Opinion
EDITORIAL
qSOFA for Identifying Sepsis Among Patients With Infection
François Lamontagne, MD; David A. Harrison, PhD; Kathryn M. Rowan, PhD
The identification of patients with possible sepsis is vitally im-
portant because timely recognition and appropriate, effec-
tive treatment substantially improves survival. Unlike some
other life-threatening condi-
tions (such as myocardial in-
Related articles pages 290 and farction), for which highly ac-
301 curate diagnostic tests are
available, no rapid diagnos-
tic tests are currently available to accurately identify patients
with sepsis (or those at high risk of developing sepsis) to help
clinicians determine the best course of action. Development
of such tests for sepsis will involve consideration of a number
of key issues, such as whether sepsis is just one or, rather,
multiple entities; whether degrees of having sepsis exist;
which test is the gold standard (an accepted benchmark
against which similar tests can be compared and diagnostic
accuracy assessed); what levels of accuracy are sufficient for
use in clinical practice; and which tests based on what mark-
ers are the most cost-effective. In the meantime, however,
clinicians must rely on clinical judgment, potentially aug-
mented by clinical criteria validated to identify sepsis among
patients with infection.
In 2016, sepsis was redefined as a life-threatening organ
dysfunction caused by a dysregulated host response to
infection.1 Along with this new conceptual definition for sep-
sis, members of the Third International Consensus Defini-
tions for Sepsis and Septic Shock (Sepsis-3) task force pro-
posed qSOFA (quick Sequential [Sepsis-related] Organ Failure
Assessment)—an empirically derived score using simple clini-
cal criteria—to potentially assist bedside clinicians in identi-
fying, among patients with infection, those with sepsis or
those likely to develop it.2 To develop this score, Seymour et
al2 and the Sepsis-3 Task Force analyzed several, very large,
hospital databases, selecting patients with suspected infec-
tion (defined by a combination of use of antibiotics and body
fluid culture within a specific time-window). Based on rou-
tinely available, clinical data, the authors identified the most
parsimonious model, over and above baseline risk, that could
distinguish a suspected infection likely to be, or lead to, sep-
sis from one that likely was not or would not.
When a gold standard exists for a disease or condition, it
is possible to assign true-positives, false-positives, and false-
negatives and calculate traditional metrics such as sensitivity
and specificity. However, when there is no gold standard,
true vs false assignment cannot be determined. Instead, the
value of a test must be assessed on its performance across
different aspects of validity, reliability, and usefulness. The
principal domain used to assess qSOFA was predictive valid-
ity. Specifically, Seymour et al explored the extent to which
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qSOFA and other more complex measures predicted excess
deaths or prolonged intensive care unit (ICU) stay beyond
that explained by baseline risk. These outcomes were used
because, if sepsis differs from a simple infection because of
organ dysfunction and increased threat to life, then death or
prolonged ICU stay should be more common among patients
with sepsis than among those with simple infection.
After validation in 4 external data sets and multiple sen-
sitivity analyses, the final qSOFA model included 3 para-
meters: Glasgow Coma Scale score of less than 15 (1 point),
systolic blood pressure of 100 mm Hg or less (1 point), and
respiratory rate of 22/min or more (1 point). Among patients
with infection outside the ICU, qSOFA had similar or better
predictive validity for the selected outcomes expected to be
more common following sepsis than the more complex mea-
sures tested—SOFA 3 and the Logistic Organ Dysfunction
System4—that require a greater number of clinical and labo-
ratory variables. However, among patients with infection in
the ICU, qSOFA had statistically worse predictive validity.
Both the new definition of sepsis and qSOFA have been
discussed and debated.5-10 qSOFA and, more specifically, its
measurement properties appear to have generated and
attracted the most concern. Two studies in this issue of
JAMA, despite apparently focusing on prognosis (predicting
outcome, regardless of the cause of the outcome) rather than
diagnosis (identifying a disease or condition−the original
intention of qSOFA), provide an opportunity to revisit qSOFA
and its measurement properties both outside and inside the
ICU.11,12 Because so many patients worldwide are at risk of
sepsis and because evaluation for sepsis may occur in the
ambulatory setting, emergency department (ED), or during
hospitalization, understanding whether qSOFA is a good
measure is an enormously important question.
Freund et al11 evaluated the predictive validity of qSOFA
in a prospective study of patients presenting to EDs in
France, Switzerland, Spain, and Belgium. 11 Among 879
patients (median age 67 years, 379 with respiratory tract
infection, in-hospital mortality of 8%) presenting with sus-
pected infection to 30 EDs over a 4-week period, the investi-
gators confirmed that the predictive validity of qSOFA in the
ED setting was similar to that of the full SOFA score and that
the addition of lactate did not improve predictive validity.
The in-hospital mortality was 3% for patients with a qSOFA
score of less than 2 and 24% for qSOFA score of 2 or more.
qSOFA performed better than systemic inflammatory
response syndrome (SIRS) criteria and severe sepsis to pre-
dict in-hospital mortality. The study does have some limita-
tions. Patients who were initially suspected to have infection
but subsequently adjudic ated not to have infection
(Reprinted) JAMA January 17, 2017 Volume 317, Number 3 267
 Opinion Editorial

(on expert review) were excluded, limiting generalizability.
The study also calls into question the applicability of qSOFA
in the ED setting because, despite its reliance on only 3
simple parameters, 14% of recruited patients were excluded
from the analysis due to missing values.
In another report, Raith et al12 evaluated the predictive
validity of qSOFA in a retrospective analysis of the large,
internationally respected, Australian and New Zealand Inten-
sive Care Society (ANZICS) Adult Patient Database of admis-
sions to adult general ICUs. Among 184 875 patients (mean
age, 62.9 years; most common diagnosis, bacterial pneumo-
nia [17.7%]; in-hospital mortality, 18.7%) with an infection-
related primary diagnosis admitted to 182 ICUs over a 16-year
period, the authors confirmed that the predictive validity of
qSOFA in the ICU setting was inferior to the full SOFA score.
The SOFA score increased by 2 or more points in 90.1% of the
patients; 86.7% manifested 2 or more SIRS criteria, and
54.4% had a qSOFA score of 2 or more. Based on area under
the receiver operating curve (AUROC) analysis, SOFA (0.753;
99% CI, 0.750-0.757) demonstrated significantly greater
prognostic accuracy for in-hospital mortality than did SIRS
(0.589; 99% CI, 0.585-0.593) or qSOFA (0.607; 99% CI,
0.603-0.611). It is neither surprising that qSOFA did not per-
form as well as the SOFA score in the ICU, given that this find-
ing was already reported by Seymour et al in their initial
work, nor is it critically important because qSOFA is more
likely to be useful outside of the ICU setting.
Thus, the findings from these 2 studies support the re-
sults reported by Seymour et al that qSOFA is potentially help-
ful in settings outside the ICU in rapidly identifying patients
with suspected infection who have, or will likely develop, sep-
sis. However, qSOFA still warrants further testing, particu-
larly in lower- and middle-income settings where context (for
example, timing of presentation to the hospital among pa-
tients with a suspected infection) might vary considerably and
such contextual factors might affect predictive validity. In ad-
dition, prospective studies may evaluate the utility of qSOFA
when used longitudinally, with repeated measurements
throughout the hospital stay. Arguably, the highest-quality evi-
dence for validation of any tool to support clinical decision
making would come from an analysis to establish whether de-
cisions made with the support of the tool lead to better pa-
tient outcomes than those made by clinical judgment alone.13
Ultimately, the utility of qSOFA will likely become sur-
passed if and when highly accurate, rapid diagnostic tests for
sepsis emerge. For now, however, outside the ICU in the high-
income settings where it has been tested, qSOFA appears a
simple, rapid, inexpensive, and valid way to identify—among
patients with suspected infection—those at a higher risk of hav-
ing or developing sepsis.

ARTICLE INFORMATION
Author Affiliations: Department of Medicine,
Université de Sherbrooke, Sherbrooke, Canada
(Lamontagne); Intensive Care National Audit &
Research Centre (ICNARC), London, United
Kingdom (Lamontagne, Harrison, Rowan).
Corresponding Author: Kathryn M. Rowan, PhD,
Intensive Care National Audit & Research Centre,
Napier House, 24 High Holborn, London WC1V 6AZ,
United Kingdom (kathy.rowan@icnarc.org).
Conflict of Interest Disclosures: All authors have
completed and submitted the ICMJE Form for
Disclosure of Potential Conflicts of Interest.
Dr Lamontagne reported serving as investigator for
a study funded by GlaxoSmithKline and E-Motion,
both of which funded remuneration of research
staff. No other disclosures were reported.
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