J Clin Epidemiol Vol. 47, No. I, pp.

81-87, 1994
Copyright 0 1994 Elsevier Science Ltd
Pergamon 0895-4356(93)EOO2O-C Printed in Great Britain. All rights reserved
08954356/94166.00
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DETERMINING A MINIMAL IMPORTANT CHANGE IN A

DISEASE-SPECIFIC QUALITY OF LIFE QUESTIONNAIRE

ELIZABETH F. JUNIPER,‘* GORDON H. GuYA’rr,‘*Zt ANDREW WILLAN’ and

LAUREN E. GRIFFITH’
‘Department of Clinical Epidemiology and Biostatistics and 2Department of Medicine, McMaster
University Medical Centre, Hamilton, Ontario, Canada

(Received 31 May 1993)

Abstract-This study was carried out to determine whether the minimal important
difference, in evaluative quality of life instruments which use a 7-point scale, is similar
across individual domains and for both improvement and deterioration. Thirty nine
adults with asthma were studied, using an 8 week cohort with assessments at 0, 4 and
8 weeks. The outcomes were the Asthma Quality of Life Questionnaire and global rating
of change. For overall asthma-specific quality of life and for all individual domains
(activities, emotions, symptoms), the minimal important difference of quality of life
score per item was very close to 0.5 (range: 0.42-0.58); differences of approximately 1.O
represented a moderate change (range: 0.77-1.51); differences greater than 1.5 rep-
resented large changes. Changes for improvement and deterioration were very similar.
The changes in quality of life score that represent a minimal important difference are
very similar to those observed for other evaluative instruments. The observation that
the minimal important difference is consistent across domains and for both improve-
ment and deterioration will facilitate interpretation of results of studies examining
quality of life.

Quality of life Asthma

INTRODUCTION professionals seldom use quality of life measures

in clinical practice. In clinical trials, where qual-
Repeated experience with a wide variety of
ity of life instruments are being used increasingly
physiological measures allows clinicians to
as primary outcome measures, it is simple to
make meaningful interpretation of results.
determine the statistical significance of changes
For instance, experienced clinicians have
in quality of life but placing the magnitude of
little difficulty interpreting a 10mmHg fall
these changes in a context that is meaningful for
in diastolic blood pressure or a 0.5 litre increase
health professionals has not been so easy.
in forced expiratory volume in one second
Ascertaining the magnitude of change that
(FEV,). In contrast, the meaning of a change
corresponds to a minimal important difference
in score of 1.0 on a quality of life instrument
would help to address this problem. The mini-
is less intuitively apparent, not only because it
mal important difference can be defined as “the
has no familiar units, but also because health
smallest difference in score in the domain of
interest which patients perceive as beneficial and
*Requests for reprints and the questionnaire should he
addressed to: Elizabeth Juniper MCSP MSc., Depart- which would mandate, in the absence of trou-
ment of Clinical Epidemiology and Biostatistics, Mc- blesome side-effects and excessive cost, a change
Master University Medical Centre, 1200 Main Street in the patient’s management” [I]. A variety of
West, Hamilton, Ontario, Canada L8N 325.
tDr Guyatt is a Career Scientist of the Ontario Ministry of methods has been proposed for estimating the
Health. minimal important difference [2]. In this study,

81
82 ELIZABETHF. JUNIPERet al.
we have focused on one of these methods
which relates change in quality of life scores to
patients’ estimate of their global rating of change.
Seven point scales are frequently used as
response options in disease-specific quality of
life instruments that have been developed for
assessing within-subject change over time (eval-
uative instruments) [3]. During the validation
studies for the Chronic Respiratory Question-
naire [4] and the Chronic Heart Failure Ques-
tionnaire [5], pooled results suggested that a
change in mean score of 0.5 may be considered
the smallest difference which the patient per-
ceives as beneficial and hence can be considered
the minimal important difference [l]. This value
was substantiated by further work in random-
ized trials in individual subjects [6]. In this
study, we have investigated whether similar
changes in score in the newly validated Asthma
Quality of Life Questionnaire [7] also represent
a minimal important difference. If so, this would
suggest that similar evaluative quality of life
instruments, which present response options as
7-point scales, would show similar measurement
characteristics, thus making it unnecessary to
determine the magnitude of the minimal import-
ant difference in every new instrument. We have
also investigated whether the significance of
improvements are similar to those of deterio-
ration and have estimated whether the magni-
tude of the important change for the instrument
as a whole is similar to that of each of the
individual domains.
MATERIALS AND METHODS
Subjects
Thirty nine adults with symptomatic asthma
participated in the study. If asthma symptoms
were inadequately controlled at either the first
or second visits, inhaled steroids were either
added or increased above the current treatment
regimen. The subjects were selected to represent
a wide range of clinical asthma severity and
airway hyperresponsiveness (Table 1).
Study design
Subjects were evaluated on three occasions,
each assessment being separated by 4 weeks. At
each visit, the Asthma Quality of Life Question-
naire was administered and at the two follow-up
visits Global Rating of Change Questionnaires
were completed for the domains of activities,
asthma symptoms and emotional function as
well as for overall asthma-related quality of life.
Asthma Quality of Life Questionnaire
The Asthma Quality of Life Questionnaire
contains 32 items in four domains: activities (12
items, 5 of which are individualized), asthma
symptoms (11 items), emotional function (5
items) and environmental exposure (4 items) [7,
Appendix]. Patients are asked to indicate how
they have been during the previous 2 weeks.
Response options are presented as 7-point
scales. We have demonstrated that the question-
naire is reproducible when patients are stable
(intraclass correlation coefficient of 0.92) [8].
The questionnaire has proved responsive in
before-after studies [8,9] and in clinical trials
[lo]. Construct validity has been supported by
significant relationships with both conventional
measures of asthma severity and generic quality
of life instruments [S, 91.
We calculate scores on the questionnaire do-
mains as averages of all items on that domain.
Scores thus have a range of l-7.
Global Rating of Change Questionnaires
Four global questions were used to classify
patients according to whether they had im-
proved or deteriorated. The questions were
worded as follows: “Since your last clinic visit,
has there been any change in activity limitation/
symptoms/emotions/overall quality of life, re-
lated to your asthma?“. If patients indicated
that there had been no change, they were given
a score of zero. If they indicated that there had
been an improvement or a deterioration, they
were asked to score the change on the following
scale:
-7 A very great deal worse
-6 A great deal worse
-5 A good deal worse
-4 Moderately worse
-3 Somewhat worse
-2 A little worse
-1 Almost the same, hardly any worse at all
0 No change
1 Almost the same, hardly any better at all
2 A little better
3 Somewhat better
4 Moderately better
5 A good deal better
6 A great deal better
7 A very great deal better
During each clinic visit, patients completed
two generic quality of life questionnaires and a
clinical asthma questionnaire. A methacholine
 Minimal Important Difference
Table 1. Patient characteristics
Number
Age, yr (SD) :;.0 (13.7)
24115
Gender F/M
FEV,% pred. (SD) 84.8 (14.2)
PC,, mg/ml (range) 1.16(0.03-15.9)
Medication requirements-number
No medications 2 the current data set, we decided to reverse our
Bronchodilators only 8
Inhaled steroid and bronchodilators 29
Baseline quality of life scores-mean and (SD)
Activities 5.21 (0.97)
Symptoms 4.97 (1.01)
Emotions 5.17(1.14)
4.99 (1.22)
Environment
Overall Quality of Life 5.07 (0.86)
inhalation test was conducted. In order to maxi-
mize independence of response, the Asthma
Quality of Life Questionnaire was always com-
pleted at the beginning of the visit and the
global rating questions were completed at the
end.
Statistical analysis
We calculated the change in mean item score
for each domain of the Asthma Quality of Life
Questionnaire for each patient for each time
interval. Change in overall quality of life was
calculated from the mean of all the items. We
classified patients whose score on the Global
Rating of Change Questionnaire was 0, 1 or - 1
as unchanged. We considered patients whose
score was 2, 3, - 2 or - 3 as having experienced
a small change equivalent to the minimal im-
portant difference [l]. Those with scores of 4, 5,
-4 and - 5 were considered to have experi-
enced moderate change and those with scores of
6, 7, -6 and - 7 were considered to have
experienced large change. In patients who re-
ported a change (global rating 22 or > -2)
the change in quality of life scores was com-
bined by changing the sign of the scores for
those who deteriorated.
The designation of what global ratings
suggest patients are fundamentally unchanged
and what global ratings suggest patients have
experienced a small but important improvement
or deterioration is inevitably subjective and
arbitrary. In our initial work [l, 61 we classified
patients as unchanged only if they said there was
no change whatsoever. Patients were classified
as having small but important change if their
global rating was -1, -2 -3, 1, 2 or 3. In
presenting our results at scientific meetings and
to our colleagues locally we have found dis-
agreement as to whether patients with ratings of
CE47:1-F
83
- 1 (Almost the same, hardly any worse at ail)
and 1 (Almost the same, hardly any better at all)
should be classified as fundamentally un-
changed, or having experienced a small but
important change. This disagreement led us to
ponder the issue further, and before analyzing
prior decision and count those scoring - 1 and
1 as unchanged. Fortunately, only a very small
proportion (2%) of those who were classified as
unchanged chose - 1 or 1, and this was also true
in prior studies.
For the three domains of the Asthma Quality
of Life Questionnaire (activities, symptoms and
emotions), the scores have been compared with
their corresponding global ratings of change.
There was no global rating of change for prob-
lems experienced as a result of environmental
exposure, and we have therefore omitted the
environmental domain from further consider-
ation.
In the analysis, data from the two time inter-
vals were combined. For the present analysis,
combining the data assumes only that the re-
lationship between the Global Ratings of
Change and the Asthma Quality of Life Ques-
tionnaire were similar during the two periods,
which proved to be the case.
RESULTS
Thirty nine subjects completed the first time
interval (visit l-visit 2) and 37 completed the
entire study. The two subjects who dropped out
did so for non-medical reasons. We present
demographic characteristics of the patients, and
the mean and standard deviation of the scores
on each of the four relevant domains and the
overall score of the questionnaire, in Table 1.
For patients who reported that they had not
changed (global rating score = 0) or that they
had hardly changed at all (score = 1 or - l), the
mean change in overall quality of life score was
0.11 with the individual domains ranging from
0.07 to 0.20 (Table 2). For those indicating a
change of 2, 3, - 2 or - 3 on the global rating,
the mean change in quality of life score was 0.52
for overall quality of life, with the individual
domains ranging from 0.42 to 0.58. As global
rating of change increased further there was a
corresponding increase in the mean change in
quality of life scores both overall and for all
domains. For a moderate change (global rating
4, 5, -4 and -5), the mean change in overall
asthma quality of life score was 1.03 and when
 ELIZABETH
F. JUNIPERet al.

Table 2. Changes in quality of life scores vs global rating of change-better

and worse data combined
Quality of life Global rating of change
Mean change/item 2-3 45
Overall QGL 0.1 Ci.391’ 0.52 [0.41] 1.03 [0.62] 2.29Ti.711
(n = 38) (n = 10) (n = 23) (n = 5)
Activity limitation 0.12 [0.34] 0.47 [0.51] 0.87 [0.54] 1.83 [0.76]
(?I = 39) (n = 10) (n = 23) (n = 4)
Symptoms 0.20 [0.52] 0.49 [0.56] 1.13 [0.83] 2.21 [1.34]
(n = 23) (n = 23) (n = 21) (n = 9)
Emotional function 0.20 [0.87] 0.58 [0.56] 1.51 [1.23] 2.70 [1.56]
(n = 54) (n = 11) (n = 9) (?I = 2)
*Standard deviations in square brackets.

the change was large (global rating 6,7, -6 and
- 7), the mean change in overall asthma quality
of life was 2.29.
When improvement and deterioration were
examined individually, the same pattern
emerged (Table 3). In patients who were con-
sidered to have experienced a minimal import-
ant improvement (global rating 2 and 3), the
overall change in quality of life score was 0.41
and for a minimally important deterioration
(global rating - 2 and - 3), the change in score
was -0.62. For a moderate improvement, the
change was 1.10 and for a deterioration -0.93.
For a large improvement, the change was 2.29
and for a deterioration the change was -2.67.
A similar pattern was observed in all the indi-
vidual domains.
DISCUSSION
The results of this study demonstrate that,
when using 7-point scale response options in the
Asthma Quality of Life Questionnaire, a within-
subject change in score of 0.5 represents the
minimal important difference. A change in score
of 1.0 may be considered a moderate change in
quality of life. Because only a small number of
patients had a large change in health-related
quality of life, the current study’s estimate of
what constitutes a large change in score is
extremely imprecise. Taking into account data
from the current study and previous work [ 1,6],
a change in score of greater than 1.5 is likely to
represent a large change. The results further
demonstrate that these interpretations apply not
only to the instrument as a whole but also to the
individual domains, and both to patients who
improve and those who deteriorate.
This is the third study to demonstrate that in
disease-specific quality of life instruments, using
‘I-point scale response options, a change in score
of 0.5 represents the minimal important differ-
ence [l, 51. The finding that comparable changes
in score represent minimal, moderate and large
changes across individual domains suggests that
the results are generalizable to all areas of
health-related quality of life The importance of
this observation lies in the fact that health
professionals interpreting the results of health-
related quality of life studies can apply the same
standards for judging the magnitude of effects
across a wide variety of instruments.
In some clinical trials, treatments may be
designed to affect only one domain of a quality
of life instrument (e.g. a coping skills program
might be expected to focus primarily on
emotional function). Since the results were con-
sistent across domains and also consistent with
the overall score, changes of greater than 0.5 per
item within an individual domain signifies an

Table 3. Change in quality of life scores vs global rating of change

Global rating of change

Quality of life Better Same Worse

Mean change/item 7&6 5&4 3&2 l&O&- 1 -2&-3 -4&L-5 -6&r-7
Overall QOL 2.19 1.10 0.41 0.11 -0.62 -0.93 -2.67
(n = 4) (n = 14) (n = 5) (n = 1)
Activity limitation 1.83 0.92 0.56 (Z!
(n=4) (n=l3) (n=5) (n-0.81
=‘lO) (!=oo,)
Symptoms 1.19 1.37 0.40
(n = 7) (PI= 12) (n = 8) (n = 2)
Emotional function 2.70 0.96 0.73
(n = 2) (n = 5) (n = 6) (n -= 0)
 Minimal Important Difference 85

important improvement or deterioration in that 2. Guyatt GH, Feeny D, Patrick D. Proceedings of

aspect of quality of life.
The same development strategy was used in
each of the instruments in which we have estab-
lished the minimal important difference [3, 111.
It would be very convenient if all evaluative
instruments using 7-point scale response options
demonstrated similar properties. Full confi-
dence in this conclusion must await replication
of these findings by other investigators. Our
sample was small and may not have been repre-
sentative, and this further highlights the need
for replication. Our findings are also limited in
that a change in score of 0.5 is important when
the international conference on the measurement
of quality of life as an outcome in clinical
trials: postscript. CoatroBed CIin Trials 1991; 12:
266S-2698.
3. Kirshner B, Guyatt GH. A methodologic framework
for assessing health indices. J Cbron Dis 1985; 38:
27-36.
4. Guyatt GH, Berman LB, Townsend M, Pugsley SO,
Chambers LW. A measure of quality of life for clinical
trials in chronic lung disease. Thorax 1987; 42:
773-778.
5. Guyatt GH, Nogradi S, Halcrow S et al. Development
and testing of a new measure of health status for
clinical trials in heart failure. J Can Intern Med 1989:
4: 101-107.
6. Jaeschke R, Guyatt GH, Keller J, Singer J. Interpret-
ing changes in quality of life score in N of 1 random-
ized trials. Controlled Clin Trials 1991: 12t4Sl: ~I

the instrument is used for examining within- 226-233.

patient changes but this does not necessarily
mean that a difference of 0.5 will signify the
minimal important difference when the instru-
ment is used to discriminate between patients
[12]. Nevertheless, the results provide grounds
for optimism regarding the easy interpretation
of results of health-related quality of life
measures.
Acknowledgements-We thank MS Penelope Ferrie for
carrying out the interviews and collating the data and Derek
King for his help with the data analysis. This study was
supported in part by a grant from Astra Pharma.
REFERENCES
1. Jaeschke R, Singer J, Guyatt GH. Measurements of
health status: ascertaining the minimal clinically im-
portant difference Controlled Clin Trials 1989; 10:
407415.
7. Juniper EF, Guyatt GH, Epstein RS, Ferrie PJ,
Jaeschke R. Hiller TK. Evaluation of imoairment of
health-related quality of life in asthma: devklopment of
a questionnaire for use in clinical trials. Thorax 1992;
47: 76-83.
8. Juniper EF, Guyatt GH, Ferrie PJ, Griffith LE.
Measuring quality of life in asthma. Ant Rev Respir Dis
1993; 147: 832-838.
9. Rowe BH. Steroid treatment of asthma exacerbations:
a meta-analysis, evaluation of a quality of life instru-
ment, and design of a randomized factorial trial. Msc.
Thesis 1991; McMaster University, Hamilton, Canada.
10. Juniper EF, Johnston P, Borkhoff C, Haukioja A.
Effect of salmeterol on asthma quality of life. Am Rev
Respir Dis 1993; 147: A60.
11. Guyatt GH, Bombardier C, Tugwell PX. Measuring
disease-specific quality of life in clinical trials. Can Med
Assoc J 1986; 134: 889-895.
12. Malo J-L, Boulet L-P, Dcwitte J-D, Cartier A,
L’Archeveque J, Cote J, Bedard G, Boucher S, Cham-
pagne F, Messier G, Contandriopoulos A-P, Juniper
EF, Guyatt GH. A quality of life questionnaire for
asthma: clinical validation of discriminative properties.
J AUergy Clin Immunol 1993; 91: 1121-I 127.

APPENDIX

The Asthma Quality of Life Questionnaire

This questionnaire is designed to find out how you have been feeling during the last 2 weeks. You will be asked about
ways in which your asthma has limited your activities, the symptoms you have experienced as a result of your asthma,
and how these have made you feel.
I should like you to think of the ways in which your asthma limits your life. I am particularly interested in activities
that you still do, but which are limited by your asthma. You may be limited because you do these activities less often, or
less well, or because they are less enjoyable. These should be activities which you do frequently and which are important
in your day-to-day life.

[RECORD IDENTIFIED ACTIVITIES]

I shall now read a list of activities in which some people with asthma are limited. I shall pause after each item long enough
for you to tell me if you have been limited in this activity because of your asthma in the last 2 weeks. If you have not
done the activity or it hasn’t bothered you during the last 2 weeks, just answer “no”.
[READ ACTIVITIES, OMITTING THOSE WHICH THE RESPONDENT HAS VOLUNTEERED
SPONTANEOUSLY]

1. Bicycling 6. Gardening
2. Clearing snow off car 7. Hurrying
3. Dancing 8. Jogging/exercising/running
4. Doing home maintenance 9. Laughing
5. Doing housework 10. Mopping/scrubbing the floor
86 F. JUNIPERet al.
ELIZABETH

11. Mowing the lawn 19. Talking

12. Playing with pets 20. Running upstairs or uphill
13. Playing with children 2 1. Vacuuming
14. Playing sports 22. Visiting friends or relatives
15. Shovelling snow 23. Going for a walk
16. Singing 24. Walking upstairs or uphill
17. Social activities 25. Woodwork or carpentry
18. Sexual intercourse 26. Work activities

(The aim of this list is to help patients select activities that are important in their day-to-day lives. The list may be altered
to suit different cultures and climates.)
Of the activities which you have identified, I should like you to tell me which are the five most important in your
day-to-day life.

[READ ALOUD THE LIST OF IDENTIFIED ACTIVITIES-WRITE THE FIVE ACTIVITIES IN

QUESTIONS l-5 OF THE QUALITY OF LIFE QUESTIONNAIRE]

1. Please indicate how much you have been limited by your asthma in [Activity 1: . . . . . . . .] during the last two weeks
by choosing one of the following options. [GREEN CARD]
[REPEAT FOR EACH OF THE 5 IDENTIFIED ACTIVITIES]
6. How much discomfort or distress have you felt over the last two weeks as a result of CHEST TIGHTNESS? [RED
CARD]
7. In general, how much of the time during the last two weeks have you FELT CONCERNED ABOUT HAVING
ASTHMA? [BLUE CARD]
8. How often during the past two weeks did you feel SHORT OF BREATH as a result of your asthma? [BLUE CARD]
9. How often during the past two weeks did you experience asthma symptoms as a result of being EXPOSED TO
CIGARETTE SMOKE? [BLUE CARD]
10. How often during the past two weeks did you experience a WHEEZE in your chest? [BLUE CARD]
11. How often during the past two weeks did you feel that you had to AVOID A SITUATION OR ENVIRONMENT
BECAUSE OF CIGARETTE SMOKE? [BLUE CARD]
12. How much discomfort or distress have you felt over the last two weeks as a result of COUGHING? [RED CARD]
13. In general, how often during the past two weeks did you feel FRUSTRATED as a result of your asthma? [BLUE
CARD]
14. How often during the past two weeks did you experience a feeling of CHEST HEAVINESS? [BLUE CARD]
15. How often during the past two weeks did you feel CONCERNED ABOUT THE NEED TO USE MEDICATION
for your asthma? [BLUE CARD]
16. How often during the past two weeks did you feel the need to CLEAR YOUR THROAT? [BLUE CARD]
17. How often during the past two weeks did you experience asthma symptoms as a result of being EXPOSED TO DUST?
[BLUE CARD]
18. How often during the past two weeks did you experience DIFFICULTY BREATHING OUT as a result of your
asthma? [BLUE CARD]
19. How often during the past two weeks did you feel that you had to AVOID A SITUATION OR ENVIRONMENT
BECAUSE OF DUST? [BLUE CARD]
20. How often during the past two weeks did you WAKE UP IN THE MORNING WITH ASTHMA SYMPTOMS?
[BLUE CARD]
21. How often during the past two weeks did you feel AFRAID OF NOT HAVING YOUR ASTHMA MEDICATIONS
AVAILABLE? [BLUE CARD]
22. How often during the past two weeks were you bothered by HEAVY BREATHING? [BLUE CARD]
23. How often during the past two weeks did you experience asthma symptoms as a result of WEATHER OR THE AIR
POLLUTION OUTSIDE? [BLUE CARD]
24. How often during the past two weeks have you been WOKEN AT NIGHT by your asthma symptoms? [BLUE CARD]
25. How often durina the uast two weeks did vou feel that vou had to AVOID OR LIMIT GOING OUTSIDE BECAUSE
OF THE WEAfHER OR AIR POLLUTION? [BLUE CARD]
26. How often during the past two weeks did you experience asthma symptoms as a result of BEING EXPOSED TO
STRONG SMELLS OR PERFUME? [BLUE CARD]
27. How often during the past two weeks did you feel AFRAID OF GETTING OUT OF BREATH? [BLUE CARD]
28. How often during the past two weeks did you feel that you had to AVOID A SITUATION OR ENVIRONMENT
BECAUSE OF STRONG SMELLS OR PERFUME? [BLUE CARD]
29. How often during the past two weeks has your asthma INTERFERED WITH GETTING A GOOD NIGHTS
SLEEP7 [BLUE CARD]
30. How often during the past two weeks have you had a feeling of FIGHTING FOR AIR? [BLUE CARD]
31. Think of the OVERALL RANGE OF ACTIVITIES that you would have liked to have done during the past two weeks.
How much has your range of activities been limited by your asthma? PELLOW CARD]
32. Overall, among ALL THE ACTIVITIES that you have done during the past two weeks, how limited have you been
by your asthma? [GREEN CARD]

DOMAIN QUESTIONS
SYMPTOMS 6,8,10,12,14,16,18,20,22,24,29,30
ACTIVITIES 1I2I3,4 15, 11,19,25,28,31,32
EMOTIONS 7,13,15,21,27
 Minimal Important Difference 87

RESPONSE OPTIONS
GREEN CARD RED CARD
I. Totally limited, couldn’t do activity at all 1. A very great deal of discomfort or distress
2. Extremely limited 2. A great deal of discomfort or distress
3. Very limited 3. A good deal of discomfort or distress
4. Moderate limitation 4. A moderate amount of discomfort or distress
5. Some limitation 5. Some discomfort or distress
6. A little limitation 6. Very little discomfort or distress
7. Not at all limited 7. No discomfort or distress

BLUE CARD YELLOW CARD

1. All of the time 1. Severely limited-most activities not done
2. Most of the time 2. Very limited
3. A good bit of the time 3. Moderately limited-several activities not done
4. Some of the time 4. Slightly limited
5. A little of the time 5. Very slightly limited-very few activities not done
6. Hardly any of the time 6. Hardly limited at all
7. None of the time 7. Not limited at all-have done all activities that I wanted
to do