Psychometric Properties of the Brief Fatigue Inventory in Greek Patients with Advanced Cancer

Vol. 36 No. 4 October 2008 Journal of Pain and Symptom Management 367 Original Article Psychometric Properties of the Brief Fatigue Inventory in Greek Patients with Advanced Cancer Kyriaki Mystakidou, MD, PhD, Eleni Tsilika, BSc, MSc, Efi Parpa, BA, MA, Tito R. Mendoza, PhD, Kyriaki Pistevou-Gombaki, MD, PhD, Lambros Vlahos, MD, PhD, and Charles S. Cleeland, MD, PhD Pain Relief and Palliative Care Unit (K.M., E.T., E.P.), Department of Radiology (L.V.), Areteion Hospital, School of Medicine, University of Athens, Athens, Greece; Pain Research Group (T.R.M., C.S.C.), University of Texas, M. D. Anderson Cancer Center, Houston, Texas, USA; and Radiotherapy Department (K.P.-G.), University of Thessaloniki, Thessaloniki, Greece Abstract To validate the Greek version of the Brief Fatigue Inventory (BFI-Gr) in a sample of cancer patients, the scale was translated with the forwardebackward procedure to Greek. It was administered twice, at a three-day interval, to 102 eligible patients with cancer. Together with the BFI-Gr scale, the patients also completed the European Organization for Research and Treatment of Cancer QLQ-C30 (version 3.0) subscales of fatigue and emotional functioning, and the M. D. Anderson Symptom Inventory. The BFI-Gr had an overall Cronbach alpha for the nine items of 0.954. The assessment of the relationships between the BFI-Gr and the other measurements showed statistically significant correlations between all the assessed measurements (r values between 0.47 and 0.76, P < 0.0005), except with the emotional subscale of the European Organization for Research and Treatment of Cancer scale. Factor analysis yielded a one-factor solution, explaining 73.6% of the variance. Interitem correlations were high and ranged from 0.567 to 0.882 (P < 0.0005). The testeretest reliability of scale showed that the coefficient agreement was 0.901 (P < 0.0005). Univariate analysis revealed significant correlations between hemoglobin and fatigue (r ¼ 0.21, P ¼ 0.037), and between performance status (P < 0.0005) and opioids (P ¼ 0.009). These results support that the BFI- Gr is an instrument with satisfactory psychometric properties, and is a valid research tool for cancer-related fatigue in Greek cancer patients J Pain Symptom Manage 2008;36:367e373. Ó 2008 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. Key Words Fatigue, cancer quality of life, symptom distress Address correspondence to: Kyriaki Mystakidou, MD, PhD, Pain Relief and Palliative Care Unit, Department of Radiology, Areteion Hospital, School of Medicine, University of Athens, 27 Korinthias Street, 115 26 Athens, Greece. E-mail: mistakidou@ yahoo.com Accepted for publication: November 1, 2007. Ó 2008 U.S. Cancer Pain Relief Committee Published by Elsevier Inc. All rights reserved. Introduction Fatigue is one of the most common symptoms in cancer patients. The prevalence of fatigue has been reported to be over 50% in those with advanced disease 1e3 and over 30% in newly diagnosed cancer patients 4 and cancer survivors. 5 It is also known that patients 0885-3924/08/$esee front matter doi:10.1016/j.jpainsymman.2007.10.021

368 Mystakidou et al. Vol. 36 No. 4 October 2008 who undergo anticancer treatment modalities such as chemotherapy, radiotherapy, and bone marrow transplantation often experience fatigue as a significant treatment side effect. 6,7 Patients who experience severe fatigue may withdraw prematurely from potentially curative treatment, or be unwilling to take adequate doses of various forms of treatment. 8 It frequently and significantly interferes with quality of life. 9 Both physical and psychological factors are thought to be associated with fatigue. 10 Although the physiological mechanisms are unknown, it has been recognized that a low hemoglobin level is associated with severe fatigue. An association between fatigue and albumin level also has been reported, 11 but is still controversial. Numerous other factors may contribute. Because fatigue is not often assessed and is undertreated, concise assessment is the key to better management of this symptom. Selfrating scales have enabled physicians to assess patient symptoms without introducing observer bias. The Multidimensional Fatigue Inventory 12 is a 24-item questionnaire in which the patient has to indicate on seven-point scales to what extent the particular statement applies to him or her; the statements refer to aspects of fatigue experienced during the previous days, and higher scores indicate a higher degree of fatigue. The Functional Assessment of Cancer Therapy-Fatigue 13 measures multiple fatigue characteristics and their impact on function. The Schwartz Cancer Fatigue Scale 14 is a 28-item scale comprising four subscales (physical, emotional, cognitive, and temporal). The Fatigue Symptom Inventory 15 is a 13-item self-report measure designed to measure the intensity and duration of fatigue and its impact on quality of life. The revised Piper Fatigue Scale 16 is a 22-item scale comprising four subscales (behavioral/severity, affective meaning, sensory, and cognitive/mood). The main characteristic of these recently developed scales is their multidimensionality. However, multidimensional scales are often too long for very sick patients to complete. There currently exists no gold standard for assessing and managing cancer-related fatigue, although guidelines have been developed. 17 These guidelines emphasize the importance of assessment. Fatigue assessment has rarely been part of routine cancer care, as both patients and health care professionals historically have regarded cancer-related fatigue as an expected part of the disease. The science of measuring fatigue is only recently becoming well developed. A challenge in measuring fatigue in cancer patients is distinguishing patients having severe fatigue from those having moderate or mild fatigue. In studies of another validated questionnaire, the Brief Fatigue Inventory (BFI), Levels 1e3 fatigue indicated mild fatigue, Levels 4e6 fatigue was moderate, and Levels 7e10 fatigue was severe. 18 In a study of American cancer patients, BFI responses showed that 50% of patients with hematological malignancies experienced severe fatigue (defined as seven or greater on a 0e10 scale), as did 34% of patients with solid tumors. In contrast, severe fatigue was reported by only 17% of the community-dwelling sample. 18e20 The BFI 18 was specifically developed to measure fatigue in cancer populations. The BFI has been translated into a variety of languages (Chinese, Japanese, German, and Taiwanese) and the psychometric properties have been established. 20e23 The validation and translation of the BFI in Greek will provide further evidence for the measurement s adaptability in different cultures, and also will allow study results to be compared across different countries. The aim of the present study was to assess the psychometric properties of the BFI translated into Greek, including validity and reliability in a sample of Greek cancer patients receiving palliative care. Patients and Methods A total of 190 consecutive patients suffering from incurable cancer were treated in a palliative care unit in Athens, Greece, for pain relief and cancer-related symptoms during the study period. Criteria for inclusion were histologically confirmed malignancy, age >18 years, ability to communicate effectively with health care professionals, and patient informed consent. Patients were excluded if there was a history of drug abuse, a diagnosis of a psychotic illness, or significant cognitive impairment. A total of 155 patients fulfilled the study criteria and were considered eligible for entry into the study.

Vol. 36 No. 4 October 2008 Brief Fatigue Inventory in Greek 369 Participants were invited on a face-to-face basis. Forty-eight (31%) patients did not complete the assessment forms, either due to refusal or due to long distance, and thus were excluded from the study. The final sample consisted of 102 cancer patients. Patients were seen individually either at outpatient clinics or on the wards. Participants were asked to complete three self-report questionnaires: the BFI, the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (version 3.0) subscales of fatigue and emotional functioning, and the M. D. Anderson Symptom Inventory (MDASI). Research workers recorded data on disease status, treatment regimen, and demographic characteristics (age, sex, family status, and educational level). The sociodemographic and clinical data of the participants are presented in Table 1. Disease status information included cancer diagnosis, anticancer treatment (chemotherapy, radiotherapy), and performance status as defined by the Eastern Cooperative Oncology Group. 24 Treatment regimen data consisted of the opioid analgesics the patients were already receiving. The study was performed in accordance with the Helsinki Declaration and according to European guidelines for good clinical practice, and was approved by the institutional review board. Translation To develop the BFI-Greek (BFI-Gr), the forwardebackward translation method was used. The items were first translated into Greek by two independent translators whose native language was Greek and then backtranslated into English by another two independent translators whose native language was English and who had not seen the original English version. Next, the English back-translated items were compared with the originals. Instruments The BFI was developed to measure fatigue in cancer populations. The three important characteristics of this scale are (1) it is brief and easy for patients to complete, (2) it is easily translated into other languages, and (3) it includes interference items. The validity and reliability of the original scale has been established. 18 The questionnaire uses an 11-point scale (0 ¼ no fatigue to 10 ¼ fatigue as bad Table 1 Demographic and Disease-Related Patient Characteristics n % Age Mean SD: 64.32 11.58 years Range (39e84) Years of education Mean SD: 10.20 3.80 years Range (6e16) Gender Male 55 53.9 Female 47 46.1 Diagnosis Urogenital 32 31.4 Lung 27 26.5 Breast 19 18.6 Other 13 12.7 Gastrointestinal 11 10.8 Family status Married 90 88.2 Unmarried 12 11.8 ECOG score 0e1 good 59 57.8 2e3 poor 43 42.2 Metastasis No 23 22.5 Yes 79 77.5 Chemotherapy No 34 33.3 Yes 68 66.7 Radiotherapy No 31 30.4 Yes 71 69.6 Opioids Mild 20 19.6 Strong 82 80.4 ECOG ¼ Eastern Cooperative Oncology Group. as you can imagine ) to measure the specific symptom of cancer-related fatigue in a single dimension. Three items ask patients to rate the severity of their fatigue at its worst, usual, and now during the past 24 hours. Cutpoints for fatigue severity were defined in two categories: a fatigue worst rating of $7 indicates severe and 0e6 indicates nonsevere. Six additional items describe how much fatigue has interfered with different aspects of the patient s life during the past 24 hours. These items include general activity, mood, walking ability, normal work, relationships with other people, and enjoyment of life. Interference is measured with 0 ¼ does not interfere and 10 ¼ completely interferes. The global score for the BFI is calculated as the mean value of these nine items. The EORTC QLQ-C30 is one of the most frequently used self-rating questionnaires in

370 Mystakidou et al. Vol. 36 No. 4 October 2008 assessing patients quality of life. 25 It has 30 items and consists of five multi-item function subscales and a global health status/quality of life (physical, role, emotional, cognitive, and social function), four multi-item symptom scales (fatigue, pain, nausea, and vomiting) and six items that assess symptoms (dyspnea, sleep disturbance, appetite loss, diarrhea, and constipation) and financial impact. In the present study, we used the fatigue subscale and the emotional subscale in the analysis, using a four-point Likert scale for each. All scales range in a transformed score from 0 to 100. A high score for a functional scale represents a high/healthy level of functioning. A high score for the global health status/quality of life represents a high quality of life. A high score for a symptom scale/item represents a high level of symptomatology/problems. Originally, the EORTC QLQ-C30 (version 3.0) was designed for prospective randomized trials in cancer patients, but today, it also is used as a screening instrument in cross-sectional studies. The questionnaire has been validated, by the authors of the present study, in a Greek sample of cancer patients attending a palliative care unit. 26 The MDASI is a brief measure of the severity and impact of cancer-related symptoms. 19 The Greek version of the MDASI was used for the assessment of symptom prevalence and distress. 27 The MDASI consists of 13 core symptom items that are rated based on their presence and severity. Each symptom is rated on an 11-point scale (0e10) to indicate the presence and severity of the symptom, with 0 meaning not present and 10 meaning as bad as you can imagine in the last 24 hours. It also includes six symptom interference items that are rated based on the level of symptom interference with the function of a patient s life in the last 24 hours. The interference items were also measured on scales from 0 to 10, with 0 meaning did not interfere and 10 meaning interfered completely. The MDASI was administered to all patients. Statistical Analysis Descriptive statistics, including means, and counts and percentages for the variables were calculated. The psychometric properties of the BFI-Gr were assessed. Exploratory factor analysis (principal axis factoring with varimax rotation) was used to examine the structure of the questionnaire. Criterion validity was evaluated by calculating the Pearson product moment correlation coefficient between the BFI-Gr scores and the EORTC QLQ-C30 fatigue and emotional subscales and the MDASI total score, the MDASI fatigue item, and the MDASI total score omitting the fatigue item. Convergent validity was evaluated by calculating the interinstrument correlations. The internal consistency was evaluated by calculating the Cronbach alpha coefficient, which ranges from 0 to 1, higher values indicating less measurement error. The testeretest reliability was evaluated by calculating the Pearson product moment correlation coefficient with a three-day interval in the whole sample. A three-day interval was chosen because fatigue severity is not expected to change within this time period. We also investigated the association between fatigue scale scores and the demographic and clinical data. Results Of the 102 patients, 53.9% were males and 88.2% were married. Urogenital and lung cancer were diagnosed in 31.4% and 26.5%, respectively. A significant proportion (42.2%) had a poor performance status, 77.5% had metastasis, 66.7% had undergone chemotherapy, and 69.6% had received radiotherapy. A total of 80.4% were already receiving strong opioids (Table 1). Validity Factor Analysis. Factor analysis was performed to determine whether the BFI-Gr measures the same constructs as the original BFI. The Keiser Meyer-Olkin measure of sampling adequacy was equal to 0.921, showing that the data are suitable for factor analysis. The results of the scree test for the BFI-Gr suggested a one-factor solution. The eigenvalue was 6.62 for this factor, followed by 0.75 and 0.45 for the second and third factor, respectively. Moreover, the first factor explained 73.6% of the variability in the data. The single-factor model fits well according to Harman s 28 rule that the standard deviation of the residuals be slightly less than or approximately equal to the standard error of a correlation coefficient, which

Vol. 36 No. 4 October 2008 Brief Fatigue Inventory in Greek 371 is the reciprocal of the square root of the sample size. The eigenvalues and amount of explained variability indicate that most of the data can be explained by a single construct, consistent with the original BFI. Because the BFI-Gr measures a single construct, the mean of the nine BFI-Gr items can be used as a global BFI-Gr score. Criterion Validity. Pearson s product moment correlation was used to calculate the relationships among the BFI-Gr, and the EORTC fatigue and emotional subscales, and the MDASI total score, MDASI fatigue item, and MDASI total score without the fatigue item. The results showed statistically significant correlations between BFI-Gr and all the assessed measurements (r values between 0.471 and 0.769, P < 0.0005), except with the emotional subscale of the EORTC instrument (Table 2). Convergent Validity. Convergent validity is one aspect of construct validity of psychological measurements. 29 It was demonstrated that the questionnaire was able to show a correspondence or convergence between the items of the scale. Correlation coefficients (Pearson s r) were high and ranged from 0.567 to 0.882 (P < 0.0005) (Table 3). Reliability Internal Consistency. In an attempt to estimate the internal consistency of the BFI-Gr, Cronbach s alpha (estimates of a magnitude of 0.70 or greater were sought) was calculated for the nine items in the scale. The overall alpha was 0.954. The fact that the reliability coefficient of the scale is high emphasized the increased internal consistency and reliability of the scale. TesteRetest (Stability). Data from 102 patients who responded both at the first and the Table 2 Construct Validity Between BFI-Gr, EORTC QLQ-C30, and MDASI BFI-Gr Pearson s Correlation Coefficient P value MDASI total score 0.525 <0.0005 MDASI fatigue item 0.769 <0.0005 MDASI total score 0.471 <0.0005 without fatigue item EORTC fatigue subscale 0.695 <0.0005 EORTC emotional subscale 0.106 NS NS ¼ Not significant. second assessment (three-day interval) were used to examine the stability of the BFI-Gr over time. The testeretest reliability of scale (Pearson s r), showed that the coefficient agreement was 0.901 (P < 0.0005). These results indicate that the BFI-Gr scores were remarkably consistent across the two occasions and were significantly correlated. Univariate Analysis Significant correlations were found between the continuous variable hemoglobin and fatigue (r ¼ 0.210, P ¼ 0.037), whereas the associations between the categorical variables and fatigue revealed statistically significant correlation between performance status (P < 0.0005) and opioids (P ¼ 0.009) (Table 4). Discussion Fatigue, weakness, and lack of energy are three very frequent symptoms in advanced cancer patients. 30 Fatigue is one of the top complaints in Western cancer patients 19 and is also a major concern to Greek cancer patients. It has been recognized by many oncology professionals that fatigue almost always clusters with other significant symptoms, either caused by disease or therapy. 31 Fatigue is commonly conceptualized as a multidimensional symptom that incorporates sensory, cognitive, affective, behavioral, and physiologic components. 32 Although the BFI- Gr does not capture the multiple dimensions of fatigue, it is sufficient to screen for patients with high levels of fatigue. The one-factor solution provided a good model fit for the nine BFI-Gr items, in accordance with the original English, Japanese, German, and Taiwanese versions of the BFI. The construct validity analysis confirmed that the BFI-Gr composite score was highly correlated with items of the MDASI, as well as with the fatigue scale from the EORTC QLQ-C30 (version 3.0). This result encourages the use of BFI-Gr in clinical studies on fatigue as a simple measure of fatigue-related physical functional impairment. Moreover, this finding shows that using a multisymptom or quality-of-life questionnaire may be beneficial in screening for fatigue. Furthermore, patients in the present study related fatigue with symptom distress rather than affective areas, as seen in the findings of construct validity, where BFI-Gr had no significant

372 Mystakidou et al. Vol. 36 No. 4 October 2008 Table 3 Convergent Validity: Interitem Correlation Items 1 2 3 4a 4b 4c 4d 4e 4f 1 1.000 0.818 0.838 0.807 0.618 0.733 0.782 0.567 0.678 2 1.000 0.882 0.759 0.604 0.677 0.731 0.583 0.638 3 1.000 0.793 0.613 0.662 0.746 0.584 0.665 4a 1.000 0.653 0.730 0.824 0.651 0.770 4b 1.000 0.589 0.625 0.678 0.762 4c 1.000 0.813 0.599 0.595 4d 1.000 0.669 0.736 4e 1.000 0.780 4f 1.000 correlation with the emotional subscale of the EORTC QLQ-C30 (version 3.0). An interesting finding of the present study is the statistically significant correlation between BFI-Gr and opioids. Patients receiving mild opioids scored higher in BFI-Gr. As participants had been referred to the Pain Relief Table 4 Means of Categorical Demographics, Clinical Variables, and BFI-Gr BFI-Gr n Mean SD P value Gender Male 55 50.91 12.67 NS Female 47 49.51 12.05 Family status Married 90 49.92 11.44 NS Unmarried 12 53.33 18.38 ECOG 0e1 59 45.89 12.02 <0.0005 2e3 43 56.25 10.17 Chemotherapy No 34 50.03 11.97 NS Yes 68 50.38 12.62 Radiotherapy No 31 50.74 13.06 NS Yes 71 50.06 12.11 Metastasis No 23 49.43 13.37 NS Yes 79 50.51 12.12 Opioids Mild 20 51.69 11.92 0.009 Strong 82 43.70 12.07 NSAID No 27 49.22 13.36 NS Yes 75 50.64 12.04 Primary site Gastrointestinal 11 55.45 8.39 NS Lung 27 52.33 10.73 Urogenital 32 46.78 13.48 Breast 19 47.26 13.37 Other 13 54.54 11.70 ECOG ¼ Eastern Cooperative Oncology Group, NSAID ¼ Nonsteroidal anti-inflammatory drug, NS¼Not significant. and Palliative Care Unit for pain relief, among other symptoms, it can be assumed that these patients were undertreated, because pain has been found 33 to be a significant predictor for fatigue. Consistent with previous research, the current study showed that cancer patients, and those with anemia had a strong relationship with fatigue. 20 In addition, patients having poor Eastern Cooperative Oncology Group performance status scores had higher BFI-Gr scores, as in the study of the Japanese version of the BFI. 21 The study had a few limitations. The relatively small sample of the study means a further investigation is needed in a larger sample. Moreover, the present study did not examine the ability of the BFI to distinguish patients according to disease severity. Conclusion The BFI-Gr compares favorably to other fatigue assessment tools. Moreover, it is short, easily understood, with comprehensible and standardized rules for administration and scoring, and well-documented reliability and validity. These qualities make the BFI-Gr a useful screening and monitoring instrument even for patients with reduced performance status. This study proved that the BFI-Gr is a reliable and valid self-rating assessment tool for fatigue. References 1. Vainio A, Auvinen A, with Members of the Symptom Prevalence Group. Prevalence of symptoms among patients with advanced cancer: an international collaborative study. J Pain Symptom Manage 1996;12(1):3e10. 2. Stone P, Hardy J, Broadley K, et al. Fatigue in advanced cancer: a prospective controlled crosssectional study. Br J Cancer 1999;79:1479e1486.

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