertainty:
assure patients that they will answer all questions
about their health, refer patients to other sources
such as reputable Web sites, remain open and
sympathetic to patients, inform patients of physi-
cians’ own biases and values, and inform patients
of alternative treatments.101, 102 Others propose
that physicians should clarify the type of uncer-
tainty that is the most distressing to patients (e.g.,
uncertainty about probabilities, uncertainty about
sources of information, uncertainty about evidence)
and be available to explain the complexities of
each.84 Although these tasks make sense and are
ethically justifiable, it remains unclear whether they
are truly beneficial and feasible for physicians to
perform.
RECOMMENDATIONS BY EXPERT GROUPS
Some organizations have made explicit recommen-
dations concerning the need for and possible app-
roaches to communicating uncertainty. The Interna-
tional Patient Decision Aids Standards collaboration
recommends communicating uncertainty and provid-
ing concrete examples to help explain it103 :
It’s very important to acknowledge uncertainty in prob-
ability estimates. Often the uncertainty is large, espe-
cially if evidence is scarce or events are rare. It’s
probably wise to do simple things such as rounding off
numbers (to avoid false illusions of precision), using
phrases like ‘‘our best guess is . . . ,’’ give ranges, or pro-
vide 95% confidence intervals.
Even with the best evidence from large studies, the
issue of stochastic uncertainty remains. Essentially, we
never quite know who are the patients who are going to
be affected, and who the treatment is going to be most
useful for. One way to deal with this uncertainty might
be to say: ‘‘If 100 patients like you are given no treat-
ment for five years, 92 will live and eight will die.
Whether you are one of the 92 or one of the eight, I do
not know. Then, if 100 patients like you take a certain
drug every day for five years, 95 will live and five will
die. Again, I do not know whether you are one of the 95
or one of the five . . . .’’
Despite these limitations from uncertainty, practi-
tioners generally feel that we can still try to make deci-
sions about what the best treatment plan is for an
individual person, based on what happens to these
groups of patients in the studies. Hence the value, it is
thought, of presenting the information about benefits and
WHITE PAPER SERIES
harms to aid the decision making process. Both sources
of uncertainty should be acknowledged in comprehen-
sive discussions of risks in patient decision aids.’’103ðp14Þ
In addition, there have been numerous articles in
the medical literature advocating that physicians
discuss uncertainty. One states,
While often difficult, a discussion of uncertainties is
crucial for a patient’s comprehensive understanding of
the options. Thoughtful discussion can promote trust
and encourage adherence. Examples: ‘‘The chance that
this will help is excellent,’’ ‘‘Most patients with this
condition respond well to this medication, but not
all.’’2ðp2314Þ
On the other hand, some104;105 argue that the dis-
persion around a point estimate is irrelevant when a
choice needs to be made between 2 uncertain options
and that the decision in such cases should be based
on which option has the highest expected net bene-
fit.105 The costs of failing to adopt a new treat-
ment simply because the difference in net benefit is
not statistically significant can be substantial. This
approach does not imply that treatment decisions
should be based on poor-quality evidence but rather
that the amount of information that should be
acquired is an empirical rather than ideological ques-
tion, differing across different clinical decisions.
CONCLUSIONS: CRITICAL KNOWLEDGE GAPS
AND FUTURE RESEARCH NEEDS
Although the ideal of informed or shared decision
making implies a need for communicating uncer-
tainty to patients, this task is problematic for many
reasons. From a conceptual standpoint, it is unclear
which of the many types and sources of uncertainty
clinicians should communicate to their patients.
Exactly what is meant by the term uncertainty and
the ethical justification for communicating different
types of uncertainty are themselves uncertain. More
work is needed to define the circumstances in
which uncertainty ought to be communicated.
Should this be a function of the magnitude of uncer-
tainty surrounding these options and/or the magni-
tude of the consequences of these choices? Should it
depend on the number of choices available, the
novelty of the treatments being considered, or
whether there is a clear dominant option? What
aspects of uncertainty should be communicated,
given the task? Are there patient characteristics that
may influence when we should or should not
691
 UNCERTAINTY OF HARMS AND BENEFITS OF MEDICAL INTERVENTIONS
include uncertainty in risk communication or how
the subject should be approached?
Many of these questions are conceptual and ethical
in nature, rather than empirical, and raise the larger
question of whether there is any level of acceptable
uncertainty. Deciding between various treatment
options is inherently situation specific, and there is
no universally acceptable absolute level of acceptable
risk; one’s acceptance of risk is contingent on many
factors.106;107 Acceptable risk refers to the risk asso-
ciated with the most acceptable option in a particular
decision.107 Is there an analogous concept of accepta-
ble uncertainty? If so, how might different ways of
judging thresholds of acceptable uncertainty be
defined, and from whose perspective?
From an empirical standpoint, we know little
about how to measure and quantify uncertainty and
the various factors contributing to it. What types of
uncertainty do commonly used measures of uncer-
tainty (such as confidence intervals) actually cap-
ture? Can measures of specific contributors to
uncertainty be combined to estimate the total or
composite uncertainty in a finding? Exploration of
the use of different characterizations of risk and
uncertainty (i.e., uncertainty about the time to event,
a continuous variable, rather than the likelihood of
the event, a dichotomous variable at the individual
level) may help move the field forward given the
irreducible uncertainty surrounding individual pre-
dictions when using the likelihood of an event as the
outcome measure. Research is needed to develop
these measures of component and composite uncer-
tainty and to validate them; they then need to be dis-
seminated to decision makers and researchers.
A further empirical problem is that the optimal
methods and outcomes of communicating different
types of uncertainty are not known. There is sugges-
tive, but not definitive, evidence about how various
types of uncertainty are differentially interpreted by
patients, clinicians, and researchers and how these
interpretations affect clinical decision making as
well as other patient-centered outcomes such as per-
ceptions and well-being. The manner in which
uncertainty is communicated can affect how it is
perceived and responded to, but little is known about
the mechanisms of these framing effects. It is unclear
whether uncertainty is best presented verbally,
numerically, graphically, or using multiple formats.
Studies exploring how perceptions of and responses
to uncertainty are potentially affected by its framing
(i.e, certainty v. uncertainty, gain v. loss), choice of
specific terms, measurement units and scale, and gra-
phics would help to clarify this critical issue.
692 • MEDICAL DECISION MAKING/SEP–OCT 2007
More research is needed on potential tradeoffs in
communicating uncertainty. Tailoring information
to the individual’s risks has the advantages of mak-
ing information more relevant and reducing the
volume of information, but the more tailored the
information, the greater the uncertainty associated
with risk prediction. Thus, there may be an inherent
tradeoff between the degree of personalization of
risk information and its uncertainty. There may also
be a tradeoff between the completeness of informa-
tion given and the efficacy of this information in
terms of how it is processed and responded to. In
addition, there may be a tradeoff between the preci-
sion of a risk estimate and its accuracy. Further
exploration of these potential tradeoffs could help
inform discussion of when and how to communi-
cate uncertainty.
The increasing focus on personalized medicine108
mandates a more sophisticated understanding of the
limitations and errors in applying and communicat-
ing population-based, epidemiologic findings to the
individual. Because of the poor positive predictive
value of most of the risk factors (including genetic
markers) for common noninfectious diseases, most
people who will eventually get a disease will not be
designated as high risk by population-based risk
prediction tools.14, 109 Furthermore, how patients
respond to personalized risk estimates is poorly
understood. Fischoff writes, ‘‘Asking people about
the risks to others like themselves is not the same as
asking them about their personal risk. Nor need
reports about others’ risk levels be taken perso-
nally.’’109 Exactly how to use risk estimates and risk
prediction tools to improve and inform individual
treatment decisions, while acknowledging and com-
municating their limited power to predict indivi-
dual futures, is a critical challenge that will become
even more important as new disease biomarkers are
discovered.
More work is also needed to differentiate the con-
struct of uncertainty from risk in various conceptual
models and theories of health behavior. Divergent
conceptual models exist for understanding how
people perceive and respond to uncertainty; further
exploration of new models and attempts to reconcile
differences across models could help advance these
fields of inquiry.
RECOMMENDATIONS
At this time, there are no clear best practices for
presenting uncertainty. The best method of present-
ing uncertainty depends on the task required of the
 POLITI, HAN, COL
patient and the type of uncertainty presented. There
is little evidence about the effect of alternate types
or presentations of uncertainty on patient under-
standing, satisfaction, and informed decision mak-
ing in clinical medicine.
More conceptual, qualitative, and quantitative
studies are needed to explore fundamental ques-
tions about how people process, interpret, and
respond to various types of uncertainty inherent in
clinical decisions. Much more research is also
needed to broaden the scope of inquiry beyond the
problems of communicating statistical uncertainty
around a point estimate to the many other types of
uncertainty relevant to the numerous decisions that
patients and clinicians face.
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