The Fatigue Symptom Inventory: a systematic review of its psychometric properties

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1 DOI /s REVIEW ARTICLE The Fatigue Symptom Inventory: a systematic review of its psychometric properties Kristine A. Donovan & Paul B. Jacobsen Received: 9 June 2010 /Accepted: 16 August 2010 # Springer-Verlag 2010 Abstract Purpose Fatigue is one of the most common symptoms experienced by persons with chronic illness, including cancer. The effective management of fatigue hinges in part on the accuracy and reliability of its measurement. The purpose of this study was to review and characterize the use of the 14-item Fatigue Symptom Inventory (FSI) in published studies and to evaluate the available evidence for its psychometric properties. Methods A systematic review of the literature identified 55 studies reporting results for the FSI. Data were analyzed to characterize internal consistency reliability of multi-item FSI scales and test retest reliability. Correlation coefficients were summarized to characterize concurrent, convergent, and divergent validity. Standardized effect sizes were calculated to characterize the discriminative validity of the FSI and its sensitivity to change. Results Sample sizes across studies ranged from 9 1,756. Approximately half of the samples consisted exclusively of females. Alpha coefficients for multi-item scales ranged from Most items demonstrated low to moderate test retest correlations. Correlations with other fatigue measures ranged from Correlations with depression and anxiety measures were positive (range= ). Correlations with measures of vitality and vigor were negative (range= 0.28 to 0.77). Effect sizes for discriminative K. A. Donovan (*) : P. B. Jacobsen Health Outcomes and Behavior Program, H. Lee Moffitt Cancer Center & Research Institute, Magnolia Drive, MRC-PSY, Tampa, FL 33612, USA kristine.donovan@moffitt.org P. B. Jacobsen Department of Psychology, University of South Florida, Tampa, FL, USA validity and sensitivity to change ranged from small to medium and from small to large, respectively. Conclusions Findings provide good empirical evidence of the usefulness of the FSI and strongly support its use in future studies. Keywords Fatigue. Chronic illness. Cancer. Fatigue Symptom Inventory Introduction Fatigue is generally defined as a sense of persistent tiredness or exhaustion that is often distressing to the individual. It is a common symptom of many diseases; evidence suggests it is one of the most common and distressing symptoms experienced by cancer patients [34, 56, 61, 75] and may persist for years following cancer treatment [6, 9, 56]. Fatigue is a subjective phenomenon and is thus assessed most accurately by individual self-report. To this end, researchers have developed a number of self-report measures designed to assess fatigue in chronic diseases, including cancer. These include both single-item or multi-item unidimensional measures and multidimensional measures of fatigue. Examples of unidimensional measures include a single item embedded in a symptom checklist such as the Symptom Distress Scale [53] or the Rotterdam Symptom Checklist [17], the 7-item Fatigue Scale of the Profile of Mood States [54], and the Brief Fatigue Inventory [55]. Examples of multidimensional measures include the Revised Piper Fatigue Scale [60], the Functional Assessment of Cancer Therapy-Fatigue Scale [77], and the Multidimensional Fatigue Inventory [69]. The large number and variety of fatigue measures currently available for use make the decision of which scale to use a challenging one. In general, the choice

2 depends on several considerations [18, 44, 73]. These include what dimensions of fatigue one wishes to measure (including e.g., physical or mental aspects of fatigue, and the time intervals covered by the assessment), the practical aspects of any one measure's usability (e.g., whether it represents a minimal burden for the respondent), the measure's clinical and/or research utility (e.g., whether it discriminates cases of fatigue from noncases, with acceptable levels of sensitivity and specificity), and whether the scale possesses robust psychometric properties, including the strength of the evidence for the measure's reliability and validity and the population(s) on which the psychometric data are based [38]. While several reviews [18, 44, 57, 73] have commented on the psychometric properties of fatigue measures in chronic illness, including cancer, the psychometric data provided in these reviews generally have been limited to the original studies on the development and validation of the measures. As these measures continue to be used and the data based on these measures accumulate, it is important to examine how the various fatigue measures have been used subsequent to their original validation studies and to characterize the evidence base supporting their current and future use. The Fatigue Symptom Inventory [27] (FSI), first published in 1998, is a 14-item self-report measure designed to assess fatigue severity, fatigue frequency, perceived associated with fatigue, and the daily pattern of fatigue. Severity is measured with separate 11-point items (0=not at all fatigued, 10=as fatigued as I could be) that assess most, least, and average fatigue in the past week and fatigue right now. Each of these is scored as an individual item. Frequency is measured as the number of days (from 0 to 7 days) in the past week that respondents felt fatigued and the amount of each day on average respondents felt fatigued (0=none of the day, 10=the entire day). Each of these is scored as an individual item. Perceived is measured with separate 11-point items (0=no, 10=extreme ) that assess the degree to which fatigue in the past week interfered with general level of activity, ability to bathe and dress, normal work activity, ability to concentrate, relations with others, enjoyment with life, and mood. These 7 items are averaged to obtain an scale score. The final item asks respondents to indicate their daily pattern of fatigue and so provides descriptive information about possible diurnal variation in the daily experience of fatigue. A score of 3 or greater on the average fatigue severity item or a mean score of 3 or greater on those items assessing fatigue severity in the past week is the recommended cut-off for discriminating cases of clinically meaningful fatigue from noncases [20]. The psychometric properties of the FSI were originally established in women with a diagnosis of breast cancer and women with no history of cancer [27]. The measure was further validated in a study of males and females with a variety of different cancer diagnoses [70]. Since its development, the FSI has been used to assess fatigue in clinical and nonclinical populations and as an outcome measure in clinical studies. The aims of this paper are to review and characterize the use of the FSI in published studies and to evaluate the available evidence for its psychometric properties. We conducted a systematic review of the literature to identify studies that used the FSI as a measure of fatigue and reported results on the FSI. These data were analyzed based on statistical considerations, and the results were synthesized to characterize the reliability, validity, and sensitivity of the FSI and the studies on which these psychometric data are based. Methods Search strategy The identification of relevant studies began with an electronic search of Web of Science to identify journal articles citing one of two published papers on the development and early validation of the FSI [27, 28]. We also searched Medline, PsycINFO, and CINAHL using the search term Fatigue Symptom Inventory. Finally, reference lists from relevant studies were reviewed to ensure that we identified all possible studies that derived empirical results for the FSI. Selection strategy Inclusion criteria were articles written in the English language, articles published in peer-reviewed journals, and articles reporting results based on administration of the FSI. Exclusion criteria were reviews of existing research that summarized results of published studies using the FSI. Review strategy Each author separately reviewed the identified studies, and information was abstracted from each study that met inclusion criteria. This information included basic descriptive data from each study about participants, including demographic and clinical characteristics, the purpose and design of the study, and the FSI items or scales for which results were reported. Abstraction of results focused on published findings that provided information about the reliability and validity of the FSI. With respect to reliability, evidence for the internal consistency and reproducibility of measurement over time was abstracted. With respect to construct validity, evidence of concurrent, convergent,

3 divergent, and discriminative validity was abstracted. Finally, evidence of the sensitivity to change of the FSI as a result of an intervention or disease treatment likely to alter the level of fatigue was abstracted. Statistical analysis Descriptive statistics, including means and percentages, were calculated to characterize the samples identified in the relevant articles. The psychometric properties were evaluated using information available from the published articles. Cronbach's alpha coefficients, when reported, were used to assess the internal consistency reliability of multi-item FSI scales. Correlation coefficients between FSI items or scales and other published measures were examined when available to characterize the concurrent, convergent, and divergent validity of the FSI. Summary statistics in the form of mean correlation coefficients with two-sided 95% confidence intervals for the mean were calculated in some instances for illustrative purposes. By convention, the magnitude of a correlation coefficient less than 0.20 was considered low, between 0.20 and 0.40 moderate, and greater than 0.40 was considered high. Finally, Cohen's d [14], a measure of effect size, was calculated to characterize the difference between two groups on the FSI. A standardized effect size [36] using baseline and follow-up scores and the standard deviation of baseline scores was calculated to characterize the sensitivity of the FSI to change. When effect sizes were calculated by the authors of the published studies, we did not recalculate these statistics but reproduced them in our results. Results We identified 55 articles published between the initial publication of the FSI and November 2009 that reported results on the administration of the FSI (see Table 1) [1 5, 7, 8, 10 13, 15, 16, 19 31, 35, 37, 39 43, 45, 46, 48 52, 58, 59, 62 68, 70 72, 74, 76, 78]. Fifty studies involved cancer patients; of these, 22 studies were exclusively of women with a diagnosis of breast cancer, and 21 were of a mix of cancer. Among studies of cancer patients, nine studies included noncancer controls and two studies included caregivers. Various points in the cancer treatment trajectory were represented; results are reported for patients who completed the FSI before beginning treatment, while undergoing treatment, after having completed treatment, and well into post-treatment survivorship. While the FSI has been used predominantly to assess fatigue in cancer patients, results also were reported for persons with schizophrenia or schizoaffective disorder [31], chronic fatigue syndrome [67], and heart failure [23]. Sample sizes in the identified publications ranged from a low of nine in a study to determine the feasibility of participating in a structured group exercise intervention among cancer patients undergoing chemotherapy [51] to a high of 1,756 in a study to develop a measure of fatigue and functional impairment in cancer patients with anemia [13]. Twenty-seven of the samples included in the studies were 100% female; only one study included a sample that was 100% male [16]. Two studies did not report gender characteristics of the sample [15, 16]. Fifty-two of the 55 studies reported mean age of the sample; 20 of these studies also reported age range in addition to mean age. The mean/ median age of participants ranged from 38 to 78 years. There were few studies of older cancer patients; only four reported a mean/median age greater than 65 years of age [16, 46, 52, 62]. The FSI was administered across a range of study designs. Thirty studies employed a cross-sectional design and 18 employed a longitudinal design. The FSI was also administered in single-arm trials [31, 51, 74] and randomized controlled trials [17, 21]. Forty-nine studies administered the English version of the FSI; Swedish, [29, 30] Chinese, [50, 65, 66], and Hebrew [15] translations of the FSI also were administered. Although many studies reportedly administered the complete 14-item FSI, only one study reported results for the 14th item assessing the daily pattern of fatigue [78]. Twenty-one studies expressly reported results on each of the three fatigue dimensions of severity, frequency, and. In 27 studies, results were limited to one or two of these dimensions. Two studies did not specifically identify the FSI items or scales used [9, 26]. Eight studies [15, 20, 21, 29, 30, 59, 65, 66] reported results based on modified approaches for scoring the FSI. These approaches included calculating a mean score across all four of the fatigue severity items [21], calculating a mean score across the most, least, and average fatigue severity items [20], creating a fatigue score ranging from by summing the first 13 FSI items [59], and creating an index score with a value between 0 and 10 by averaging participant responses to the four severity items, one frequency item, and the seven items [29, 30]. Reliability Table 2 presents data related to the reliability of the FSI. Of the 34 studies that reported results for the scale, 12 studies also reported Cronbach's alpha coefficient for this scale. Coefficients ranged from , indicating good internal consistency reliability. Among the ten studies that used other multi-item scales, only three reported internal consistency reliability data. Donovan and colleagues

4 Table 1 Characteristics of studies reporting results on the administration of the Fatigue Symptom Inventory Authors Disease Position in disease/ treatment trajectory Study purpose Sample size Sex Age (mean and SD) (range) Design Language version Items reported in analyses Hann et al. [22] Broeckel et al. [25] Hann et al. [26] Hann et al. [19] Hann et al. [27] Jacobsen et al. [28] Jacobsen et al. [29] Hann et al. [30] Stein et al. [31] Kirsh et al. [32] Breast cancer Completed autologous bone marrow transplantation at least 3 months previously and without evidence of disease Breast cancer Completed chemotherapy between 3 and 36 months previously Breast cancer Treated with surgery and completed radiotherapy Breast cancer Scheduled for radiotherapy, chemotherapy or bone marrow transplantation; completed radiotherapy or bone marrow transplantation Breast cancer Scheduled for autologous stem cell transplantation Breast cancer Completed or undergoing bone marrow transplantation, chemotherapy or radiotherapy Breast cancer Scheduled to receive minimum of four cycles of chemotherapy Active treatment to more than 1 year posttreatment Breast cancer Receiving chemotherapy or radiotherapy Compare fatigue severity in breast cancer patients treated with autologous bone marrow transplantation to noncancer controls and examine fatigue correlates Assess severity and nature of fatigue after chemotherapy and examine fatigue correlates Compare fatigue in patients treated with radiotherapy to noncancer controls and examine fatigue correlates 43 patients; 43 noncancer controls 61 patients; 59 noncancer controls 45 patients; 44 noncancer controls Develop and validate FSI 117 active treatment patients; 113 posttreatment patients; 94 noncancer controls Compare fatigue over time in patients treated with autologous stem cell transplantation to noncancer controls and examine fatigue correlates Investigate relationship of catastrophizing to individual differences in fatigue, emotional distress, and quality of life Examine characteristics, course and correlates of fatigue during chemotherapy Describe psychometric properties of FSI Investigate prevalence and severity of hot flashes and identify impact of hot flashes on quality of life In treatment Develop single-item screen for fatigue 31 patients; 49 noncancer controls 100% female Patients, 44.4 (5.6) (32 57); noncancer controls, 46.6 (5.7) (32 56) 100% female Patients, (11.10); noncancer controls, (11.25) 100% female Patients, 63.9 (12.60) (36 86); noncancer controls, 59.8 (9.0) (47 77) 100% female Active treatment patients, 52.0 (13.6); posttreatment patients, 53.0 (13.1); noncancer controls, 52.0 (10.9) 100% female Patients, 51.3 (15.4) (36 74), noncancer controls, 50.6 (7.9) (36 55) Cross-sectional English Severity, frequency, Cross-sectional English Severity, frequency, Cross-sectional English Severity, frequency, Mixed crosssectional and longitudinal English Severity, frequency, Longitudinal English Severity, frequency, 146 patients 100% female 55 (13) Cross-sectional English Severity, frequency, 54 patients; 54 noncancer controls 100% female Patients, 51 (10) (28 77); noncancer controls, 54 (11) (32 77) Longitudinal English Severity, frequency, 342 patients 29% male, 71% female 59 (12.7) Cross-sectional English Severity, frequency, 70 patients 100% female 57.1 (8.9) (39 81) Cross-sectional English 52 patients 31% male, 69% female 62.8 (14.8) Cross-sectional English Severity, frequency,

5 Table 1 (continued) Authors Disease Position in disease/ treatment trajectory Study purpose Sample size Sex Age (mean and SD) (range) Design Language version Items reported in analyses Ahles et al. [33] Bower et al. [34] Sadler et al. [35] Ahles et al. [36] Respini et al. [37] Donovan et al. [38] Jacobsen et al. [39] Jacobsen et al. [40] Kumar et al. [41] Stein et al. [21] Andrykowski et al. [42] Breast cancer or lymphoma At least 5 years post diagnosis Breast cancer Between 1 and 5 years post diagnosis Breast cancer or lymphoma Between 5 and 12 months post-bone marrow transplantation At least 5 years post diagnosis Patients>60 years of age undergoing outpatient chemotherapy or pamidronate Breast cancer Receiving chemotherapy plus radiotherapy or radiotherapy only Scheduled to receive minimum of four cycles of chemotherapy Breast cancer Post surgery and scheduled to receive radiotherapy or chemotherapy Compare cognitive functioning of long-term survivors treated with systemic or local chemotherapy; fatigue evaluated as potential confound Examine differences in proinflammatory cytokines and markers of cytokine activity between fatigued and nonfatigued patients Evaluate clinical syndrome approach to assessing cancer-related fatigue Compare cognitive functioning of long-term survivors treated with standard dose chemotherapy based on presence or absence of APOE E4 allele; fatigue evaluated as potential confound Examine correlates of fatigue in senior adult cancer patients Compare fatigue over time in patients undergoing chemotherapy plus radiotherapy or radiotherapy only Examine relationship of changes in hemoglobin levels over course of chemotherapy to changes in fatigue and cognitive functioning Examine relationship of catastrophizing in response to fatigue over course of radiotherapy or chemotherapy Breast cancer Receiving chemotherapy Observe relative contribution of fatigue on changes in body weight in patients receiving adjuvant chemotherapy After fourth cycle of chemotherapy Breast cancer Post surgery and scheduled for chemotherapy or radiotherapy Evaluate factorial and construct validity of MFSI-SF Identify prevalence of cancer-related fatigue, predictors of cancerrelated fatigue, and psychosocial correlates 128 patients NR for sample Cross-sectional English Severity, 40 patients 100% female Fatigued patients, 57.1 (8.7), nonfatigued patients, 58.4 (10.1) Cross-sectional English Severity, frequency, 51 patients 25% male, 75% female 48 (9) (23 63) Cross-sectional English Severity, frequency, 80 patients 20% male, 80% female APOE E4 positive 58.0 (10.4), APOE E4 negative 55.3 (9.7) Cross-sectional English Severity 77 patients 42% male, 58% female 71 (60 82) Cross-sectional English Severity, 134 patients 100% female Chemotherapy plus radiotherapy patients, 51 (9); radiotherapy patients, 58 (10) Longitudinal English Severity, 77 patients 23% male, 77% female 60 Longitudinal English Severity, frequency, 80 patients 100% female 55.3 (10.0) (32 78) Longitudinal English Severity, 198 patients 100% female 49.7 (10.0) Longitudinal English Frequency 304 patients 20% male, 80% female 54.9 (11.46) (28 88) Cross-sectional English Severity, 288 patients 100% female 54.5 (10.1) Longitudinal English Severity, frequency,

6 Table 1 (continued) Authors Disease Position in disease/ treatment trajectory Study purpose Sample size Sex Age (mean and SD) (range) Design Language version Items reported in analyses Booth-Jones et al. [43] Dahn et al. [44] Passik and Kirsh [45] Wilson et al. [46] Hartvig et al. [47] Hartvig et al. [48] Henderson et al. [49] Losito et al. [50] Monk et al. [51] 6 months after bone marrow transplantation Prostate cancer Completed radiotherapy within past 18 months Spousal caregivers of cancer patients Chronic schizophrenia or schizoaffective disorder of cancer-related fatigue Determine relationship of cognitive complaints and cognitive impairment to quality of life following bone marrow transplantation Examine relationship between physical activity and sexual functioning in patients treated with radiotherapy NA Examine quality of life of spouses of cancer patients with fatigue Post blood stem cell or bone marrow transplantation at least 6 months previously Receiving cytotoxic therapy Receiving cytotoxic therapy Explore safety, feasibility and potential efficacy of home-based aerobic exercise program Assess frequency, severity and consequence of fatigue and its impact on quality of life during chemotherapy; compare fatigue in cancer patients to noncancer caregivers Examine effect of providing information on fatigue and physical exercise in patients undergoing chemotherapy NA Investigate efficacy for positive and negative symptoms, safety and metabolic consequences of addition of aripiprazole to clozapine Receiving chemotherapy Determine feasibility of participating in structured group exercise program while undergoing chemotherapy; test impact of program on cancer-related fatigue No major surgery, radiotherapy or chemotherapy within 4 weeks Assess feasibility of etanercept and weekly docetaxel; determine whether inactivation of TNF by etanercept is associated with decrease in fatigue 65 patients 22% male, 78% female 47 (9) Cross-sectional English Severity, frequency, 111 patients 100% male 69 Cross-sectional English Severity, 25 patients 84% male, 16% female (12.49) Longitudinal English Sum of severity, frequency, 17 patients 35% male, 65% female 48.9 (10.4) Single-arm trial English Severity, frequency, 148 patients; 47 noncancer caregivers Patients, 32% male, 68% female; noncancer caregivers, 23% male, 77% female Patients, NR; noncancer caregivers, 44 (10) (26 79) Longitudinal Swedish Mean of severity, one frequency item, 74 patients 34% male, 66% female 60 (10) Longitudinal Swedish Mean of severity, one frequency item, 10 patients 80% male, 20% female 38.7 (8.9) Single-arm trial English Not reported 9 patients 100% female 58 Single-arm trial English Severity, frequency, 28 patients 61% male, 39% female Median=56 Randomized controlled trial English

7 Table 1 (continued) Authors Disease Position in disease/ treatment trajectory Study purpose Sample size Sex Age (mean and SD) (range) Design Language version Items reported in analyses Shun et al. [51] Siegel et al. [52] Temel et al. [53] Young and White [54] Cohen and Fried [55] Donovan et al. [56] Jacobs et al. [57] Jacobsen et al. [58] Karvinen et al. [59] Chronic fatigue syndrome Breast cancer Completed curative treatment at least 6 months previously Receiving chemotherapy Evaluate Chinese version of FSI and two other fatigue measures NA compare cognitive function and physical symptoms in patients characterized by low versus normal natural killer cell activity Not specified Establish convergent validity of one-item fatigue screen using FSI Breast cancer 2 12 months post surgery and receiving chemotherapy or radiotherapy Breast cancer End of treatment and 2, 4, and 6 months later Completed allogeneic or autologous hematopoietic stem cell transplant 6 or 12 months previously Breast cancer End of treatment and 2, 4, and 6 months later Bladder cancer Diagnosed within last 15 years Lai et al. [60] Liver cancer Over first 6 weeks of stereotactic radiotherapy Shun et al. [61] Ahles et al. [62] Cella et al. [63] Donovan et al. [20] Estimate prevalence of severe fatigue according to draft ICD-10 criteria for cancer-related fatigue; identify prevalence and moderators of clinical syndrome Randomized controlled trial of relaxation and guided imagery training and cognitive behavioral group therapy compared to standard care Examine utility of a cognitive behavioral model to predict fatigue Evaluate FACT-Cog and determine relationship of cognitive complaints to quality of life Characterize fatigue 221 patients; 221 noncancer controls Examine relationship of exercise to quality of life, including fatigue Compare fatigue and related factors during stereotactic radiotherapy Undergoing chemotherapy Assess responsiveness of Chinese versions of 3 fatigue measures, including FSI Breast cancer Post surgery and scheduled to receive chemotherapy, radiotherapy or hormonal therapy Women with no history of cancer Compare cognitive functioning of breast cancer patients prior to adjuvant therapy to noncancer controls and identify medical and psychological correlates Undergoing chemotherapy Develop measure of fatigue and functional impairment for patients with anemia NA Determine optimal FSI cutoff score 243 patients 47% male, 54% female Cross-sectional Chinese Sum of severity, frequency, 41 patients 100% female 44.5 (9.21) Cross-sectional English Severity, 100 patients NR for the 100 participants in cross validation study NR for the 100 participants in cross validation study Cross-sectional English Severity 69 patients 100% female 59 Cross-sectional English Severity, frequency,, daily pattern 114 patients 100% female 53.5 Randomized controlled trial Hebrew Mean of severity, frequency, 261 patients 100% female Not reported Longitudinal English Severity 101 patients 56% male, 44% female (12.18) Cross-sectional English Not reported 100% female Patients, 54.6 (9.53), noncancer controls, (9.01) Longitudinal English Severity, frequency, 525 patients 75% male, 25% female 70.2 (11.2) Cross-sectional English Severity, frequency, 91 patients 71% male, 29% female 62.4 (12.0) Longitudinal Chinese Severity, T1=243, T2=158; complete T1 and T2 data= patients, 45 noncancer controls 43% male, 57% female 51.2 Longitudinal Chinese Severity, frequency, 100% female Stage (8), stage (8.2), noncancer controls 52.9 (10) 1,756 patients 34% male, 66% female SDS (56.44 (13.28) (20 85); A (60.00 (12.95) (20 90) need to combine Cross-sectional English Severity Longitudinal English Severity 265 patients 100% female (9.42) (28 79) Cross-sectional English Severity

8 Table 1 (continued) Authors Disease Position in disease/ treatment trajectory Study purpose Sample size Sex Age (mean and SD) (range) Design Language version Items reported in analyses Espie et al. [64] Hormes et al. [65] Luciani et al. [66] Rogers et al. [67] Simonelli et al. [68] Yang et al. [69] Andrykowski et al. [70] Bower et al. [71] Carpenter et al. [72] Fink et al. [73] Jim et al. [74] At least 1 month post chemotherapy or radiotherapy Breast cancer Between 5 and 15 years post diagnosis Head and neck cancer Gynecologic cancers Not currently receiving chemotherapy Receiving treatment or completed treatment Between 2 and 10 years post-treatment and without evidence of disease Breast cancer Recently diagnosed with first disease recurrence Breast cancer Receiving radiotherapy and chemotherapy or radiotherapy only Breast or prostate cancer Gynecologic cancers Before, during and after radiotherapy At least 6 months posttreatment and between 2 and 10 years post diagnosis Randomized controlled trial of cognitive behavior therapy compared to treatment as usual for persistent insomnia Develop and validate body image measure Examine relationship of fatigue to functional dependence in older cancer patients Determine factors associated with fatigue, sleep and cognitive function Examine meaning of life as mechanism for relationship between physical and depressive symptoms Examine role of coping in relationship between stress and mental health quality of life Examine magnitude and correlates of fatigue measurement response shift Examine relationship of proinflammatory biomarkers to fatigue during radiotherapy Examine sexual self schema as potential moderator of sexual and psychological outcomes; fatigue evaluated as potential confound Heart failure NA Assess psychometric Breast cancer 6 months post chemotherapy or radiotherapy properties of 2 fatigue measures, including FSI, in heart failure patients and examine correlates of fatigue Characterize post-treatment cognitive function 150 patients 41% male, 69% female 61 (10.5) (38 86) Randomized controlled trial English 96 patients 100% female 56.9 (37 77) Cross-sectional English Not reported 214 patients 37% male, 63% female 78 (4.73) (70 89) Cross-sectional English Severity, frequency, 58 patients 74% male, 26% female 60.4 (13.1) Cross-sectional English Severity, 260 patients 100% female 56 (12) (23 83) Cross-sectional English 65 patients 100% female 54 (11) Longitudinal English 102 patients 100% female 54.7 (10.6) (29 82) Longitudinal English Severity, then-test severity 48 patients 42% male,%58 female Breast cancer 57.1 (29 75), prostate 70.6 (54 79) Longitudinal English Severity, frequency 175 patients 100% female 55 (12) (23 82) Cross-sectional English 87 patients 44% male, 56% female 57 (14) (21 89) Cross-sectional English 187 patients;187 noncancer controls 100% female Chemotherapy patients 50 (9), noncancer controls 53 (8), radiotherapy patients 58 (9), noncancer controls 59 (9) Cross-sectional English

9 Table 2 Reliability of the Fatigue Symptom Inventory Authors Multi-item scales reported Internal consistency reliability (Cronbach's alpha coefficient) Broeckel et al. [25] Hann et al. [26] Hann et al. [19] scores range= Jacobsen et al. [28] Jacobsen et al. [29] Hann et al. [30] score range= Stein et al. [31] Kirsh et al. [32] Ahles et al. [33] Bower et al. [34] Sadler et al. [35] Respini et al. [37] Donovan et al. [38] score range= Jacobsen et al. [39] Jacobsen et al. [40] score range= Stein et al. [21] score=0.95 Andrykowski et al. [42] score=0.95 Booth-Jones et al. [43] Dahn et al. [44] Passik and Kirsh [45] Sum of severity, frequency, Wilson et al. [46] Hartvig et al. [47] Mean of severity, one frequency item, Hartvig et al. [48] Mean of severity, one frequency item, Losito et al. [50] Monk et al. [51] Shun et al. [51] Sum of severity, frequency, Sum of severity, frequency, =0.92 Siegel et al. [52] Temel et al. [53] Mean of 4 severity items Young and White [54] Cohen and Fried [55] Mean of severity, frequency, score range= ; alpha for sum not reported Donovan et al. [56] Mean of 4 severity items 4-item severity score range= Jacobsen et al. [58] Karvinen et al. [59] Lai et al. [60] score range= Shun et al. [61] Sum of severity, frequency, Sum of severity, frequency, range= Donovan et al. [20] Mean of 3 severity items Mean of average, most, least=0.84 Espie et al. [64] Luciani et al. [66] Rogers et al. [67] Simonelli et al. [68] score=0.94 Yang et al. [69] combined with 3 other measures to score=0.93 create symptom stress score Carpenter et al. [72] score=0.94 Fink et al. [73] score=0.93 Jim et al. [74]

10 reported high alpha coefficients for the mean of the four severity items (range= ) [21] and the mean of three severity items (0.84) [20]. Shun et al. [23, 24] reported alpha coefficients ranging from for the sum of severity, frequency, and. The only published data on the test retest reliability of the FSI are derived from the original study [27] detailing the development and psychometric evaluation of the instrument. In that study, most of the scales produced low to moderate correlations between assessments at 3- and 6-week intervals in a group of breast cancer patients in active treatment and in a noncancer control group. For example, the test retest correlations for the active treatment group for number of days fatigued was r=0.53 from just prior to treatment to 2 3 weeks after the start of treatment, r=0.42 from just prior to treatment to 4 6 weeks after the start of treatment, and r=0.69 from 2 3 weeks after the start of treatment to 4 6 weeks after the start of treatment. Validity Concurrent validity Evidence bearing on the concurrent validity of the FSI, that is, the degree to which FSI items and scales are correlated with other published measures of fatigue, was reported in seven studies identified. As shown in Table 3, FSI severity and frequency items and the scale have been shown to be positively correlated with the Profile of Mood States (POMS) Fatigue subscale [23, 24, 27], the Cancer Fatigue Scale [65], the Schwartz Cancer Fatigue Scale-Revised [65], the Global Rating Scale [66], and the Multidimensional Fatigue Symptom Inventory-Short Form [70]. The correlation coefficients for the fatigue dimensions range from a low of r=0.50 between the average fatigue scale on the FSI and the Multidimensional Fatigue Symptom Inventory-Short Form mental fatigue subscale [70] and r=0.86 between the FSI scale and the POMS- Fatigue subscale [27]. FSI severity was negatively correlated (r= 0.87) with the FACIT-Fatigue Scale [72], a scale for which higher scores represent lower levels of fatigue [77]. The POMS-Fatigue subscale was the instrument used most frequently in combination with the FSI, and results support the validity of the FSI. For example, the mean correlations of the average fatigue severity item and scale with the POMS-Fatigue subscale were r=0.70 (95% CI= ) and r=0.76 (95% CI= ), respectively. Convergent validity Evidence bearing on the convergent validity of the FSI, that is, the degree to which FSI items or scales correlated with measures of conceptually related constructs was reported in ten studies (see Table 3). Correlations were reported with measures of depression and anxiety, including the Center for Epidemiologic Studies-Depression Scale (CES-D) [12, 24, 26, 27, 63], Geriatric Depression Scale [62], POMS-Depression subscale [23], Hospital Anxiety and Depression Scale [72], and State Trait Anxiety Inventory [26, 27]. Results support the convergent validity of the FSI. Among the studies reporting associations with the CES-D, for example, correlation coefficients range from The mean correlations of the FSI average fatigue severity item and the FSI scale with the CES-D were r=0.55 (95% CI= ) and r=0.68 (95% CI= ), respectively. The FSI has also been shown to be positively correlated with measures of symptom burden [3, 29] and self-reported cognitive impairment [37, 63]. Divergent validity Evidence bearing on the divergent validity of the FSI, that is, the degree to which FSI items and scales are either negatively correlated or not correlated with measures of constructs believed to be conceptually distinct from fatigue was reported in eight of studies (see Table 3). Most notably, negative correlations were reported between the FSI and the Medical Outcomes Study 36-Item Short Form (MOS SF-36) Vitality Scale [27] and the POMS-Vigor subscale [23]. Correlations near zero were reported between the FSI and the Marlowe-Crowne Social Desirability Scale [27]. Discriminative validity An instrument is said to have discriminative validity if the scores of one group differ as expected from those of a comparison group. For purposes of this review, we limited our evaluation of discriminative validity to those studies that compared patient groups to nonpatient control groups on the FSI. As shown in Table 4, all of the studies identified included cancer patients and noncancer controls with results presented such that effect sizes could be calculated for comparisons between these groups on the FSI. One of these studies did not include information about the specific FSI items used [2]. Seven studies provided data sufficient for us to calculate the mean effect size across studies on FSI severity and frequency items and on the scale. Results are as follows: most fatigue severity mean d=0.02 (95% CI= ), least fatigue severity mean d=0.30 (95% CI= ), average fatigue severity mean d= 0.24 (95% CI= ), fatigue right now mean d=0.28 (95% CI= ), number of days fatigued mean d= 0.48 (95% CI= ), amount of time fatigued each day mean d=0.56 (95% CI= ), mean d=0.34 (95% CI= ). Consistent with Cohen's categorization of effect sizes [14], with the exception of most fatigue severity, the magnitude of these effects ranged from small to medium with cancer patients consistently reporting worse scores on the FSI than noncancer controls.

11 Table 3 Concurrent, convergent, and divergent validity of the Fatigue Symptom Inventory Authors Concurrent validity Convergent validity Divergent validity Hann et al. [26] Patients: STAI state with (0.58); STAI trait with (0.48); CES-D with (0.73); MSAS symptom prevalence with (0.59); MSAS symptom severity with (0.65), MSAS symptom distress with (0.80); Controls: STAI state with (0.46); STAI trait with (0.50); CES-D with (0.56) Hann et al. [19] Hann et al. [31] Active treatment group: POMS-F with most (0.65), least (0.66), average (0.65), right now (0.69), number of days fatigued (0.57), amount of time each day fatigued (0.75), (0.78); post-treatment group: POMS-F with most (0.70), least (0.72), average (0.78), right now (0.74), number of days fatigued (0.65), amount of time each day fatigued (0.80), (0.86); controls: POMS-F with most (0.53), least (0.51), average (0.62), right now (0.63), number of days fatigued (0.75), amount of time each day fatigued (0.62), (0.73) POMS-F with most fatigue (0.71), least fatigue (0.65), average fatigue (0.75), fatigue right now (0.66), number of days fatigued (0.71), amount of time each day fatigued (0.64), and (0.78) Active treatment group: STAI with most (0.43), least (0.53), average (0.48), right now (0.63), number of days fatigued (0.34), amount of time each day fatigued (0.53), (0.59); Post-treatment group: STAI with most (0.52), least (0.61), average (0.56), right now (0.58), number of days fatigued (0.53), amount of time each day fatigued (0.67), (0.66); controls: STAI with most (0.28), least (0.23), average (0.38), right now (0.47), number of days fatigued (0.33), amount of time each day fatigued (0.38), (0.47); active treatment group: CES-D with most (0.43), least (0.42), average (0.46), right now (0.53), number of days fatigued (0.36), amount of time each day fatigued (0.57), (0.66); post-treatment group: CES-D with most (0.53), least (0.53), average (0.63), right now (0.60), number of days fatigued (0.55), amount of time each day fatigued (0.72), (0.76); controls: CES-D with most (0.34), least (0.37), average (0.48), right now (0.53), number of days fatigued (0.47), amount of time each day fatigued (0.47), (0.67) CES-D with most fatigue (0.47), least fatigue (0.40), average fatigue (0.55), fatigue right now (0.45), number of days fatigued (0.37), amount of time each day fatigued (0.52), and (0.63) Respini et al. [37] GDS with severity (0.29), (0.44) Stein et al. [21] MFSI-SF total (0.74), general (0.82), emotional (0.36), physical (0.58), mental (0.50) with average fatigue Shun et al. [51] CFS with fatigue sum (0.62), SCFS-R with fatigue sum (0.68) Temel et al. [53] FACIT-F with fatigue severity ( 0.87) HADS with fatigue severity (0.62) Jacobs et al. [57] FACT-Cog total score (0.60), FACT-Cog cognitive domain (0.53), mental acuity (0.41), concentration (0.40), verbal and nonverbal memory (0.43), verbal fluency (0.53), of functioning domain (0.58), functional (0.58), other people noticed deficits (0.45), change from previous functioning (0.55), quality of life domain (0.61); EORTC-cognitive functioning total (0.61) with fatigue Shun et al. [61] GRS with sum of severity, frequency, (0.41) Rogers et al. [67] CES-D (0.64), FACT/NCCN H&N Symptom Index (0.57), PSQI (0.40), FACT-Cog impact of cognitive dysfunction on quality of life (0.49) with average severity; CES-D (0.75), FACT/NCCN H&N Symptom Index (0.65), PSQI (0.43), FACT-Cog impact of cognitive dysfunction on quality of life (0.53) with Simonelli et al. [68] DEP1 (0.64), DEP2 (0.64), DEP3 (0.68) with Patients: SF-36 PCS with ( 0.50); SF-36 MCS with ( 0.71); Controls: SF-36 PCS with ( 0.49); SF-36 MCS with ( 0.61) Active treatment group: MC-20 with most ( 0.12), least ( 0.02), average ( 0.05), right now ( 0.03), number of days fatigued ( 0.26), amount of time each day fatigued ( 0.25), ; post-treatment group: MC-20 with most ( 0.16), least ( 0.15), average ( 0.12), right now ( 0.23), number of days fatigued ( 0.23), amount of time each day fatigued ( 0.22), ( 0.27); controls: MC-20 with most ( 0.08), least ( 0.03), average ( 0.16), right now ( 0.22), number of days fatigued ( 0.16), amount of time each day fatigued ( 0.13), ( 0.19); active treatment group: SF-36 vitality with most ( 0.64), least ( 0.62), average ( 0.61), right now ( 0.63), number of days fatigued ( 0.68), amount of time each day fatigued ( 0.72), ( 0.64); post-treatment group: SF- 36 vitality with most ( 0.66), least ( 0.64), average ( 0.75), right now ( 0.67), number of days fatigued ( 0.69), amount of time each day fatigued ( 0.72), ( 0.77); controls: SF-36 vitality with most ( 0.55), least ( 0.51), average ( 0.63), right now ( 0.55), number of days fatigued ( 0.60), amount of time each day fatigued ( 0.52), ( 0.73) SLDS-C with most fatigue ( 0.53), least fatigue ( 0.46), average fatigue ( 0.54), fatigue right now ( 0.47), number of days fatigued ( 0.49), amount of time each day fatigued ( 0.49), and ( 0.61) MFSI-SF vigor with average fatigue ( 0.60) FACT-Cog with average severity ( 0.41), ( 0.49) SF-12 PCS with ( 0.52), FACT with ( 0.30)

12 Table 3 (continued) Authors Concurrent validity Convergent validity Divergent validity Carpenter et al. [72] CES-D with (0.68) SF-12 MCS with ( 0.48), FACT with ( 0.50) Fink et al. [73] POMS-F with (0.66) POMS-D with (0.43) POMS-V with ( 0.28), SF-36 PF with ( 0.44) GDS Geriatric Depression Scale, DEP1-3 depression parcels (CES-D, SF-12 MCS, POMS-SF plus Anxiety Tension subscale, PTSD Symptom Checklist-Civilian version), PSQI Pittsburgh Sleep Quality Index, CFS Cancer Fatigue Scale, SCFS-R Schwartz Cancer Fatigue Scale-R, IOQ Information and Opinion Questionnaire, POMS-F Profile of Mood States Fatigue subscale, POMS-V Profile of Mood States Vigor subscale, SLDS-C Satisfaction with Life Domains Scale-Cancer, SF-36 PCS MOS Short Form-36 Physical Composite Score, SF-36 MCS MOS Short Form- 36 Mental Composite Score, SF-12 PCS MOS Short Form-12 Physical Composite Score, SF-12 MCS MOS Short Form-12 Mental Composite Score, SF-36 PF MOS Short Form-36 Physical Functioning subscale, GRS Global Rating Scale Sensitivity to change Data reflecting sensitivity of the FSI to change are presented in Table 5. For purposes of this study, we limited our evaluation of sensitivity to change to longitudinal studies involving the effects of an intervention or disease treatment that is likely to alter the level of fatigue relative to a pre-treatment baseline. Five studies reported results in the context of nonpharmacological interventions designed to ameliorate symptoms that included fatigue [15, 22, 30, 51, 74]. Three of these studies either reported an effect size or provided data sufficient for us to calculate standardized effect sizes. Espie et al. [22] conducted a randomized controlled trial of cognitive behavior therapy compared to treatment as usual for persistent insomnia. The FSI scale was used as a secondary outcome measure to evaluate the effectiveness of the intervention. Fatigue decreased significantly relative to the treatment as usual group from baseline to post-intervention and at the 6-month follow-up assessment. The standardized effect size for the scale for the cognitive behavioral intervention group versus treatment as usual was 0.81 from baseline to post-test and 0.82 from baseline to 6-month follow-up. Cohen and Fried [15] conducted a randomized controlled trial of relaxation and guided imagery group training and cognitive behavioral group therapy compared to standard care for physical and psychological symptoms and health locus of control perceptions. The FSI was used as a primary outcome measure to assess the different effects of the group interventions on fatigue. Fatigue decreased significantly in both intervention groups from pre-intervention to post-intervention. Effect sizes for the mean of 13 FSI items from pre-intervention to post- Table 4 Discriminative validity of the Fatigue Symptom Inventory Authors Discriminative validity Hann et al. [22] Broeckel et al. [25] Patients versus noncancer controls: most (0.31), least (0.33), average (0.40), right now (0.37), number of days fatigued (0.43), amount of time fatigued each day (0.37), items ( ) Patients versus noncancer controls: most (0.25), least (0.33), average (0.30), right now (0.40), number of days fatigued (0.24), amount of time fatigued each day (0.36), (0.42) Hann et al. [26] Patients versus noncancer controls: most ( 0.46), least ( 0.06), average ( 0.18), right now (0.04), number of days fatigued (0.80), amount of time fatigued each day ( 0.09), (0.06) Hann et al. [19] Active treatment patients versus noncancer controls: most ( 0.04), least (0.39), average (0.28), right now (0.39), number of days fatigued (0.42), amount of time fatigued each day (0.42), (0.54); post-treatment patients versus noncancer controls: most (0.03), least (0.31), average (0.28), right now (0.34), number of days fatigued (0.37), amount of time fatigued each day (0.37), (0.42) Hann et al. [27] Patients versus noncancer controls at mid-treatment: most ( 0.04), least (0.26), average (0.37), right now (0.32), number of days fatigued (0.71), amount of time fatigued each day (0.82), items ( ); patients versus noncancer controls near treatment completion: most (0.44), least (0.52), average (0.59), right now (0.18), number of days fatigued (0.60), amount of time fatigued each day (0.90), items ( ) Jacobsen et al. [29] Patients versus noncancer controls prior to second chemotherapy: average (0.43), number of days fatigued (0.50), amount of time fatigued each day (0.86), (0.62); patients versus noncancer controls prior to third chemotherapy: average (0.65), number of days fatigued (0.80), amount of time fatigued each day (1.01), (0.95) Jacobsen et al. [58] Ahles et al. [62] Patients versus noncancer controls end of treatment: most (0.26), average (0.33), right now (0.53), number of days fatigued (0.75), (0.33); patients versus noncancer controls 2-month follow-up: most ( 0.14), average ( 0.06), right now (0.25), number of days fatigued (0.23), (0.05); patients versus noncancer controls 4-month follow-up: most ( 0.19), average ( 0.09), right now (0.18), number of days fatigued (0.21), (0.00); patients versus noncancer controls 6-month follow-up: most ( 0.24), average ( 0.12), right now (0.11), number of days fatigued (0.18), (0.03) Patient stage 0 versus noncancer control: fatigue (0.59), patient stages 1 3 versus noncancer control: fatigue (0.48), patient stage 0 versus patient stages 1 3: fatigue ( 0.06), lower than expected cognitive performance versus normal performance: fatigue (0.06); fatigue item not specified

13 Table 5 Sensitivity of the Fatigue Symptom Inventory to change Authors Sensitivity to change/treatment Sensitivity to change/intervention Hann et al. [27] From prior to treatment to near treatment completion: most (0.14), least (0.16), average (0.03), right now (0.0), number of days fatigued (0.21), amount of time fatigued each day (0.90), items ( ) Jacobsen et al. [29] From prior to chemotherapy cycle 1 to after chemotherapy cycle 3: average (0.05), number of days fatigued ( 0.08), amount fatigued each day (0.36), (0.09) Jacobsen et al. [39] From prior to chemotherapy cycle 1 to after chemotherapy cycle 3: average (0.0), number of days fatigued ( 0.20), ( 0.03) Wilson et al. [46] Hartvig et al. [47] Henderson et al. [49] Cohen and Fried [55] Shun et al. [61] Espie et al. [64] Andrykowski et al. [70] From prior to chemotherapy cycle 1 2 weeks after chemotherapy cycle 1: fatigue index (0.32) From prior to addition of adjuvant medication to 6 weeks later: fatigue item not specified ( 0.58) From day of chemotherapy to 2 days after chemotherapy: total of 13 FSI items (0.70); Responsiveness of FSI: effect sizes for four groups based on responses to the Global Rating Scale: no increase=0.41, small increase=0.97, moderate increase=1.20, large increase=0.75 From pre-treatment to post-treatment for CT or RT group: most (0.53), average (0.57); from pre-treatment to post-treatment for CT+RT group: most (0.48), average (0.44) From pre-intervention to post-intervention: severity ( 0.35), frequency ( 0.53), ( 0.43) From pre-intervention to post-intervention for CB therapy group: mean of 13 FSI items ( 1.26); from pre-intervention to post-intervention for relaxation therapy group: mean of 13 FSI items ( 1.96) Cognitive behavioral intervention group versus treatment as usual from baseline to post-test: ( 0.81); cognitive behavioral intervention group versus treatment as usual from baseline to 6-month follow-up: ( 0.82) intervention were 1.96 for the relaxation and guided imagery group and 1.26 for the cognitive behavioral therapy group. Wilson et al. [74] conducted a single-arm trial of home-based aerobic exercise for sedentary cancer survivors treated with hematopoietic stem cell transplantation. The stated purpose of the study was to explore the safety, feasibility, and potential efficacy of home-based aerobic exercise in this population. The FSI was used as one of the outcome measures. Compared to the pre-intervention assessment, participants reported less fatigue after completing the home-based exercise program. The effect sizes for postintervention versus pre-intervention fatigue were 0.35 for fatigue severity, 0.53 for frequency, and 0.43 for the scale. As shown in Table 5, we also identified seven studies that assessed fatigue related to disease treatment. Six studies included cancer patients undergoing cancer treatment, including chemotherapy, radiotherapy, and autologous stem cell transplantation; four of these provided data sufficient for us to calculate effect sizes for FSI severity items, frequency items, and the scale [4, 25, 42, 43]. Mean effect sizes were calculated across more than one study for several FSI items: most fatigue severity=0.38 (95% CI= ), average fatigue severity=0.22 (95% CI= ), number of days fatigued= 0.02 (95% CI= ), amount of time fatigued each day=0.63 (95% CI= ), =0.03 (95% CI= ). The effect sizes for least fatigue severity and for fatigue right now were calculated using data from a single study as 0.16 and 0.0, respectively [25]. With the exception of fatigue right now, number of days fatigued, and, the magnitude of these effects ranged from small to medium with patients generally reporting worsening fatigue over the course of treatment. Finally, one treatment study investigated the efficacy of adding aripiprazole to clozapine therapy in patients with chronic schizophrenia. In this study, the effect size for self-reported fatigue on the FSI at the end of the 6-week trial compared to baseline was 0.62 [31]. Compared to baseline, patients reported less fatigue on the FSI at completion of the trial. Shun et al. [66] conducted a study designed specifically to evaluate the responsiveness, including sensitivity to change, of three commonly used fatigue measures, including the FSI, in patients undergoing chemotherapy. Fatigue was assessed before and 2 days after the administration of chemotherapy. Fatigue as assessed by the FSI increased

14 significantly over this time period. Shun et al. reported an effect size of 0.70 for the mean of 13 FSI items. They also reported effect sizes for four groups for the 13-item FSI mean based on responses to a global rating scale for selfreported change in fatigue: no increase=0.41, small increase=0.97, moderate increase=1.20, large increase= 0.75; these results suggest that the FSI effectively discriminated between these groups although the effect size for the group self-reporting a large change was less than that of the group reporting a moderate change in fatigue. Discussion We identified 55 articles published between 1997 and November 2009 that reported results on the FSI. The instrument has thus far been used predominantly with cancer patients, but results also have been reported for other chronic disease patients. In general, the studies reflect a broad range of sample sizes of men and women across a wide age range. They also reflect a variety of study designs, including randomized controlled trials. Nearly half of the studies identified used the first 13 items of the FSI. Only one study reported results for the last item assessing respondent's daily pattern of fatigue. Reliability of the FSI was assessed in terms of internal consistency and test retest reliability. With respect to internal consistency, 12 studies reported Cronbach's alpha coefficients for the scale, two studies reported alpha coefficients for the mean of select severity scales, and one study reported alpha coefficients for the sum of the first 13 items. These coefficients ranged from 0.84 to 0.96, indicating good internal consistency reliability of multiitem scales on the FSI. Test retest reliability of the FSI was reported in only one study; this study reported low to moderate correlations between administrations approximately 3 and 6 weeks apart. It is important to note that the study's methodological approach to evaluating test retest reliability, including the time intervals within which the assessments were made and the inclusion of patients in active treatment, may account, at least in part, for the relatively weak test retest reliability. Validity of the FSI was assessed in terms of concurrent, convergent, divergent, and discriminative validity. Evidence for the concurrent validity of the FSI was available from studies that generated moderate to high correlations between the FSI and other measures of fatigue, most of which have been widely used with medically ill patients, including cancer patients. Convergent validity of the FSI was demonstrated by studies that generated moderate to high correlations between the FSI and measures of depressive and anxious symptomatology, in particular, as well as correlations between the FSI and measures of symptom burden and cognitive impairment. Divergent validity of the FSI was demonstrated by correlation coefficients near zero with the Marlowe-Crowne Social Desirability Scale and by moderate to high negative correlations between the FSI and MOS SF-36 Vitality scale and POMS-Vigor subscale. Discriminative validity was demonstrated in studies comparing cancer patients and noncancer controls. Examination of effect sizes indicates that in general, cancer patients reported scores indicative of greater fatigue severity, fatigue frequency, and perceived associated with fatigue than noncancer controls. With one exception, effect sizes reported or calculated based on available data ranged from small to medium. The sensitivity of the FSI to change was demonstrated in studies designed to test the effect of an intervention with fatigue as a primary or secondary outcome and in disease treatment studies. Across intervention studies, effect sizes ranged from small to large and were negative, indicating that the interventions generally were effective in reducing fatigue as measured by the FSI. Across treatment studies, with few exceptions, effect sizes were distributed across a range of small to medium and positive, indicating that fatigue as measured by the FSI generally increased over the course of treatment. A 2007 review of publications in MEDLINE and PsycINFO by Hjollund et al. [33] reported that the FSI is one of the more frequently used fatigue-specific measures. The authors noted that it had been used in ten studies prior to February 2004, and that its use was limited to cancer patients. Our broader, more recent review demonstrates that the FSI has been even more widely used than previously identified and that its utility has not been limited to the assessment of fatigue in cancer patients. Hjollund et al. [33] did not comment on the psychometric properties of the FSI, however, and as previously noted, the use of any fatigue measure is predicated, in part, on the strength of a scale's psychometric properties. To this end, several systematic reviews have reported and provided commentary on the psychometric properties of the FSI. Consistent with the present review, previous systematic reviews [18, 44, 57] have noted the fact that the FSI has been validated in both men and women, across a wide age range, including the elderly, and in a variety of cancer diagnoses, including patients in active treatment and survivors. The results of the present review demonstrate its use not only in cancer patients but in persons without a diagnosis of cancer and in individuals with other serious physical illnesses and mental disorders. With respect to the specific psychometric properties of the FSI, reviewers have noted, as we have, that the data are limited with respect to the measure's test retest reliability and that the available data suggests weak test retest reliability [44, 57]. More research regarding this aspect of the FSI is needed. One review [57] noted that data are also lacking with respect to

15 its use with patients receiving palliative care. The present review confirms that to date, there has been little use of the FSI in studies of patients with advanced disease or at the end of life. One review [57] also noted that the measure has been used in numerous studies but with an overall small number of patients. The results of the present review indicate that while early studies included relatively small sample sizes, more recent research has included samples sizes of more than 200 and 300 patients. Two reviews [18, 73] also noted the absence of an FSI cut-off score. This is no longer the case as the publication by Donovan et al. [20] explicitly identified an optimal cut-off score on the FSI to identify clinically meaningful fatigue. Finally, two reviews [18, 57] noted the lack of evidence for the sensitivity of the FSI to change, while another [73] noted that the measure demonstrates moderate sensitivity to change. We believe the present review clarifies this issue. Data were available from several published studies to calculate standardized effect sizes, a commonly used indicator of the magnitude and meaning of change over time [32, 36, 47]. Although we were unable to calculate the standardized response mean or Guyatt's responsiveness index, two statistics that might better characterize the ability of the FSI to change over time [36], we nevertheless believe that the results of the present review provide good empirical evidence of the sensitivity of the FSI to change. In conclusion, the purpose of this paper was to systematically review and evaluate the psychometric properties of the FSI based on its use in published research studies and to characterize the evidence base supporting its current and future use. Previous reviews of fatigue measures have cited the earliest studies documenting the psychometric properties of the FSI and concluded that its psychometric properties are moderately good [18] or good [73]. 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