REVIE W Open Access
Patient global assessment in measuring
disease activity in rheumatoid arthritis: a
review of the literature
Elena Nikiphorou
1*
, Helga Radner
2
, Katerina Chatzidionysiou
3,4
, Carole Desthieux
5,6
, Codruta Zabalan
7
,
Yvonne van Eijk-Hustings
8,9
, William G. Dixon
10
, Kimme L. Hyrich
11
, Johan Askling
3,4
and Laure Gossec
5,6
Abstract
Patient-reported outcomes (PROs) reflect the patient’s perspective and are used in rheumatoid arthritis (RA) routine
clinical practice. Patient global assessment (PGA) is one of the most widely used PROs in RA practice and research and
is included in several composite scores such as the 28-joint Disease Activity Score (DAS28). PGA is often assessed by a
single question with a 0–10 or 0–100 response. The content can vary and relates either to global health (e.g., how is
your health overall) or to disease activity (e.g., how active is your arthritis). The wordings used as anchors, i.e., for the
score of 0, 10, or 100 according to the scale used, and the timing (i.e., this day or this week) also vary. The different
possible ways of measuring PGA translate into variations in its interpretation and reporting and may impact on
measures of disease activity and consequently achievement of treat-to-target goals. Furthermore, although PGA is
associated with objective measures of disease activity, it is also associated with other aspects of health, such as
psychological distress or comorbidities, which leads to situations of discordance between objective RA assessments
and PGA. Focusing on the role of PGA, its use and interpretation in RA, this review explores its validity and correlations
with other disease measures and its overall value for research and routine clinical practice.
Keywords: Rheumatoid arthritis, Patient global assessment, Discordance
Background
Patient-reported outcomes (PROs) are increasingly recog-
nized for their value in providing the patient’sperspectiveon
aspects of their condition or their overall health status. Their
incorporation into clinical practice and in research in
rheumatoid arthritis (RA) is widely supported by international
organizations and professional bodies [1, 2], including the
European Patients’ Academy on Therapeutic Innovations
(EUP ATI; http://www.patientsacademy.eu/index.php/en/) and
the Patient-Centered Outcomes Research Institute (PCORI;
http://www.pcori.org/resea rch-results) in the United States, as
well as regulatory agencies such as the Food and Drug
Administration (http://www.fda.gov/) and the European
Medicines Agency (http://www.ema.europa.eu/ema/), all of
whom recognize the patient’s unique position in providing
direct feedback on their disease.
Patient global assessment (PGA) is one of the most
widely reported PROs in RA. The considerable burden of
RA on the individual is related to both inflammation and
damage but also to broader aspects of disease, including
psychological and societal impact. The use of PROs like the
widely used Health Assessment Questionnaire (HAQ) or
thePGAallowsamoreholisticassessmentofdiseasebe-
yond objective measures of inflammation or structural
damage, such as acute phase reactants or radiographic
damage. Experts from the American College of Rheumatol-
ogy (A CR), the European League Against Rheumatism
(EULAR), and the Outcome Measures in Rheumatology
Clinical Trials (OMERACT) have endorsed a “core set” of
data for use in RA clinical trials which includes PGA [3, 4].
In recent randomized controlled trials and observational
studies in RA, PGA has been reported in 49 % of studies,
making it the second most frequently collected PRO after
physical function (68 %) [5]. PGA is also incorporated into
several of the major outcome and disease activity scores in
RA,oftenastheonlyPRO:theseincludetheACR/EULAR
* Correspondence: enikiphorou@gmail.com
1
Department of Rheumatology, Whittington Hospital NHS Trust, London, UK
Full list of author information is available at the end of the article
© The Author(s). 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Nikiphorou et al. Arthritis Research & Therapy (2016) 18:251
DOI 10.1186/s13075-016-1151-6
remission criteria, the 28-joint count Disease Activity Score
(DAS28), the Simplified Disease Activity Index (SDAI), the
Clinical Disease Activity Index (CDAI), and the Routine
Assessment of Patient Index Data (RAPID3).
However, the use of PGA in RA presents many chal-
lenges and limitations. The several possible ways of meas-
uring PGA, including the intended assessment or
underlying concept (i.e., global health versus disease activ-
ity) and variations in wording/phrasing and time period
assessed may lead to differences in interpretation of PGA.
Discordance with objective RA measures is also an issue
that needs to be addressed. The latter is particularly im-
portant in the context of treating to target aiming for re-
mission and shared decision-making [6, 7]. What the
different formulations of PGA are, their impact, and justi-
fications for their use remain to be clarified.
To provide readers with a complete overview regard-
ing PGA in RA, a review of the literature was under-
taken based on a hierarchical literature search including
hand searches an d expert opinion searches covering key
publications in the field. The objectives were to explore
the value of PGA as an outcome measure in RA, focus-
ing on its psychometric properties (feasibility, validity,
reliability, and sensitivity to change). Specifically, this re-
view discusses the validity and impact of different word-
ings/phrasings and time period assessed as part of PGA
on patients’ assessment of disease, as well as discordance
between physician global assessment and PGA.
Description and practical application
Concepts behind PGA
PGA was developed in the late 1970s and was initially de-
signed for the measurement of self-assessed pain in RA
[8], although it has since been used to evaluate RA more
globally. It is interesting to note that the way PGA is used
in clinical practice covers, in fact, two very different con-
cepts, one related to global health and the other to overall
disease activity. They are both usually used under the
heading of PGA without further specification for which is
being assessed.
PGA wording and phrasing
It is well-recognized that the wording/specific phrasing
used for PROs may result in a varied response [9–12]. In
the case of PGA, its exact wording/phrasing was not spe-
cified when developed; however, it was suggested that it
could be used for two main purposes—either a patient as-
sessment of global health or of disease activity—stemming
from the two basic concepts (Table 1) [11, 13]. Over the
past years many different wordings/phrasings of PGA have
been formulated, covering variations of these two con-
cepts [14–18]. Furthermore, anchor wordings may also
vary, e.g., words used to describe the right end of the score
(corresponding to scores of 10 or 100) from “worst pos-
sible” to “most active” to “very active”, for example.
Although the wording/phrasing of PGA remains un-
standardized to date, the ACR/EULAR remission criteria
do specifically propose the following phrasing related to
disease activity: “Considering all the ways your arthritis
has affected you, how do you feel your arthritis is
today?” [19].
PGA reference period
Aside from different wording/phrasing used for the
question stem, the reference periods to describe the time
component (i.e., the period of recall the patient should
refer to when answering the question) can also vary
(Table 1). As we will see in this review, the different for-
mulations of PGA lead to differences in interpretation.
In the context of a EULAR taskforce to standardize data
collection across registries, in 2015 we contacted registries
and cohorts across Europe to explore outcomes being
assessed: 52 out of 67 (78 %) registries were collecting
some form of PGA [20]. The versions of the PGA used
varied with regard to the concept, wording/phrasing, and
reference period used. More recently, a smaller pilot sur-
vey in 2016 (unpublished data) indicated that 6/16 (38 %)
cohorts were assessing disease activity-PGA (either related
to RA or not specifically related to RA) whereas 6/16
(38 %) were assessing global health PGA and 4/16 (25 %)
were assessing both concepts. Some wordings as trans-
lated by the investigators are shown in Table 1. With re-
gard to the reference period, 41 % reported “today” as
being the time reference used, with the second most com-
mon being “last week” (35 %).
PGA scoring
Depending on the type of score used, the PGA can range
from 0–100 mm, although is often reported from 0–
10 cm. Higher scores represent a higher level of disease
activity or a worse global health. The proposed definition
of “low global assessment” is ≤2.0 (scale 0–10) [21].
PGA may be scored using a numeric rating scale (NRS),
a verbally administered NRS, or a visual analogue scale
(VAS). The PGA-VAS is classically anchored on an unnum-
bered 10-cm/100-mm horizontal line but may also be ad-
ministered as a vertical VAS. The VAS may be anchored at
the ends (e.g., with defined adjectives at the ends such as
best versus worst) or open. Sometimes the PGA is pre-
sented with tick marks at periodic intervals or as a VAS
consisting of 21 circles at 0.5-mm intervals, the latter
shown to be similar to a classic 10/100 scale [22]. In prac-
tice, sometimes these exact definitions are not followed
(e.g., the line is not 10 cm long or there are not 21 circles
evenly spaced) and these technical difficulties may hamper
the use of PGA (as is the case with other PROs). A Likert-
Nikiphorou et al. Arthritis Research & Therapy (2016) 18:251 Page 2 of 11
style scale may also be used, though its metric properties
are different.
A study comparing responses to a global health VAS
presented both as a 10/100 cm horizontal scale with no
incremental markers and as a vertical 20/100 cm VAS
with 1-cm markers concluded that different presentation
of scales, order effect, and incremental markers can affect
scoring [14]. Another study comparing different scaling of
PGA revealed similar construct validity for VAS and NRS
but higher sensitivity to change of VAS [23]. Although
some differences can be seen in scoring methods for PGA,
all methods appear at this point similarly valid. We would,
however, recommend the use of either an unnumbered
horizontal VAS or a numbered horizontal NRS since these
formats are the most usual and most used.
Psychometric properties of PGA
The main strengths and weaknesses of PGA are summa-
rized in Table 2. Below, we review each psychometric
property of PGA.
Feasibility
Like other PROs, including, for example, the HAQ, PGA
is a very feasible measure. PGA is administered as a sim-
ple, single-item (with no subscale), patient-completed
question measuring the overall way RA affects the pa-
tient and/or disease activity at a specific point in time.
There is no cost attached to it, it is practical, and can be
self-administered. The single question takes only a few
seconds to ask, making it feasible in routine clinical set-
tings but also as an end-point in clinical trials in RA and
is one of the main strengths of the PGA, making it one
of the most frequently reported domains across pub-
lished RA studies [6].
Face validity
PGA is a global, “gestalt” measure of disease which ap-
pears to encompass many aspects of disease which are im-
portant for patients. Physicians’ assessment of RA disease
activity is mainly driven by objective criteria, i.e., tender/
swollen joint counts and level of inflammation, whereas it
seems patients place more focus on overall well-being,
levels of pain, and health-related quality of life [24]. The
latter, in particular, seems to have the greatest relevance
and meaning to patients. However, it is often difficult to
capture health-related quality of life with simple question-
naires. In this sense, PGA appears of interest since it may
summarize in one simple measure many aspects of disease
and health which are important to patients.
Although PGA has high face validity (Table 2), it does
present some challenges. A major point is the patient’sin-
terpretation of the PGA, both depending on the concept
(i.e., global health versus disease activity) and on the pa-
tient’s individual comprehension of this broad question.
For both concepts behind PGA, a criticism is that the re-
sponse to the question may both reflect a broad under-
standing of the patient’s health and also be influenced by a
number of factors, making it difficult to discern what as-
pect of disease contributes to the overall score. Structural
damage (related to disease duration) and other aspects of
patients’ lives (such as comorbidities or psychological dis-
tress) may have an impact on the scoring of PGA [1].
In both cases of PGA (i.e., global health versus disease
activity), interpretation of the question by the patient may
depend on duration of disease through a “response shift”
(i.e., a change in the meaning of a patient’s self-evaluation)
resulting from a better knowledge of symptoms and
changes in patient expectations [25]. In the current bio-
logic era, however, cumulative damage is considerably
Table 1 Different concepts covered by PGA and examples of different types of wording used
Concept Attribution
to RA
Example question Reference period
Disease
activity
Related to
arthritis
“Considering all the ways your arthritis has affected you, how active do you feel your arthritis is
…”
“Considering the tenderness, pain, and swelling of joints, how active is your rheumatoid arthritis
....”
“In general, how active has your rheumatic condition been?”
“How active do you consider your arthritis?”
“In terms of joint tenderness (i.e., joint pain associated with light touch) and joint swelling (i.e.,
joint enlargement due to inflammation), how active would you say your rheumatic condition is
today?’
Today
Over the past 2 days
Last week
Last month
Unspecified time period
Overall “How do you estimate your disease activity ..?”
Global
health
Related to
arthritis
“Considering all the ways your arthritis has affected you, how would you say your health is …”
“Considering all the ways in which your illness affects you at this time, please make a mark
below to show how you are doing”
“How has your arthritis affected you today?”
“Considering all the ways your arthritis affects you, rate how well you are doing on the
following scale…”
Overall “Considering all the ways in which illness and health conditions may affect you at this time,
please make a mark below to show how you are doing”
“In general how would you say your health is”
Nikiphorou et al. Arthritis Research & Therapy (2016) 18:251 Page 3 of 11
lower despite longer disease duration and therefore the ef-
fect and meaning of a response shift may have a different
interpretation. Differences in patients’ perceptions regard-
ing internal standards, values, or conceptualization of
health-related quality of life can result in “ambiguous” or
“paradoxical” findings [25]. For example, patients with
long-standing disability may report a good or high quality
of life (despite what externally might appear paradoxically
untrue) due to several factors, such as acceptance and the
opportunity to adjust and achieve stability through several
transition phases while living with disability. All these fac-
tors need to be taken into account when interpreting indi-
viduals’ PGA scores.
Reliability
Data on the reliability of PGA, which refers to the repro-
ducibility in a test–retest setting, are reassuring [26–28].
Studies have shown the PGA intraclass correlation coef-
ficient (as a measure of test–retest reliability) to be gen-
erally acceptable to high, though lower than ones noted
for physician global assessment [29, 30]. The data avail-
able in the literature do not allow us to directly compare
reliability of PGA–global health versus PGA–disease ac-
tivity; although when tested separately, both appear to
have acceptable reliability.
Sensitivity to change
Sensitivity to change indicates that the measure will im-
prove when the underlying conceptual framework (here,
either global health or disease activity) improves. PGA
has been shown to be sensitive to change, which makes
it a very useful clinical measure in a ssessing RA, particu-
larly in clinical trials. PGA detects improvement after ac-
tive treatment better than, for example, tender joint
count [31]. Table 3 summarizes key findings in this area.
Furthermore, PGA has been shown to discriminate
active treatment from placebo in randomized controlled
trials, with treatment-associated changes being congru-
ent with measures of inflammation, suggesting close re-
flection of other criteria related to the R A process , such
as joint counts [32].
In support of the above, in an analysis of the efficien-
cies to distinguish active treatment from control treat-
ments in clinical trials, among the seven RA core set
measures, the highest relative efficiencies were for the
physician global estimate followed by PGA and physical
function [33]. “Objective” measures of disease, such as
acute phase reactants and tender and swollen joint
counts, were not superior to “subjective” global esti-
mates of the physician or patient self-report measures of
physical function or pain to differentiate active from
control treatments. These findings challenge the view
that laboratory and clinica l examination findings are
more robust than patient self-report measures in asses-
sing and monitoring disease progression and treatment
response in RA [33].
Consequences of different wordings/phrasings
The heterogeneity in the wording/phrasing of PGA re-
quires caution when interpreting the results [34]. The
DAS28 is one of the most commonly used composite
scores in routine clinical practice; the PGA component
of the score carries a small weighting of 0.014, which
may still result in differences to the overall DAS28 score
(the maximum di fference being 1.4 when holding the
other variables constant and using first a PGA-VAS
score of 0 mm, then of 100 mm). French et al. [11]
performed a study where DAS28 was calculated in the
same patients when using different PGAs. Five different
versions of the PGA-VAS were assessed based on: (1)
“Feeling” (“How do you feel con cerning your arthritis
over the last week?”); (2) Disease activity (“How active
Table 2 Major strengths and weaknesses of PGA in RA
Strengths Weaknesses
Practical and feasible to collect: much more easily
collected than joint counts, acute phase reactants,
or radiographic damage
(simple, single-item tool)
Heterogeneity in concept (i.e., global health versus disease activity) and attribution to RA
or other co-existing health conditions and wording/phrasing, all leading to possible het-
erogeneity in the responses
No cost, non-invasive and self-administered Heterogeneous phrasing of the time-frame (today, last week, etc.) applied to PGA
May summarize all aspects of disease important
to the patient
(face validity)
Very broad concept leading to interpretation difficulties
Practical and feasible to interpret: easy to score,
incorporate in composite scores, and analyze
Difficulties of interpretation due to uncertainty regarding attribution to permanent
damage related to RA compared to inflammation and disease activity
Good test–retest reliability Difficulties of interpretation due to uncertainty regarding attribution to RA versus non-RA
disease, including psychological distress and comorbidities
Good sensitivity to change in clinical trials May be influenced by patient education level
Discordance between PGA and physician assessment:
brings in additional information
Discordance between PGA and physician assessment: what impact on decision making?
Nikiphorou et al. Arthritis Research & Therapy (2016) 18:251 Page 4 of 11
has your disease been this week?”); (3) “Well-being”
(“How has your overall well-being been this week?”); (4)
“Best/worst” (“If 0 is the best you have ever been and
100 is the worst you have ever been, where do you think
you have been over the last week?”); and (5) “Arthritis
impact measurement scales” (AIMS; “Considering all the
ways your arthritis affects you….”). All PGA-VAS ver-
sions correlated strongly with each other (rho = 0.67–
0.87, p < 0.0001) [11]. However, when the phrasing of
PGA varied there was a difference in DAS28 scores, the
largest being 0.63 points. Such differences in score,
though small, could have clinical implications, i.e., on
the eligibility for biologic disease-modifying anti-
rheumatic drugs in countries where access to these
drugs is restricted based on strict DAS28 cutoffs.
However, although there are differences at the individual
level according to the concepts, wordings/phrasing used,
and time period assessed, these differences do not always
reflect differences at the group level [11, 12]. Direct com-
parison between studies is limited due to differences in
techniques used to assess the PGA and the population
used. Although this has not been explored, it is possible
PGA interpretation may be different in clinical trials
versus in “clinical practice”, in particular given population
selection and the often multiple use of PROs in studies.
Table 4 summarizes the main aspects of the PGA and
key messages presented in this review.
Interpretation of PGA levels for remission
Both DAS28-based remission and ACR/EULAR defined re-
mission criteria incorporate PGA into their scores [2, 35].
ACR/EULAR Boolean-based remission is defined as PGA
≤1usinga0–10 VAS. Therefore, PGA plays a major role in
determining fulfillment of remission criteria in RA [6, 7, 35,
36]. In fact, PGA appears to be often a limiting factor for
remission—i.e., in patients with no visible inflammation, re-
mission may not be reached because of PGA. In a study
based on the DREAM remission induction cohort, ACR/
EULAR remission was present in 20.1 % of the patients. In
108 out of 512 patients, the PGA score was >1 using a 0–
10 VAS despite fulfillment of the remaining criteria (TJC28,
SJC28, and C-reactive protein in mg/dl ≤1). The specific
wording of questions and anchors used for the PGA were:
“Considering all of the ways your arthritis affects you, mark
“X” on the scale for how well you are doing” (“very well” to
“very poor”)” [37]. Similarly, close to half the pat ients
without visible inflammation in the ESPOIR cohort
did not achieve ACR/EUL AR remission be cause of
PGA levels above 1/10 cm [38]. Thus, near-remission
defined as three of the four criteria (PGA excluded)
Table 3 Sensitivity of PGA to change in disease activity and comparison with other measures of disease
Study
group
Study details Main findings
Kaneko et
al. 2014
[46]
Prospective study
Newly diagnosed RA
75 patients
Discordance between PGA and EGA
PGA more sensitive for indicating progressive joint destruction and
functional impairment when compared with EGA
Discrepancy directed toward a worse assessment by patients
Pope et al.
2009 [52]
Prospective study of a large clinical practice
225 RA patients
MID estimates for: (1) HAQ-DI improvement and worsening
using PGA anchor; and (2) pain using a patient-reported pain
anchor.
MID scores for HAQ-DI in clinical practice were smaller than those seen
in clinical trials
MID scores were influenced by baseline HRQOL scores and may be
influenced by disease duration
MID changes were different for worsening (usually needing a larger
value) than for improving
MID for deterioration was much less than for improvement in patients
with more pain and impairment in physical function
Wells et al.
2008 [31]
Randomized controlled trial comparing abatacept (n = 258)
with placebo (n = 133) in anti-TNF poor respondents (ATTAIN
study)
Evaluation of the responsiveness of PROs in RA patients
PGA had larger relative percentage improvement with treatment (24 %)
than the generic quality of life outcomes SF-36 domains and compo-
nent scores (range 8–21 %)
PGA was more efficient than TJC in detecting a treatment effect
PGA was found to be in close proximity to the ESR, physician global
assessment and the PROs pain assessment, HAQ, bodily pain and
physical component score in terms of the standardized response means
Lassere et
al. 2001
[53]
Literature review on reliability for different classes of RA
measures
The SDD for the PGA (as well as for SJC, TJC, and pain) was found to be
large and it had poor reliability compared to multi-item measures of
physical and psychological function and radiologic measures
Ward 1994
[54]
Prospective study
24 RA patients
Determination of the relative accuracy and sensitivity to
change of 14 measures commonly used to assess arthritis
activity
High correlation between EGA, PGA, and pain scores
The PGA along with other measures of disease severity have been
shown to be more sensitive to change than laboratory measures (ESR)
EGA estimator global assessment, ESR erythrocyte sedimentation rate, HAQ-DI Health Assessment Questionnaire-Disability Index, HRQOL Health Related Quality of
Life, MID minimally important difference, PGA patient global assessment, SDD smallest detectable difference, SF-36 36-item Short Form Health Survey, SJC swollen
joint count, TJC tender joint count, TNF tumor necrosis factor
Nikiphorou et al. Arthritis Research & Therapy (2016) 18:251 Page 5 of 11