ORIGINAL CONTRIBUTION

The Clinically Important Difference on the

Unified Parkinson’s Disease Rating Scale
Lisa M. Shulman, MD; Ann L. Gruber-Baldini, PhD; Karen E. Anderson, MD; Paul S. Fishman, MD, PhD;
Stephen G. Reich, MD; William J. Weiner, MD

Objective: To determine the estimates of minimal,
moderate, and large clinically important differences
(CIDs) for the Unified Parkinson’s Disease Rating
Scale (UPDRS).
Design: Cross-sectional analysis of the CIDs for UPDRS
total and motor scores was performed on patients with
Parkinson disease (PD) using distribution- and anchor-
based approaches based on the following 3 external stan-
dards: disability (10% on the Schwab and England Ac-
tivities of Daily Living Scale), disease stage (1 stage on
the Hoehn and Yahr Scale), and quality of life (1 SD on
the 12-Item Short Form Health Survey).
Setting: University of Maryland Parkinson Disease and
Movement Disorders Center,
Results: A minimal CID was 2.3 to 2.7 points on the
UPDRS motor score and 4.1 to 4.5 on the UPDRS total
score. A moderate CID was 4.5 to 6.7 points on the UPDRS
motor score and 8.5 to 10.3 on the UPDRS total score. A
large CID was 10.7 to 10.8 points on the UPDRS motor
score and 16.4 to 17.8 on the UPDRS total score.
Conclusions: Concordance among multiple ap-
proaches of analysis based on subjective and objective
data show that reasonable estimates for the CID on the
UPDRS motor score are 2.5 points for minimal, 5.2 for
moderate, and 10.8 for large CIDs. Estimates for the
UPDRS total score are 4.3 points for minimal, 9.1 for mod-
erate, and 17.1 for large CIDs. These estimates will as-
sist in determining clinically meaningful changes in PD
progression and response to therapeutic interventions.

Patients: Six hundred fifty-three patients with PD. Arch Neurol. 2010;67(1):64-70

Author Affiliations:
Departments of Neurology
(Drs Shulman, Anderson,
Fishman, Reich, and Weiner),
Epidemiology and Preventive
Medicine (Dr Gruber-Baldini),
and Psychiatry (Dr Anderson),
University of Maryland School
of Medicine, Baltimore.
A
CLINICALLY IMPORTANT DIF-
ference (CID) is the
amount of change on a
measure that patients can
recognize and value. 1
Growing interest in CIDs stems from a
greater emphasis on evidence-based and
patient-centered medicine.2 Large ran-
domized clinical trials frequently show sig-
nificant differences on outcome mea-
sures that are so small that clinicians are
unsure how to apply them to clinical de-
cision making.3 The Movement Disorder
Society Task Force on Rating Scales for
Parkinson’s Disease highlighted the im-
portance of identifying thresholds on the
Unified Parkinson’s Disease Rating Scale
(UPDRS) that represent clinically rel-
evant differences.4,5 The US Food and Drug
Administration also described the need to
define minimally important differences on
patient-reported outcome measures used
to support the labeling claims of medical
products.6
The 2 key methods of CID assessment
are the distribution- and anchor-based ap-
proaches.7,8 The distribution-based ap-
proach relies on the empirical distribu-
tion of a measure in a population and the
derived effect size. The anchor-based ap-
proach uses a familiar and relevant exter-
nal standard to determine the correspond-
ing magnitude of change. This study uses
both of these approaches and relies on 3
different external standards (anchors) to
assess the CID on the UPDRS total scale
and its motor subscale.
The minimal clinically important
change on the UPDRS was previously de-
termined based on data from 2 clinical
trials of dopamine agonist monotherapy
in early Parkinson disease (PD).9 Study
limitations included the inability to gen-
eralize the results to more advanced PD
and the reliance on a clinician-based mea-
sure (Clinical Global Impression of Im-
provement) as the anchor for assessing
clinical relevance. Assessments by clini-
cians do not always match patient evalu-
ations because of limitations in aware-
ness of the patient experience.6,10 The belief
that clinically relevant differences in health

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 should be defined by patients is fundamental to patient-
centered medicine.11
The primary objective of this study was to determine
the CID for the UPDRS by using multiple methods of as-
sessment and a large patient sample representing all stages
of PD. The goal was to create estimates of minimal, mod-
erate, and large CIDs by looking for concordance of the
results from multiple approaches of CID analysis.
METHODS
The sample consists of patients diagnosed as having PD by a
movement disorder specialist (L.M.S., P.S.F., S.G.R., or W.J.W.)
at the University of Maryland Parkinson Disease and Move-
ment Disorders Center who underwent assessment during rou-
tine office visits from April 1, 2003, through August 31, 2006.
The criteria for the diagnosis of PD were asymmetrical onset
of at least 2 of the following 3 cardinal signs: resting tremor,
rigidity, and bradykinesia, with no atypical signs or exposure
to dopamine-blocking drugs. Patients attending the move-
ment disorders center are routinely asked to enroll in the Uni-
versity of Maryland Quality of Life and Function Study. Dur-
ing the study period, 86% of patients with PD agreed to
participate and signed an informed consent form approved by
the University of Maryland institutional review board. The treat-
ing neurologist completed the UPDRS, staging with the Hoehn
and Yahr Scale (HY),12 the Schwab and England Activities of
Daily Living Scale (SE Scale),13 and the Mini-Mental State Ex-
amination14 for all subjects. Patients with a Mini-Mental State
Examination score of less than 26 required the assistance of a
caregiver for consent and questionnaire completion. Patients
completed the 12-Item Short Form Health Survey, version 2
(SF-12)15 during the office visit. The HY data reported herein
are based on a combination of the single rating for patients for
whom the stage did not fluctuate and the “on” rating for those
whose stage did fluctuate (30% of the sample consisted of pa-
tients whose stage fluctuated and the results were similar when
“off” ratings were analyzed).
DETERMINING THE CID WITH DISTRIBUTION-
AND ANCHOR-BASED ANALYSES
There are many accepted methods of assessing CID; because
all methods have strengths and weaknesses, it is preferable to
rely on several methods.7,10,16-19 There is also no single re-
sponse or precise threshold for the CID of a measure; instead
it is best to represent the CID of a measure as a range (eg, small,
moderate, or large).1,7,17,20 Therefore, in this cross-sectional study
we used a combination of distribution- and anchor-based ap-
proaches, and we designated predetermined cut points of small,
moderate, and large CIDs for the UPDRS.
For the distribution-based approach, means and standard
deviations were derived from the current sample of data, and
effect sizes were calculated relative to 1 SD. The most com-
mon approach to the analysis of the distribution-based CID in
the literature relies on the Cohen effect size, in which an effect
size of 0.2 (0.2 of an SD) is small, 0.5 is moderate, and 0.8 is
large.7,10,18,21-26
In anchor-based methods, the measures chosen as anchors
should be familiar to clinicians in the field, relevant, interpret-
able, and significantly correlated with the instrument being ex-
plored.7,18 Three measures were used as anchors in this study:
(1) the SF-12,15 (2) the SE Scale,13 and (3) the HY stages.12 Pear-
son correlations were performed, showing that the UPDRS total
and motor scores have moderate to large correlations with the
SE Scale (r=−0.64 to −0.78), HY stages (r=0.70 to 0.75), and
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Table 1. Demographics of 653 Subjects With PD a
Mean (SD) Median (Range)
Age, y 65.9 (11.0) 66.9 (30.3-91.0)
PD duration, y 6.3 (5.8) 4.8 (0.0-28.7)
MMSE score 27.9 (3.1) 29.0 (12.0-30.0)
HY stages 2.3 (0.9) 2.0 (1.0-5.0)
UPDRS
Total score 41.0 (20.5) 37.0 (1.0-118.0)
Motor score 27.2 (13.4) 25.5 (1.0-77.0)
SE Scale score 76.4 (18.7) 80.0 (10.0-100.0)
SF-12
PH score 40.0 (11.8) 40.5 (7.4-70.5)
MH score 47.0 (9.4) 48.4 (17.1-68.8)
Abbreviations: HY, Hoehn and Yahr Scale (“on” for patients whose stage
fluctuated); MH, mental health summary; MMSE, Mini-Mental State
Examination; PD, Parkinson disease; PH, physical health summary; SE,
Schwab and England Activities of Daily Living Scale; SF-12, 12-Item Short
Form Health Survey; UPDRS, Unified Parkinson’s Disease Rating Scale.
a Of the total sample, 63.3% were male; 92.9%, white; 59.3%, college
graduates; 76.6%, married; and 48.6% had a yearly income of more than
$70 000.
SF-12 (physical health [PH], r=−0.44 to −0.52; mental health
[MH], r = −0.35 to −0.45) (for all, P ⬍ .001). Previously ac-
cepted thresholds for the CID have been published for the 36-
Item Short Form Health Status Survey (SF-36) and the SF-12,
but thresholds have not been defined for the SE Scale or the
HY stages.
CUT POINTS FOR THE SF-36 AND SF-12
The SF-36 and SF-12 have 2 summary scores—PH and MH—
that yield t scores based on a US normative population in which
the average score is the 50th percentile and 10 units is 1 SD.
An analysis of effect sizes for the SF-36 was performed by Samsa
et al7 for about 25 medical conditions. Conforming to clinical
intuition, conditions such as congestive heart failure or em-
physema were associated with large effect sizes on the SF-36,
conditions such as arthritis had moderate effect sizes, and con-
ditions such as hypertension had small effect sizes. Based on
the published literature, the small CID for the SF-36 or the SF-12
is in the range of 3 to 5 points, whereas the moderate CID is 9
to 10 points.7,27-30 These ranges for small and moderate CID were
used in our study.
CUT POINTS FOR THE SE SCALE AND
HY STAGES
In the absence of previous analysis of thresholds for effect sizes
on the SE Scale or the HY stages, we used a combination of clini-
cal judgment and analysis of each scale’s distribution (based
on the standard deviation). Specifically, we made a predeter-
mined judgment of small, medium, or large CID on the SE Scale
and the HY stages based on our clinical experience. Then we
analyzed the SE Scale and HY stage distributions in our sample
to assess whether they conformed to our clinical impressions.
On the SE Scale, clinicians assign scores based on descriptors
that coincide with 10% increments on the scale; therefore, a
10% change (10 points on the SE Scale) is clinically relevant.
Furthermore, the standard deviation on the SE Scale for our
sample was 18.7 (Table 1). Therefore, our criterion for a 10%
change is 0.53 SD (10 per 18.7) or approximately half of an
SD for every 10% change: a moderate CID based on the Cohen
effect size. On the HY stages, clinicians assign the 5 stages based
on the clinical descriptions at each stage. Because PD is a gradu-
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 Table 2. Cross-Sectional Analyses of Ratings on the UPDRS by Levels of Disability on the SE Scale

UPDRS Motor Score UPDRS Total Score

No. of Difference per Difference per

SE Subgroup Scores, % a Patients Mean (SD) [Range] 10% SE Change Mean (SD) [Range] 10% SE Change
100 (Completely 63 15.3 (8.2) [1-42] 19.9 (9.5) [7-53]
independent)
90 175 19.7 (8.1) [1-50] b 4.5 28.1 (9.3) [4-63] c 8.3
80 164 26.4 (9.1) [6-48] c 6.7 39.8 (10.9) [17-66] c 11.7
70 65 32.4 (12.1) [6-58] c 6.0 50.3 (14.6) [25-85] c 10.8
60 (Some dependency) 56 37.1 (10.4) [14-62] b 4.7 57.6 (13.6) [30-88] c 7.4
50 34 34.2 (14.4) [12-61] −2.9 59.4 (18.3) [24-87] 1.8
40 28 41.7 (12.6) [20-66] d 7.5 70.1 (13.8) [49-99] c 10.8
30 13 43.6 (18.1) [11-72] 1.9 73.0 (23.0) [31-112] 2.9
20 5 53.8 (10.3) [46-69] 10.2 89.0 (16.2) [73-107] d 16.0
10 (Bedridden) 4 60.0 (7.1) [51-68] 6.2 107.5 (7.2) [102-118] d 18.5

Abbreviations: SE, Schwab and England Activities of Daily Living Scale; UPDRS, Unified Parkinson’s Disease Rating Scale.
a The regression coefficients (4.5 [0.22] for the motor score and 8.6 [0.27] for the total score) show the UPDRS score change for every level of change on the
SE Scale with level of significance. Level of significance is also indicated for post hoc t test comparisons between adjacent levels on the SE Scale. Differences
between regression coefficients were significant at P ⬍.001.
b P ⬍ .01.
c P ⬍ .001.
d P ⬍ .05 (trend).

ally progressive disorder, moving from one stage to another gen-
erally takes several years. Therefore, the HY stages are clini-
cally relevant and represent a relatively large change in disease
severity. The standard deviation on the HY stages for our sample
was 0.9 (Table 1). Therefore, a change of 1 stage on the HY
stages is equivalent to 1.1 SD (1 stage per 0.9 SD), or greater
than the large effect size (0.8) based on the Cohen effect size.
DATA ANALYSIS
Because the HY stages and SE Scale are not normally distributed
(and because the HY scale is not an interval or ratio scale but rather
an ordinal scale), general linear model analyses (using SAS sta-
tistical software, version 9.1; SAS Institute Inc, Cary, North Caro-
lina) were performed to calculate averaged groups for the UPDRS
total and motor scores by the SE and HY groups (analysis of vari-
ance model). Average differences between these group means were
then calculated. Regression models (general linear model and or-
dinary least squares) were run to examine linear changes for the
UPDRS measures by differences on the SF-12 because the SF-12
is a normally distributed interval scale. We reported the regres-
sion weight change per specified unit on the SF-12 (eg, 5 units
as a small change and 10 units as a moderate change). A separate
general linear model was run for every predictor (HY stages, SE
Scale, and SF-12 PH and MH) on each outcome (UPDRS total
and motor scores), resulting in 8 separate analyses. The critical
P value for interpretation was set to P⬍.01 to adjust for multiple
comparisons. Unless otherwise indicated, scores are expressed as
mean (SD).
RESULTS
The study sample of 653 subjects with PD is described in
Table 1. The sample was predominantly white, male, and
married, with relatively high education and income.
UPDRS MOTOR SCORE
The mean UPDRS motor score (subscale III) was 27.2
(13.4). Based on the SE Scale ratings, the mean UPDRS
motor scores ranged from a low of 15.3 (8.2) for the sub-
jects reporting no disability (SE Scale, 100% [com-
pletely independent]) to a high of 60.0 (7.1) for sub-
jects rated as totally dependent (SE Scale, 10%
[bedridden]) (Table 2). Based on the HY stages, the mean
UPDRS motor scores ranged from a low of 11.2 (4.9) for
subjects with unilateral parkinsonism (stage 1) to a high
of 54.4 (11.4) for subjects assessed as wheelchair bound
or bedridden (stage 5) (Table 3). Regression analysis
showed the average difference on the UPDRS motor score
to be 4.5 points for a 10% change on the SE Scale and
10.8 points for a 1-stage change on the HY stages. On
the SF-12, 1 unit on the PH or the MH summary score
was equivalent to a change of 0.47 points on the UPDRS
motor score. Therefore, a difference of 1 SD (defined as
10 units) was 4.7 points on the UPDRS motor score and
half of a standard deviation was equivalent to 2.3 or 2.4
points (Table 4). The distribution-based analysis showed
that the minimal CID was 2.7 points, the moderate CID
was 6.7, and the large CID was 10.7 (Table 4). Based on
a combination of the anchor- and distribution-based analy-
ses (averaging across the results), 2.5 points is an appro-
priate estimate for the minimal CID, 5.2 points for the
moderate CID, and 10.8 points for the large CID (Table 4).
UPDRS TOTAL SCORE
The mean UPDRS total score (subscales I, II, and III) was
41.0 (20.5). Based on the SE Scale ratings, the mean
UPDRS total score ranged from a low of 19.9 (9.5) for
subjects reporting no disability (SE Scale, 100%) to a high
of 107.5 (7.2) for subjects rated as bedridden (SE Scale,
10%) (Table 2). Based on the HY stages, the mean UPDRS
total score ranged from a low of 16.6 (6.6) for subjects
with unilateral parkinsonism (stage 1) to a high of 90.2
(25.0) for subjects assessed as wheelchair bound or bed-
ridden (stage 5) (Table 3). Regression analysis showed
the average change on the UPDRS total score to be 8.6

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 Table 3. Cross-Sectional Analyses of Ratings on the UPDRS by HY Stages

UPDRS Motor Score UPDRS Total Score

No. of ⌬ From ⌬ From

HY Stage a Patients Mean (SD) [Range] Previous Stage b Mean (SD) [Range] Previous Stage b
0-1.5 66 11.2 (4.9) [1-23] 16.6 (6.6) [7-36]
2 347 23.7 (9.3) [1-58] 12.5 35.5 (13.3) [4-87] 18.9
2.5 72 30.2 (10.5) [10-50] 6.5 45.3 (13.6) [17-75] 9.8
3 61 35.9 (9.3) [15-56] 5.8 54.7 (12.4) [33-86] 9.9
4 67 44.1 (12.7) [26-77] 8.2 69.1 (16.5) [29-106] 14.4
5 14 54.4 (11.4) [36-72] 10.3 90.2 (25.0) [64-118] 21.1

Abbreviations: ⌬, change; HY, Hoehn and Yahr Scale (“on” for patients whose stage fluctuated); UPDRS, Unified Parkinson’s Disease Rating Scale.
a The regression coefficients were 10.8 (0.44) for the UPDRS motor score and 17.8 (0.61) for the UPDRS total score.
b All increments are significantly different at P ⬍.001.

Table 4. Summary of Distribution- and Anchor-Based Analyses of the CID on the UPDRS Total and Motor Scores

CID, UPDRS Motor Score CID, UPDRS Total Score

Minimal Moderate Large Minimal Moderate Large

Distribution-based analysis 2.7 6.7 10.7 4.1 10.3 16.4
Anchor-based analysis
SF-12 PH 2.4 4.7 ... 4.2 8.5 ...
SF-12 MH 2.3 4.7 ... 4.5 9.1 ...
SE Scale ... 4.5 ... ... 8.6 ...
HY stages ... ... 10.8 ... ... 17.8
Mean of all analyses 2.5 5.2 10.8 4.3 9.1 17.1

Abbreviations: CID, clinically important difference; ellipses, not applicable. For other abbreviations, see Table 1.

points for a 10% change on the SE Scale and 17.8 points
for a 1-stage change on the HY stage. On the SF-12, 1 unit
on the PH summary score was equivalent to a change of
0.85 points on the UPDRS total score, and 1 unit on the
MH summary score was 0.91 points on the UPDRS total
score. Therefore, a change of 1 SD (defined as 10 units)
was 8.5 (PH) or 9.1 points (MH) on the UPDRS total score,
and half of an SD was equivalent to 4.2 or 4.5 points, re-
spectively (Table 4). The distribution-based analysis showed
that the minimal CID was 4.1 points, the moderate CID
was 10.3 points, and the large CID was 16.4 points on the
UPDRS total score (Table 4). Based on a combination of
the anchor- and distribution-based analyses, a change of
4.3 points is an appropriate estimate for the minimal CID,
9.1 points for the moderate CID, and 17.1 points for the
large CID on the UPDRS total score (Table 4).
COMMENT
Concordance across a combination of distribution- and
anchor-based approaches for analysis of the CID dem-
onstrates that the moderate CID for the UPDRS motor
score is approximately 5 points and for the UPDRS total
score it is 9 points. Variability across sample popula-
tions and clinical settings suggests that a range of CID
values is likely to be more useful than a single esti-
mate.18,23 This study describes a range from minimal to
moderate to large CID, corresponding to about 2.5, 5,
and 11 points for the UPDRS motor score and 4.5, 9, and
17 points for the UPDRS total score.
The minimal clinically important change on the UPDRS
was previously studied in a sample of individuals with
early PD who participated in 2 clinical trials of dopa-
mine agonist monotherapy.9 An anchor-based analysis
using the Clinical Global Impression of Improvement
found that the minimal clinically important change was
5 points on the UPDRS motor score and 8 points on the
UPDRS total score.9 Our results show that the minimal
CID was smaller: 2.5 points on the UPDRS motor score
and 4.5 points on the UPDRS total score. Because the CID
may vary at different stages of disease, this discrepancy
may indicate that the CID is larger in earlier PD. Samsa
et al7 questioned whether the initial decrement from per-
fect health to early symptoms may be more meaningful
than the impact of similar decrements in the middle part
of the scale. The discrepancies in the results between the
present and earlier studies underscore the importance of
replicating these analyses in different sample popula-
tions and in longitudinal studies. There were several dif-
ferences between these 2 studies, including stage of dis-
ease, the anchor chosen, and the clinical setting
(naturalistic vs clinical trial).
The presence of a larger CID in early PD is not sup-
ported by our analysis of UPDRS ratings by 10% decre-
ments on the SE Scale (Table 2). If this were the case,
one would anticipate larger increments in the UPDRS rat-
ings between SE levels associated with earlier disability.
However, the largest increment in the UPDRS motor score
was associated with the change in SE Scale ratings from
30% to 20% in advanced PD, corresponding to the change

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 Table 5. Effect Sizes in Published Clinical Trials in PD a
Study Drug Source
Selegiline hydrochloride PSG,35 1989
Pramipexole Guttman and International Pramipexole-Bromocriptine
Study Group,36 1997
Bromocriptine mesylate Guttman and International Pramipexole-Bromocriptine
Study Group,36 1997
Pramipexole Shannon et al,37 1997
Pramipexole PSG,34 1997
Ropinirole hydrochloride Rascol et al,38 1998
Levodopa Rascol et al,38 1998
Ropinirole Sethi et al,39 1998
Pramipexole PSG,40 2000
Levodopa PSG,40 2000
Rasagiline mesylate PSG,41 2002
Rasagiline PSG,42 2004
Levodopa, 150 mg/d Fahn et al,43 2004
Levodopa, 300 mg/d Fahn et al,43 2004
Levodopa, 600 mg/d Fahn et al,43 2004
Rasagiline PSG,44 2005
Abbreviations: ⌬, change; PD, Parkinson disease; PSG, Parkinson Study Group; UPDRS, Unified Parkinson’s Disease Rating Scale.
a Data are not comparable owing to differences in adjustment for placebo and study duration in the different clinical trials. Missing data reflect absence of data in
the publication.
in SE responses from “With effort, now and then does a
few chores alone. . . . Much help needed” to “Nothing
alone. Can be a slight help. . . . Severe invalid.” These
larger UPDRS score increments associated with selected
levels of 10% change on the SE Scale may simply iden-
tify SE Scale cut points that signal clinical distinctions
more clearly. A single aberration is seen between SE Scale
scores of 60% and 50%, where the UPDRS motor score
goes down rather than up. The reason is unclear and re-
quires further investigation.
Clinical trials in PD have applied arbitrary defini-
tions of responders such as improvement of 20%, 30%,
3 points, and 5 points on the UPDRS motor scale.31-34 Three
to 5 points on the UPDRS motor scale is precisely the
minimal to moderate CID range in this analysis.
Establishing the CID for a measure is particularly mean-
ingful when this magnitude of improvement can be real-
istically achieved. In fact, the CID results in this study are
consistent with effect sizes on the UPDRS found in recent
clinical trials (Table 5). For example, in the Earlier vs Later
Levodopa Therapy in Parkinson Disease study,43 in which
3 dosages of levodopa were studied (150, 300, and 600 mg/
d), the change in UPDRS total score was 5.9 points for the
low and moderate doses and 9.2 for the highest dose, cor-
responding to the minimal to moderate CID in this study.
However, UPDRS score changes of 1 to 2 points for sele-
giline hydrochloride35 and rasagiline mesylate42 were be-
low the minimal CID. Although the effect sizes in differ-
ent trials described in Table 5 are not comparable owing
to differences in study duration and variable adjustment
for placebo, the range of effect sizes (1.1-8.4 for the UPDRS
motor score and 1.8-9.2 for the UPDRS total score) are in
the range of the CIDs found in this study.
This study relied on a combination of patient-
reported (SF-12) and clinician-reported (SE Scale and HY
stage) assessments. Similarly, the UPDRS has elements
of patient and clinician assessment, with subscales I (men-
tation, behavior, and mood) and II (activities of daily liv-
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⌬ UPDRS Motor Score ⌬ UPDRS Total Score
1.09 1.82
6
3
4.7
5.24
5.8
8.4
5.7
3.4 4.5
7.3 9.2
4.2
2.29
5.9
5.9
9.2
2.87
ing) based on patient responses by history and subscale
III (motor examination) based on clinical observation.
The CID analysis was initially developed as a tool for pa-
tient-reported outcomes, particularly quality-of-life mea-
sures,7 and more recently has been applied to a greater
diversity of measures, including physical performance
measures.25,45
Clinically important differences may vary across dis-
eases, ethnicity, and socioeconomic status. Therefore,
these findings may not be applicable to patients who are
nonwhite, have lower socioeconomic status, or have
other forms of parkinsonism. The CID in a cross-sec-
tional sample is conceptually distinct from CID analysis
in a longitudinal sample, although cross-sectional and
longitudinal analyses have yielded similar results in
previous studies.7 The predetermined estimates of
minimal, moderate, and large CID for each of 3 anchors
may be subject to criticism as inaccurate representa-
tions of a clinically meaningful difference in PD. How-
ever, the results compare favorably with the calculated
values of CID based on accepted standard effect sizes21
in the distribution-based analysis, and the ranges of
computed values of CID based on each of the methods
were in close agreement.
The minimum CID was originally defined as “the small-
est difference in score in the domain of interest which
patients perceive as beneficial and which would man-
date, in the absence of troublesome side effects and ex-
cessive cost, a change in the patient’s management.”1 The
role of a CID in clinical decision making is highlighted
in this definition, although there is controversy about
whether the CID is more applicable to the interpreta-
tion of group or individual differences.8,10,18,46 Indeed, as-
sessing the risk to benefit ratio may be more straightfor-
ward on the individual level, where the treatment response
may need to be especially robust to compensate for
troublesome adverse effects or financial limitations. A
range of CID values as demonstrated in this study (mini-
WWW.ARCHNEUROL.COM
 mal, moderate, and large) may help meet the needs of
individual and group variability. For example, the use
of the moderate to large CID range may be more suit-
able for interpreting change on the individual level,
whereas the low end of the range (minimal to moder-
ate) may be preferable when interpreting group differ-
ences.18
Establishing CID estimates for common outcome mea-
sures such as the UPDRS will not only influence patient
management and clinical trials but also influence deci-
sion making by government and industry. Clinically im-
portant differences are a tool to aid clinicians in trans-
lating the results of statistically significant differences in
large clinical trials to their individual patients. From a
broader perspective, CIDs can facilitate the calculation
of sample sizes in trials and may serve as a benchmark
for interpreting treatment effects. This study shows that
concordance of estimates of the CID on the UPDRS score
can be achieved using multiple approaches of analysis
and a large PD sample. Changes of 2.5 to 5.2 points on
the UPDRS motor score and 4.5 to 9.1 points on the
UPDRS total score represent clinically meaningful dif-
ferences based on a combination of objective and sub-
jective analyses and should be used to assess therapeu-
tic interventions in PD.
Accepted for Publication: August 11, 2009.
Correspondence: Lisa M. Shulman, MD, Department
of Neurology, University of Maryland School of Medi-
cine, 110 S Paca St, Room 3-S-127, Baltimore, MD
21201 (lshulman@som.umaryland.edu).
Author Contributions: Study concept and design: Shul-
man, Gruber-Baldini, and Anderson. Acquisition of
data: Shulman, Anderson, Fishman, Reich, and
Weiner. Analysis and interpretation of data: Shulman,
Gruber-Baldini, and Anderson. Drafting of the manu-
script: Shulman, Gruber-Baldini, and Weiner. Critical
revision of the manuscript for important intellectual con-
tent: Shulman, Gruber-Baldini, Anderson, Fishman,
Reich, and Weiner. Statistical analysis: Gruber-Baldini.
Obtained funding: Shulman and Weiner. Administrative,
technical, and material support: Shulman, Fishman, and
Weiner. Study supervision: Shulman, Anderson, and
Weiner.
Financial Disclosure: None reported.
Funding/Support: This study was supported by the Ro-
salyn Newman Foundation.
Previous Presentation: This study was a platform pre-
sentation at the American Academy of Neurology An-
nual Meeting; May 1, 2007; Boston, Massachusetts.
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