Br. J. Cancer
14 S23 S23 (I 992), 66, Suppl. XIX, SS14
Br. J. Cancer (1992), 66, Suppl. XIX,
'." ©
Macmillan Press Ltd., 1992
Macmillan
Press
Ltd.,
The impact of nausea and vomiting upon quality of life measures J.M. Bliss', B. Robertson' & P.J. Selby2 'Sections of Medicine and Epidemiology, Institute of Cancer Research, Royal Marsden Hospital, Sutton, Surrey SM2 5PT; 2Institute for Cancer Studies, Yorkshire Cancer Research Campaign, Institute for Cancer Studies, University of Leeds, St James's University Hospital, Leeds LS9 7TF, UK. Summary The measurement of quality of life in cancer patients has achieved prominence in recent years. This results from recognition of the limitations of available therapies and a clearer view of the goals of treatment in patients whose diseases may not be curable. Many different approaches to the measurement of quality of life have been proposed and these will be reviewed. In a recent survey of available methods, the Medical Research Council's Working Party on Quality of Life Measurement systematically analysed available instruments for measuring quality of life specifically in cancer patients and commented on a number of instruments of general purpose that may be used in oncology. It was concluded that no instrument is entirely satisfactory for all purposes and that available instruments have to be selected carefully for a particular study or a particular aspect of clinical practice. However, among the existing instruments, the Rotterdam Symptom Checklist for a general assessment of many facets of quality of life and the Hospital Anxiety and Depression Scale, for detecting psychosocial morbidity quickly and easily, were useful. In our own studies we have used a multiple linear analogue scale system to measure aspects of quarity of life in breast cancer patients and have recently addressed the determinants of overall quality of life. Our studies identify the importance of evaluating the psychometric properties of measurement instruments in quality of life. Reliability and validity and the ability to discriminate changes with time and between clinically distinct groups have to be carefully assessed. Among the items in the multiple linear analogue scale system, nausea and vomiting proved to present particular problems in assessing their psychometric properties because of the rapid change in these symptoms in relation to cancer chemotherapy. The important determinants of good quality of life in cancer patients appear to be their ability to complete the activities of everyday living and their emotional well-being. In a general patient population with breast cancer most of whom had not received recent chemotherapy, nausea and vomiting when present were not powerful independent predictors of variation in overall QL. The full impact of interventions which control nausea and vomiting upon quality of life has not been adequately described. Patients rank nausea and vomiting high on their list of important toxicities and nausea and vomiting certainly has a high profile in discussions surrounding decisions about the choice of cancer chemotherapy and decisions to treat cancer patients with chemotherapy. Improvements in control of nausea and vomiting will improve the QL of cancer patients particularly in the few days following chemotherapy. However, other issues may be more important general determinants of QL in the long term.
The impact of cancer and its treatment upon patients is best assessed by considering their likely survival and changes in the quality of their lives. Analysis of survival results has been standard practice in oncology for many decades but the evaluation of quality of life is more recent and only in the last decade have systematic attempts been made to develop measurement methods. (For reviews see Fayers & Jones 1983; Holland, 1984; De Haes & Van Knippenberg 1985; Ventrafridda et al., 1986; Clark & Fallowfield 1986; Selby & Robertson, 1987; McDowell & Newell 1987 and Walker & Rosser 1988). Although there is as yet no consensus about the best methods for measuring quality of life in any particular circumstance, a number of instruments have been developed specifically for the cancer patient. These may now be added to a wide range of instruments available to assess the impact of illness on a general patients' physical and emotional well-being. Among these are methods which can be suitably used for many purposes in evaluating the outcome of cancer treatments. In this paper, we will briefly review methods for measuring quality of life which have been developed specifically for cancer patients. We will then examine in more detail the items within these questionnaires which relate to the evaluation of nausea and vomiting. We will describe our own results evaluating the psychometric properties of linear analogue scales for measuring nausea and vomiting and the contribution of these scores in explaining variation in overall QL. Correspondence: P. Selby, Yorkshire Cancer Research Campaign Institute for Cancer Studies, St James's University Hospital, Leeds LS9 7TF, UK.
Nausea and vomiting are important symptoms of cancer and its treatment. Patients have reported nausea and vomiting as the immediate symptom of greatest concern when receiving chemotherapy (Coates et al., 1983). Half of patients who receive cancer chemotherapy feel sick on that day and one quarter of them vomit. This will persist for several days in a significant minority of patients (Lindley et al., 1989). The importance of nausea and vomiting as a major toxicity of cancer chemotherapy is well recognised and a large body of research has focused upon the development of antiemetics. Elsewhere in this supplement the impact of 5-hydroxytryptamine 3 receptor blockers will be discussed and evaluated. Methods for measuring nausea and vomiting in the context of clinical trials have been developed and are discussed, again, elsewhere in this symposium. It can safely be assumed that the presence of nausea and vomiting has a deleterious effect upon the quality of a patient's life. It is less clear precisely how important nausea and vomiting may be and to what extent their effects are independent of the other toxicities of chemotherapy and indeed of the effects of the diagnosis and disease itself. We will describe here data derived from a large number of patients with breast cancer evaluated using a linear analogue self assessment system (Selby et al., 1984). Using data derived from this system it is possible to assess the independent contribution of nausea and vomiting to patients' overall perception of quality of life and also by regression analysis to estimate the weight given to nausea and vomiting in forming that overall score. The aspects of these studies that relate to nausea and vomiting will be described. The wider features of this study evaluating the contribution of many items to QL and the factor structure of the data will be published elsewhere (Bliss, Robertson and Selby in preparation).
IMPACT OF NAUSEA AND VOMITING ON QUALITY OF LIFE The measurement of quality of life in cancer patients
The feeling that patient's quality of life should be measured in clinical practice and cancer clinical trials has led to the development of a wide range of questionnaires for this purpose. Between them, these assessments cover physical, emotional and social well-being as well as sexual functioning, body image and problems particular to individual cancers. Some are designed to encompass all of oncology and others are entirely or partly committed to individual disease sites. Some instruments have been developed carefully with attention to evaluation of their psychometric properties whilst others are essentially descriptive. The United Kingdom Medical Research Council Working Party on quality of life recently systematically evaluated the majority of the available methods. Questionnaires evaluated were:
Global measures (i) Gough's visual analogue scale (Gough et al., 1983). (ii) Rosser and Kind's distress/disability matrix (Rosser & Kind, 1978). (viii) Quality of life adjusted years (QUALYS) (Williams, 1985).
Performance indices
(i) Karnofsky et al. (1948) (ii) ECOG, Eastern Co-operative Oncology Group (Zubrod et al., 1960). (iii) Katz activities of daily living (Katz & Akpom, 1976) (iv) World Health Organisation scales (WHO, 1979).
(ii) Priestman and Baum (1976) linear self assessment system. (iii) Functional Living Index for Cancer (Schipper et al., 1984). (iv) Ontario Cancer Institute quality of life questionnaire (Selby et al., 1984). (v) Padilla QL questionnaire (Padilla et al., 1981). (vi) QL index (Spitzer et al., 1981). (vii) EORTC QL questionnaire (Aaronson et al., 1986). (viii) Rotterdam symptom checklist (De Haes et al., 1986). Psychological dimension (i) Hospital anxiety and depression scale (Zigmond & Snaith, 1983). (ii) General health questionnaire (Goldberg & Hillier,
1979).
The group attempted to assess the function, format, administration, scoring, structure, clinical usage, reliability and validity of each questionnaire. For a detailed assessment readers are referred to the report of the MRC Working Party (Maguire & Selby, 1989). The conclusions of the Working Party may be summarised briefly. (i) A multi-dimensional scale which is specific to patients with cancer, meets all of the assessment criteria set by the committee and provides scores which have relevance to clinical judgements remains yet to be developed. It was felt that this may be done by further work but in the meantime practical suggestions were
required. (ii) The current 'best bet' for tapping key dimensions of quality of life is the Rotterdam Symptom Checklist. (iii) Linear analogue self assessment systems (Priestman & Baum, 1976, Selby et al., 1984; Schipper et al., 1984) are
useful to detect differences between treatment
regimens and changes within patients over time but the scores are difficult to interpret both clinically and statistically in any absolute way.
Scales measuring several dimensions (i) Iszack and Medalie index (1971).
Rotterdam Symptom Checklist patient number
date of completion
19
In this questionnaire you vill be asked about your symptoms. Would you please, for all symptoms mntioned, indicate to vhat extent you have been bothered by it, by circling the ansver most applicable to you. The questions are related to the past seek
anxiety
Example
hdartburn/belchinc
not at all
a
little
quite a bit
very much
shivering
not at all
a
little
quite a bit
very such
not at all
a
little
quite a bit
very such
not at all
a
little
quite a bit
very much very much
constipation
constipation haartbu-n-be-ching
divrrhoin Have you been bothered by
headaches
not at
all
a
little
quite
a
bit
very much
tingling hani Have you. during the past, week been bothered by not at
all
a
little
quite
a
bit
very
much
irritability
not at all
a
little
quite
a
bit
vary
much
not-at-all-a-littlequite-a-bitnot at little quite bit very.much much
worryinb
not at
all
a
all
a
little
s or feet
quite
sore mouth/psin when svallohing
not at all
a
little
quite a bit
loss of hair
not at all
a
little
quite a bit
very much
burning/sore eyes
not at all
a
little
quite
a
bit
very such
very
a
a
bit
very
uch
sore muscles
not at
all
a
little
quite
a
bit
very
uch
depressed food
not at
all
a
little
quite
a
bit
very
much
lack of energy
not at
all
a
little
quite
a
bit
very
much
low btck pnin
not at
all
a
little
quite
a
bit
very
much
much
nervousness
not atall
little
quite
a
bit
very
nausea
not at
little
quite
a
bit
very much
little
quite
a
bit
very such
all
not at all a little quite a bit very much not-at-all-a-little-q-ite-a-bit-ery.much not at all a little quite a bit vary much ot at alla-littlequite-a bit-very.much not at all a little quite a bit very much
difficulty concentrating
lack of appetite
tiredness tiredness
shortness of breath
not at all
a
little
quite
a
bit
very much
dry mouth
not at all
a
little
quite
a
bit
very much
A number of activities is listed below. We do not wvnt to know whether you actually do these, but only whether you are able to perform them presently. Would you please mark the ansver that applies most to your condition of the past week.
%amble
desperate feelinss about the future
not at all
a
difficulty sleeping
not at all
a
little
quite
a
bit
very much
headaches
not at all
a
little
quite
a
bit
very much
nely withe tlp
siemt Imip, widt
care for myself (wash etc.)
0
0
0
0
0
0
0
0
housekeeping
0
0
0
0
climb stairs
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
vomiting
not at all
a
little
quite
a
bit
very much
not at all
a
little
quite
a
bit
very much
decreased sexual interest
odd jobs
0
not at all
a
little
quite
a
bit
very much
walk out of doors
0
tension
not at all
a
little
quite
a
bit
very such
shopping
0
abdominal aches
not at all
a
little
quite
a
bit
very much
go to work
0
Would you please check whether you answered all questions? Thank you for your help.
1
The Rotterdam Symptom Checklist.
sitham difficulty help
walk about the house
dizziness
Figure
S15
c~ ~ ~
J.M. BLISS et al.
S16
Functional Living Index: Cancer (FLIC)
people experIencsom tesllngs d d_bepreson at tews. Rat how testigs.p Lr i i ~ ~ ~~~4
1.
Most
oten
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j
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wagsbout
e
5
N
yourgimen?
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5.
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4
17. Howmnuch nauss he you hod In s pst 2 wsw.
5
7
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7. Do you fel we enough to me a mea or do ffwor household rsplsod? R
\
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16 y
oday?
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essi E
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12. Ratinyowfophor
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10. Faeyoursdbbfcdbonwthywwortkand ywrpberound1Xhoueminf1pmtmonth. 3
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7
2
3
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20. How wcdot you appnrbd 1
E2xowsdSsretdy
os
4 4
5
5 7
Figure 2 The Functional Living Index: Cancer (FLIC).
(iv) The Hospital Anxiety and Depression Scale (Zigmond & Snaith, 1983) is useful in detecting anxiety and depression in cancer patients. It should be possible to add additional items to existing questionnaires such as the Rotterdam Symptom Checklist when additional data is required. These may be added in a simple categorical form. Four examples of QL questionnaires are discussed further here:
The Rotterdam Symptom Checklist (Figure 1) This questionnaire was carefully derived from a pool of items based upon existing questionnaires together with checklists from interviews with cancer patients. There are 38 items and each item is rated on a four point scale (O = not at all and 3 = very much). Its time focus has been the week prior to completion of the questionnaire but it may be adjusted to times between 3 days and 2 weeks. It is usually self administered but may be administered by nurses and takes 5 to 10min to complete. All items appear understandable and acceptable and it is easy to score and produces distinct sub-scale scores. It generally provides two main sub-scales measuring physical and psychological dimensions. It was considered by the MRC committee to be a good clear and simple questionnaire which has been validated against independent interviews and found to have high sensitivity and specificity in measuring psychological dimensions. It has been used successfully within busy clinics and seems as effective in advanced cancer patients as in patients with early disease. It seems to measure physical and social dimensions equally well but this requires confirmation. Recently its factor structure has been shown to be substantially stable in three separate patient populations (De Haes et al., 1990). The weight attributed to each item by patients has not been deduced in most studies.
The Functional Living Index for Cancer (Figure 2) The FLIC includes 22 items covering physical symptoms, mood, physical activity, work and social interaction. Items are presented in a linear analogue format. Each linear scale is marked with seven points and scores are taken by summing the total of the items. A panel of patients and health professionals suggested a pool of items from which the questionnaire was derived and factor analysis has been replicated for several patient populations. The FLIC is easy to use and score and has been validated in a cross-sectional study of patients with different stages of cancer and on different treatments. Validity has been tested by comparing different patient groups and by correlation with other self rating instruments. Relatively few physical symptoms are included in the questionnaire and its ability to detect significant change over time has not been confirmed.
The EORTC Questionnaire (Figure 3) This questionnaire was designed for heterogeneous groups of cancer patients. It assesses a wide range of features for the quality of life in cancer patients and can be self administered with the format varying according to the dimension being addressed. Items on physical activity comprise of 'yes' or 'no' responses whereas questions on symptoms use a categorical form asking for answers ranging from 'not at all' to 'very much'. The instrument can be administered by nurses in clinics and takes about 10 min to complete and is quite easy to score and produces both an overall score and scores on a series of sub-scales. Work on reliability and validity is ongoing. The questionnaire is designed to have a 'core' for all cancers and add-on questions for particular cancer sites.
IMPACT OF NAUSEA AND VOMITING ON QUALITY OF LIFE
S17
EORTC Core Quality of Life Questionnaire* I
We welam d i - 6W boa yeoau a our h_ali. lme msur allof die qedam ymo by deuag do smawdioeehi appA ao yu. Tweroms 'eig'
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DURIG 1THK PAST Wsm Nots AN
11158611 Yow b hikU (Day. Moik. Yer :..............................................................
(Day. 1Moea. Yr)
Today's d
:.................................................................
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20. Rm yo hed dileaby ia omueameag ou ikiup. lik readblg a _e ur or amblig boe
PA
2. Do y 3. Do yoo
bm my tale sb g a b wk? kme sy trbl ebog a st walk }oide alke kouo?
oy i a bed or acbiar wramof dt
4. Do you l
1
2
tt
24. Did youhfd depessd
2
tLJ
25. Hor yo hed dlfiosy reasabweig kIng?
2
24LJ
26.
dy?
2
howdbold jop?
booseoldjobs?
2
2
aoe yyo bad psin?
9
o rest?
11. Hme you bad
roobk sleeping?
12. Have yo feite
4
2
3
4
2
3
4
2
3
4
2
3
4
3
4
2
3
4
15. Hew you oited?
2
3
4
16. Haee yoo bm constipod?
2
3
4
HOyeep
lockd
k?
3
2
13.
ppetioe?
14. Hae you skit asoe
?
17 Hae you hbd diorrbe?
1. Were yoy
red?
19. Did pas iAnrlare wik yoer daily wrsvities?
2
3
4
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2
3
4
-4Li
2
3
4
2
3
4
1
2
3
4
1
2
3
4
1
2
3
4
3
4
27. Nm yor pkyisal eaaido or _dloa mlemoa ism*rwd wi yramt id usli?
2
3
4
28. Has your physkloa condition or medical trtmeul caused you ficil dilbeolsica?
2
3
4
I_
dlo or _eadlc e
1 eat
47L_ 1LJ 41L_
tLJ
Not at Quise Very All Likle a Bit Much
i. Were you sbor of breth?
10. Did youo
2
1
DURING THE PAST WEEK:
4 4
2
yor pkyiol
2
1
5. Do yu te belp wit iling. dressiog. wahing youruof or osiag the Mkt?
a job or o do
3 3
dwli1vweo oh?
a
a
6 Areyo limised i ay way indoing either your work or doing 7 Are you copWlyuoabkle o ork
2 2
23. Di you ad irrlube?
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4QLJ
1 1
22. Didyou sorry?
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21. Di you l
A Qul Very Le e Ubltrb
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FOR THE FOLLOWING QUESTIONS PLEASE CICLE THE NUMBER BETWEEN AND 7 THAT REST APPLIES TO YOU 29. Hoew woul you rue your overaO pkylel condidi
2
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4
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during ke pmwtk? 6
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30. How weod yo re your 0,ell qoality al We doring ie pe week?
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Figure 3 The EORTC QL Questionnaire.
The Hospital Anxiety and Depression Scale (Figure 4) This is a 14 item scale which was developed for patients who had physical illness and therefore items like tiredness that can occur in depression but can also be symptoms of physical illness were in general excluded. It is quickly and easily completed by patients and is capable of measuring change over time within different groups of cancer patients. Studies suggest that it is capable of detecting psychological morbidity in cancer patients and that it is a reasonable tool for measuring the psychological dimension of quality of life in cancer patients. It is still possible to reiterate the recommendations made by the Medical Research Council Working Party 2 years ago. Many of the questionnaires evaluated have been tested further since the report and their usefulness confirmed. We remain in a phase of proliferation of measurement indices (Cella & Tulsky, 1990). Many of these have much in common with the ones described above but few have been so thoroughly tested, although some may have particular advantages for individual applications. It is unlikely that a simple gold standard quality of life measurement questionnaire will emerge in the near future but there appears to be a great deal in common between different techniques. A large number of items are common to different questionnaires and the length of questionnaires developed for a comprehensive assessment of quality of life in cancer patients tends to be similar with consistent numbers of items.
Nausea and vomiting scales within quality of life questionnaires
Figure 5a-d shows the nausea and vomiting scales of four well characterised quality of life questionnaires: (A) The Linear Analogue Self Assessment system (Selby et al., 1984) (B) Rotterdam Symptom Checklist (De Haes et al., 1986)
(C) The Functional Living Index for Cancer (Schipper et al., 1984) (D) EORTC QL questionnaire (Aaronson et al., 1986) Although superficially they appear different, each represents a relatively simple rating system using descriptive categories or linear analogue scales. Similar scales have been used in research into antiemetics and their reliabiltiy and validity is supported in many cases. There are particular problems in assessing the psychometric properties of nausea and vomiting scales. The symptoms when due to cancer chemotherapy are often short-lived and patients re-call may be hindered by the circumstances of the symptom, by concurrent sedative medication or the effects of their illness. To assess the reproducibility of such items test retest scoring is often applied. In our own studies (Selby et al., 1984) evaluating 31 different linear analogue scales in 96 patients the scores for Nausea and Vomiting had co-efficients of agreement of less than 0.40 (Table I) when retested 24 h apart. The explanation for this apparently low reproducibility of items scored for Nausea and Vomiting is not entirely clear. In a small group of 31 patients who completed the items in the evening before attending an outpatient clinic and again on arrival at the clinic the test re-test correlation co-efficients for Nausea and Vomiting were greater than 0.70 suggesting that clinic attendance and presumably the administration of chemotherapy reduced the reliability scores. The time between the two scores in this study was 12-24 h. However, in another study in which patients receiving chemotherapy at clinic were excluded co-efficients of agreement for nausea and vomiting were 0.40 and 0.30 respectively and were the lowest among the 31 items assessed. There are a number of ways of assessing the validity (i.e. the extent to which a score measures that which it reports to measure) of items in quality of life questionnaires. The scores may be compared to scores obtained by alternative methods or by alternative observers. Scores for Nausea and Vomiting were closely correlated with each other in our studies. The
S18
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14 S23 S23 (I 992), 66, Suppl. XIX, SS14
Br. J. Cancer (1992), 66, Suppl. XIX,
'." ©
Macmillan Press Ltd., 1992
Macmillan
Press
Ltd.,
The impact of nausea and vomiting upon quality of life measures J.M. Bliss', B. Robertson' & P.J. Selby2 'Sections of Medicine and Epidemiology, Institute of Cancer Research, Royal Marsden Hospital, Sutton, Surrey SM2 5PT; 2Institute for Cancer Studies, Yorkshire Cancer Research Campaign, Institute for Cancer Studies, University of Leeds, St James's University Hospital, Leeds LS9 7TF, UK. Summary The measurement of quality of life in cancer patients has achieved prominence in recent years. This results from recognition of the limitations of available therapies and a clearer view of the goals of treatment in patients whose diseases may not be curable. Many different approaches to the measurement of quality of life have been proposed and these will be reviewed. In a recent survey of available methods, the Medical Research Council's Working Party on Quality of Life Measurement systematically analysed available instruments for measuring quality of life specifically in cancer patients and commented on a number of instruments of general purpose that may be used in oncology. It was concluded that no instrument is entirely satisfactory for all purposes and that available instruments have to be selected carefully for a particular study or a particular aspect of clinical practice. However, among the existing instruments, the Rotterdam Symptom Checklist for a general assessment of many facets of quality of life and the Hospital Anxiety and Depression Scale, for detecting psychosocial morbidity quickly and easily, were useful. In our own studies we have used a multiple linear analogue scale system to measure aspects of quarity of life in breast cancer patients and have recently addressed the determinants of overall quality of life. Our studies identify the importance of evaluating the psychometric properties of measurement instruments in quality of life. Reliability and validity and the ability to discriminate changes with time and between clinically distinct groups have to be carefully assessed. Among the items in the multiple linear analogue scale system, nausea and vomiting proved to present particular problems in assessing their psychometric properties because of the rapid change in these symptoms in relation to cancer chemotherapy. The important determinants of good quality of life in cancer patients appear to be their ability to complete the activities of everyday living and their emotional well-being. In a general patient population with breast cancer most of whom had not received recent chemotherapy, nausea and vomiting when present were not powerful independent predictors of variation in overall QL. The full impact of interventions which control nausea and vomiting upon quality of life has not been adequately described. Patients rank nausea and vomiting high on their list of important toxicities and nausea and vomiting certainly has a high profile in discussions surrounding decisions about the choice of cancer chemotherapy and decisions to treat cancer patients with chemotherapy. Improvements in control of nausea and vomiting will improve the QL of cancer patients particularly in the few days following chemotherapy. However, other issues may be more important general determinants of QL in the long term.
The impact of cancer and its treatment upon patients is best assessed by considering their likely survival and changes in the quality of their lives. Analysis of survival results has been standard practice in oncology for many decades but the evaluation of quality of life is more recent and only in the last decade have systematic attempts been made to develop measurement methods. (For reviews see Fayers & Jones 1983; Holland, 1984; De Haes & Van Knippenberg 1985; Ventrafridda et al., 1986; Clark & Fallowfield 1986; Selby & Robertson, 1987; McDowell & Newell 1987 and Walker & Rosser 1988). Although there is as yet no consensus about the best methods for measuring quality of life in any particular circumstance, a number of instruments have been developed specifically for the cancer patient. These may now be added to a wide range of instruments available to assess the impact of illness on a general patients' physical and emotional well-being. Among these are methods which can be suitably used for many purposes in evaluating the outcome of cancer treatments. In this paper, we will briefly review methods for measuring quality of life which have been developed specifically for cancer patients. We will then examine in more detail the items within these questionnaires which relate to the evaluation of nausea and vomiting. We will describe our own results evaluating the psychometric properties of linear analogue scales for measuring nausea and vomiting and the contribution of these scores in explaining variation in overall QL. Correspondence: P. Selby, Yorkshire Cancer Research Campaign Institute for Cancer Studies, St James's University Hospital, Leeds LS9 7TF, UK.
Nausea and vomiting are important symptoms of cancer and its treatment. Patients have reported nausea and vomiting as the immediate symptom of greatest concern when receiving chemotherapy (Coates et al., 1983). Half of patients who receive cancer chemotherapy feel sick on that day and one quarter of them vomit. This will persist for several days in a significant minority of patients (Lindley et al., 1989). The importance of nausea and vomiting as a major toxicity of cancer chemotherapy is well recognised and a large body of research has focused upon the development of antiemetics. Elsewhere in this supplement the impact of 5-hydroxytryptamine 3 receptor blockers will be discussed and evaluated. Methods for measuring nausea and vomiting in the context of clinical trials have been developed and are discussed, again, elsewhere in this symposium. It can safely be assumed that the presence of nausea and vomiting has a deleterious effect upon the quality of a patient's life. It is less clear precisely how important nausea and vomiting may be and to what extent their effects are independent of the other toxicities of chemotherapy and indeed of the effects of the diagnosis and disease itself. We will describe here data derived from a large number of patients with breast cancer evaluated using a linear analogue self assessment system (Selby et al., 1984). Using data derived from this system it is possible to assess the independent contribution of nausea and vomiting to patients' overall perception of quality of life and also by regression analysis to estimate the weight given to nausea and vomiting in forming that overall score. The aspects of these studies that relate to nausea and vomiting will be described. The wider features of this study evaluating the contribution of many items to QL and the factor structure of the data will be published elsewhere (Bliss, Robertson and Selby in preparation).
IMPACT OF NAUSEA AND VOMITING ON QUALITY OF LIFE The measurement of quality of life in cancer patients
The feeling that patient's quality of life should be measured in clinical practice and cancer clinical trials has led to the development of a wide range of questionnaires for this purpose. Between them, these assessments cover physical, emotional and social well-being as well as sexual functioning, body image and problems particular to individual cancers. Some are designed to encompass all of oncology and others are entirely or partly committed to individual disease sites. Some instruments have been developed carefully with attention to evaluation of their psychometric properties whilst others are essentially descriptive. The United Kingdom Medical Research Council Working Party on quality of life recently systematically evaluated the majority of the available methods. Questionnaires evaluated were:
Global measures (i) Gough's visual analogue scale (Gough et al., 1983). (ii) Rosser and Kind's distress/disability matrix (Rosser & Kind, 1978). (viii) Quality of life adjusted years (QUALYS) (Williams, 1985).
Performance indices
(i) Karnofsky et al. (1948) (ii) ECOG, Eastern Co-operative Oncology Group (Zubrod et al., 1960). (iii) Katz activities of daily living (Katz & Akpom, 1976) (iv) World Health Organisation scales (WHO, 1979).
(ii) Priestman and Baum (1976) linear self assessment system. (iii) Functional Living Index for Cancer (Schipper et al., 1984). (iv) Ontario Cancer Institute quality of life questionnaire (Selby et al., 1984). (v) Padilla QL questionnaire (Padilla et al., 1981). (vi) QL index (Spitzer et al., 1981). (vii) EORTC QL questionnaire (Aaronson et al., 1986). (viii) Rotterdam symptom checklist (De Haes et al., 1986). Psychological dimension (i) Hospital anxiety and depression scale (Zigmond & Snaith, 1983). (ii) General health questionnaire (Goldberg & Hillier,
1979).
The group attempted to assess the function, format, administration, scoring, structure, clinical usage, reliability and validity of each questionnaire. For a detailed assessment readers are referred to the report of the MRC Working Party (Maguire & Selby, 1989). The conclusions of the Working Party may be summarised briefly. (i) A multi-dimensional scale which is specific to patients with cancer, meets all of the assessment criteria set by the committee and provides scores which have relevance to clinical judgements remains yet to be developed. It was felt that this may be done by further work but in the meantime practical suggestions were
required. (ii) The current 'best bet' for tapping key dimensions of quality of life is the Rotterdam Symptom Checklist. (iii) Linear analogue self assessment systems (Priestman & Baum, 1976, Selby et al., 1984; Schipper et al., 1984) are
useful to detect differences between treatment
regimens and changes within patients over time but the scores are difficult to interpret both clinically and statistically in any absolute way.
Scales measuring several dimensions (i) Iszack and Medalie index (1971).
Rotterdam Symptom Checklist patient number
date of completion
19
In this questionnaire you vill be asked about your symptoms. Would you please, for all symptoms mntioned, indicate to vhat extent you have been bothered by it, by circling the ansver most applicable to you. The questions are related to the past seek
anxiety
Example
hdartburn/belchinc
not at all
a
little
quite a bit
very much
shivering
not at all
a
little
quite a bit
very such
not at all
a
little
quite a bit
very such
not at all
a
little
quite a bit
very much very much
constipation
constipation haartbu-n-be-ching
divrrhoin Have you been bothered by
headaches
not at
all
a
little
quite
a
bit
very much
tingling hani Have you. during the past, week been bothered by not at
all
a
little
quite
a
bit
very
much
irritability
not at all
a
little
quite
a
bit
vary
much
not-at-all-a-littlequite-a-bitnot at little quite bit very.much much
worryinb
not at
all
a
all
a
little
s or feet
quite
sore mouth/psin when svallohing
not at all
a
little
quite a bit
loss of hair
not at all
a
little
quite a bit
very much
burning/sore eyes
not at all
a
little
quite
a
bit
very such
very
a
a
bit
very
uch
sore muscles
not at
all
a
little
quite
a
bit
very
uch
depressed food
not at
all
a
little
quite
a
bit
very
much
lack of energy
not at
all
a
little
quite
a
bit
very
much
low btck pnin
not at
all
a
little
quite
a
bit
very
much
much
nervousness
not atall
little
quite
a
bit
very
nausea
not at
little
quite
a
bit
very much
little
quite
a
bit
very such
all
not at all a little quite a bit very much not-at-all-a-little-q-ite-a-bit-ery.much not at all a little quite a bit vary much ot at alla-littlequite-a bit-very.much not at all a little quite a bit very much
difficulty concentrating
lack of appetite
tiredness tiredness
shortness of breath
not at all
a
little
quite
a
bit
very much
dry mouth
not at all
a
little
quite
a
bit
very much
A number of activities is listed below. We do not wvnt to know whether you actually do these, but only whether you are able to perform them presently. Would you please mark the ansver that applies most to your condition of the past week.
%amble
desperate feelinss about the future
not at all
a
difficulty sleeping
not at all
a
little
quite
a
bit
very much
headaches
not at all
a
little
quite
a
bit
very much
nely withe tlp
siemt Imip, widt
care for myself (wash etc.)
0
0
0
0
0
0
0
0
housekeeping
0
0
0
0
climb stairs
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
vomiting
not at all
a
little
quite
a
bit
very much
not at all
a
little
quite
a
bit
very much
decreased sexual interest
odd jobs
0
not at all
a
little
quite
a
bit
very much
walk out of doors
0
tension
not at all
a
little
quite
a
bit
very such
shopping
0
abdominal aches
not at all
a
little
quite
a
bit
very much
go to work
0
Would you please check whether you answered all questions? Thank you for your help.
1
The Rotterdam Symptom Checklist.
sitham difficulty help
walk about the house
dizziness
Figure
S15
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J.M. BLISS et al.
S16
Functional Living Index: Cancer (FLIC)
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Figure 2 The Functional Living Index: Cancer (FLIC).
(iv) The Hospital Anxiety and Depression Scale (Zigmond & Snaith, 1983) is useful in detecting anxiety and depression in cancer patients. It should be possible to add additional items to existing questionnaires such as the Rotterdam Symptom Checklist when additional data is required. These may be added in a simple categorical form. Four examples of QL questionnaires are discussed further here:
The Rotterdam Symptom Checklist (Figure 1) This questionnaire was carefully derived from a pool of items based upon existing questionnaires together with checklists from interviews with cancer patients. There are 38 items and each item is rated on a four point scale (O = not at all and 3 = very much). Its time focus has been the week prior to completion of the questionnaire but it may be adjusted to times between 3 days and 2 weeks. It is usually self administered but may be administered by nurses and takes 5 to 10min to complete. All items appear understandable and acceptable and it is easy to score and produces distinct sub-scale scores. It generally provides two main sub-scales measuring physical and psychological dimensions. It was considered by the MRC committee to be a good clear and simple questionnaire which has been validated against independent interviews and found to have high sensitivity and specificity in measuring psychological dimensions. It has been used successfully within busy clinics and seems as effective in advanced cancer patients as in patients with early disease. It seems to measure physical and social dimensions equally well but this requires confirmation. Recently its factor structure has been shown to be substantially stable in three separate patient populations (De Haes et al., 1990). The weight attributed to each item by patients has not been deduced in most studies.
The Functional Living Index for Cancer (Figure 2) The FLIC includes 22 items covering physical symptoms, mood, physical activity, work and social interaction. Items are presented in a linear analogue format. Each linear scale is marked with seven points and scores are taken by summing the total of the items. A panel of patients and health professionals suggested a pool of items from which the questionnaire was derived and factor analysis has been replicated for several patient populations. The FLIC is easy to use and score and has been validated in a cross-sectional study of patients with different stages of cancer and on different treatments. Validity has been tested by comparing different patient groups and by correlation with other self rating instruments. Relatively few physical symptoms are included in the questionnaire and its ability to detect significant change over time has not been confirmed.
The EORTC Questionnaire (Figure 3) This questionnaire was designed for heterogeneous groups of cancer patients. It assesses a wide range of features for the quality of life in cancer patients and can be self administered with the format varying according to the dimension being addressed. Items on physical activity comprise of 'yes' or 'no' responses whereas questions on symptoms use a categorical form asking for answers ranging from 'not at all' to 'very much'. The instrument can be administered by nurses in clinics and takes about 10 min to complete and is quite easy to score and produces both an overall score and scores on a series of sub-scales. Work on reliability and validity is ongoing. The questionnaire is designed to have a 'core' for all cancers and add-on questions for particular cancer sites.
IMPACT OF NAUSEA AND VOMITING ON QUALITY OF LIFE
S17
EORTC Core Quality of Life Questionnaire* I
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4
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14. Hae you skit asoe
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The Hospital Anxiety and Depression Scale (Figure 4) This is a 14 item scale which was developed for patients who had physical illness and therefore items like tiredness that can occur in depression but can also be symptoms of physical illness were in general excluded. It is quickly and easily completed by patients and is capable of measuring change over time within different groups of cancer patients. Studies suggest that it is capable of detecting psychological morbidity in cancer patients and that it is a reasonable tool for measuring the psychological dimension of quality of life in cancer patients. It is still possible to reiterate the recommendations made by the Medical Research Council Working Party 2 years ago. Many of the questionnaires evaluated have been tested further since the report and their usefulness confirmed. We remain in a phase of proliferation of measurement indices (Cella & Tulsky, 1990). Many of these have much in common with the ones described above but few have been so thoroughly tested, although some may have particular advantages for individual applications. It is unlikely that a simple gold standard quality of life measurement questionnaire will emerge in the near future but there appears to be a great deal in common between different techniques. A large number of items are common to different questionnaires and the length of questionnaires developed for a comprehensive assessment of quality of life in cancer patients tends to be similar with consistent numbers of items.
Nausea and vomiting scales within quality of life questionnaires
Figure 5a-d shows the nausea and vomiting scales of four well characterised quality of life questionnaires: (A) The Linear Analogue Self Assessment system (Selby et al., 1984) (B) Rotterdam Symptom Checklist (De Haes et al., 1986)
(C) The Functional Living Index for Cancer (Schipper et al., 1984) (D) EORTC QL questionnaire (Aaronson et al., 1986) Although superficially they appear different, each represents a relatively simple rating system using descriptive categories or linear analogue scales. Similar scales have been used in research into antiemetics and their reliabiltiy and validity is supported in many cases. There are particular problems in assessing the psychometric properties of nausea and vomiting scales. The symptoms when due to cancer chemotherapy are often short-lived and patients re-call may be hindered by the circumstances of the symptom, by concurrent sedative medication or the effects of their illness. To assess the reproducibility of such items test retest scoring is often applied. In our own studies (Selby et al., 1984) evaluating 31 different linear analogue scales in 96 patients the scores for Nausea and Vomiting had co-efficients of agreement of less than 0.40 (Table I) when retested 24 h apart. The explanation for this apparently low reproducibility of items scored for Nausea and Vomiting is not entirely clear. In a small group of 31 patients who completed the items in the evening before attending an outpatient clinic and again on arrival at the clinic the test re-test correlation co-efficients for Nausea and Vomiting were greater than 0.70 suggesting that clinic attendance and presumably the administration of chemotherapy reduced the reliability scores. The time between the two scores in this study was 12-24 h. However, in another study in which patients receiving chemotherapy at clinic were excluded co-efficients of agreement for nausea and vomiting were 0.40 and 0.30 respectively and were the lowest among the 31 items assessed. There are a number of ways of assessing the validity (i.e. the extent to which a score measures that which it reports to measure) of items in quality of life questionnaires. The scores may be compared to scores obtained by alternative methods or by alternative observers. Scores for Nausea and Vomiting were closely correlated with each other in our studies. The
S18
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