Aliment Pharmacol Ther 2001; 15: 207216.

Quality of life in functional dyspepsia: responsiveness of the Nepean

Dyspepsia Index and development of a new 10-item short form
N. J. TALLEY*, M. VERLINDEN & M . JONES*
*Department of Medicine, University of Sydney, Nepean Hospital, Australia; and Abbott Laboratories, USA
Accepted for publication 5 September 2000

SUMMARY

Background: The Nepean Dyspepsia Index is a reliable

and valid measure of quality of life in functional
dyspepsia, but responsiveness has been little studied.
The Nepean Dyspepsia Index originally contained 42
items designed to measure impairment of a subject's
ability to engage in relevant aspects of their life because
of dyspepsia, and their enjoyment of these aspects; in
addition, the individual importance of areas was
assessed. It was subsequently shortened to 25 items,
yielding ve sub-scales.
Aim: To test the Nepean Dyspepsia Index's responsiveness and develop a responsive, very short form.
Methods: A randomized, double-blind controlled trial
was performed in 589 patients with documented
functional dyspepsia. Symptoms and quality of life were
measured at baseline, 2 and 4 weeks. Responsiveness of
the Nepean Dyspepsia Index quality-of-life section was
evaluated by correlation with symptom scores and
calculation of standardized changes in scores. Two

INTRODUCTION

Health-related quality of life refers to how disease

impacts on those areas of life that make it worth living,
including physical and emotional functioning.1 Substantially reduced quality of life has recently been
documented in patients with functional dyspepsia.27

Correspondence to: Professor N. J. Talley, Department of Medicine,

University of Sydney, Nepean Hospital, Penrith, 2751, N.S.W., Australia.
1 E-mail: talleyn@wahs.health.nsw.gov.au
2001 Blackwell Science Ltd

items from each sub-scale which best represented the

area of life (by factor loadings) were selected to create
the 10-item short form (SF; short form-Nepean Dyspepsia Index). Internal consistency was assessed by Cronbach's alpha and responsiveness was assessed as above.
Results: The Nepean Dyspepsia Index quality-of-life
scales demonstrated excellent responsiveness to change
in both the active and placebo arms (standardized
response means all > 1.0). The Nepean Dyspepsia Index
accounted for only 8% of the variance in percentage
change in symptoms (by visual analogue scales),
indicating that it was evaluating areas of life not
covered by symptoms. The 10-item short form had
adequate internal consistency (all scales 0.70) and all
strongly (and signicantly) correlated with the long
form sub-scales; it was also highly responsive.
Conclusion: The Nepean Dyspepsia Index is a responsive
disease-specic quality-of-life measure; the 10-item
short form can be applied in clinical trials of functional
dyspepsia.

However, earlier studies primarily applied non-specic

quality of life instruments, such as the short form-36
(SF-36) or the Psychological General Well-Being Index,
which contain multiple items, many of which may be
irrelevant to dyspepsia.1, 810
Only recently has serious attention been given to
developing accurate symptom and quality-of-life outcome measures in functional dyspepsia.8, 9 In clinical
trials, quality of life is often considered as a secondary
outcome to symptom relief, but there is increasing
interest in considering quality-of-life improvement as a
primary objective of therapy in conditions such as
207

208

N. J. TALLEY et al.

functional dyspepsia, which cause no mortality.8, 9

However, there would be no value in assessing quality
of life if the symptom measures cover essentially the
same patient concerns. In functional dyspepsia, this has
been a little-studied area.
A self-report disease specic questionnaire for functional dyspepsia, the Nepean Dyspepsia Index, has been
developed to measure both symptom status and quality
of life.3, 4 In previous studies, we have demonstrated
that the 42-item Nepean Dyspepsia Index quality-of-life
2 questionnaire appeared to be reliable and accurate. It
could also discriminate dyspepsia from health in
uninvestigated patients with dyspepsia recruited from
family practice in Australia and in a random population
sample from New Zealand.3 The Nepean Dyspepsia
Index had four sub-scales identied originally. A
subsequent study of 101 US patients with functional
dyspepsia showed that the Nepean Dyspepsia Index
could be shortened to 25 quality-of-life items with ve
sub-scales; the revised instrument remained reliable and
valid.4 Its ability to measure change (i.e. responsiveness) was assessed but not in the setting of a large
randomized controlled trial; the initial responsiveness
data were encouraging but not denitive.4
The aim of this study was to develop an even briefer,
easy to score self-report measure that reliably and
validly measures symptoms and quality of life in
functional dyspepsia, and is sensitive to change in
clinical status. We also wished to determine whether
symptom assessment alone is adequate in clinical trials
to capture the impact of functional dyspepsia. We
therefore applied the Nepean Dyspepsia Index in a large
multicentre trial in Europe and the United States, which
provided an opportunity to prospectively test the
instrument in functional dyspepsia.
METHODS

Instrument development
The conceptual basis of the Nepean Dyspepsia Index
was rst developed in Sydney in consultation with an
international research team.3 Initial items were chosen
through consultation with patients, and local gastroenterology and psychology staff. These items were then
pre-tested amongst patient populations in four countries
(Australia, Germany, Italy and the Netherlands) using
focus groups and face-to-face interviews to identify a
comprehensive set of relevant disease specic items. To

ensure all the relevant issues were measured, the

Nepean Dyspepsia Index was reviewed by an international panel of experts in gastroenterology and items
were carefully selected. A revised version of the Nepean
Dyspepsia Index was then created; this incorporated 42
items which assessed quality of life across 17 key
aspects of life.3 A completely separate symptom checklist was included that measured the frequency, intensity
and bothersomeness of 15 upper gastrointestinal symptoms over the prior 2 weeks. A 2-week period was
chosen in order to minimize recall bias yet cover an
adequate period for measurement of usual activities and
symptom status.8 The inclusion of a symptom checklist
provides the instrument with an internal standard
against which to compare the Nepean Dyspepsia Index's
quality of life measurement.
An important aspect of the philosophy underlying the
Nepean Dyspepsia Index was that it be sensitive to the
differing priorities and individual value systems of
dyspepsia patients. This was achieved by allowing
individuals to apply differing weights (equivalent to
priorities) to common groups of items or themes (based
on key aspects of life) in the Nepean Dyspepsia Index,
such as the impact of dyspepsia on daily living or sleep.
These weights were incorporated into the Nepean
Dyspepsia Index scoring system that was developed. In
the initial validation study, weighting did not inuence
the discriminant value of the questionnaire but it did
appear to be of value in a subsequent report.3, 4 The
questionnaire has undergone validated translation from
Australian English to French, Dutch, Italian, German,
Spanish and American English.
Trial design
The major results of this trial have been reported
elsewhere.11 The trial was approved by local Institutional Review Boards, and all patients gave informed
consent. Patients at least 18 years of age with a
minimum 3-month history of chronic upper abdominal
discomfort (i.e. postprandial fullness, bloating, epigastric
discomfort, early satiety, belching after meals, postprandial nausea, vomiting or epigastric pain) were
eligible for enrolment. A total of 738 patients were
screened by 19 investigators in Europe and 21 investigators in the US between May 1997 and June 1998.
Patients were required to have a normal upper
endoscopy (i.e. no ulcers or erosions in the oesophagus and gastroduodenum) in the 3 months before
2001 Blackwell Science Ltd, Aliment Pharmacol Ther 15, 207216

QUALITY OF LIFE IN FUNCTIONAL DYSPEPSIA

randomization. Furthermore, during the baseline evaluation over 14 days, patients had to have experienced
postprandial upper abdominal discomfort on 3 or more
days per week and have sufciently severe symptoms,
dened as a total upper abdominal discomfort severity
score of > 149 mm and a postprandial fullness severity
score of > 29 mm on visual analogue scales, as
described below. Patients were only enrolled if there
were no serious co-morbid illnesses and screening
laboratory values were normal.
Excluded were patients with gastro-oesophageal reux
disease, based on a normal endoscopy (only erythema
was permitted) and those with an absence of predominant daytime or night-time heartburn (predominant
being dened as a severity score for heartburn equal to
or greater than the postprandial fullness severity score,
as described below). Predominant ulcer-like dyspepsia
(pain) and symptoms suggestive of irritable bowel
syndrome also resulted in exclusion. Patients with
organic causes of gastroparesis (e.g. diabetes mellitus)
and other serious disease (including alcoholism and
drug dependence, any bowel surgery or malignancy)
were excluded. Occasional non-steroidal anti-inammatory drug use (< 11 days per month) or aspirin
(< 101 mg daily) was permitted, but prokinetic, antisecretory or antacid therapy within 3 days of screening
and throughout the treatment period was not.
A total of 612 patients were randomized but three
were lost to follow-up after drug was dispensed and
were excluded. Patients treated (n 609) were randomly assigned to the motilin agonist ABT 229
1.25 mg (n 118), 2.5 mg (n 121), 5 mg (n
126), 10 mg (n 123) or placebo (n 121) twice
daily for 4 weeks. Nepean Dyspepsia Index data were
available for 589 of these patients. A total of 47 patients
prematurely discontinued because of adverse events
(n 18), non-compliance (n 7), treatment failure
(n 14), or other reasons (n 5), or were lost to
follow-up (n 3); the distribution was similar in each
arm and 562 patients completed the trial.
Outcome assessments
Patient Symptom Questionnaire: visual analogue scales. At
baseline, 2 and 4 weeks, all patients completed an
independent self-report measure of the severity, frequency, duration and impact of symptoms over the
prior 2 weeks. The target symptoms were postprandial
fullness, early satiety, bloating, epigastric discomfort (an
2001 Blackwell Science Ltd, Aliment Pharmacol Ther 15, 207216

209

ache or discomfort after eating, poorly localized),

epigastric pain (a sharp, easy to pinpoint pain after
eating), postprandial nausea, belching after meals and
vomiting. Severity was scored for each symptom on a
100-mm visual analogue scale. The primary outcome
was dened a priori as the sum of severities of the eight
symptoms, to create the total upper abdominal discomfort severity score (minimum 0, maximum 800 mm).
Dening each symptom in lay-person terms standardized the questionnaire, and cultural differences were
minimized by comprehensive forward and backward
linguistic translations of all measures. A visual analogue scale is sensitive to change and is well-accepted as
a tool for evaluating symptoms.8
Nepean Dyspepsia Index. Quality of life was lled in by
each patient at baseline and at 4 weeks. The Nepean
Dyspepsia Index quality-of-life scale consisted of the
original questions, measuring health-related quality of
life structured around 17 key areas of life.
For most of the quality-of-life areas, the impact of the
illness was considered to occur in two dimensions:
interference with a subject's ability to perform or engage
in the area (e.g. a reduced ability to spend time with
friends because of dyspepsia); and interference with
their enjoyment of that area of life (e.g. impaired
enjoyment of time spent with friends because of
dyspepsia). These were measured by 5-point Likert
scales from 0 (not at all or not applicable), 1 (a little),
2 (moderately), 3 (quite a lot) to 4 (extremely).
Five sub-scales, namely interference with daily activities (nine question items), knowledge/control (six
items), tension (three items), work/study (four items)
and eating/drinking (three items) were derived, as
previously described.4 These ve sub-scales comprising
the full Nepean Dyspepsia Index were subsequently
evaluated.
The Nepean Dyspepsia Index symptom scale measured
the frequency, severity and bothersomeness of 15 upper
gastrointestinal symptoms, applying a scale of 0 (not at
all) to 4 (daily) for frequency, 0 (not at all) to 5 (very
severe) for intensity, and 0 (not at all) to 4 (extremely
bothersome) for bothersomeness. Scores were added
over the three groups of symptoms.
Statistical analyses
Three patient-reported assessments of dyspepsia were
evaluated: (i) eight symptoms according to the

210

N. J. TALLEY et al.

independent visual analogue scales in the Patient

Symptom Questionnaire; (ii) 15 symptoms according
to the Nepean Dyspepsia Index symptom checklist; and
(iii) health-related quality of life according to the ve
Nepean Dyspepsia Index scales.
Internal consistency (reliability). In combining responses
to several questions, it is assumed that they are all
measuring some common underlying concept (construct). This can be assessed by measuring the internal
consistency of the items. A common and well-accepted
index of internal consistency is Cronbach's alpha.12
Internal consistency was assessed by Cronbach's alpha
by rst using all quality-of-life items in the full Nepean
Dyspepsia Index, then using the 10-item short form as
described below.
Responsiveness (ability to measure change). Responsiveness of the Nepean Dyspepsia Index symptom and
quality-of-life scales to changes in the patient's underlying status was rst assessed by correlation (Spearman
rank) with the Patient Symptom Questionnaire and
secondly by descriptive comparison of percentage
change in each of the three patient-reported assessments. Correlations between quality-of-life and symptom scores were undertaken both at xed times
(baseline and end of study) and in terms of change
from baseline to end of study. The latter correlations
directly assess responsiveness, while the former provide
insight into the equivalence of these scales.
The standardized change in score (standardized
response mean) was calculated by dividing the mean
change by the standard deviation of the change. Values
> 1.0 indicate excellent responsiveness.
Item reduction to create a short form Nepean Dyspepsia
Index. A simpler form of the quality-of-life index was
calculated to assess the viability of a much shorter scale.
The item reduction strategy was based on the knowledge that multiple items measuring a single construct
are likely to be strongly correlated and hence involve
some redundancy. It was hypothesized that the two
items with the highest factor loadings on each of the ve
sub-scales would provide an adequate representation of
the relevant areas, yielding a 10-item quality-of-life
scale. The pairs of items were combined in an
unweighted sum (Appendix 1).
The extent to which the short form Nepean Dyspepsia
Index quality-of-life scales provided representation of

the full-item scales was assessed in several ways. Each

simplied sub-scale score was correlated with its
original, complete counterpart. In addition, canonical
correlation and multivariate regression were used to
assess how the simplied scales provided representation
of the complete scales. Responsiveness was estimated as
described above.
All P-values calculated were two-tailed; the alpha level
of signicance was set at P < 0.05.
RESULTS

Trial outcome: Patient Symptom Questionnaire

Patients (n 589) were on average middle aged (mean
46 years, s.d. 14), with a preponderance of females
(69%, n 409) and mostly of Caucasian origin (91%,
n 537). A total of 474 patients received a dose of the
motilin agonist and 115 received placebo.
The upper abdominal discomfort severity score signicantly decreased in all treatment arms from baseline
on the intention-to-treat analysis. However, there were
no signicant differences between each of the active
treatment arms and placebo for mean change from
baseline to week 2 or week 4, as previously reported.11
Therefore, all the active treatment arms were combined
for the subsequent analyses.
Symptom responsiveness
Placebo and active drug patients were very similar in
terms of baseline symptom levels according to both the
Nepean Dyspepsia Index symptom checklist and the
visual analogue scales from the Patient Symptom
Questionnaire, and in terms of quality of life as assessed
by the full Nepean Dyspepsia Index (Table 1). The same
was apparent at the end of the study (Table 1).
Percentage changes in symptom scores were very
similar in the active drug and placebo groups, and
were also similar between the Patient Symptom Questionnaire and the Nepean Dyspepsia Index symptom
scales (Table 2).
Strong correlations were observed between the change
in Nepean Dyspepsia Index symptoms and the Patient
Symptom Questionnaire visual analogue scales, both
when assessed as absolute change (r 0.54,
P < 0.0001) and when assessed as percentage change
(r 0.66, P < 0.0001).

2001 Blackwell Science Ltd, Aliment Pharmacol Ther 15, 207216

Placebo
ABT-229

Placebo
ABT-229

Baseline

4 weeks

227.8 (174.0) 115

238.8 (159.0) 474

382.4 (133.3) 115

380.3 (135.6) 474

Patient symptom questionnaire (VAS 0800)

2001 Blackwell Science Ltd, Aliment Pharmacol Ther 15, 207216

50.8 (34.4) 111
53.8 (34.0) 460

75.8 (33.8) 110

77.7 (31.8) 469

NDI symptom
checklist

27.1 (17.8) 110

29.6 (19.7) 457

37.7 (22.7) 112

38.3 (21.1) 465

NDI
tension

115
115
107
107
108
108
105
107
108
108
107
108
107
108

Symptom ratings
Patient Symptom Questionnaire (VAS) change
Patient Symptom Questionnaire (% change)
NDI Symptom Checklist change
NDI Symptom Checklist (% change)

Quality of life scores

NDI tension (% change)
NDI interference with daily activities (% change)
NDI eating/drinking (% change)
NDI knowledge/control (% change)
NDI work/study (% change)
SF-NDI tension (% change)
SF-NDI interference with daily activities (% change)
SF-NDI eating/drinking (% change)
SF-NDI knowledge/control (% change)
SF-NDI work/study (% change)

NDI, Nepean Dyspepsia Index (long form); SF-NDI, short form NDI (two-item scales).

Placebo

Change

449
448
442
447
445
448
444
448
444
446

474
474
456
456

ABT-229

Table 2. Change in symptoms and quality of life (full and short form Nepean Dyspepsia Index)

VAS, visual analogue scale; ABT-229, motilin agonist.

Treatment
group

Time
period

Mean (s.d.) N

)18
)23.8
)11.5
)28.2
)16.6
)19.5
)15.9
)21.6
)12.7
)15.5

)154.6
)37.1
)25.7
)30

Placebo

Mean

21.4 (14.8) 110

25.3 (17.8) 457

31.8 (20.3) 112

33.5 (20.2) 464

NDI
interference

)20.5
)18.1
)2.6
)14.6
)5.8
)14.3
)12.4
)12.3
)6.3
)12.3

)141.5
)34.3
)24.9
)30.7

ABT-229

27 (19.7) 109
31.8 (20.7) 454

41.1 (23.8) 110

40 (23.7) 461

NDI eating/
drinking

65.1
51.7
164.6
48.5
110.9
33.9
)34.6
32.7
30.6
37.5

176.2
47.4
34.5
45.2

Placebo

45.3
60.6
152
139
135.7
37
45.5
42.9
37.2
44.2

159.4
46.3
28
35.9

ABT-229

23.9 (18.6) 110

27.9 (20.4) 454

36.7 (24.4) 112

36.3 (23.4) 463

NDI work/
study

Standard deviation

26.5 (21.5) 109

26.4 (19.9) 455

36.9 (23.0) 112

36.2 (23.0) 464

NDI knowledge/
control

Table 1. Mean symptom scores from the Patient Symptom Questionnaire and the full Nepean Dyspepsia Index (NDI) at baseline and 4 weeks

QUALITY OF LIFE IN FUNCTIONAL DYSPEPSIA

211

212

N. J. TALLEY et al.

Quality of life responsiveness

Considering the full-item Nepean Dyspepsia Index, the
largest percentage changes in quality of life were
observed in the knowledge/control, interference with
daily activities and tension sub-scales. Larger changes
were present in the placebo group than in the active
drug group for some sub-scales, consistent with the
changes in symptom scores (Table 2). Percentage
changes in the eating/drinking and work/study subscales were relatively modest (Table 2). A similar
pattern was observed for the 10-item short form Nepean
Dyspepsia Index (Table 2).
Statistically signicant correlations were found
between changes in the Patient Symptom Questionnaire
scale and changes in full Nepean Dyspepsia Index
quality-of-life sub-scales on both an absolute and
percentage basis (Table 3). The percentage change
yielded somewhat larger correlations than absolute
change. This is logical because percentage change
corrects more completely for differences in `potential'
to change. Considered jointly, through multiple regression, Nepean Dyspepsia Index quality-of-life items
accounted for only 8% of the variance in percentage
change in Patient Symptom Questionnaire scores and
14% of the absolute change.
The Nepean Dyspepsia Index quality-of-life sub-scales
all demonstrated excellent responsiveness, because all
standardized effect sizes exceeded 1.0 (Table 4). Similarly, the Nepean Dyspepsia Index symptom scales
showed good responsiveness with a standardized effect
score > 1.0 in the active group and just under 1.0
(0.98) in the placebo group. The Patient Symptom
Questionnaire scale showed moderate responsiveness
with a standardized effect size of around 0.8 in both
study groups (Table 4).
Table 3. Spearman rank correlations of quality-of-life changes in
the Nepean Dyspepsia Index with the Patient Symptom
Questionnaire
Quality-of-life
sub-scale
Tension
Interference with
daily activities
Eating/drinking
Knowledge/control
Work/study

Long form: full item Short form: 2 item

Absolute Percentage Absolute Percentage
0.27
0.31

0.33
0.35

0.28
0.26

0.34
0.29

0.25
0.26
0.24

0.26
0.33
0.22

0.4
0.3
0.32

0.44
0.33
0.36

In terms of clinical trial planning, given the sample size

achieved in this trial, and had the difference between
the active and placebo arms been as large as 15%
(assuming a s.d. of change of 40% as an average across
scores), the statistical power would have been 0.93.
Conversely, to achieve a statistical power of 0.80 under
the same conditions, 112 subjects would have been
required per study group.
Performance of the short form
Adequate internal consistency (Cronbach's alpha) was
found for all ve two-item short form quality-of-life subscales between baseline and the end of the study
(tension 0.71, interference with daily activities 0.70,
eating/drinking 0.71, knowledge/control 0.76, and
work/study 0.74). The full item quality-of-life sub-scale
scores were all very strongly correlated with their twoitem equivalents (Table 5, all P < 0.0001), whether
considering scores at baseline, absolute change or
percentage change.
The percentage reductions in the ve short form
Nepean Dyspepsia Index quality-of-life sub-scales were
of similar magnitude to those observed for the full-item
scales. The exception was the knowledge/control subscale, which exhibited the largest change on a full-item
basis but the smallest on the reduced item basis.
Statistically signicant correlations were found
between changes in the Patient Symptom Questionnaire
scales and changes in the short form Nepean Dyspepsia
Index quality-of-life sub-scales, on both an absolute and
percentage basis (Table 3). These were equal to or
greater than those observed among the full-item scales
(Table 3). Considered jointly, through multiple regression, Nepean Dyspepsia Index short form quality-of-life
items accounted for 19% of the variance in percentage
change in the Patient Symptom Questionnaire visual
analogue symptom score and 22% of the absolute
change. This was actually larger than found for the full
Nepean Dyspepsia Index item data.
Strong correlations were found at baseline between the
full-item sub-scales and both the 10 individual items
which make up the reduced scale (rst two canonical
correlations 0.93, 0.78) and the ve reduced item subscales (rst two canonical correlations 0.93, 0.77).
Similar canonical correlations were found after treatment.

2001 Blackwell Science Ltd, Aliment Pharmacol Ther 15, 207216

QUALITY OF LIFE IN FUNCTIONAL DYSPEPSIA

Table 4. Responsiveness of the symptom
and quality-of-life scales in the active and
placebo arms

213

Cohort

Parameter

Change
in score

Standardized
change in score

Placebo

Patient Symptom Questionnaire

NDI Symptom Checklist
NDI Tension
NDI Interference with daily activities
NDI Eating/drinking
NDI Knowledge/control
NDI Work/Study

)154.6
)25.7
)10.6
)10.5
)14.2
)10.9
)12.8

0.76
0.98
1.28
1.22
1.18
1.26
1.21

ABT-229

Patient Symptom Questionnaire

NDI Symptom Checklist
NDI Tension
NDI Interference with daily activities
NDI Eating/drinking
NDI Knowledge/control
NDI Work/Study

)151.5
)24.9
)9.3
)9.3
)8.3
)9
)8.7

0.85
1.14
1.28
1.26
1.2
1.26
1.24

Standardized response mean.

NDI, Nepean Dyspepsia Index (long form).

Table 5. Correlations between full-item and two-item scores

quality-of-life scales in the Nepean Dyspepsia Index
Domain

Baseline Absolute Percentage

Tension
0.83
Interference with daily activities 0.85
Eating/drinking
0.83
Knowledge/control
0.78
Work/study
0.71

0.74
0.72
0.72
0.58
0.55

0.68
0.67
0.7
0.56
0.54

DISCUSSION

While dyspepsia is a recognized major health problem in

the community, probably costing billions annually in
the United States, treatment remains unsatisfactory.13
When testing new therapies, validated measures of
outcome are needed which are responsive to change,
yet these have been largely unavailable.3 The Rome II
Working Teams have recommended the use of validated
quality-of-life instruments in clinical trials of patients
with functional gastrointestinal disorders, especially
when such instruments have been shown to be able
to detect change.14 Generic instruments are unlikely to
be as useful as a disease-specic measure for quantifying
changes in impaired quality of life in functional
dyspepsia with therapy.15 The lack of availability of a
disease specic quality-of-life measure for functional
dyspepsia has, in the past, limited the options for
researchers.16
The Nepean Dyspepsia Index questionnaire described
in this study is actually composed of two distinct,
2001 Blackwell Science Ltd, Aliment Pharmacol Ther 15, 207216

separately scored and interpreted instruments: a symptom checklist and a disease specic quality-of-life
measure. The former is made up of a list of common
upper gastrointestinal symptoms which respondents
rate in terms of three dimensions, whilst the full Nepean
Dyspepsia Index quality-of-life section is composed of
25 items which include disease impact items and an
importance rating.4 A measurement instrument is valid
if the information recorded corresponds to the true state
of affairs.17 For this to be the case, the instrument must
be reliable; hence repeated measurements should fall
closely to each other assuming the situation is stable.17
We have previously shown that the full version of the
Nepean Dyspepsia Index was reliable on two distinct
occasions by testretest and had high internal consistency. In the present study, we conrmed the internal
consistency of the long form and found that the short
10-item version also had high internal consistency.
Hence, we conclude that the Nepean Dyspepsia Index
has excellent reliability across various study populations.
However, reliability alone does not necessarily establish validity; an instrument may reliably measure
concepts that are systematically missing the mark.17
Because no gold standard exists to establish the validity
of a quality-of-life measure, determining an instrument's validity requires a number of steps. We have
previously established that the full Nepean Dyspepsia
Index quality-of-life items measure relevant areas of
life in patients with functional dyspepsia (i.e. the

214

N. J. TALLEY et al.

instrument has face and content validity) and the long

form Nepean Dyspepsia Index discriminates patients
with uninvestigated dyspepsia from healthy subjects
(discriminant validity).3, 4 Furthermore, the instrument
measures concepts that are linked to but are not
covered by the symptom evaluation.4 Importantly, in
the present study we conrmed that symptom items did
not adequately explain the quality-of-life domains
captured by the Nepean Dyspepsia Index. Similarly,
we have previously reported that the SF-36 (a wellestablished generic quality-of-life measure) correlated
with the Nepean Dyspepsia Index, and anxiety and
depression also correlated with the Nepean Dyspepsia
Index, but none of these measures alone or combined
could replace the Nepean Dyspepsia Index (convergent
validity).4 It therefore appears that the Nepean Dyspepsia Index can be usefully and condently applied in
studies of functional dyspepsia.
A potential omission with all previous quality-of-life
instruments in gastroenterology has been the lack of
weighting of items relating to the relative importance to
each individual.1 In individuals, certain activities that
really matter to that person are likely to be more
affected by an illness. Theoretically, weighting the
importance of domains could improve the performance
of an instrument. In our original report, rating of
importance in the Nepean Dyspepsia Index was not of
additional discriminatory value.3 While we have subsequently shown that weighting may be of some relevance, it appears not to be essential, based on the
present results.4 We found that the originally constructed quality-of-life instrument could be further simplied
into ve two-item sub-scales, with a total of just 10
items. Applying individual weights from the original
groups of items was not required, based on the
psychometric testing performed.
In previous work, initial data on responsiveness were
also gathered but only a 2-week period was measured.4
While the data suggested that the instrument was at
least modestly responsive, as there was no specic
intervention tested in this study, large changes were not
expected. For this reason, we set out to test the Nepean
Dyspepsia Index in a large clinical trial, to determine its
level of responsiveness and set the scene for future work.
We found that symptoms and quality of life signicantly
changed from baseline in parallel in the present trial.
Concordant with the independent symptom measures,
large changes were observed in the placebo and active
therapy groups. We assessed the standardized response

mean to document sensitivity to change; similar, high

responsiveness scores for both the full and short
versions of the Nepean Dyspepsia Index were observed.
Hence, we now have available a very brief, valid
disease-specic quality-of-life measure that can be
applied in clinical trials of functional dyspepsia. A
strength of the study is that we did include a wide range
of patients from multiple countries in this trial, and
hence the results should be broadly generalizable.
There are few other disease-specic quality-of-life
measures available for dyspepsia. Rabeneck and colleagues reported the development of the SODA (severity
of dyspepsia assessment).18 However, this is a complex
instrument to score and does not measure quality of life
but rather symptoms and satisfaction. Furthermore, its
responsiveness is not established and the generalizability
outside of males in a Veterans Administration (VA)
4 hospital setting needs to be determined. An international
research group has independently developed the quality
of life in reux and dyspepsia (QOLRAD) questionnaire.19 This instrument is psychometrically sound; it
contains 25 items measuring emotions, vitality, sleep,
diet and physical/social functioning, and is very responsive to change in GERD.20 On the other hand, a
distinction between dyspepsia and reux was not a goal
of instrument development and its responsiveness in
functional dyspepsia is uncertain. The Gastrointestinal
Symptom Rating Scale (GSRS) is a valuable symptom
measure but it is not specic for dyspepsia and does not
assess quality of life.21 McColl and co-workers have
developed the Glasgow Dyspepsia Severity Score.22
Rather than a comprehensive disease-specic qualityof-life measure, the Glasgow scale is an investigatorbased global measure of dyspepsia (which is not dened
in the instrument); specic symptom items are not
assessed. It also asks about the global effect on routine
activities, time off work, consultations, tests and medications, and importantly is relatively brief and responsive. However, a disadvantage of the Glasgow scale is its
reliance on the investigator (and his or her denition of
dyspepsia, which is likely to not be standardized). A
study from Ireland has also reported the validation of a
new dyspepsia measure, but it only measures four
symptoms and the validity remains to be adequately
established.23 A study from the US reported excellent
psychometrics for the Digestive Health Status Instrument (DHSI), but this is not a quality-of-life measure.24
In conclusion, we have developed a valid multidimensional disease-specic quality-of-life measure that was
2001 Blackwell Science Ltd, Aliment Pharmacol Ther 15, 207216

QUALITY OF LIFE IN FUNCTIONAL DYSPEPSIA

highly responsive to change in a clinical trial. The

available results suggest that the short form Nepean
Dyspepsia Index will be useful in future clinical trials of
dyspepsia and functional dyspepsia.
ACKNOWLEDGEMENTS

This study was supported by an unrestricted research

grant from Abbott Laboratories, USA.
A copy of the full Nepean Dyspepsia Index is available
from Dr N. J. Talley.
REFERENCES
1 Guyatt GH, Feeny DH, Patrick DL. Measuring health-related
quality of life. Ann Intern Med 1993; 118: 6229.
2 Talley NJ, Weaver AL, Zinsmeister AR. Impact of functional
dyspepsia on quality of life. Dig Dis Sci 1995; 40: 5849.
3 Talley NJ, Haque M, Wyeth JW, et al. Development of a new
dyspepsia impact scale. The Nepean Dyspepsia Index (NDI).
Aliment Pharmacol Ther 1998; 12: 106778.
4 Talley NJ, Verlinden M, Jones MP. Validity of a new quality of
life scale for functional dyspepsia: a United States multicenter
trial of the Nepean Dyspepsia Index (NDI). Am J Gastroenterol
1999; 94: 23907.
5 Enck P, Dubois D, Marquis P. Quality of life in patients with
upper gastrointestinal symptoms. Results from the Domestic
International Gastroenterology Surveillance Study (DIGEST).
Scand J Gastroenterol 1999; 34(Suppl. 231): 4854.
6 Dimenas E, Glise H, Hallerback B, Hernqvist H, Svedlund J,
Wiklund I. Well-being and gastrointestinal symptoms among
patients referred to endoscopy owing to suspected duodenal
ulcer. Scand J Gastroenterol 1995; 30: 104652.
7 Wiklund I, Glise H, Jerndal P, Carlsson J, Talley NJ. Does
endoscopy have a positive impact on quality of life in
dyspepsia? Gastrointest Endosc 1998; 47: 44954.
8 Veldhuyzen Zanten SJO, Cleary C, Talley NJ, et al. Drug
treatment of functional dyspepsia: a systematic analysis of
trial methodology with recommendations for design of future
trials. Am J Gastroenterol 1996; 91: 66073.
9 Talley NJ. A critique of therapeutic trials in Helicobacter pyloripositive functional dyspepsia. Gastroenterology 1994; 106:
117483.
10 Guyatt GH. Measuring quality of life: a review of means of
measurement in clinical trials of new medicines. Pharm Med
1987; 2: 4960.
11 Talley NJ, Verlinden M, Snape W, et al. Failure of a motilin
receptor agonist (ABT-229) to relieve the symptoms of functional dyspepsia in patients with and without delayed gastric
emptying: a randomized double blind placebo controlled trial.
5
Aliment Pharmacol Ther 2000; 14: 165361.
12 Cronbach LJ. Coefcient alpha and the internal structure of
tests. Psychometrika 1951; 16: 297334.
13 Jones RH. Clinical economics review: gastrointestinal disease
in primary care. Aliment Pharmacol Ther 1996; 10: 2339.
2001 Blackwell Science Ltd, Aliment Pharmacol Ther 15, 207216

215

14 Drossman DA, Corazziari E, Talley NJ, et al. eds. Rome II The

Functional Gastrointestinal Disorders, 2nd edn. Degnon
6
Associates, McLean, Virginia, 2000: 603.
15 Guyatt G, Deyo RA, Charlson M, Levine MN, Mitchell A.
Responsiveness and validity in health status measurement: a
clarication. J Clin Epidemiol 1989; 42: 4038.
16 Glise H, Hallerback B, Wiklund I. Quality of life: a reection of
symptoms and concerns. Scand J Gastroenterol 1996;
31(Suppl. 221): 147.
17 Fletcher RH, Fletcher SW, Wagner EH. Clinical Epidemiology.
The Essentials, 3rd edn. Williams & Wilkins, Baltimore, 1996.
18 Cook KF, Rabeneck L, Campbell CJ, Wray NP. Evaluation of a
multidimensional measure of dyspepsiarelated health for
use in a randomized clinical trial. J Clin Epidemiol 1999; 52:
38192.
19 Wiklund I, Junghard O, Grace E, et al. Quality of life in reux
and dyspepsia. Psychometric documentation of a new diseasespecic questionnaire (QOLRAD). Eur J Surg 1998;
164(Suppl. 583): 419.
20 Talley NJ, Fullerton S, Junghard O, Wiklund O. Reliability and
sensitivity of quality of life changes in patients with heart7
burn. Am J Gastroenterol in press.
21 Svedlund J, Sjodin I, Dotevall G. GSRSA clinical rating scale
for gastrointestinal symptoms in patients with irritable bowel
syndrome and peptic ulcer disease. Dig Dis Sci 1988; 33:
12934.
22 El-Omar EM, Banerjee S, Wirz A, McColl KE. The Glasgow
dyspepsia severity scorea tool for the global measurement of
dyspepsia. Eur J Gastroenterol Hepatol 1996; 8: 96771.
23 Buckley MJ, Scanlon C, McGurgan P, O'Morain CA. A validated dyspepsia symptom score. Ital J Gastroenterol 1997; 29:
495500.
24 Shaw M, Talley NJ, Beebe T, et al. Development of a digestive
health status instrument: Tests of scaling assumptions,
structure and reliability in a primary care population. Aliment
Pharmacol Ther 1998; 12: 106778.

APPENDIX 1: SHORT FORM NEPEAN DYSPEPSIA

INDEX

Tension
1. Has your general emotional well-being been disturbed by your stomach problems in the last 2 weeks?
1
2
3
4
5

not at all
a little
moderately
quite a lot
extremely.

2. Have you been irritable, tense or frustrated in the

last 2 weeks because of your stomach problems?
1 not at all
2 a little

216

N. J. TALLEY et al.

3 moderately
4 quite a lot
5 extremely.
Interference with daily activities
3. Has your ability to engage in things you usually do
for fun (recreations, going out, hobbies, sports, etc.)
been disturbed by your stomach problems in the last
2 weeks?
1
2
3
4
5

not at all
a little
moderately
quite a lot
extremely.

4. Has your enjoyment of things you usually do for fun

(recreations, going out, hobbies, sports, etc.) been
disturbed by your stomach problems in the last
2 weeks?
1
2
3
4
5
1

not at all
a little
moderately
quite a lot
extremely
not applicable (I have not been able to do any of these
things in the past 2 weeks)

Eating/drinking
5. Has your ability to eat or drink (including when,
what, and how much) been disturbed by your stomach
problems in the last 2 weeks?
1
2
3
4
5

not at all
a little
moderately
quite a lot
extremely.

6. Has your enjoyment of eating and/or drinking been

disturbed by your stomach problems in the last
2 weeks? (Please also include your appetite, and how
you feel after food or drink).
1 not at all
2 a little
3 moderately

4 quite a lot
5 extremely
Knowledge/control
7. Have you wondered whether you will always have
these stomach problems, in the last 2 weeks?
1
2
3
4
5

almost never
sometimes
fairly often
very often
always

8. Have you thought that your stomach problems might

be due to a very serious illness (e.g. cancer or a heart
problem), in the last 2 weeks?
1
2
3
4
5

almost never
sometimes
fairly often
very often
always

Work/study
9. Has your ability to work or study been disturbed by
your stomach problems in the last 2 weeks?
1
2
3
4
5
1

not at all
a little
moderately
quite a lot
extremely
not applicable (I do not work or study).

10. Has your enjoyment of work or study been

disturbed by your stomach problems in the last
2 weeks?
1
2
3
4
5
1

not at all
a little
moderately
quite a lot
extremely
not applicable (I have not worked or studied in the
last 2 weeks).

Scoring: Add up the items for each of the ve sub-scale

scores (range of each sub-scale 210).

2001 Blackwell Science Ltd, Aliment Pharmacol Ther 15, 207216