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66, Suppl.

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- 0-100 is determined by measuring the distance from the
standard' method for its measurement. Thus assessment of bottom to the mark placed along the line by the patient.
the sensitivity and specificity of various methods of measure- In some cases a VAS has incorporated intermediate
ment and comparisons between them are difficult. Therefore, divisions and/or discrete descriptive terms (i.e. nausea slight,
uncertainties still exist regarding the 'best' method of assess- mild, severe) in the line. These types of scales do not seem to
ing chemotherapy-induced nausea in cancer patients enrolled offer any advantage or, even worse, introduce some bias in
in clinical trials of antiemetics. the measurement provided by the usual VAS.
Nausea is not an observable phenomenon. It is very Another type of analogue scale used to evaluate the inten-
unlikely that an external observer can be aware that the sity of nausea is the analogue continuous chromatic scale
patient is nauseated unless the patient tells him. Therefore, it (ACCS).
is always the patient that allows nausea to be measured. This This scale consists of a coloured horizontal strip, 100 mm
can be done by the patient using a self report scale, or long and 25 mm wide, containing no markings except for the
through an interview with the patient by an external anchor point at each end: the extremes are labelled 'no
observer, who subsequently scores the patient's nausea using nausea' (left) and 'worst nausea I have ever felt' (right), with
one of the available measurement methods. Observer-rated the words on a white background. The colour was graduated
nausea is used less than self report methodology (Table I). from left to right from pale pink to dark red.
Many instruments are available and have been used to Many types of descriptive scales have been employed using
measure the quantitative and qualitative aspects of nausea, 3 or more points with various verbal ratings.
but they have not been adequately validated and standar- A scale rating 0, no nausea; 1, slight nausea; 2, moderate
dised. nausea and 3, severe nausea, is one of the simplest and most
widely used.
What has to be measured
Our experience in assessment of nausea
Frequency, intensity and duration of nausea are the most
important characteristics usually measured in clinical trials We have studied the performance of these three different
(see Table I). methods (a discrete scale and two types of analogue scales) in
The measurement of frequency can be a simple one, based assessing nausea in 840 patients receiving chemotherapy, who
on a yes/no answer to a specific question by the patient on were enrolled in randomised clinical trials of antiemetic
the presence of nausea or it can be based on a four, or more, therapy (Del Favero et al., 1990):
point scale. (1) By measuring agreement between the different
The duration of nausea has been reported only in a low methods of measurement-good agreement between
percentage of studies, probably because it is an intermittent different methods of measurements is generally judged
phenomenon and its assessment may be difficult and/or as good evidence of reliability of the methods.
requires frequent evaluations. Patients are asked, at each (2) By measuring the sensitivity of scales
point of evaluation, how many minutes they have experi- - sensitivity was evaluated as capability of various
enced nausea during the previous time period. Measurement scales to show variations with time of the parameters
can be biased by the recall capability of patients and by the considered, and as
number and/or time intervals of evaluations. However, con- - their ability to differentiate two populations of
sidering that duration of nausea could be equal or more patients with different degree of nausea.
distressing than intensity, it would be wise to have it The VAS and ACCS were presented to patients in ran-
evaluated in all antiemetic trials. domised order. Nausea in each patient was measured by
Intensity is a frequently used dimension of nausea. Two these methods before and 2, 4, 6, 8 and 24 h after
types of scales have been employed: analogue scales and chemotherapy. These six specific time points were chosen for
descriptive ordinal scales (DS). the assessment both for practicality and because the need to
The visual analogue scale (VAS) is usually in a 100mm evaluate the usual time course of acute nausea after
long vertical line with the extremes marked as 'no nausea' chemotherapy. Nausea was evaluated according to four
(bottom) and the 'worst nausea I have ever felt' (top), with different dimensions:
no intermediate divisions or descriptive terms. A score from (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
Correspondence: A. Del Favero, Istituto Clinica Medica 1, Polic- intensity of nausea (I) recorded at each evaluation
linico Monteluce, 06100 Perugia, Italy. 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 The second main conclusion concerns the type of measure-
asked at each point of evaluation how many minutes ment which might best represent the experience of nausea.
they had experienced nausea during the previous time Measurement of agreement between the different dimensions
period. has shown that there is a good correlation between MI and E
(4) Quantity (Q): defined as the sum of the products of (Table IV), and Q and E, both with VAS and DS. However,
the intensity multiplied by the duration recorded at the advantage of using E and Q may become apparent when
each evaluation time (Q = Z(I x D)). 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
Results Table III shows that when combined measurements (E or Q)
of efficacy are adopted, the power of the statistical analysis in
Two main conclusions can be drawn from our study. First, discriminating between groups of patients (irrespective of the
no major differences were found between the two analogue measurement scale employed) is slightly improved. Another
(VAS or ACCS) scales employed, nor was a clear advantage finding from our study is that in untreated patients a good
found in using an analogue scale rather than a discrete scale. correlation between the severity of nausea and vomiting was
The substantial equivalence of the scales used was demon- found. When the MI of nausea was plotted against the
strated by the very high correlation coefficients found number of vomiting episodes the correlation was good both
between the scales (Table II). While the best agreement was for DS (r = 0.54; P<0.001) and VAS (r = 0.55; P<0.001).
that between the two analogue scales (VAS and ACCS), the However when the same correlation was measured in patients
VAS appeared to offer some slight advantages over ACCS, receiving antiemetic treatment the correlation was poor for
as it gave a uniform distribution of baseline MI values, it all dimensions of nausea irrespective of the scale used. The
showed a greater sensitivity in assessment of the variations of weaker correlation is due to the fact that with antiemetic
the same values in treated patients, and it gave a better treatment some patients were suffering from nausea but not
correlation between certain dimensions of nausea. The from vomiting.
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 Conclusions
analysing separately, with the two types of scales, the results
of the same clinical trials. The results of the analysis did not Measurement of nausea is an essential part of evaluation of
show any significant difference, and the P-values calculated efficacy of any antiemetic treatment. Nausea assessment relies
for DS and VAS, for each dimension of nausea considered, entirely upon reports by the patient and must be carried out
were similar, although slightly lower with the discrete scale separately from vomiting. The best way to measure nausea is
(see Table III). 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
Table II Spearman correlation coefficient (R) among scale sfor various the distribution of maximal intensity values obtained is
dimensions of nausea uniform and this may be relevant with respect to the choice
MI E Q
of statistical analysis method to be employed in clinical trials
on antiemetics.
DS vs VAS 0.68a 0.80a 0.95a However, the most evident disadvantage of a VAS is the
DS vs ACCS 0.60a 0.80a ND requirement of a careful explanation of its use, to the patient
VAS vs ACCS 0.74a 0.87a ND
by a trained assistant, on the first few occasions. Despite this,
ap<0.001; ND: Not determined. 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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