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Development of validated disease activity and damage indices for the juvenile idiopathic inflammatory myopathies. I. Physician parent and patient global assessments

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ARTHRITIS & RHEUMATISM
Vol. 40, No. 11, November 1997, pp 1976-1983
0 1997, American College of Rheurnatology
1976
DEVELOPMENT OF VALIDATED DISEASE ACTIVITY
AND DAMAGE INDICES FOR THE JUVENILE IDIOPATHIC
INFLAMMATORY MYOPATHIES
I. Physician, Parent, and Patient Global Assessments
LISA G. RIDER, BRIAN M. FELDMAN, MARIA D. PEREZ, ROBERT M. RENNEBOHM,
CAROL B. LINDSLEY, LAWRENCE S. ZEMEL, CAROL A. WALLACE, SUSAN H. BALLINGER,
SUZANNE L. BOWYER, ANN M. REED, MURRAY H. PASSO, ILDY M. KATONA,
FREDERICK W. MILLER, and PETER A. LACHENBRUCH, in cooperation with the JUVENILE
DERMATOMYOSITIS DISEASE ACTIVITY COLLABORATIVE STUDY GROUP
Objective. To determine the reliability, content
validity, and responsiveness of physician global assessments of disease activity and damage in the juvenile
idiopathic inflammatory myopathies (IIM), and to investigate concordance among physician, parent, and
patient global ratings.
Methods. Sixteen pediatric rheumatologists rated
The statements made in this article are those of the authors
and do not necessarily reflect those of their affiliated institutions.
Supported by funds from the intramural research programs of
CBER, Food and Drug Administration, and NIAMS, NIH, to Drs.
Rider, Miller, and Lachenbruch. Dr. Feldman is an Ontario Ministry
of Health Career Scientist.
Lisa G. Rider, MD, Frederick W. Miller, MD, PhD: Food and
Drug Administration, and National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda,
Maryland; Brian M. Feldman, MD, MSC: Hospital for Sick Children,
University of Toronto, Toronto, Ontario, Canada; Maria D. Perez,
MD: Texas Children’s Hospital, Baylor College of Medicine, Houston,
Texas; Robert M. Rennebohm, MD: Columbus Children’s Hospital,
Ohio State University, Columbus; Carol B. Lindsley, MD: University
of Kansas, Kansas City; Lawrence S . Zemel, MD: Connecticut Children’s Medical Center, University of Connecticut, Hartford; Carol A.
Wallace, MD: Children’s Hospital, University of Washington, Seattle;
Susan H. Ballinger, MD, Suzanne L. Bowyer, MD: Riley Children’s
Hospital, Indiana University, Indianapolis; Ann M. Reed, MD: University of North Carolina, Chapel Hill; Murray H. Passo, MD:
Children’s Hospital, University of Cincinnati, Cincinnati, Ohio; Ildy
M. Katona, MD: Uniformed Services University of the Health Sciences, Bethesda, Maryland; Peter A. Lachenbruch, PhD: Food and
Drug Administration, Rockville, Maryland.
Address reprint requests to Lisa G. Rider, MD, Medical
Officer, Division of Monoclonal Antibodies, Center for Biologics
Evaluation and Research, Food and Drug Administration, Building
29B, Room 2G11, HFM-561, 8800 Rockville Pike, Bethesda, MD
20892.
Submitted for publication March 25,1997; accepted in revised
form June 27, 1997.
10 juvenile IIM paper patient cases for global disease
activity and damage, and assessed the importance of 51
clinical and laboratory parameters in formulating their
global assessments. Then, 117 juvenile IIM patients
were enrolled in a protocol to examine the relationship
between Likert and visual analog scale global assessments, their sensitivity to change, and the comparability
of physician, parent, and patient global ratings.
Results. Pediatric rheumatologists demonstrated
excellent interrater reliability in their global assessments of juvenile IIM disease activity and damage
(97.7% and 94.7% agreement among raters, respectively), and agreed on a core set of clinical parameters in
formulating their judgments. Likert scale ratings correlated with those on a visual analog scale, and both were
comparable in responsiveness (standardized response
means -0.56 for disease activity, 0.02 [Likert] and 0.14
[visual analog] for damage, measured over 8 months).
Parent global ratings of disease activity correlated with
physician assessments, but were not colinear (Spearman’s correlation [r] = 0.41-0.45). Patient global disease activity assessments correlated with those done by
parents (r = 0.57-0.84) and physicians (r = 0.37-0.63),
but demonstrated less responsiveness (standardized
response means -0.21 and -0.12, respectively, over 8
months).
Conclusion. Physician global assessments of juvenile IIM disease activity and damage demonstrated
high interrater reliability and were shown to be comprehensive measures. Both physician and parent disease
activity assessments should be considered valuable as
GLOBAL ASSESSMENTS OF ACTIVITY AND DAMAGE IN JUVENILE IIM
quantitative measures for evaluating therapeutic responses in juvenile IIM patients.
Juvenile idiopathic inflammatory myopathies
(IIM) are systemic connective tissue diseases that are
characterized by chronic inflammation in skeletal muscle, skin, and other target organs (3,2). Juvenile dermatomyositis (DM) is the most common of these disorders, but polymyositis (PM) and myositis overlapping
with another connective tissue disease (CTM) have been
increasingly recognized in children (3). Despite the
improved medical therapy and prognosis for these diseases over the decades (2), up to one-third of patients
develop residual functional impairment (1,4).
There are limited measures available to assess
juvenile IIM disease activity and damage. Disease activity has been defined as the severity of reversible disease
manifestations resulting from the degree of inflammation in all affected organs, and disease damage constitutes the irreversible, accumulated changes from prior
active disease, including atrophy, scarring, and deformity from past inflammation (5). At present, only manual
muscle testing and the Childhood Health Assessment
Questionnaire (CHAQ), which evaluates functional disability, have been validated for use in assessing disease
activity in juvenile IIM patients (4,6,7). Validated instruments that are quantitative, assess the multiple organ
systems involved in these systemic diseases, and discriminate between active disease and disease damage have
not yet been developed (8). The absence of such tools
compromises the ability to measure therapeutic responses and outcomes for individual juvenile IIM patients, and precludes the conduct of clinical trials.
The lack of standardized outcome assessment
measures for juvenile IIM prompted the Juvenile Dermatomyositis Collaborative Study Group to initiate a
multicenter study devoted to the development and validation of a variety of evaluation techniques. The goals of
this collaborative effort are to validate the assessment of
commonly affected organ systems, and to develop comprehensive disease activity and disease damage indices
(9-13).
Physician and patient global evaluations have
become a standardized part of validated activity indices
for many rheumatic diseases (9,lO). Global assessments,
defined as a composite of all the ways the illness affects
disease activity or general health (14), provide unique
content not obtained through other disease activity
measures (15,16), are highly sensitive to change (16,17),
and predict future disability. Despite their widespread
acceptance, little work has been done to assess the
1977
reliability and content validity of global assessments in
the rheumatic diseases (18). Often both physician and
patient or parent global evaluations are included in
monitoring clinical trials, yet their potential for redundancy has not been well studied. In addition, the use of
both the Likert scale and visual analog scale (VAS) (19)
to measure pain responses (20-22) has been studied, but
has not been well characterized or compared in rheumatic diseases.
Therefore, in developing validated measures of
disease activity and disease damage in juvenile IIM, we
first studied the interrater reliability and content validity
of physician global assessments, evaluated the correlation of physician, parent, and patient global disease
activity ratings, and compared the properties of 2 measurement scales. the Likert scale and the VAS.
PATIENTS AND METHODS
Survey. The Juvenile Dermatomyositis Collaborative
Study Group was formed by 16 pediatric rheumatologists who
were experienced in the care of juvenile IIM patients and who
volunteered their resources to a multicenter study devoted to
the development and validation of evaluation measures for
juvenile TIM. The study was initiated with the rheumatologists’
completion of a 2-part survey regarding physician assessment
of global disease activity and global disease damage in juvenile
DM patients. Global disease activity was defined as the
pediatric rheumatologist’s expert clinical judgment of the
extent and severity of reversible manifestations due to underlying disease. Global disease damage was defined as an overall
rating, developed by the rheumatologist, of irreversible
changes due to longstanding active disease, which do not
contribute to an active disease process; whenever possible,
this assessment excluded toxic reactions secondary to drug
therapy (19).
Part 1 of the survey consisted of rating the global
disease activity and damage in 10 juvenile DM paper patient
cases. These cases were chosen because they represented case
histories of real patients who had a range of disease activity
and damage. Physicians rated the global disease activity and
disease damage on a 5-point Likcrt scale (0 = no evidence of
disease activity or damage, 1 = mild disease activity or
damage, 2 = moderate disease activity or damage, 3 = severe
disease activity or damage, and 4 = extremely severe disease
activity or damage). Fourteen physicians completed the second
part of the survey, which consisted of ranking 51 clinical signs,
symptoms, or laboratory tests on a scale of 0-4 (0 = unimportant, 1 = mildly important, 2 = moderately important, 3 = very
important, 4 = extremely important) for their value in developing a global rating of disease activity and damage in patients
with juvenile DM. Mean ranks and the percentage of agreement for each variable were used in determining the content
validity of global assessments, defined as a measure of comprehensiveness and sampling of all clinically important aspects
of juvenile IIM (19). The physicians participating in these
RIDER ET AL
1978
surveys saw, on average, 18 juvenile D M patients per year
(range 3-55, median 15 patients) in their practices.
Study design and population. Children with juvenile
IIM were studied at the Arthritis and Rheumatism Branch,
National Institute of Arthritis and Musculoskeletal and Skin
Diseases (NIAMS), National Institutes of Health, or at a
participating center, at predefined evaluation points: study
entry at any time in the patient’s illness course, an optional
assessment 3-5 months later, and a required assessment 7-9
months after protocol entry. One hundred five patients with
juvenile DM, 6 with juvenile PM, and 4 with juvenile CTM who
met the criteria for probable or definite IIM (23) and whose
age at onset was <18 years were enrolled; 2 juvenile DM
patients who met possible criteria were also included. Their
mean age was 9.5 years (range 2-18 years), and mean disease
duration was 30 months (range 0-143 months). Sixty-eight
percent of the patients were girls, and 78% were white, 9%
African American, 5% Hispanic, 2% Asian, and 6% ethnically
mixed. Fifty-five patients completed the 3-5-month assessment, and 74 patients completed the 7--9-month assessment.
Patient dropout was primarily related to patient and physician
self-incurred expenses for study participation.
Physicians evaluated global disease activity and damage, using the standardized definitions, within 24 hours of
completing their assessment of each patient. Global disease
activity and damage were rated on a 10-cm VAS (0 cm =
inactive or no disease damage, 10 cm = extreme activity or
damage) (19), as well as on a 5-point Likert scale (0 = inactive
or no disease damage, 4 = extreme activity or damage). The
assessment of global disease activity and damage was based on
a history and physical examination obtained from the patient
and his or her accompanying parents, and on review of
diagnostic laboratory test results.
Parents accompanying patients, and patients >10 years
of age, also completed a global assessment of disease activity
using a 10-cm VAS, which was anchored with happy and sad
faces. These individuals were blinded to each others’ ratings
and to the physicians’ ratings.
Statistical analysis. The database for this study was
maintained in SPSSiData Entry IT (SPSS, Chicago, Illinois),
and statistical analysis was performed using STATA (version
5.0; STATA, College Station, Texas). Percentage of agreement, Cohen’s kappa, and Cronbach’s alpha were calculated
from 2 X 2 tables of pairs of raters (120 pairs of raters) for cach
of the 10 ideal cases, and the average of all pairs was taken
(1 9). For ordinal ratings (0-4), the weighted percentage of
agreement and kappa values were calculated using quadratic
weights (24). Analysis of variance (ANOVA) was performed to
determine the variation in patients versus physician global
ratings of the 10 paper patient cases; reliability was estimated
from the ANOVA (19).
The correlation between global disease activity and
damage ratings using the Likert scale and VAS was calculated
from Spearman’s rank and intraclass correlations. To estimate
the sensitivity to change in global assessments, standardized
response means were calculated, as described by Liang et al
(25). Mean or median global disease activity and damage
ratings were compared with Student’s 2-tailed t-test or Wilcoxon signed rank test, respectively. To calculate weighted
kappa values for parent and patient ratings of disease activity,
the VAS ratings were converted to Likert scale ratings by
Table 1. Agreement among 16 pediatric rheumatologists on global
disease activity and disease damage ratings for 10 paper juvenile
dermatomyositis cases“
Variable
Agreement,
mean i SD%
Kappa
coefficient,
mean ? SD
~
Global disease activity
Inactive vs. active
All ranks
Global disease damage
Inactive vs. active
All ranks
*
Cronbach’s
alpha
~~
~
89.8 -t 8.6
97.7 -t 1.2
0.67 0.33
0.88 1 0 . 0 6
0.98
0.99
90.0 5 8.8
94.7 -t 3.3
0.67 t 0.33
0.76 -t 0.13
0.98
0.98
“ Dichotomous ratings (inactive vs. active) compared the global rating
of 0 with thc range 1-4, whereas ordinal ratings (all ranks) reflected
the complcte range of ratings 0-4.
defining 0-2 cm as a Likert score of 0,2-4 cm as a Likert score
of 1, 4-6 cm as 2, 6-8 cm as 3, and 8-10 cm as 4.
RESULTS
Interrater reliability. Table 1 summarizes the
agreement in global ratings of disease activity and
disease damage for 16 pediatric rheumatologists’ assessments of 10 juvenile DM paper cases. Substantial agreement among physician ratings of disease activity and
damage in juvenile DM occurred, both with dichotomous ratings and with ordinal ratings (19,24). Because
the weighted percentage of agreement for ordinal ratings is not directly comparable with the unweighted
percentage of agreement for dichotomous ratings, unweighted agreements were also obtained. Using the
ordinal 0-4 ratings, the unweighted agreement was
67.6% for global disease activity and 57.8% f o r global
disease damage. Cronbach’s alpha, an additional measure of reliability, was acceptable (20.8) for global
juvenile DM disease activity and damage (19). There
was no difference in the level of agreement among
physicians’ ratings of global disease activity and global
disease damage.
The variation in patients (cases) versus physicians, as well as an estimate of reliability, were determined by ANOVA (19). The variation in cases was due
to variance in patients (variance 1.8 for disease activity,
2.1 for disease damage), but not the result of variance in
physician ratings (variance 0). Global disease activity
and disease damage ratings were both estimated to have
a reliability coefficient of 1.O.
Content validity. To determine which clinical
variables were important in formulating global disease
activity and damage assessments, pediatric rheumatologists ranked the importance (on a scale of 0-4) of 51
GLOBAL ASSESSMENTS OF ACTIVITY AND DAMAGE IN JUVENILE IIM
Table 2. Clinical variables used in the physicians’ determinations of
global disease activity in juvenile dermatomyositis*
Variables with consensus ( 2 7 5 % agreement) in
assessing disease activity
Veryiextremely important
Muscle strength
Dysph agia
Dysphonia
Gastrointestinal bleeding
Gastrointestinal ulceration
Cutaneous ulceration
Pneumatosis intestinalis
Creatine kinase
Aldolase
Shortness of breath
Interstitial lung disease on chest radiograph
Restrictive lung disease on PFT
Reduced diffusing capacity for Carbon
monoxide on PFT
Gastrointestinal regurgitation
Ventricular dysfunction on cchocardiogram
Muscle biopsy findings
Arrhythmia on electrocardiogram
Moderately important
Periungual capillary changes
Erythematous rashes
Fatigue
Mildly importantiunimportant
Lipodystrophy
Acanthosis nigricans
Atrophic rashes
Calcinosis
Muscle atrophy
Creatine kinase isoenzymes
Muscle atrophy or fatty replacement on
muscle MRI
Poikiloderma atrophicans vasculare
Creatinine
Mean
%
rank consensus
(0-4) agreement
3.9
3.8
3.8
3.8
3.8
3.6
3.6
3.5
3.3
3.3
3.2
3.2
3.2
100
100
100
100
92
92
75
75
92
75
83
83
83
3.2
3.2
3.1
2.8
83
75
75
15
2.5
2.5
2.5
83
75
75
0.4
0.5
0.5
0.6
1.0
1.1
1.5
92
92
83
75
75
83
75
1.6
1.1
15
75
* Clinical variables that were rated, but with no consensus ( 5 7 5 %
agreement) achieved on global disease activity assessment, are listed in
rank order as follows: current drug therapy, neopterin, electromyography findings, edema on muscle magnetic resonance imaging (MRI)
scan, abdominal pain, abnormal barium swallow, cytoid bodies or
retinal hemorrhage on eye examination, erythroderma, fever, palpitations or chest pain, transaminases (alanine aminotransferase, aspartate
aminotransferase), arthritis, heliotrope rash. lactate dehydrogenase,
Gottron’s papules, von Willebrand factor-related antigen, sinus tachycardia, joint flexion contractures, mechanic’s hands, Steinbrocker
functional class. PFT = pulmonary function test.
clinical signs, symptoms, and laboratory tests. Seventeen
parameters were determined as being very or extremely
important in the determination of juvenile DM global
disease activity (mean rank 3.5, 275% agreement in
grades 3 or 4) (Table 2). Three clinical variables were
found to be of moderate importance in their formulation
of global disease activity (mean rank 2.5, 275% agreement in grades 2 or 3), 9 variables were unimportant
(mean rank 1.0, 275% agreement in grades 0 or l),and
1979
for 20 variables, there was no consensus ( 5 7 5 % agreement within 1 rank) on their importance in assessing
disease activity (mean rank 2.5).
For assessing global disease damage, only 4 clinical variables (calcinosis, muscle atrophy, functional
assessment, and joint flexion contractures) were determined to be very or extremely important (mean rank
3.4) (Table 3). Sixteen variables were agreed to be
unimportant in the assessment of disease damage (mean
rank 0.9), and for 26 clinical measures, consensus was not
achieved (<75% agreement within 1rank) for their role in
rating juvenile DM disease damage (mean rank 1.9).
Measurement scales and responsiveness. From
the multicenter juvenile IIM evaluation study, there was
a significant correlation between the physician global
Table 3. Clinical variables used in the physicians’ determinations of
global disease damage in juvenile dermatomyositis*
Variables with consensus ( 2 7 5 %
agreement) in assessing disease damage
Veryiextremely important
Calcinosis
Muscle atrophy
Functional assessment (activities of
daily living)
Joint flexion contractures
Mildly importantiunimportant
Sinus tachycardia
Transaminases (ALT, AST)
Creatine kinase isoenzymes
Fever
Gastrointestinal ulceration
Lactate dehydrogenase
Gastrointestinal bleeding
Palpitations or chest pain
Pneumatosis intestinalis
Cytoid bodies or retinal hemorrhage on
eye examination
Creatine kinase
Dysphon ia
Heliotrope rash
Arrhythmia on electrocardiogram
Electromyography findings
Aldolase
Mean
rank
(0-4)
%
consensus
agreement
3.8
3.7
3.0
100
100
75
3.0
15
0.4
0.5
0.5
0.5
0.5
0.6
0.7
0.8
0.8
0.9
92
92
83
83
83
83
75
83
75
83
0.9
0.9
0.9
1.0
1.8
3.0
15
75
75
75
75
83
* Clinical variables that were rated, but with no consensus ( 5 7 5 %
agreement) achieved on global disease damage assessment, are listed
in rank order as follows: lipodystrophy, muscle atrophy or fatty
replacement on muscle magnetic resonance imaging scan, acanthosis
nigricans, atrophic rashes, current drug therapy, poikiloderma atrophicans vasculare, muscle strength, muscle biopsy findings, Steinbrocker
functional class, interstitial lung disease on chest radiograph, reduced
diffusing capacity for carbon monoxide on pulmonary function testing,
restrictive lung disease on pulmonary function testing, shortness of
breath, periungual capillary changes, creatinine, abnormal barium
swallow, mechanic’s hands, ventricular dysfunction on echocardiogram, Gottron’s papules, cutaneous ulceration, dysphagia, erythroderma, fatigue, gastrointcstinal regurgitation, abdominal pain. ALT =
alanine aminotransferase; AST = aspartate aminotransferase.
RIDER ET AL
1980
I
0
I
1
I
2
I
3
I
4
Disease Activity Likert
Figure 1. Correlation of the Likert scale and the visual analog scale
(VAS) ratings as given by physicians in their baseline global assessments of disease activity in patients with juvenile idiopathic inflammatory myopathies. Combining data from the baseline and other 2
evaluations, a Likert score of 0 (inactive) corresponded with a mean
VAS score of 0.1 cm (95% confidence interval [95% CI] 0.1-0.2); a
Likert score of 1 (mild activity) corresponded with a mean VAS score
of 1.5 cm (95% CI 1.3-1.6); a Likert score of 2 (moderate activity)
corresponded with a mean VAS score of 4.8 cm (95% C1 4.4-5.2); a
Likert score of 3 (severe activity) corresponded with a mean VAS
score of 7.6 cm (95% CI 7.0-8.2); and a Likcrt score of 4 (extremely
active) corresponded with a mean VAS score of 9.2 (95% CI 7.9-10.4).
In correlating Likert versus VAS scores at baseline evaluation, Spearman’s rank correlation was 0.89 and the intraclass correlation coefficient was 0.85 ( P < 0.0001).
ratings of disease activity measured on the Likert scale
and on the VAS at study entry (Figure I), which
continued to show a correlation on subsequent assessments at 4 and 8 months later (data not shown).
Physician global ratings of disease damage demonstrated
a similar correlation between the Likert ratings and VAS
scores (Spearman’s rank correlation 0.89, intraclass correlation coefficient 0.85 on baseline assessment, P <
0.0001).
The sensitivity to change in the Likert scale
versus the VAS for physician global assessments of
juvenile IIM disease activity and damage were studied in
74 patients who completed initial and 8-month followup
evaluations. The mean change in global disease activity
over 8 months correlated between the S-point Likert
scale (mean -+ SD change -0.5 ? 0.9) and 10-cm VAS
(mean -+ SD change -1.4 ? 2.5; Spearman’s rank
correlation 0.85, P < 0.0001). Similar results were
obtained over 4-month intervals (data not shown). The
standardized response mean, an appraisal of instrument
responsiveness that compares the magnitude of change
with the variability in the measure, was comparable
between the Likert scale and the 10-cm VAS (standard-
ized response means -0.56 for each; a negative value
indicates improvement in disease activity over the 8month study interval). Both measurement scales also
demonstrated moderate responsiveness over 4-month
intervals (standardized response mean -0.71 for Likert
versus -0.62 for VAS, baseline to 4-month followup;
standardized response mean -0.33 for Likert versus
-0.54 for VAS, 4- to 8-month followup).
Because patients were enrolled after various durations of illness, we examined whether the responsiveness of physician global disease activity assessments
would improve when limited to patients early in their
illness course. For 21 patients whose illness duration was
<7 months from diagnosis to study enrollment, the
standardized response mean during an %month period
was -0.75 on the Likert scale and -0.87 using VAS,
suggesting that global activity assessments are more
sensitive to change for patients earlier in their illness
course, because the condition of the patients tends to
change more.
Over the %month study interval, little change was
observed in global disease damage. The mean disease
damage scores and standardized response means were
comparable between the Likert and VAS damage ratings (mean -+ SD change in Likert damage score 0.0 ?
0.6, standardized response mean 0.02 versus change in
VAS damage score 0.2 ? 1.2, standardized response
mean 0.14). Global disease damage also changed little in
a subset of 35 patients who had disease for >2 years at
study entry (mean change in VAS damage score 0.29 2
1.5, standardized response mean 0.19). Global assessment of disease activity did not correlate with global
assessment of disease damage (data not shown).
Physician versus parent versus patient global
disease activity assessments. Physician global ratings of
juvenile IIM disease activity correlated significantly with
parent and patient global evaluations (Table 4), and the
median ratings did not significantly differ between raters
for any assessment, by Wilcoxon signed rank test (P >
0.05). Parent and patient global activity assessments
correlated significantly both at baseline and at the
8-month evaluation. There was also substantial agreement between parent and patient ratings at the baseline
examination. The absence of agreement between parent
and patient ratings at the 8-month evaluation was related to the conversion of VAS to Likert scale ratings in
order to calculate the kappa coefficient, resulting in an
artefactual lack of variability in parent ratings.
The change in global disease activity between the
baseline and 8-month followup assessments did not
significantly differ for physicians and parents (P > 0.06,
GLOBAL ASSESSMENTS OF ACTIVITY AND DAMAGE IN JUVENILE IIM
Table 4. Relationship of physician, parent, and patient global ratings
of disease activity over an &month study interval*
Initial
assessment
%month
assessment
~
Physician vs. parent
No. of patients
Spearman’s rank
correlation, r
Weighted kappa
Standardizcd response mean
Physician
Parent
Physician vs. patient >10 years
No. of patients
Spearman’s rank
correlation; r
Weighted kappa
Standardized response mean
Physician
Patient >10 years
Parent vs. patient >10 years
No. of patients
Spearman’s rank
correlation, r
Weighted kappa
Standardized response mean
Parent
Patient >10 years
99
0.41 (50.001)
0.45(50.001)
0.34 (50.001)
0.24 (50.001)
57
-0.58
-0.54
28
0.37 (50.05)
21
0.63 (50.05)
0.33 (50.05)
0.39 (50.05)
-0.48
-0.12
22
0.84 (50.05)
0.84 (%0.05)
14
0.57 (50.05)
0.0
-0.56
-0.21
* Values in parentheses are P values.
Wilcoxon signed rank test). The standardized response
means were moderate for both physician and parent
global ratings over this 8-month period (Table 4). In
contrast, patient global ratings were less sensitive to
change compared with those of physicians and parents.
This finding is compromised by the small numbers of
patients who completed global ratings over the &month
assessment interval.
DISCUSSION
As a first effort toward our ultimate goal of
developing comprehensive, validated indices for assessing disease activity and disease damage in juvenile IIM,
we examined the interrater reliability, content validity,
and sensitivity to change of physician and parent/patient
global assessments. This study demonstrated that physician global assessments of disease activity and disease
damage in juvenile IIM had excellent interrater reliability. The reliability of the physician global VAS assessments of juvenile IIM disease activity was comparable
with the interrater reliability found in studies of global
disease activity evaluations for other chronic rheumatic
diseases of children and adults (18,26,27).
The pediatric rheumatologists agreed on a com-
1981
mon set of 17 clinical variables as very or extremely
important in deriving their global evaluation of juvenile
IIM disease activity, and on the importance of 4 clinical
measures in the assessment of disease damage. Physician
global ratings of disease activity and damage were
comprehensive and not limited to proximal skeletal
muscle inflammation. Such variables included not only
common disease manifestations from many different
organ systems, but also complications associated with
severe illness courses and poor prognostic factors (1,2831). There was no consensus on the value of many other
clinical variables for assessing juvenile IIM disease activity and damage. This may result from actual variability in their clinical utility, because physicians differ in
their experiences in using some laboratory tests, such as
magnetic resonance imaging of muscle, factor VIIIrelated antigen testing, and neopterin testing, or because
these parameters are only of modest importance to some
of the physicians, rather than very important to the
majority in formulating assessments. Many of the variables considered very or extremely important in formulating global disease activity and damage assessments
are undergoing further investigation and validation
through the development of detailed clinical assessment
tools and comparison of these with laboratory testing.
Likert and VAS measurements of juvenile IIM
global disease activity and damage were highly correlated and were comparable in responsiveness. Although
physician global assessments of disease activity have
often been highly responsive measures in other rheumatic diseases (16,17,32), it is likely that only moderate
sensitivity to change was observed in this study due to
variability in disease duration, with many patients who
had little capacity for change in their disease severity
due to longstanding disease. In the analysis of a subset of
juvenile IIM patients who were within 7 months of
diagnosis at study entry, the physician global assessment
of disease activity was similar in responsiveness to the
CHAQ in a comparable cohort of patients with early
juvenile DM (4). Diminished sensitivity to change in
global assessments may also be due to the diverse
therapeutic approaches used in the population under
study. The responsiveness of physician global assessments varies with different types of medications in
clinical trials of adult and juvenile rheumatoid arthritis
patients (17,32). Comparison of the sensitivity to change
in global disease activity assessments with other measures of juvenile IIM disease activity, such as manual
muscle strength testing, serum muscle enzyme levels,
and CHAQ scores, is in progress as part of the collaborative study.
RIDER ET AL
1982
Over an %month interval, there was no appreciable change in juvenile IIM global disease damage. The
clinical parameters that pediatric rheumatologists
agreed were important in their formulation of global
disease damage largely were related to the sequelae of
muscle dysfunction, and may therefore correlate with
overall functional disability (4,33). Although long-term
functional disability has not been systematically studied
in juvenile IIM, in adult PM/DM patients, functional
disability, as measured by serial use of the HAQ, may
remain relatively stable over a period of 5 or more years.
Patients with sequelae such as fractures or avascular
necrosis, related to prolonged corticosteroid use, may
develop changes in functional disability over shorter
durations (33).
Requiring that patients provide self-reports of
overall well-being and specific target organ inflammation has been common in the management of rheumatic
diseases. Although adult patient global activity ratings
are often comparable with physician ratings, colinearity
in these 2 assessments has not been demonstrated
(34,35). In pediatric rheumatic diseases, including juvenile rheumatoid arthritis (JRA) and juvenile DM, parents often, but not uniformly, have been reliable surrogate reporters in assessing their child’s illncss severity
and physical function (4,36-39). Patients >8 years of age
with JRA can also reliably report on their own physical
function (36,37,39,40), but not necessarily assess JRA
disease severity (41).
In this study, parent global ratings of disease
activity did not differ significantly from those of physicians, and demonstrated comparable responsiveness.
The size of the correlation coefficients, albeit statistically
significant, suggested that the parent global ratings of
disease activity were not colinear with physician ratings
(42). Nonredundancy in parent and physician global
ratings may be the result of each evaluating different
aspects of the disease or assessing the patient using
different measures. In contrast, the global ratings by
juvenile IIM patients who were >10 years of age highly
correlated with parent global disease activity assessments, but their ratings were less sensitive to change
than those of parents and physicians. The small sample
size available for patient global ratings limits the generalizability of these results. Because the parent ratings
appeared to strongly correlate with the patient global
assessments, suggesting parents are suitable surrogate
raters for their children, and because parents were
available for patients of all ages, we recommend that
parent ratings be uniformly used in juvenile IIM global
disease activity assessments, rather than patient ratings.
In summary, physician global assessments of juvenile IIM disease activity and disease damage demonstrated acceptable interrater reliability, content validity,
and sensitivity to change. Parent global disease activity
ratings appeared to provide some information that differed from that provided by the physician. Global disease activity assessments should be considered valuable
quantitative and comprehensive measures to be included
in assessment of therapeutic responses in juvenile IIM,
whereas use of global disease damage ratings, over a
longer duration, may enhance our knowledge of the
long-term outcomes of juvenile IIM patients. The excellent interrater reliability of these measures will also
permit future collaborative studies of these rare
disorders.
ACKNOWLEDGMENTS
We thank Drs. Elizabeth Adams and Margaret Mitrane for critical reading of the manuscript; Drs. Paul Plotz and
John Klippel for support of the NIAMS study protocol under
which this study was conducted; and the following participants
in the Juvenile Dermatomyositis Disease Activity Collaborative Study Group, who either completed the global rating
survey or referred patients to the study: Drs. Balu Athreya,
Deborah Kredich, Daniel Lovell, Robert Sundel, Scott Vogelgesang, and Patience White.
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