Int. J. Cancer: 94, 135–139 (2001) © 2001 Wiley-Liss, Inc.
Publication of the International Union Against Cancer
THE EORTC CORE QUALITY OF LIFE QUESTIONNAIRE (QLQ-C30, VERSION 3.0) IN TERMINALLY ILL CANCER PATIENTS UNDER PALLIATIVE CARE: VALIDITY AND RELIABILITY IN A HELLENIC SAMPLE Kyriaki MYSTAKIDOU1,2*, Eleni TSILIKA1, Efi PARPA1, Ourania KALAIDOPOULOU1, Vassilios SMYRNIOTIS3 and Lambros VLAHOS2 1 Pain Relief and Palliative Care Unit, University of Athens, Areteion Hospital, Athens, Greece 2 Department of Radiology, University of Athens, Areteion Hospital, Athens, Greece 3 Department of Surgery, University of Athens, Areteion Hospital, Athens, Greece In 1986, the European Organization for Research and Treatment (EORTC) initiated a research program to develop an integrated, modular approach for evaluating the quality of life of patients participating in international clinical trials. The questionnaire was designed to measure cancer patients’ physical, psychological and social functions. The questionnaire is composed of 5 multiitem scales (physical, role, social, emotional and cognitive functioning) and 9 single items (pain, fatigue, financial impact, appetite loss, nausea/ vomiting, diarrhea, constipation, sleep disturbance and quality of life). It was administered to the patients before the initiation of palliative treatment and then once again during the treatment. The validation of the questionnaire took place at Areteion Hospital, while the translation was conducted by the EORTC bureau. The final validation sample consisted of 120 cancer patients. The clinical variable assessed was the performance status. The aim of our study was to assess the applicability of this quality of life measurement on a Hellenic sample of cancer patients receiving palliative care. The results showed that the questionnaire was well accepted in the present patient population. In addition, the questionnaire was found to be useful in detecting the effectiveness of palliative treatment over time. The scale reliability was very good (pretreatment from 0.57– 0.79, ontreatment from 0.56 – 0.75), especially for the functioning scale. In addition, very good validity was found in all the approaches used. Moreover, the factor analysis results in a 6-factor solution that satisfies the criteria of reproducibility, interpretability and confirmatory setting. Performance status showed an improvement (p < 0.0025) during the studied period. These results support that the QLQ-C30 (version 3.0) has proven to be a reliable and valid measure of the quality of life in Greek cancer patients receiving palliative care treatment. © 2001 Wiley-Liss, Inc. Key words: EORTC; quality of life; palliative care; cancer; Hellas
The past decade has witnessed a growing interest in broadening the evaluation criteria employed in cancer clinical trials beyond the traditional biologic markers of therapeutic outcome—tumour response, time to progression and disease-free and overall survival—to include an assessment of the impact of the disease and its treatment on the physical, psychological and social functioning of the patient. Support for such “quality of life” investigations has been expressed by prominent clinical trial groups in North America1 and Europe,2 national and international cancer institutes and societies,3 regulatory agencies responsible for the approval of new antineoplastic agents4 and the pharmaceutical industry.5 Nevertheless, such investigations remain the exception. The most important obstacle has been the absence of widely accepted, standardized methods for carrying out such assessments. For this reason, in 1986 the European Organization for Research and Treatment of Cancer (EORTC) study group on quality of life initiated a research program whose long-term objective was to develop an integrated measurement system for evaluating the quality of life patients participating in international clinical trials.6 Over the last decades a growing interest in the impact of disease and treatment on the patient’s life and functioning has emerged. Systematic evaluations of health-related quality of life (HRQoL) might enable clinicians to identify patients who are at increased
risk of encountering psychosocial problems, so that proper intervention strategies can be initiated when necessary. Sufficient validity and reliability are mandatory for measurement tools. The EORTC quality of life questionnaire is an integral system for assessing the QoL of cancer patients participating in international clinical trials. A first-generation core questionnaire, the EORTC QLQ C36, was developed in 1987.2 The EORTC QLQ C30 is a second-generation questionnaire. Following its general release in 1993,6 the QLQ-C30 has been used in a wide range of cancer clinical trials by a large number of research groups; it has additionally been used in various other nontrial studies. It is a 30-item questionnaire. Version 3.0 differs from version 2.0 in that it has 4-point scales for the first 5 items. These are coded with the same response categories as items 6 to 28, namely “not at all,” “a little,” “quite a bit” and “very much.” To allow for these categories, question 4 has been reworded as: “Do you have to stay in bed or a chair during the day?” The EORTC QLQ-C30 comprises distinct scales, each of which represents a different aspect of QoL. We report here the results of a study for the evaluation of the practicality, reliability and validity of the revised questionnaire EORTC QLQ-C30 (version 3.0) in a Hellenic sample of cancer patients in a palliative care unit. MATERIAL AND METHODS
Our study was performed over a period of 15 days at the outpatient clinic of a palliative care unit in Athens, Hellas. This unit is approached by cancer patients from all over Greece. All patients suffered from cancer and approached the unit for pain relief and management of cancer-related symptoms. The study was conducted from March 1999 to June 2000. A representative sample of 144 patients was drawn from a total of 600 patients who were treated in the unit that period using stratified random sampling method according to the performance status, representative to the population of cancer patients in Greece. A total of 24 (16.7%) patients were excluded from our sample due to difficulties in reaching them and due to refusal to participate in the study. The patient sample consisted of 46 males (38.3%) and 74 females (61.7%) with a mean age of 62.65 years (range 38 – 87 years). Criteria for inclusion were age ⬎18 years, no cerebral metastases, no known psychiatric disorder, Karnofsky performance status no less than 50 or to be cognitively capable of filling in the questionnaire, as well as fluent in the Hellenic language. The patients were asked to complete the first pretreatment questionnaire at the unit *Correspondence to: Pain Relief and Palliative Care Unit, Areteion Hospital, University of Athens, School of Medicine, 76 Vas. Sofias Ave., Athens 11528, Greece. Fax: ⫹30-1-7247126. E-mail:
[email protected] Received 1 December 2000; Revised 17 April 2001; Accepted 8 May 2001 Published online 24 July 2001; DOI 10.1002/ijc.1439
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and then to complete the questionnaire for the second time 15 days later while they were on palliative treatment at the unit. If necessary, the patients were given brief instructions on how the questionnaire should be completed. The palliative treatment aimed at relieving and controlling pain, anaemia, as well as symptoms like dyspnea, nausea, vomiting and anorexia. Palliative treatment also included antioedematic treatment. The staff of the outpatient clinic and the study investigator were available for questions about the study and on how to fill in the forms. Demographic and clinical data were recorded on a separate sheet by the study investigators or the staff at the clinic. The sample was heterogeneous with regard to histologic type of cancer (adenoCa, sarcoma, squamous), extent of disease and pretreatment Karnofsky performance status. The most prevalent diagnoses were lung cancer (25%), breast cancer (13.3%), pancreas (13.3%), cervical (10%) and ovarian (8.3%). The average time required to complete the QLQ-C30 (version 3.0) was similar at both points of administration, 9 min (S.D. ⫽ 5 min) and 7 min (S.D. ⫽ 4 min) for the pretreatment and ontreatment, respectively. No patients reported difficulty or confusion regarding the questionnaire items. The participating patients were off anticancer treatment for at least 3 months. All patients signed an informed consent prior to completing the questionnaire. Statistical analysis The first phase involved presentation of the descriptive statistics. Means, standard deviations for the continuous variables and counts and percentages for the categorical variables were computed. The second phase involved the actual validation of the Hellenic version. To assess the reliability (which involves the relationship of the items in a test in order to ensure that all test items measure the same variable) of the EORTC QLQ-C30, we calculated Cronbach’s alpha coefficient for the functioning and symptom scales.7 Internal consistency estimates of a magnitude of 0.70 or greater were sought. Four approaches were taken to evaluate the validity (a measurement may be said to be valid if it successfully measures what it is intended to measure) of the studied questionnaire. The first approach involved an examination of the correlations among the scales. In the second approach, the method of known-group comparison was used to evaluate the clinical validity of the questionnaire. The clinical parameters employed to form mutually exclusive patient subgroups for the analysis of the pretreatment QLQC30 (version 3.0) included initial performance status (Karnofsky scale scores of ⱖ60 vs. 50 –59). For the analysis of the data from the second administration of the questionnaire, the clinical param-
eters used were performance status ontreatment. In the third approach, the availability of 2 questionnaires, 1 administered during the treatment period, permitted a preliminary evaluation of the responsiveness of the questionnaire to changes in health status over time. In the fourth approach, we used an exploratory factor analysis (to highlight the construct validity of the scales and, consequently, to provide a standard to assess future versions and compatibility with versions in other languages) using principal components with varimax rotation to investigate the questionnaire’s factorial structure. No cases were omitted from the analyses due to missing data. The statistical software SPSS PC for Windows (version 8.0) was used in the statistical analyses. RESULTS
The QLQ-C30 (version 3.0) is composed of both multiitem scales and single-item measures. These include 5 functional scales (cognitive, CF; emotional, EF; physical, PF; role, RF; and social functioning, SF), 3 symptom scales (fatigue, FA; nausea/vomiting, NV; and pain, PA), a global health status/QoL scale and 5 single items assessing additional symptoms (appetite loss, AP; constipation, CO; diarrhea, DI; dyspnea, DY; and sleep disturbance, SL) and perceived financial impact, FI. Each of the multiitem scales includes a different set of items—no item occurs in more than 1 scale. All of the scales and single-item measures range in score from 0 –100. A high scale score represents a higher response level. Thus, a high score for a functional scale represents a high/healthy level of functioning. A high score for the global health status/QoL represents a high QoL. A high score for a symptom scale/item represents a high level of symptomatology/problems. (Figs. 1, 2). Descriptive statistics and scale reliability To estimate the internal consistency reliability of the Greek version, the Cronbach alphas were calculated for the functioning scales and symptom scales. The reliability coefficients for the functioning scales ranged from 0.71– 0.79 and for the symptom scales/items ranged from 0.57– 0.61. In the second administration of the questionnaire, the reliability coefficients for these scales ranged from 0.68 – 0.75 and 0.56 – 0.58, respectively. The high values indicate little measurement error because the higher the coefficient value the higher the reliability and the level of measurement. The fact that the reliability coefficient of the scale remains high emphasizes the increased internal consistency reliability of the scale. Table I shows the alpha coefficient for the
TABLE I – DESCRIPTIVE STATISTICS AND SCALE RELIABILITY OF THE QLQ-C30 Items1
Functioning scales3 Physical Role Cognitive Emotional Social Global quality of life Symptom Scales4 Fatigue Nausea and vomiting Pain Dyspnea Sleep disturbance Appetite loss Constipation Diarrhea Financial impact
Pretreatment
Ontreatment
Mean score
S.D.
Cronbach’s alpha2
Mean score
S.D.
Cronbach’s alpha2
1–5 6, 7 20, 25 21–24 26, 27 29, 30
39.89 29.44 50.28 65.00 44.72 28.19
22.62 26.10 22.55 31.69 23.27 19.95
0.73 0.79 0.76 0.78 0.71 0.75
64.89 61.94 71.39 79.17 55.83 79.86
19.32 22.77 13.23 16.70 26.72 18.24
0.68 0.73 0.75 0.73 0.71 0.73
10, 12, 18 14, 15 9, 19 8 11 13 16 17 28
85.55 30.83 88.06 37.22 61.11 57.22 51.67 11.67 53.33
19.22 33.73 17.92 39.34 32.57 42.11 40.90 28.00 27.58
0.61 0.58 0.57
43.89 9.72 37.78 18.89 20.00 26.67 19.44 3.89 40.56
21.49 14.16 20.55 27.69 17.57 28.65 28.32 12.41 28.84
0.58 0.57 0.56
1 Numbers correspond to the item numbers in the questionnaire.–2Cronbach’s alphas can only be determined for multiitem symptom scales.–3Scores range from 0 to 100 with a higher score representing a higher level of functioning.–4Scores range from 0 to 100 with a higher score representing a greater degree of symptoms.
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THE HELLENIC VERSION OF QLQ-C30 TABLE II – CORRELATIONS AMONG THE QLQ-C30 SCALES BEFORE AND AFTER TREATMENT PF
PF RF CF EF SF F P NV QL
RF
CF 2
0.462 0.482 0.482 0.24 ⫺0.442 ⫺0.612 ⫺0.10 0.452
EF 2
0.51
0.44 0.08
0.23 0.19 0.392 ⫺0.632 ⫺0.602 ⫺0.12 0.24
0.552 0.532 ⫺0.482 ⫺0.21 ⫺0.292 0.11
SF 2
0.40 0.05 0.512 0.18 ⫺0.362 ⫺0.422 ⫺0.262 0.02
F 2
0.55 0.482 0.502 0.442 ⫺0.302 ⫺0.06 ⫺0.08 0.06
P
⫺0.69 ⫺0.302 ⫺0.322 ⫺0.422 ⫺0.362 2
0.622 0.382 ⫺0.272
⫺0.48 ⫺0.20 ⫺0.342 ⫺0.512 ⫺0.502 0.442 2
0.03 ⫺0.282
1
NV
QL
⫺0.18 ⫺0.10 ⫺0.21 ⫺0.11 ⫺0.08 0.07 ⫺0.272
0.402 0.402 0.282 0.412 0.572 ⫺0.272 ⫺0.542 0.07
0.01
1
Before treatment above the diagonal; during treatment under the diagonal. Values are Pearson’s r. Negative correlations are an artifact of the scoring procedures.–2Indicates statistical significant correlation.
FIGURE 1 – Comparison between pretreatment and ontreatment assessments in scores on the functioning scales (a, p ⬍ 0.0005).
multiitem and single-item measures for both the pretreatment and ontreatment administrations of the questionnaire. Validity, interscale correlations Table II presents the correlations among the scales of the QLQC30 (version 3.0) for both the pretreatment and ontreatment administrations. Most interscale correlations were statistically significant (p ⬍ 0.01). The strongest correlations before treatment were observed between the physical functioning, social functioning and fatigue, while ontreatment it was observed between pain, physical functioning, role functioning and fatigue scales. Substantial correlations (ⱖ0.40), pretreatment and ontreatment, were also noted between the physical functioning scale, emotional functioning, social functioning and quality of life item. Conversely, a relatively weak correlation was observed between the nausea/vomiting scale and the functioning scales. In general, the interscale correlations were of only a moderate size, indicating that, although related, they are assessing distinct components of the quality of life instrument. Clinical validity, known-groups comparison In all of the studies on QLQ-C30, validity has been examined in terms of the ability of its scales to distinguish between subgroups of patients formed on the basis of their clinical or treatment status (i.e., clinical validity, known-groups comparisons). Figures 3 and 4 summarize the results of the pretreatment administration of the QLQ-C30, with performance status as a grouping variable. Compared to patients with a poorer performance status, those with a better performance status reported statistically significant higher levels of all functioning scales, higher overall quality of life (p ⫽ 0.01) and lower levels of fatigue and financial impact scale. No comparison was performed during the ontreatment assessment between patients with a poorer and better performance status because of a small number of patients with poor performance status (n ⫽ 6).
FIGURE 2 – Comparison between pretreatment and ontreatment assessments in scores on the symptom scales (a, p ⬍ 0.0005; b, p ⬍ 0.001).
Responsiveness to change in health status With the use of the total sample, a statistically significant difference was detected (p ⬍ 0.001) between pretreatment and ontreatment scores for all functioning and symptom scales of the QLQ-C30 using paired Student’s t-test. This was more evident in physical, role functioning and quality of life scales, as well as in fatigue, pain and sleep disturbance items. Although responsiveness to change is sometimes viewed as a distinct psychometric property, recent arguments suggest that it can best be regarded as additional evidence of the validity of an instrument. Factor analysis Exploratory factor analysis (principle components extraction with varimax rotation) was undertaken to further explore the validity of the Hellenic version of the EORTC. The correlations between the variables were high. The Bartlett test of sphericity was 358.9 and was statistically significant (p ⬍ 0.0005). The KeiserMeyer-Olkin measure of sampling adequacy was equal to 0.71, showing that the data is suitable for factor analysis. Principal components extraction was used. Six factors with eigenvalue higher than 1 were extracted. These factors explained 76.85% of the total variance. For the interpretation of the factor solution, varimax rotation was performed. The factor analysis resulted in a 6-factor solution that satisfies the criteria of reproducibility, interpretability and confirmatory setting. Factor 1: the scales of physical, role, social functioning and the items of quality of life, pain and financial impact (loadings more than 0.44). Social functioning had the highest loading (0.803). Factor 2: the scales of emotional and cognitive functioning and the items of fatigue, pain and appetite loss (loadings more than
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FIGURE 3 – Comparison between Karnofsky performance status groups in scores on the functioning scales (a, p ⬍ 0.0005; b, p ⬍ 0.001; c, p ⬍ 0.05).
FIGURE 4 – Comparison between Karnofsky performance status groups in scores on the symptom scores (b, p ⬍ 0.001).
0.44). Cognitive functioning scale had the highest loading (0.78). Factor 3: the items of nausea/vomiting and diarrhea (loadings more than 0.84). Diarrhea had the highest loading (0.85). Factor 4: the scales of physical functioning, fatigue, dyspnea and cognitive functioning. Cognitive functioning had the highest loading (0.805), while the other scales had loadings more than 0.62. Factors 5, 6: the items of constipation and sleep disturbance (loadings 0.938 and 0.90). DISCUSSION
In this article, we have presented the results of a validation study of the Hellenic version of the EORTC QLQ C-30 (version 3.0), which is designed to assess the quality of life of advanced cancer patients receiving palliative treatment. The primary goal of palliative treatment is to reduce symptoms, to stabilize or improve patients’ level of functioning, to reduce hospitalization and to improve patients’ overall quality of life (QoL). Traditionally, the effect of such treatment has been evaluated by the frequency or intensity of a given symptom measured by the physicians.8,9 More recently, however, efforts have been mounted to measure treatment effect by means of patients’ self-rating of their HRQoL. Following its release for general use in 1993, the QLQ-C30 has been introduced into a wide range of non-EORTC, university- and industry-based clinical trials. The multinational nature of many of these studies has necessitated translating the questionnaire into a
large number of languages. All of these translations have been generated according to standard guidelines, have been accompanied by written documentation of the translation process and have been submitted to a centralized review process. The EORTC, with its clinical focus, its multidisciplinary membership and its multicultural orientation, provides a rather unique context for developing and testing quality of life questionnaires. Clinical research in oncology is characterized by close international cooperation and collaboration. Moreover, in multinational research, the geographic and cultural background of patients and investigators do not influence the definition of measurement of the biologic end points of primary interest, such as tumor response and survival. However, we cannot expect a culture-free research environment when one is measuring subjective outcomes such as symptoms, psychological well-being and social functioning. Indeed, the ways in which individuals define, recognize and report their illness experience can be highly influenced by such factors as gender, culture and socioeconomic status.10 –12 Therefore, it becomes clear how important it is to have the validation of the QLQ-C30 in different languages. Additionally, the cultural diversity of the EORTC membership facilitates the construction of a questionnaire whose content and style of presentation are appropriate for use among patients from a wide range of countries. Many patients from our sample reported positive emotions because they were given the opportunity to talk about their health and illness experiences. The weakest scale (r: ⫺0.27– 0.07) from a psychometric perspective is the nausea/vomiting. The tests of validity yielded generally consistent results. One of the advantages of our study compared to past validation studies6 of EORTC QLQ C-30 is that the sample was not restricted on one specific type of cancer but rather included a wide spectrum. This measurement has shown the necessity to introduce an additional requirement beside the already existing measurement of Karnofsky and ECOG, which is rated by the clinicians. This has been indicated by a number of studies in which there have been documented low levels of reliability in physicians’ performance status ratings and low levels of agreement between ratings provided by physicians and those of their patients.13,14 Therefore, functionally oriented aspects of quality of life could anticipate even greater problems in assessing subjective experiences, e.g., pain and fatigue.6,13 Moreover, neither tumor response nor patients’ weight loss/gain seem to be valid clinical anchor points in this patient population. The evaluation of new cancer therapies has focused on such biomedical outcomes as tumor response, disease-free and overall survival and treatment-related toxicity. However, there is also increasing recognition of the need to assess more systematically the impact of cancer and its treatment on the functional, psychological and social health of the patient. The major strengths of the Hellenic version of the EORTC QLQ-C30 (version 3.0) were that it exhibited satisfactory psychometric properties, was found to be useful for detecting changes over time, no cases were omitted from the analysis due to missing data and the high degree of compliance, which indicates that the format and the content of the questionnaire were acceptable for patients with advanced malignant disease. On the other hand some possible limitations could be the relatively small sample and a “good” performance status. Perhaps the most efficient means of generating additional psychometric data on the QLQ-C30 is to employ it in prospective clinical trials. These results support the QLQ C 30 as a reliable and valid measure of the quality of life of Greek cancer patients under palliative care. We consider that this version can be used effectively in the Hellenic cancer population, as well as in the palliative care settings in order to assess quality of life of advanced-stage cancer patients in international clinical trials.
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