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992), 66,
(I(1992),
Br. J. Cancer
Br. J. Cancer Suppi. XIX,
S69 S71
XIX, 569-571
'."
©
Macmillan Press Ltd., 1992
Macmillan Press Ltd.,

Issues in the measurement of nausea

A. Del Faverol, M. Tonato2, & F. Roila2
'Istituto Clinica Medica 1, Universita di Perugia; 2Divisione di Oncologica Medica, Ospedale Policlinico, 06100 Perugia, Italy.
Summary Measurement of nausea is essential for the evaluation of efficacy of antiemetic treatment. Fre-
quency, duration and intensity of nausea should be assessed in all trials. Three different methods: a discrete
scale (DS), a visual analogue scale (VAS) and a continuous chromatic analogue scale (ACCS) of measuring
nausea and four different dimensions maximal intensity, (MI); entity, (E); duration, (D) and quantity, (Q) were
evaluated in 849 cancer patients undergoing chemotherapy. A substantial agreement between the different
scales was found and no advantage was shown for using an analogue (VAS) rather than a discrete (DS) scale.
There was a trend towards increasing sensitivity in detecting differences as the dimension of nausea used
encompassed wider aspects of this symptom (Q more sensitive than E more sensitive than MI).

Nausea is a subjective feeling and there is no objective 'gold-
standard' method for its measurement. Thus assessment of
the sensitivity and specificity of various methods of measure-
ment and comparisons between them are difficult. Therefore,
uncertainties still exist regarding the 'best' method of assess-
ing chemotherapy-induced nausea in cancer patients enrolled
in clinical trials of antiemetics.
Nausea is not an observable phenomenon. It is very
unlikely that an external observer can be aware that the
patient is nauseated unless the patient tells him. Therefore, it
is always the patient that allows nausea to be measured. This
can be done by the patient using a self report scale, or
through an interview with the patient by an external
observer, who subsequently scores the patient's nausea using
one of the available measurement methods. Observer-rated
nausea is used less than self report methodology (Table I).
Many instruments are available and have been used to
measure the quantitative and qualitative aspects of nausea,
but they have not been adequately validated and standar-
dised.
What has to be measured
Frequency, intensity and duration of nausea are the most
important characteristics usually measured in clinical trials
(see Table I).
The measurement of frequency can be a simple one, based
on a yes/no answer to a specific question by the patient on
the presence of nausea or it can be based on a four, or more,
point scale.
The duration of nausea has been reported only in a low
percentage of studies, probably because it is an intermittent
phenomenon and its assessment may be difficult and/or
requires frequent evaluations. Patients are asked, at each
point of evaluation, how many minutes they have experi-
enced nausea during the previous time period. Measurement
can be biased by the recall capability of patients and by the
number and/or time intervals of evaluations. However, con-
sidering that duration of nausea could be equal or more
distressing than intensity, it would be wise to have it
evaluated in all antiemetic trials.
Intensity is a frequently used dimension of nausea. Two
types of scales have been employed: analogue scales and
descriptive ordinal scales (DS).
The visual analogue scale (VAS) is usually in a 100mm
long vertical line with the extremes marked as 'no nausea'
(bottom) and the 'worst nausea I have ever felt' (top), with
no intermediate divisions or descriptive terms. A score from
Correspondence: A. Del Favero, Istituto Clinica Medica 1, Polic-
linico Monteluce, 06100 Perugia, Italy.
0-100 is determined by measuring the distance from the
bottom to the mark placed along the line by the patient.
In some cases a VAS has incorporated intermediate
divisions and/or discrete descriptive terms (i.e. nausea slight,
mild, severe) in the line. These types of scales do not seem to
offer any advantage or, even worse, introduce some bias in
the measurement provided by the usual VAS.
Another type of analogue scale used to evaluate the inten-
sity of nausea is the analogue continuous chromatic scale
(ACCS).
This scale consists of a coloured horizontal strip, 100 mm
long and 25 mm wide, containing no markings except for the
anchor point at each end: the extremes are labelled 'no
nausea' (left) and 'worst nausea I have ever felt' (right), with
the words on a white background. The colour was graduated
from left to right from pale pink to dark red.
Many types of descriptive scales have been employed using
3 or more points with various verbal ratings.
A scale rating 0, no nausea; 1, slight nausea; 2, moderate
nausea and 3, severe nausea, is one of the simplest and most
widely used.
Our experience in assessment of nausea
We have studied the performance of these three different
methods (a discrete scale and two types of analogue scales) in
assessing nausea in 840 patients receiving chemotherapy, who
were enrolled in randomised clinical trials of antiemetic
therapy (Del Favero et al., 1990):
(1) By measuring agreement between the different
methods of measurement-good agreement between
different methods of measurements is generally judged
as good evidence of reliability of the methods.
(2) By measuring the sensitivity of scales
- sensitivity was evaluated as capability of various
scales to show variations with time of the parameters
considered, and as
- their ability to differentiate two populations of
patients with different degree of nausea.
The VAS and ACCS were presented to patients in ran-
domised order. Nausea in each patient was measured by
these methods before and 2, 4, 6, 8 and 24 h after
chemotherapy. These six specific time points were chosen for
the assessment both for practicality and because the need to
evaluate the usual time course of acute nausea after
chemotherapy. Nausea was evaluated according to four
different dimensions:
(1) Maximal intensity (MI): defined as the highest value
of the score obtained with the DS, VAS or ACCS at
any evaluation carried out over the 24 h period.
(2) Entity (E): defined as the sum of all the values of
intensity of nausea (I) recorded at each evaluation
time (E = E of I).
S70 A. DEL FAVERO

Table I Measurement of nausea: review of the literature (1983-1990)

What has been
measured (%) Frequency Intensity Duration
100 70 34
Who measures (%) Patient's report Observer report Both N.S.
35 21 6 38
Scales employed (%) VAS Score Both N.S.
29 49 4 18
384/428 published reports evaluable for nausea assessment: 50% full papers, 46%
abstracts, 4% short reports or letters. N.S. = Not specified.

(3) Duration (D): expressed in minutes. Patients were
asked at each point of evaluation how many minutes
they had experienced nausea during the previous time
period.
(4) Quantity (Q): defined as the sum of the products of
the intensity multiplied by the duration recorded at
each evaluation time (Q = Z(I x D)).
Results
Two main conclusions can be drawn from our study. First,
no major differences were found between the two analogue
(VAS or ACCS) scales employed, nor was a clear advantage
found in using an analogue scale rather than a discrete scale.
The substantial equivalence of the scales used was demon-
strated by the very high correlation coefficients found
between the scales (Table II). While the best agreement was
that between the two analogue scales (VAS and ACCS), the
VAS appeared to offer some slight advantages over ACCS,
as it gave a uniform distribution of baseline MI values, it
showed a greater sensitivity in assessment of the variations of
the same values in treated patients, and it gave a better
correlation between certain dimensions of nausea. The
analogue scales did not appear to offer a specific advantage
of sensitivity over a simple discrete scale, irrespective of the
dimension of nausea considered. This was documented by
analysing separately, with the two types of scales, the results
of the same clinical trials. The results of the analysis did not
show any significant difference, and the P-values calculated
for DS and VAS, for each dimension of nausea considered,
were similar, although slightly lower with the discrete scale
(see Table III).
Table II Spearman correlation coefficient (R) among scale sfor various
dimensions of nausea
MI E Q
DS vs VAS 0.68a 0.80a 0.95a
DS vs ACCS 0.60a 0.80a ND
VAS vs ACCS 0.74a 0.87a ND
ap<0.001; ND: Not determined.
The second main conclusion concerns the type of measure-
ment which might best represent the experience of nausea.
Measurement of agreement between the different dimensions
has shown that there is a good correlation between MI and E
(Table IV), and Q and E, both with VAS and DS. However,
the advantage of using E and Q may become apparent when
assessing small differences between the results of studies of
antiemetic treatments and the agreement between measuring
instruments. In fact, non-parametric analysis of the data in
Table III shows that when combined measurements (E or Q)
of efficacy are adopted, the power of the statistical analysis in
discriminating between groups of patients (irrespective of the
measurement scale employed) is slightly improved. Another
finding from our study is that in untreated patients a good
correlation between the severity of nausea and vomiting was
found. When the MI of nausea was plotted against the
number of vomiting episodes the correlation was good both
for DS (r = 0.54; P<0.001) and VAS (r = 0.55; P<0.001).
However when the same correlation was measured in patients
receiving antiemetic treatment the correlation was poor for
all dimensions of nausea irrespective of the scale used. The
weaker correlation is due to the fact that with antiemetic
treatment some patients were suffering from nausea but not
from vomiting.
Conclusions
Measurement of nausea is an essential part of evaluation of
efficacy of any antiemetic treatment. Nausea assessment relies
entirely upon reports by the patient and must be carried out
separately from vomiting. The best way to measure nausea is
still debatable. Analogue scales have been proposed as the
best measurement of many subjective symptoms (e.g. pain)
because they offer a greater sensitivity with respect to DS,
but this has not been found in our study in evaluating
nausea. A possible advantage of a VAS could be the fact that
the distribution of maximal intensity values obtained is
uniform and this may be relevant with respect to the choice
of statistical analysis method to be employed in clinical trials
on antiemetics.
However, the most evident disadvantage of a VAS is the
requirement of a careful explanation of its use, to the patient
by a trained assistant, on the first few occasions. Despite this,
a small percentage of patients are still unable to complete a

Table III Efficacy analysis using different dimensions of nausea (Mann-Whitney U test)
Antiemetic Trial I (Roila et al., 1987) Trial 11 (Roila et al., 1989)
treatment MTC + P MTC P MT + DEX + DIP MTC + P P
Maximal Mean (SD) Mean (SD)
intensity - DS 0.3 (0.7) 0.6 (0.8) 0.0124 0.3 (0.7) 0.5 (0.8) 0.0058
(MI) - VAS 8.9 (19.3) 13.7 (20.1) 0.0155 8.9 (20.6) 11.7 (20.2) 0.0103
Entity (E) - DS 0.6 (1.3) 1.1 (1.7) 0.0086 0.7 (1.8) 1.0 (1.7) 0.0057
- VAS 13.3 (34.2) 22.5 (37.2) 0.0104 23.0 (92.4) 23.0 (49.2) 0.0080
Quantity (Q)- DS 207 (972) 556 (1790) 0.0067 112.1 (494.4) 131.5 (383) 0.0035
- VAS 4760 (22200) 12280 (38200) 0.0068 3360 (16130) 3170 (9420) 0.0041
MTC = Metoclopramide; P = Methylprednisolone; DEX = Dexamethasone; DIP = Diphenhydramine.
 ISSUES IN THE MEASUREMENT OF NAUSEA S71

Table IV Spearman correlation coefficient (R) between dimensions of circumvent this limitation we have proposed the measure-
nausea measured by different scales ment of composite dimensions of nausea such as Q or E.
DS VAS ACCS Descriptive scales, despite the well known defects common
to all discrete scales, appear to offer the important advantage
MI vs E 0.74a 0.85a 0.80a of simplicity, with no important drawbacks compared with a
MI vs Q 0.53a 0.66a ND VAS and therefore could be preferable to an analogue scale.
E vs Q 0.74a 0.79a ND Analogue and descriptive scales probably can be usefully
ap< 0.01: ND: Not determined. combined to make the evaluation process more complete and
precise. In fact, the possibility that many factors (e.g. patient
expectations, environment) influence the tolerance to, or alter
VAS. Another limitation of a VAS is the fact that this tool the perception of, severity of nausea might suggest the
measures mainly a quantitative single aspect (intensity) of a opportunity to maintain two different measurements of the
multidimensional phenomenon, which indeed nausea is. To same phenomenon.

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